Showing papers in "International Journal of Cancer in 1971"

Demonstration of cell-mediated immunity to human neoplasms of various histological types.

Abstract: Peripheral blood lymphocytes from a total of 373 tumor patients were tested by either a colony inhibition or a cytotoxicity test for cell-mediated immunity against human neoplasms of various histological types. Lymphocytes from 51 of 59 patients studied (88%) either reduced colony numbers formed by plated autochthonous tumor cells or were cytotoxic to them, and lymphocytes from 78 of 87 patients tested (89%) had a similar effect on allogeneic tumor cells of the same histological type as those of the lymphocyte donors. Evidence indicating antigenic cross-reactivity between tumors of the same histological type was obtained for the following seven groups of neoplasms: malignant melanomas, carcinomas of the colon, breast, testis, endometrium and ovary, and various sarcomas. Lymphocytes affecting tumor cells had no effect on normal cells from the same patient, or on cells from other types of neoplasms than the target cells under study. The degree of cell-mediated immunity, as detectable with the techniques employed, was approximately the same in patients having active neoplastic disease as in patients who were clinically symptom-free. Eleven of 12 patients who were tested after having been symptom-free for more than 2 years had a lymphocyte-mediated anti-tumor immunity. Mise en Evidence D'une Immunite A Mediation Cellulaire Envers les Neoplasmes Humains de Divers Types Histologiques Nous avons etudie des lymphocytes du sang peripherique de 373 cancereux au moyen de tests d'inhibition des colonies et de cytotoxicite en vue de mettre en evidence une immunite a mediation cellulaire envers les neoplasmes humains de divers types histologiques. Les lymphocytes de 51 des 59 sujets etudies (88%) ont fait diminuer le nombre de colonies formees par les cellules tumorales autochtones ou se sont montres cytotoxiques a l'egard de ces cellules; les lymphocytes de 78 des 87 sujets testes (89%) ont eu un effet analogue sur les cellules tumorales allogeneiques du měme type histologique que celles des donneurs de lymphocytes. Nous avons obtenu la preuve de l'existence d'une reactivite antigenique croisee entre les tumeurs du měme type histologique pour les 7 groupes de neoplasmes suivants: melanomes malins, epitheliomas du colon, du sein, des testicules, de l'endometre et des ovaires, et divers sarcomes. Les lymphocytes agissant sur les cellules tumorales n'ont pas eu d'effet sur les cellules normales du měme malade, ni sur les cellules de neoplasmes de types histologiques differents. Le degre d'immunite a mediation cellulaire decele au moyen des techniques utilisees etait a peu pres le meme chez les malades atteints d'une neoplasie active que chez les sujets ne presentant aucun symptǒme clinique. Nous avons observe une immunite antitumorale a mediation lymphocytaire chez 11 des 12 malades qui ont ete testes apres ětre restes asymptomatiques pendant plus de deux ans.

Blocking of cell-mediated tumor immunity by sera from patients with growing neoplasms.

Abstract: Blood lymphocytes from tumor patients can specifically destroy cultivated neoplastic cells of the same histological origin as the tumors of the lymphocyte donors, irrespective of whether or not the donors have symptoms of growing tumor. The purpose of the present study was to investigate whether sera from tumor patients could block the cytotoxic effect of lymphocytes immune to the specific antigens of the respective neoplasms. A wide variety of tumors were included in the tests, namely malignant melanomas, carcinomas of the colon, breast, ovary, endometrium, kidney, cervix uteri, lung, larynx, bladder, Fallopian tube, lip, seminomas and sarcomas. Sera from 67 out of 81 patients with growing neoplasms were found to block the cytotoxic effect of specifically immune lymphocytes. A blocking effect was seen both when the tumor cells, lymphocytes and sera were derived from the same patients and when the lymphocytes and sera were taken from different donors who had the same types of tumor as the target cells. No blocking was seen when the same sera were tested on tumors of histological types other than those of the respective serum donors. A blocking serum activity was seen in only three of 19 patients who were symptomfree after tumor therapy. The findings thus suggest that there is a correlation between tumor growth in vivo and the presence of a blocking serum activity in vitro. Blocage de L'immunite Tumorale A Mediation Cellulaire au Moyen de Serums de Malades Porteurs de Neoplasmes Evolutifs Les lymphocytes du sang de cancereux peuvent detruire specifiquement des cellules neoplasiques en culture dont l'origine histologique est la měme que celle des tumeurs des donneurs de lymphocytes, que ces donneurs presentent ou non des symptǒmes de tumeurs en pleine evolution. Nous avons cherche a savoir si les serums de cancereux peuvent bloquer l'effet cytotoxique des lymphocytes immuns envers les antigenes specifiques de chaque neoplasme. Nous avons choisi pour ces etudes une large gamme de tumeurs: melanomes malins, carcinomes du colon, du sein, des ovaires, de l'endometre, du rein, du col de l'uterus, du poumon, du larynx, de la vessie, des trompes de Fallope, de la levre, seminomes, sarcomes. Nous avons constate que le serum de 67 des 81 malades porteurs de neoplasmes evolutifs bloque l'effet cytotoxique des lymphocytes specifiquement immuns. l'effet de blocage se produit aussi bien lorsque les cellules tumorales, les lymphocytes et les serums proviennent des měmes malades que lorsque les lymphocytes et les serums proviennent de differents donneurs atteints du měine type de tumeur que les cellulescibles. Nous n'avons observe aucun blocage lorsque nous avons teste les měmes serums sur des tumeurs de type histologique different de celles de chaque donneur de serum. Nous avons remarque un blocage chez 3 malades seulement sur les 19 qui etaient devenus asymptomatiques apres traitement de la tumeur. Ces constatations donnent a penser qu'il existe une correlation entre la croissance tumorale in vivo et l'activite de blocage des serums in vitro.

The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV.

Abstract: Continuous human lymphoblastoid cell lines (LL), derived from lymphoid tissue or peripheral blood of 20 adults without histories of recent infectious mononucleosis at a frequency close to 100 %, were examined for the presence of Epstein-Barr virus (EBV) using immunofluorescence methods for the detection of EBV-dependent cell membrane and EB viral capsid antigens. All lines except one were found to be EBV carriers in the initial tests, but the antigens gradually disappeared in most during the course of an observation period of 4 months. Only eight lines maintained the initial percentage of antigen-containing cells. The results of the two immunofluorescence tests, performed simultaneously on each cell pool, were concordant in all instances. Sera were available from 16/20 donors. All cell donors, except one, possessed antibodies to EBV as an indication of prior EBV infections. The growth-promoting role of EBV in the establishment of LL was supported by studies with fetal lymphoid tissue cultured by the same grid method which yielded the high frequency of LL from adults. In sharp contrast to the results obtained with adult lymphoid tissue, no lines were established from 20 fetuses aged 13-20 weeks. However, when such tissue was exposed to a cell-free filtrate prepared from an EBV-carrying LL lymphoblastoid cell, lines were established in some instances. Filtrate from an EBV-negative line inoculated into parallel cultures failed to promote the establishment of LL. The results indicate that EBV infection in vivo or in vitro may be a prerequisite for the indefinite growth of lymphoblastoid cells in vitro and that EBV infections, as a rule, are not vertically transmitted. Dans des lignees lymphoblastoides (LL) humaines continues, constituees avec une frequence proche de 100% a partir de tissu lymphoide ou de sang peripherique de vingt adultes n'ayant pas recemment souffert de mononucleose infectieuse, les auteurs ont recherche la presence de virus d'Epstein-Barr (VEB) par immunofluorescence afin de deceler les antigenes des capsides virales EB et les antigenes de la membrane cellulaire dependant du VEB. Les tests initiaux ont montre que toutes les lignees sauf une etaient porteuses de VEB mais que les antigenes disparaissaient progressivement de la plupart de ces lignees au cours d'une periode d'observation de 4 mois. Seules 8 lignees ont conserve leur pourcentage initial de cellules contenant l'antigene. Les resultats des deux tests d'immunofluorescence effectues simultanement sur chaque pool cellulaire concordaient dans tous les cas. Les serums provenaient de 16/20 donneurs. Tous les donneurs de cellules sauf un possedaient des anticorps du VEB, signe d'infection prealable par le VEB. Le rǒle du VEB en tant qu'agent favorisant la croissance dans la constitution des LL a ete confirme par des etudes de tissu lymphoide fœtal cultive par la methode de la grille qui a permis d'obtenir une frequence elevee de LL avec des tissus d'adultes. On note un fort contraste avec les resultats obtenus en utilisant du tissu lymphoide d'adultes, puisqu'aucune lignee n'a ete etablie a partir de 20 foetus de 13 a 20 semaines. Toutefois, lorsque ces tissus ont ete exposes a un filtrat acellulaire prepare a partir de LL porteuses de VEB, des lignees lymphoblastoides ont pu ětre etablies dans certains cas. Un filtrat provenant d'une lignee VEB-negative inocule a des cultures paralleles n'a pas facilite la constitution de LL. Les resultats indiquent que l'infection par le VEB in vitro ou in vivo peut ětre une condition prealable a la croissance indefinie des cellules lymphoblastoides in vitro et que, en regie generate, les infections par le VEB ne sont pas transmises verticalement.

Demonstration of two distinct components in the early antigen complex of Epstein-Barr virus-infected cells.

Abstract: Examination of numerous sera from patients with infectious mononucleodis (IM), Burkitt's lymphoma (BL) or nasopharyngeal carcinoma (NPC) for antibodieh to Epstein-Barr virus (EBV) induced early antigens (EA) revealed two distinct patterns of immunofluorescence in abortively EBV-infected Raji cells. One showed diguse (D) staining of the nucleus and cytoplasm of invaded cells, the other (R) was restricted to masses in the cytoplasm. Although D- or R-reactive Raji cells became detectable at similar times after exposure to EBV, the percentages of D-positive cells initially exceeded R-positive cells but ultimately both were nearly equal in number. R-positive cells almost invariably contained also D. In EBV-exposed RPM1 64–10 cells, frequently only D was synthesized. D antigen, in contrast to R, resisted fixation by methanol or ethanol, whereas R proved more resistant than D to proteolytic enzymes. Comparative serum titration on acetone, respectively ethanol-fixed Raji-EBV cell smears revealed that the transitory anti-EA response observed in many IM patients was restricted almost exclusively to anti-D. Anti-EA positive sera from NPC patients also showed dominantly anti-D activity whereas, in BL sera, anti-R was usually, but not always, dominant, often being the only antibody to the EA complex present. Preliminary tests with pronase-treated Raji-EBV cell smears indicated that dominantly anti-D reactive sera from IM patients were free of anti-R whereas such sera from NPC or BL patients usually gave positive reactions which in part, however, failed to conform with the R pattern. The possible implications of these results have been discussed.

Kaposi's sarcoma in Uganda: A clinico‐pathological study

Abstract: Thirty-seven Ugandan Africans with Kaposi's sarcoma were studied prospectively and a clinical classification was devised based on the clinical presentation of the disease and the appearance of the cutaneous tumours. The disease could be sub-classified into four major groups. The first consisted of patients with nodular disease which was associated with a relatively benign clinical course. Patients in the next two groups (florid and infiltrative) had more aggressive disease with extensive cutaneous lesions on one or more extremities, generally associated with involvement of adjacent bone. Cutaneous lesions in the florid group were exophytic tumours while in the infiltrative group deep lesions associated with dense fibrosis predominated, Finally, the lymph-adenopathic variety occurred mainly in children where lymph-node involvement was usually the sole manifestation, and in young adults where skin involvement was seen concomitantly. Differing histological patterns were found to correlate with the four clinical types of involvement.

Epidemiologic patterns of Hodgkin's disease.

Abstract: The epidemiology mid histology of Hodgkin's disease in Cali, Colombia is reported on the basis of data from the Cancer Registry and a review of slides from several of the city's departments of pathology. Comparison of the results with incidence data published by UICC and with other reports on histologic subclassification has led to the identification of several epidemiologic patterns. Pattern I is characterized by high rates in children and predominance of histologic subtypes associated with poor prognosis. Pattern III is characterized by high rates in young adults and predominance of histologic subtypes associated with better prognosis. Pattern II is intermediate. These patterns are related to the economic stratification of the communities studied, and it is suggested that many of the epidemiological variegations of Hodgkin's disease may be explained on the basis of the interplay of environmental and host etiologic factors.

Studies of carcino-fetal proteins. 3. Development of a radioimmunoassay for -fetoprotein. Demonstration of -fetoprotein in serum of healthy human adults.

Abstract: A radioimmunoassay (RIA) for human alpha fetoprotein (AFP) was developed which has a sensitivity of 250 pg/ml (.25 ng) making this method 20000-40000 times more sensitive than immunodiffusion. Radioiodination of AFP was described and radiation damage to the preparation was minimal since the AFP could be used again for RIA after refractionation. AFP was detected in normal human serum as shown by the following findings: 1) Normal serum in 1:5 dilution inhibited the binding of labeled AFP by antibody. 2) Activity inhibiting in RIA could be removed from serum before treatment with anti-AFP immunoadsorbent. 3) At low pH AFP could be eluted from immunoadsorbent that had been previously treated with serum. 4) After fractionation of normal human serum by electrofocusing the activity inhibiting in RIA was present in a fraction whose isoelectric point was that previously shown for fetal AFP. The AFP found in cancer believed to be a product of an activated fetal gene which was suppressed at the adult stage may be present without carcinogenesis since these results intimate that suppression of this gene is not complete in all adult cells. This sensitive RIA is hoped to provide early cancer detection possibilities.

Serum factors in tumor‐free patients cancelling the blocking of cell‐mediated tumor immunity

Abstract: It has been previously shown that lymphocytes from cancer patients can kill cultivated neoplastic cells of the type carried by the lymphocyte donors and that sera from patients with growing tumors of the respective types can specifically block the tumor-cell destruction. The present study demonstrates that sera from all of seven tumor patients tested (one with melanoma, one with colonic carcinoma and four with breast carcinoma), who had become clinically tumor-free, could “unblock” ( = abrogate) the blocking effect of sera from patients bearing tumors of the respective types, thus making it possible for immune lymphocytes to kill cultivated neoplastic cells in the combined presence of the “unblocking” and blocking sera.

Studies of carcino‐fetal proteins. II. Biochemical comparison of α‐fetoprotein from human fetuses and patients with hepatocellular cancer

Abstract: Alpha fetoprotein (AFP) from human fetuses and hepatocellular carcinoma patients was isolated and characterized. AFP isolated from human fetuses and patients with hepatocellular cancer gave a reaction of immunological identity in immunodiffusion. The electrophoretic mobilities of these proteins in polyacrylamide gels were identical. The formation of a 140000-molecular-weight form was also similar in the fetal and carcinoma AFPs. Gel electrophoresis in the presence of sodium dodecyl sulfate gave a molecular weight of 70000 for the single polypeptide chain of both proteins. Under these conditions the mobility of the AFPs was considerably faster than that of human transferrin and just slower than that of bovine albumin. Amino acid compositions of the 2 AFPs were similar. Peptide maps of tryptic digest of reduced and alkylated AFPs were compared and each AFP showed 30 peptides. The location of each peptide seemed to be the same on the maps of the 2 proteins. Also indistinguishable were peptide maps prepared from heat-saturated protein samples. Comparison of carbohydrate analyses of the fetal and cancer AFPs also revealed close similarity in the total amount of carbohydrate (4%) and in the relative amounts of hexose (2.2 vs. 2 for fetal and cancer respectively) hexosamine (1.2 vs. 1.1) and sialic acid (.9 vs. .9 or 2 moles of sialic acid/mole of protein). Thus both fetal and cancerous liver cells produce AFP which is structurally indistinguishable and probably identical.

Studies of carcino-fetal proteins: physical and chemical properties of human alpha-fetoprotein.

Abstract: Alpha fetoprotein (AFP) which comprises 1/10th of all fetal proteins was purified and characterized from serum of human fetuses. AFP could be partially separated from other serum proteins by electrofocusing and AFP formed a single peak at pH 4.75. An anti-AFP serum was used for immunochemical purification of AFP from fetal sera. The purified AFP gave 2 electrophoretically distinct components which in immunodiffusion acted identically with anti-AFP antibodies. These were separated by gel filtration and the molecular weights obtained were 140000 and 70000 respectively for the slower and faster electrophoretic bands. The larger fetoprotein was not present in native serum but appeared after repeated freezing and thawing. AFP that had been dissociated into its polypeptide components by sodium dodecyl sulfate however gave only a single band in gel electrophoresis and molecular weight calibration gave a 70000 value for the single fetoprotein polypeptide. AFP amino acid composition is presented tabularly. AFP contained 4.3% carbohydrate consisting of 2.2% hexose 1.2% hexosamine and .9% sialic acid.

Cellular and humoral immunity against human malignant melanoma

Abstract: The humoral and cellular immunological responses of melanoma patients against tumor-associated antigens were studied by means of the indirect membrane immunofluorescence test and a microassay for cell-mediated cytotoxicity. Melanoma target cells obtained from 22 different surgical specimens were used. A total of 15 different sera were tested in 27 fluorescence assays. Humoral antibodies were found in all the 13 autochthonous sera tested: eight out of ten sera cross-reacted with one or two allogeneic melanoma cells. The 31 microassays performed with lymphocytes from 16 patients showed that effector cells specifically killed the melanoma target cells in seven out of 12 autochthonous tests and in 14 out of 19 allogeneic tests. No cytotoxicity was found when melanoma-patient lymphocytes were tested against control cells or when control lymphocytes were tested against melanoma cells. The observed cross-reactivity pattern indicates that more than one tumor-specific antigen may be present in melanoma cells.

High-frequency establishment of human immunoglobulin-producing lymphoblastoid lines from normal and malignant lymphoid tissue and peripheral blood.

Abstract: Human hematopoietic tissue and lymphocytes separated from 10-20 ml samples of peripheral blood have been grown in vitro in a lens-paper and a gelatin foam (Spongostan) grid organ culture. Lymphoblastoid cell lines were established from the lymph nodes, and in one case from the spleen, of 22/23 consecutive, unselected adult individuals without manifest malignancy or infectious mononucleosis. Biopsies from 5/8 patients with malignancy were successful. The blood tines were derived from 5/10 patients with and 4/10 donors without malignancy. The very high frequency of success from normal tissue confirms the assumption made before that the spontaneous establishment of lymphoblastoid cell lines is unrelated to manifest malignancy of the donor. The results indicate that lymphoid cells with a potential for infinite proliferation (“lymphoblastoid transformation”) are present in almost all adult individuals. The Spongostan grid culture is a superior instrument to select and/or adapt these cells in vitro. All lymphoblastoid lines produced immunoglobulins. The majority started with a “polyclonal” pattern of immunoglobulin production but changed towards stable “ monoclonality “ during the course of long-term cultivation. It is suggested that lymphoblastoid lines have a polyclonal origin and that the reason for development of a monoclonal line is a selection of one cell clone either in the organ culture during establishment or in long-term culture. Du tissu hematopoietique humain et des lymphocytes recueillis dans des echantillons de 10 a 20 ml de sang peripherique ont ete cultives in vitro dans une culture organo-typique sur grille (Spongostan) pour laquelle on a utilise de la mousse de gelatine et du papier special pour verres. Des lignees cellulaires lymphoblastoides ont ete constituees a partir des ganglions lymphatiques — et, dans un cas, a partir de la rate — d'une serie de 22/23 sujets adultes non selectionnes sans neoplasme manifeste ni mononucleose infectieuse. Les biopsies de 5/8 malades cancereux ont reussi. La tres forte frequence des succes obtenus avec le tissu normal confirme l'hypothese deja emise selon laquelle l'etablissement spontane de lignees cellulaires lymphoblastoides n'est pas lie au neoplasme manifeste du donneur. Les resultats indiquent que des cellules lymphoides capables de proliferation illimitee (“transformation lymphoblastoide”) apparaissent chez presque tous les sujets adultes. La culture Spongostan est un excellent moyen de selectionner et/ou d'adapter des cellules in vitro. Toutes les lignees lymphoblastoides produisaient des immunoglobulines. La majorite a commence par un type de production d'immunoglobulines “polyclonal”, mais s'est oriente vers une “monoclonalite” stable pendant la culturea long terme. L'auteur estime que les lignees lymphoblastoides ont une origine polyclonale et que le developpement d'une lignee monoclonale est dǔ a la selection d'un clone cellulaire, soit dans la culture organo-typique au cours de l'etablissement, soit dans la culture a long terme.

Distribution of intracisternal a-particles in a variety of normal and neoplastic mouse tissues

Abstract: Examination of various normal and neoplastic tissues reveals the presence of intracisternal A-particles in five strains of mice and their hybrids. Cell types derived from all three embryonic germ layers contain these particles, and their presence in gonadal tissue of both sexes suggests that vertical transmission can take place. Intracisternal A-particles are found in most of the tissues known to support the replication of mouse leukemia viruses and mammary tumor virus. Further, they have been shown to coexist in the same cell with C particles and intracytoplasmic A-particles (mammary tumor virus precursors). Although it has not been possible to demonstrate biological activity associated with intracisternal A-particles, there is the possibility that they represent the partial gene expression of one of the known oncogenic RNA viruses, and as such serve as a marker for an incomplete replication cycle. Repartition des Particules A Intracisternales dans Divers Tissus Neoplasiques et Normaux de Souris L'examen de divers tissus neoplasiques et normaux revele la presence de particules A intracisternales chez cinq lignees de souris et leurs hybrides. Les types cellulaires derives des trois feuillets du blastoderme contiennent ces particules, dont la presence dans le tissu des gonades de souris des deux sexes fait penser a la possibilite d'une transmission verticale. On trouve des particules A intracisternales dans la plupart des tissus connus pour entretenir la multiplication des virus de la leucemie et des tumeurs mammaires murines. En outre, il a ete demontre qu'elles coexistent dans la měme cellule avec des particules C et des particules A intracytoplasmiques (“precurseurs” des virus des tumeurs mammaires). Bien qu'il n'ait pas ete possible de faire la preuve d'une activite biologique associee aux particules A intracisternales, on peut penser qu'elles representent l'expression genique partielle de l'un des virus oncogenes a ARN connus et qu'elles servent ainsi de marqueur pour un cycle de multiplication incomplet.

Immunofluorescent study of alpha-foetoprotein (αfp) in liver and liver tumours. I. Technique of αfp localization in tissue sections

Abstract: Sections of paraffin-embedded tissue blocks fixed by ethanol/acetic acid were found to be very suitable for immunofluorescent (IF) study of αfp. In paraffin blocks the antigen was preserved for at least 1 year. It was possible to prepare serial sections for routine histological examination and simultaneous IF localization of several antigens practically in the same cells. Antibodies to αfp were obtained by glutaraldehyde immunosorbent technique. Their monospecificity was controlled by IF reaction on the αfp-negative sections and by neutralization with pure αfp. To differentiate αfp localization due to passive serum uptake from specific sites of αfp production or storage, a simultaneous study of αfp and γ-globulin γG distribution was performed. Only the structures containing αfp without γG were regarded as specifically connected with αfp metabolism. These were liver parenchyma cells in foetal and newborn liver and tumour cells in human primary liver carcinoma. Etude par Immunofluorescence de L'a-fcetoproteine (ufp) Dans le Foie et les Tumeurs Hepatiques. I. Technique de Localisation de L'afp Dans les Coupes Tissulaires Nous avons observe que des coupes tissulaires enrobees de paraffine et fixees a l'acide ethanol-acetique conviennent parfaitement a l'etude par immunofluorescence (IF) de l'afp. L'antigene s'est conserve au moins un an dans les blocs de paraffine. Nous avons pu preparer des coupes en serie pour l'examen histologique systematique et pour la localisation simultanee par IF de divers antigenes pratiquement dans les měmes cellules. Nous avons obtenu des anticorps a l'αfp par la methode d'immuno-absorption au glutaraldehyde. Leur monospecificie a ete contrǒlee par reaction d'IF sur les coupes αfp-negatives et par neutralisation au moyen d'αfp pure. Afin de differencier la localisation de l'αfp due a l'incorporation passive de serum des sites specifiques de production ou de stockage de l'αfp, nous avons effectue une etude simultanee de la distribution de l'αfp et de la γ-globuline (γg). Seules les structures contenant de l'αfp mais pas de γg ont ete considerees comme secifiquement liees au metabolisme de l'αfp. II sagissait des cellules parenchymateuses du foie de fαtus et de nouveau-ne et des cellules tumorales de carcinomes primitifs du foie humain.

Time trends of intestinal and diffuse types of gastric cancer in Norway.

Abstract: Samples of gastric cancer from three time periods (1940–1944, 1952–1953 and 1964–1966) were drawn from material of the Norwegian Radium Hospital, representing specimens collected from different hospitals throughout the country. The cases were diagnosed as belonging to the “intestinal”, “diffuse” or “other” category according to the classification of Lauren (1965). It was found that the three types showed about the same relative frequency from the first to the second time period, the intestinal one being the most common. However, from the second to the third time period the intestinal type decreased very markedly, in particular in the youngest age group. Figures are presented showing that for both males and females the death rate from gastric cancer fell from the early 1930s to the middle of the 1960s, but that this trend stopped temporarily during the latter half of the 1940s. It is concluded that this could well be due to dietary changes during the 1940–1945 war, influencing mainly the intestinal type. Such changes are probably not related to protein deficiency or lack of Vitamin A, but they could depend on factors in cereals, milk or fat. It is concluded that the long-term, pronounced decline of gastric cancer death observed in Norway for several decades may soon begin to level of, leaving a “hard core” of very slowly decreasing “diffuse” and “other” types.

Antibody to feline oncornavirus-associated cell membrane antigen in neonatal cats.

Abstract: Antibodies to a feline oncornavirus-associated cell membrane antigen have been found in newborn kittens whose mothers had previously nursed litters of kittens injected with feline leukemia virus (FeLV). These antibodies, which were apparently obtained passively from the mother, seem to protect the kittens from the development of progressive tumors following the injection of various amounts of feline sarcoma virus (FSV). That these mothers were apparently able to passively transmit immunity suggests that they became infected with FeLV in a horizontal manner while nursing previous litters and resisted the development of progressive tumors, but mounted an immune response which resulted in the production of humoral antibody. It also suggests that some degree of cross-protection exists in vivo between the feline leukemia and sarcoma viruses used in this study. Des anticorps d'un antigene de la membrane cellulaire associe a un oncornavirus felin ont ete observes chez des chatons nouveau-nes dont les meres avaient deja eleve des portees qui avaient recu une injection de virus de la leucemie feline (VLFe). Ces anticorps, apparemment transmis de facon passive par la mere, semblent proteger les chatons contre le developpement des tumeurs apres l'injection de differentes quantites de virus du sarcome felin (VSF). Le fait que les meres puissent apparemment transmettre l'immunite de facon passive donne a penser qu'elles ont ete infectees horizontale-ment par le VLFe lorsqu'elles elevaient les portees precedentes, qu'elles ont resiste au developpement tumoral, mais qu'elles ont elabore une reponse immunitaire aboutissant a la production d'anticorps circulants. Il existerait donc une certaine protection croisee in vivo a l'egard des virus de la leucemie et du sarcome felins utilises pour la presente etude.

Time trends of intestinal and diffuse types of gastric cancer in the United States.

Abstract: All histologically confirmed gastric cancer cases diagnosed during the periods 1940–1944 and 1960–1964 at the Hartford Hospital were classified into three groups: intestinal, difuse and others, according to a modified Lauren's classification. A reduction in the frequency of intestinal type carcinoma was observed between the earlier and the later time periods. Although this decrease was not statistically significant, it persisted within each sex. The cases were also subdivided into high- and low-risk groups according to the risk for gastric cancer prevailing at their place of birth. As expected, the intestinal type carcinoma was the most predominant in the high-risk group. This predominance persisted within each sex and time period category and it was more noticeable among female than among male cases. These findings support the hypothesis that these two types of gastric cancer, intestinal and difluse, differ not only structuraily and epidemiologically, but also etiologically.

The action of DNA antagonists on Epstein-Barr virus (EBV)-associated early antigen (EA) in Burkitt lymphoma lines.

Abstract: The effect of two DNA antagonists (IUDR and Ara C) on EBV-associated antigens was studied in two BL-derived carrier culture lines (P3HR-1 and Onesmas). Both drugs led to an accumulation of the early antigen (EA) from 2% in the untreated to 5–40% in the treated cultures. Ara C blocked the production of viral capsid antigen (VCA) whereas a small number of VCA + cells were still present after IUDR treatment. Reversion of Ara C-induced DNA inhibition led to the appearance of VCA + cells, reaching a higher level than in the untreated control samples. Combined immunofluorescence and autoradiography showed that the majority of VCA + cells incorporated H3-thymidine. These facts are in line with the hypothesis that EA can be made in the absence of cellular DNA synthesis, whereas VCA production is dependent on the DNA synthesis. The relationship between EA and two other EBV-associated antigens, MA (membrane antigen) and VCA (viral capsid antigen) was studied by the two-color immuno-fluorescence technique. VCA + cells were EA+ and MA+. EA + VCA - cells were partly MA + and partly MA-. This is in good agreement with the corresponding findings on the EBV-infected Raji cell system (Gergely et al., 1970a). Action des Antagonistes de L'adn Sur L'antigene Primitif (EA) Associe au Virus D'epstein-barr (VEB) dans les Souches de Lymphome de Burkitt L'effet de deux antagonistes de l'ADN (IUDR et Ara C) sur les antigenes associes au VEB a ete etudie dans des cultures de deux lignees porteuses derivees du lymphome de Burkitt (P3HR-1 et Onesmas). Les deux produits ont entraǐne une accumulation de l'antigene primitif (EA) de 2% dans les cultures non traitees a 5 a 40% dans les cultures traitees. l'Ara C bloque la production d'antigenes a capsides virales (VCA) alors qu'un petit nombre de cellules VCA + est encore present apres traitement a I'iudr. La reversion de l'inhibition de l'ADN induite par l'Ara C entraǐne l'apparition de cellules VCA + qui deviennent plus nombreuses que dans les echantillons-temoins non traites. L'immunofluorescence combinee a l'autoradiographie a montre que la majorite des cellules VCA + incorporent la thymidine tritiee, ce qui concorde avec l'hypothese selon laquelle l'EA peut apparaǐtre en l'absence de synthese de l'ADN cellulaire, alors que la production de VCA depend de la synthese de l'ADN. Les relations entre l'EA et deux autres antigenes associes au VEB, le MA (antigene de la membrane) et le VCA (antigene a capsides virales), ont ete etudiees par immunofluorescence bicolore. Les cellules VCA + etaient EA + et MA +. Les cellules EA + VCA- etaient en partie MA + et en partie MA-. Cela concorde bien avec des constatations analogues concernant le systeme cellulaire Raji infecte par le VEB (Gergely et al., 1970a).

Characteristics of established myeloma and lymphoblastoid cell lines derived from an E myeloma patient: a comparative study.

Abstract: The in vitro characteristics of two types of cell lines established from bone marrow and peripheral blood of an E myeloma patient have been compared. Both types, one with a lymphoblast morphology and the other with plasma cell/plasmablast morphology, secreted monoclonal immunoglobulins in vitro. The former produced IgGK while the latter synthesized the IgEL myeloma protein, which in a previous report was shown to be identical with the myeloma protein in vivo. The myeloma cells were difficult to establish and more stringent in their in vitro requirements than the lymphoblastoid cells. Myeloma cells could only grow in the presence of feeder cells or medium harvested from such cells, while lymphoblasts were capable of independent growth in standard media. The lymphoblastoid line was principally similar to those obtainable from normal lymph nodes (Nilsson et al., 1968; Nilsson, 1971a) and is therefore regarded as being of non-neoplastic origin. It is thus possible to obtain permanent immunoglobulin-secreting lines of non-neoplastic origin as well as myeloma lines of neoplastic origin from patients with myelomatosis. The dynamic and static morphology of the former most closely correspond to the appearance described for lymphoblasts or “immunoblasts”,i.e. lymphocytes stimulated by phyto-hemagglutinin, while myeloma cells resemble plasma cells of varying maturity. The reasons for the morphologic differences are unknown, but they were sufficiently distinctive to permit unequivocal distinction between the two types of lines. Caracteristiques de Lignees Cellulaires de Myelome et de Lymphoblastes Provenant D'un Malade Atteint de Myelome E: Une Etude Comparative L'auteur a compare les caracteristiques in vitro de deux types de lignees cellulaires constituees a partir de la moelle osseuse et du sang peripherique d'un sujet atteint de myelome E. Les deux types, dont l'un avait une morphologie lymphoblastoide et l' autre une morphologie de type blaste-cellule plasmatiques, secretaient des immunoglobulines monoclonales in vitro. Le premier type produisait des IgGK alors que le second synthe-tisait la proteine du myelome a IgEL qui, d'apres un precedent rapport, est identique a la proteine du myelome in vivo. Les cellules de myelome sont difficiles a constituer et necessitent plus de soins in vitro que les cellules lymphoblastoides. Les cellules de myelome ne peuvent croitre qu'en presence de cellules “feeder” ou dans un milieu a base de ces cellules, alors que les lymphoblastes sont capables l'une croissance independante dans un milieu standard. La lignee lymphoblastoide etait en grande partie analogue a celles que l'on obtient a partir de ganglions lymphatiques normaux (Nilsson et al., 1968; Nilsson, 1971a); elle est donc consideree comme etant d'origine neoplasique. II est ainsi possible d'obtenir des lignees permanentes secretant des immunoglobulines et ayant une origine non neoplasique ainsi que des ligees de myelomes d'origine neoplasique a partir de sujets atteints de myelomatose. La morphologie dynamique et statique des lignees non neo-plasiques correspond plus etroitement a l'aspect sous lequel se presentent les lymphoblastes ou “immunoblastes”, c'est-a-dire des lymphocytes stimules par la phytohe-magglutine, alors que les cellules de myelome ressemblent a des cellules plasmatiques de maturite variable. Les causes des differences morphologiques sont inconnues, mais ces differences sont assez caracteristiques pour permettre une distinction sans equivoque entre les deux types de lignees.

Metabolism of polycyclic hydrocarbons in mammalian cell cultures.

Abstract: Two extraction procedures were used to measure the metabolism of tritiated polycyclic hydrocarbons in cell cultures derived from several mammalian species. Metabolism of the hydrocarbons to “ alkali-extractable derivatives” was measured by extraction of the labeled medium with acetone:hexane, followed by extraction of the resulting acetone-hexane phase with NaOH (Nebert and Bausserman, 1970); metabolism to “ water-soluble derivatives “ was measured by extraction of the medium with chloroform:methanol:water (Diamond et al., 1968b). The extent of metabolism was dependent on the concentration of hydrocarbon, the number of cells and the time of incubation. The kinetics of hydrocarbon metabolism suggest that there may be sequential conversion of the parent compound first to alkali-extractable derivatives and then to water-soluble derivatives. Each of the cell cultures which was sensitive to the growth-inhibitory effects of 3,4-benzpyrene or 7,12-dimethylbenz (a) anthracene was able to metabolize the respective hydrocarbon to water-soluble derivatives. In general, little or no ability to metabolize the hydrocarbons was detected in cells which were resistant to the cytotoxic effects. Two resistant cell lines were exceptional in that they did metabolize the hydrocarbons to water-soluble derivatives; however, no alkali-extractable derivatives could be recovered from the medium of these cultures. Deux procedes d'extraction ont ete utilises pour mesurer le metabolisme des hydrocarbures polycycliques trities dans des cultures cellulaires provenant de plusieurs especes de mammiferes. Le metabolisme des hydrocarbures en “ derives pouvant ětre extraits de l'alcali” a ete mesure par extraction du milieu marque a l'acetone: hexane, puis par extraction de la phase acetone-hexane consecutive par du NaOH (Nebert et Bausserman, 1970); le metabolisme en “derives hydrosolubles “ a ete mesure par extraction du milieu au chloroforme: methanol: eau (Diamond et al., 1968). L'impor-tance du metabolisme dependait de la concentration d'hydrocarbure, du nombre des cellules et de la duree de l'incubation. La cynetique du metabolisme des hydrocarbures donne a penser qu'il peut y avoir une conversion sequentielle du compose initial, d'abord en derives pouvant ětre extraits de l'alcali, puis en derives hydrosolubles. Chacune des cultures cellulaires sensibles aux effets d'inhibition de la croissance du 3,4-benzopyrene ou du 7,12-dimethylbenzo (a) anthracene a pu metaboliser l'un ou l'autre hydrocarbure, selon le cas, en derives hydrosolubles. En general, on n'a observe que peu ou pas du tout d'aptitude a metaboliser les hydrocarbures dans les cellules resistant aux effets cytotoxiques. Deux lignees cellulaires resistantes faisaient exception en ce qu'elles metabolisaient les hydrocarbures en derives hydrosolubles; toutefois, aucun derive pouvant ětre extrait de l'alcali n'a ete recueilli dans le milieu de culture.

Occurrence of alpha-fetoprotein in acute viral hepatitis

Abstract: Using a very sensitive double antibody electrophoretic technique, we have found alpha-1 fetoprotein (AFP) to occur transiently in the serum of adults during the course of acute viral hepatitis associated with Australia antigen (Au(1)) but not with acute viral hepatitis unassociated with Au(1). Occurrence in adult serum of this protein, which is a normal embryonic serum alpha-1 globulin, has heretofore been associated with the presence of either primary hepatic malignancy or certain germinal cell cancers of the testis and ovary. The possible significance of the reappearance of AFP relative to cellular retro-differentiation in viral hepatitis and hepatic malignancy is discussed. En utilisant une technique electrophoretique double tres sensible, nous avons constate que l'alpha-1 fœtoproteine (AFP) apparaǐt passagerement dans le serum des adultes au cours d'une hepatite virale aigue, mais seulement si cette hepatite est associee a l'antigene Australia (Au(1)). L'apparition dans le serum des adultes de cette proteine, qui est une globuline alpha-1 normale du serum embryonnaire, a jusqu'ici ete associee a la presence d'une affection maligne primitive du foie ou a certains cancers des cellules germinates des testicules et des ovaires. Les auteurs analysent la signification possible de la reapparition de l'AFP sous l'angle de la retro-differenciation cellulaire dans l'hepatite virale et l'affection hepatique maligne.

Cellular immunity to nephroblastoma.

Abstract: Lymphocytes from 24 patients with nephroblastoma and 24 controls have been tested for tumor-related cytotoxicity in vitro. The micro-plate technique has been applied in 26 tests and the cytotoxic plaque test in eight. In 10 out of 24 nephroblastoma patients with two autochthonous and eight allogeneic combinations, tumor-related cell-mediated cytotoxicity has been found. Lymphocytes from control subjects were less cytotoxic against nephroblastoma cells and affected tumor and control cells to the same degree. Lymphocytes from patients treated for primary tumors showed tumor-destructive reactions more often than those from patients treated for disseminated disease. Immunite Cellulaire au Nephroblastome Les lymphocytes de 24 sujets atteints de nephroblastomes et de 24 temoins ont ete testes pour la recherche in vitro d'une cytotoxicite liee a la tumeur. La technique des microlames a ete appliquee dans 26 tests et l'epreuve de la plaque cytotoxique a ete utilisee pour 8 tests. Une cytotoxicite a mediation cellulaire et liee a la tumeur a ete observee chez 10 des 24 sujets atteints de nephroblastome (2 en combinaisons autochtones et 8 en combinaisons allogeneiques). Les lymphocytes des temoins sont moins cytotoxiques a l'egard des cellules de nephroblastome et affectent les cellules tumorales et les cellulestemoins au měme degre. Les lymphocytes de malades traites pour des tumeurs primitives ont souvent des reactions antitumorales, alors que les lymphocytes des malades traites pour une maladie deja etendue en ont plus rarement.

The mechanisms of action of anti-tumour polysaccharides. I. The effects of antilymphocyte serum on the anti-tumour activity of lentinan.

Abstract: Mechanisms of the regression of transplantated tumours in mice caused by lentinan, an anti-tumour polysaccharide, were examined. 1) Lentinan showed a marked anti-tumour effect when the animal was pretreated, starting 12 days before tumour inoculation. 2) The anti-tumour effect of lentinan was blocked by injection of anti-lymphocyte serum from 24 h after tumour transplantation. Lymphoid cells attacked by this serum apparently play an important role in tumour regression induced by lentinan. 3) Considering the selective actions of anti-lymphocyte serum as an immunosuppressor, one of the mechanisms responsible for the anti-tumour effect of lentinan may be the stimulation of cell-mediated responses. 4) Humoral antibodies against lentinan do not seem to participate in tumour regression.

Demonstration by colony inhibition methods of cellular and humoral immune reactions to tumour-specific antigens associated with aminoazo-dye-induced rat hepatomas.

Abstract: Cellular and humoral immune reactions against tumour-specific antigens on aminoazo-dye-induced rat hepatomas were demonstrated in vitro by the colony inhibition technique. Lymph-node cells from syngeneic rats immunized against individual hepatomas inhibited colony formation by cells of the immunizing tumour compared with the effects of normal lymph-node cells. Also immune lymph-node cells were not inhibitory to hepatomas other than the one used for immunization, reflecting the individual specificity of the antigens on these hepatomas. Serum-mediated inhibition of colony formation by rat hepatoma cells, in the presence of complement, was also demonstrated and these reactions were similarly directed against cells of the immunizing tumour. This specificity of colony inhibition by immune lymph-node cells and serum further amplifies the evidence for the individually distinct antigenicity of these hepatomas already revealed by transplantation and immunofluorescence tests. Mise en Evidence, Par des Methodes D'inhibition des Colonies, de Reactions Immunitaires Humorales et Cellulaires aux Antigenes Specifiques des Tumeurs Associes aux Hepatomes Induits Chez le Rat Par les Colorants Amino-azoyques Les reactions immunitaires humorales et cellulaires envers les antigenes specifiques des tumeurs associes aux hepatomes induits chez le rat par les colorants aminoazoiques ont ete mises en evidence in vitropar la methode d'inhibition des colonies. Apres comparaison avec les effets des cellules de ganglions lymphatiques normales, on a constate que les cellules de ganglions lymphatiques de rats syngeneiques immunises contre un hepatome particulier inhibent la formation de colonies de cellules de la tumeur immunisante. On a egalement observe que les cellules de ganglions lymphatiques immunisees n'ont pas d'effet inhibiteur sur les hepatomes autres que celui qui est utilise pour l'immunisation, ce qui souligne la specificite individuelle des antigenes de ces hepatomes. l'inhibition a mediation serique de la formation de colonies par des cellules d'hepatome de rat en presence de complement a egalement ete mise en evidence; ces reactions denotent elles aussi une lutte contre les cellules de la tumeur immunisante. Cette specificite de l'inhibition des colonies par du serum et des cellules immunisees de ganglions lymphatiques constitue une preuve supplementaire de l'antigenicite particuliere a chacun de ces hepatomes qui a deja ete revelee par les tests d'immunofluorescence et de transplantation.

Studies on the mechanisms of invasion in cancer. II. In vivo effects of a factor chemotactic for cancer cells

Abstract: A substance chemotactic for tumor cells was isolated from some tumor tissues of animal and human origin and highly purified. It induced an extravascular emigration of circulating tumor cells on experimental injection, but no emigration of polymorphonuclear leukocytes. The emigrated tumor cells proliferated in the extravascular tissue and invaded the surrounding tissues, and a metastatic secondary tumor was formed. This material had no activity to increase vascular permeability. Permeability factors, isolated from tumor tissues, histamine and bradykinin were ineffective for tumor-cell emigration. A factor chemotactic for polymorphonuclear leukocytes, isolated from inflamed sites, induced an emigration of the cells on experimental injection, but no emigration of tumor cells. These observations suggested that the cancer cell chemotactic factor might be associated with malignant invasion. Etude des Mecanismes D'invasion du Cancer. II. Effets In Vivo D'un Facteur Chimiotactique A L'egard des Cellules Cancereuses Une substance chimiotactique a l'egard des cellules cancereuses a ete isolee a partir de certains tissus tumoraux d'origine humaine et animale; elle a ensuite ete fortement purifiee. Une injection experimentale de cette substance a provoque une emigration extravasculaire des cellules tumorales circulantes, mais pas des leucocytes polymorphonucleaires. Les cellules tumorales emigrees ont prolifere dans le tissu extravasculaire et ont envahi les tissus environnants, ce qui a provoque la formation d'une tumeur metastasique secondaire. Ce materiel n'augmente pas la permeabilite vasculaire. Les facteurs de permeabilite isoles a partir de tissus tumoraux, l'histamine et la bradykinine, n'ont pas eu d'effet sur l'emigration des cellules tumorales. Un facteur chimiotactique envers les leucocytes polymorphonucleaires, isole sur des points enflammes, a provoque une emigration des cellules apres injection experimentale, mais n'a pas eu d'effet sur les cellules tumorales. Ces observations donnent a penser que le facteur chimiotactique a l'egard des cellules cancereuses pourrait ětre associe a l'invasion maligne.

Further investigations of circulating antibodies in colon cancer patients: On the autoantigenicity of the carcinoembryonic antigen

Abstract: Sera from 190 patients (including 125 patients with cancer of the digestive tract) have been investigated for the presence of circulating antibodies directed against the carcinoembryonic antigen (CEA). Use of three different techniques (passive hemagglutination, immunoadsorption and immunoftuorescence) revealed no evidence for the autoantigenicity of this particular antigen. The titers demonstrated in patients' sera were due to antibodies directed against normal tissue proteins which were present in perchloric acid extracts of colonic tumors.

Cellular immunity to renal carcinomas in man

Abstract: A microassay in disposable tissue-culture plates was used to demonstrate a cell-mediated immune response against human renal adenocarcinomas. Leukocytes from 12 of the 19 patients with renal carcinoma were cytotoxic for autochthonous and allogeneic renal carcinoma cells in vitro. No reproducible cytotoxic effects were produced by leukocyte suspensions from patients with pulmonary or mammary carcinoma, or by leukocytes from healthy and non-neoplastic control subjects. No cytotoxicity was observed when cells of unrelated tumours, mesothelioma and urinary bladder carcinoma were used as target cells for leukocytes from a patient who reacted positively against autochthonous renal carcinoma cells. The results indicate that human renal adenocarcinomas possess tumour-associated antigens which cross-react with each other. Cytological and electron microscopic characteristics of cultivated renal carcinoma cells are described. Les auteurs ont procede a un microtest sur des lames de culture tissulaire a jeter apres usage afin de mettre en evidence la reponse immunitaire a mediation cellulaire envers les adenocarcinomes renaux humains. Les leucocytes de 12 malades sur les 19 qui portaient un carcinome renal etaient cytotoxiques a l'egard des cellules de carcinome renal allogeneiques et autochtones in vitro. Aucun effet cytotoxique reproductible n'a ete provoque par les suspensions de leucocytes de malades atteints de carcinomes pulmonaire ou mammaire ni par les leucocytes de temoins en bonne sante ou non cancereux. Aucune cytotoxicite n'a ete observee lorsque les cellules de tumeurs non apparentees (mesotheliome et carcinome vesical) ont ete utilisees comme cellules-cibles pour les leucocytes d'un malade qui reagissait positivement aux cellules autochtones de carcinome renal. Les resultats indiquent que les adenocarcinomes renaux humains possedent des antigenes associes a la tumeur qui ont entre eux des reactions croisees. Les auteurs decrivent la caracterisation cytologique ou par microscopie electronique des cultures de cellules de carcinome renal.

Nasopharyngeal carcinoma in non-Chinese populations with special reference to south-east Asia and Africa.

Abstract: Nasopharyngeal cancer (NPC) is very common in Chinese, the incidence rates (age-adjusted to the “world” population distribution) per 100,000 per annum varying between 10 to 20 for males and 5 to 10 for females. In virtually all occidental countries, the rates are very low, generally well below 1.0 per 100,000 per annum. The evidence suggesting intermediate levels of risk in certain non-Chinese mongoloid populations in South-East Asia, in the Sudan and the Maghreb, is examined. Although whenever possible incidence rates are quoted, most of the available data are based on relative frequency series, often with rather small numbers. Rare in Japan and India, NPC is fairly common in non-Chinese mongoloid groups in South-East Asia. NPC incidence in Tunisia is raised, and the relative frequency is probably raised in the Sudan and Algeria. NPC is probably not unduly common in Kenya or Uganda but there are differences between ethnic groups in these countries which may be related to environmental factors. NPC incidence in Hawaii is raised for all ethnic groups, the rate for male Hawaiians (7.8) approaching that for male Chinese (10.4). In Israel, the incidence in the non-Jewish (Arab) population and in Jews born in Africa or Asia (many of whom were born in Morocco or Tunisia) is higher than in Israel-born Jews or in Jews born in America or Europe. The effect of intermarriage with Chinese is examined. There is a general trend suggesting that NPC is commoner in those South-East Asian groups with admixture of Chinese blood, exemplified by NPC incidence in Singapore where the rates for male and female Chinese were 20.2 and 9.0 whereas those for the mongoloid Malays were 5.8 and 2.0 respectively. By contrast, the rates for the caucasoid Indians and Pakistanis were 0.2 and 0. It is highly unlikely that these differences are artefactual. The demonstration of an intermediate NPC risk level in Tunisia and other parts of Africa should, when confirmed, permit examination of viral and other aetiological hypotheses in populations with little or no Chinese genetic material. Le cancer du rhinopharynx se rencontre tres frequemment chez les Chinois. Les taux d'incidence (ajustes a la structure d'ǎge de la population “mondiale”) pour 100 000 habitants et par an, varient en effet entre 10 et 20 chez les hommes et 5 a 10 chez les femmes. Dans la quasi totalite des pays occidentaux, les taux correspondants sont tres faibles, se situant en general bien au-dessous de 1.0 pour 100 000 habitants et par an. On etudie actuellement des indices laissant supposer l'existence de niveaux de risque intermediaires dans certaines populations mongoloides non chinoises de l'Asie du Sud-Est, au Soudan et dans le Maghreb. Bien que des taux d'incidence soient indiques chaque fois que possible, la plupart des donnees disponibles ont ete tirees de series de frequences relatives, souvent fondees sur des chiffres plutǒt faibles. Rare au Japan et en Inde, le cancer du rhinopharynx est assez contmun dans les groupes mongoloides non chinois du Sud-Est de l'Asie. L'incidence de ce cancer est elevee en Tunisie, et il est vraisemblable qu'il en est de měme de sa frequence relative au Soudan et en Algerie. Il n'est probablement pas indǔment frequent au Kenya et en Ouganda, mais on observe dans ces pays, entre groupes ethniques, des differences qui peuvent ětre liees a des facteurs de milieu. A Hawaii, l'incidence du cancer du rhinopharynx est elevee pour tous les groupes ethniques, le taux chez les Hawaiiens (hommes) (7.8) approchant de celui des Chinois (hommes) qui est 10.4. En Israel, l'incidence de ce cancer dans la population non juive (arabe), ainsi que chez les Juifs nes en Asie ou en Afrique (au Maroc ou en Tunisie pour nombre d'entre eux), est plus elevee que chez les Juifs nes en Israel ou chez ceux qui sont nes tn Amerique ou en Europe. L'influence possible de manages avec des Chinois est actuellement etudiee. On observe en effet une tendance generate suggerant que le cancer du rhinopharynx est plus commun dans les groupes de population de l'Asie du Sud-Est melanges de sang Chinois, tendance qui est mise en relief par l'incidence de ce cancer a Singapour, ou les taux pour les chinois de sexe masculin et de sexe feminin sont respectivementde 20.2 et de 9.0, tandis que les chiffres correspondants pour les Malais (mongoloids) sont respectivement de 5.8 et de 2.0. Faisant contraste avec ces chiffres, les taux chez les Indiens et Pakistanais (caucasoides) sont respectivement de 0.2 et de 0. Il est hautement improbable que ces differences soient des phenomenes artificiels ou accidentels. L'existence d'un niveau de risque intermediaire en Tunisie et dans d'autres parties du monde, si elle est confirmee, devrait permettre d'etudier dans des populations n'ayant pas ou seulement tres peu de materiel genetique chinois, les hypotheses virales ainsi que d'autres hypotheses etiologiques.

Relationship between the EBV-associated membrane antigen on Burkitt lymphoma cells and the viral envelope, demonstrated by immunoferritin labelling.

Abstract: The localization of EBV-induced, cell membrane antigens (MA) and intracellular viral capsid antigens (VCA) was studied by immunoferritin labelling. Human sera with known concordant or discordant anti-MA and anti- VCA reactivities were allowed to react with intact, viable EBV-carrier cells, and with naked and enveloped EBV-particles. The reaction was visualized by the indirect immunoferritin test, using a rabbit anti-human immunoglobulin conjugate. The following conclusions were drawn: a) MA is a structural constituent of the viral envelope. Anti-MA positive sera gave a consistently strong labelling of viral envelopes and of virus-free patches on the cell membrane as well. b) VCA is not present on the viral envelope and on the cell membrane. It is expressed on the surface of naked virus particles. c) A multispecific anti-HL.A serum gave a faint labelling with a small proportion of the enveloped viral particles. It could not be resolved whether this was due to the presence of HL.A antigens on some viral envelopes or, alternatively, to low anti-MA levels in the anti-HL.A sera.

Antigènes cellulaires transitoires du foie de rat. I. Sécrétion et synthèse des protéines sériques fetospécifiques au cours du développement et de la régénération hépatiques

Abstract: Transitory cell antigens of rat liver. I. The secretion and synthesis of fetospecific serum proteins during hepatic development and regeneration Changes in the serum concentration of albumin and α-fetoprotein (αFP) from rat fetuses and newborns were followed by a quantitative immunoprecipitation method, using specific antisera. The concentration curves of the two proteins intersected between 1 and 2 weeks after birth. On the 32nd day, when the albumin concentration was almost at the adult level, no traces of αFP were detectable. Similarly, data have been obtained for the αFP concentration in amniotic fluid and sera from pregnant rats. Radioimmunodiffusion techniques were used to show the incorporation of radiolabelled compounds into several fetospecific and adult serum proteins during normal development as well as during compensatory regeneration after acute poisoning of the liver. When newborn rats and rats aged between 30 and 50 days are subjected to a series of injections of CCl4, one or several waves of αFP secretion are observed. The reappearance of αFP cannot be provoked by CCl4in rats older than 7 weeks. These facts suggest that the resurgence of αFP in hepatic injury of newborn rats and young rats is a consequence of the enhanced activity of some incompletely differentiated cell clones.