Showing papers on "Transplantation published in 1977"

One Hundred and Twenty-Seven Cultured Human Tumor Cell Lines Producing Tumors in Nude Mice

Abstract: One hundred and twenty-seven cultured human tumor cell lines produced tumors after sc inoculation of 1-20 million cells into nude mice. They included 56 carcinoma lines, 14 sarcoma lines, and 57 lines from miscellaneous tumors and were all glucose-6-phosphate dehydrogenase type B. Twenty-nine percent of the lines produced tumors of 1 cm3 size within 1 month and 41% in the second month after inoculation. The histopathology correlated with the human tumor of origin in all cases.

Limb-somite relationship: origin of the limb musculature

Abstract: Quail-to-chick grafting experiments performed during the third day of incubation demonstrate that somites can contribute to limb development. In orthotopic recombinations, migrating cells originating from the grafted unsegmented or segmented somitic mesoderm adjacent to the wing or leg field end up in the musculature respectively of the wing or the leg, where they express exclusively myogenic properties. Thus, in these heterospecific recombinations, the anatomical muscle has a double origin: muscle bulk of somitic origin; tendons and connective tissues of somatopleural origin. Similar features are observed in heterotopic recombinations with (segmented or unsegmented) somitic mesoderm located cranially or caudally to the limb levels. In the reverse chick-to-quail grafting experiments, the somitc participation to the limb mesoderm can also be observed. But it is less regular than that obtained in the quail-to-chick recombinations, and the muscle bulk is made up in various proportions of graft-originated somitic cells and of host somatopleural cells. The possible existence of juxtaposed and interdigitated myogenic and tendinogenic compartments is discussed in view of the dissimilarity between the results of the two kinds of heterospecific recombinations.

A Simplified Method for Production and Growth of Multicellular Tumor Spheroids

Abstract: A new technique, based on the growth of tumor cells in liquid media over an agar base, has been developed for the formation and growth of multicellular tumor spheroids. All of the 11 transformed cell lines tested formed multicellular tumor spheroids, while none of the 8 normal cell types tested did so. The advantages of the present technique over older methods include its simplicity, generality, and experimental flexibility.

Covariance Analysis of Heart Transplant Survival Data

Abstract: This paper presents a number of analyses to assess the effects of various covariates on the survival of patients in the Stanford Heart Transplantation Program. The data have been updated from previously published versions and include some additional covariates, such as measures of tissue typing. The methods used allow for simultaneous investigation of several covariates and provide estimates of the relative risk of transplantation as well as significance tests.

Hormonal and follicular factors affecting maturation of sheep oocytes in vitro and their subsequent developmental capacity

Abstract: Oocytes removed from, or retained within, non-atretic and atretic follicles of different sizes were cultured for 24 h in the presence of a variety of hormones in an attempt to identify the factors affecting oocyte maturation in vitro. Resumption of meiosis was assessed morphologically; the developmental capacity of oocytes after culture was determined by transfer to the oviducts of inseminated ewes. About 70% of oocytes cultured after removal from follicles of different sizes resumed meiosis in vitro, but they did not undergo normal development after transplantation. Oocytes cultured within the follicle in hormone-free medium remained at the germinal vesicle stage. In the presence of FSH and LH some oocytes reached the second meiotic metaphase: 19% in small (2-3 mm diam.) and 73% in larger (3-5 mm diam.) non-atretic follicles, and 54% in small and 45% in larger atretic follicles. Less than 5% of oocytes cultured in follicles developed into normal blastocysts after transplantation when either no hormone or only FSH and LH were added to the culture medium. The addition of oestradiol-17beta to medium containing FSH (2 mug/ml) and LH (1 mug/ml) resulted in the development to blastocysts of 26% of oocytes from small non-atretic follicles, 46% from large non-atretic follicles and 50% from atretic follicles. Blastocyst formation was greatly depressed and fragmentation rate signinificantly increased with concentrations of 10 mugFSH/ml and 2 mug LH/ml. Developmental capacity after culture was further demonstrated by the birth of lambs from 63% of blastocysts derived from oocytes matured in vitro; 52% of control blastocysts developed to lambs after transfer.

Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts.

Abstract: BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days).

Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure of cancer

Abstract: Concentrations of meperidine and its active metabolite, normeperidine, were measured in plasma of patients receiving the drug for analgesia. Meperidine levels in cancer patients were 0.10 to 0.55 microng/ml 1 h after a dose and were 0.05 to 0.14 in patients in the oliguric period after renal transplantation. Normeperidine levels were 0.05 to 0.28 microng/ml in the cancer patients and 0.13 to 0.36 in the renal failure patients. The ratio of normeperidine to meperidine levels was always higher in the renal failure patients than in the cancer patients. Additionally, two patients receiving multiple doses of meperidine had high normeperidine levels and very high normeperidine/meperidine ratios when they showed signs of central nervous system excitation. These data indicate that normeperidine can contribute to the excitatory effects seen after multiple doses of meperidine and suggest that patients with renal failure are particularly susceptible to this problem.

Total hip replacement and femoral-head bone-grafting for severe acetabular deficiency in adults

Abstract: We performed total hip replacement in twenty-seven hips of twenty-two patients with osteoarthritis secondary to congenital dislocation, congenital dysplasia, or acetabular insufficiency due to persistent fracture-dislocation. The femoral head was used as a bone graft, attaching it to the acetabular wall to provide bone stock for reconstruction. There were few postoperative complications. In thirteen hips followed for over one year, all grafts appeared to be united and none showed evidence of resorption. Eleven of the thirteen hips were pain-free and two were slightly painful. Eleven hips had a range of motion of 90 degrees or more.

Marrow transplantation for treatment of aplastic anaemia.

Abstract: Seventy-three consecutive patients with severe aplastic anemia were treated by marrow grafts from normal, HLA-identical siblings, and 68 lived long enough to demonstrate engraftment. In 21 patients the garft was rejected, and 19 of these patients died. This analysis, using a binary logistic regression model, was aimed at identifying factors that predicted marrow-graft rejection. Of the 24 factors entered into the analysis, only two strongly correlated with graft rejection: a positive relative response index in mixed leukocyte culture indicating sensitization of patient against donor (P less than 0.01); and a low number of marrow cells ( less than 3 X 10(8) cells per kilogram) used for transplantation (P less than 0.01). These findings suggest that more powerful immunosuppressive conditioning regimens should be used in patients who are sensitized, and that the greatest possible amount of donor marrow, perhaps supplemented by stem cells derived from the peripheral blood, should be obtained.

A Prospective Analysis of Interstitial Pneumonia and Opportunistic Viral Infection among Recipients of Allogeneic Bone Marrow Grafts

Abstract: A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.

Role of non-conventional natural killer cells in resistance against syngeneic tumour cells in vivo

Abstract: IMMUNE reactions of ‘conventional’ T and B lymphocytes are generally thought to constitute major parts of any measurable, ‘specific’ tumour resistance against autologous tumours. There is no doubt that protective immunity can be induced against subsequently transplanted syngeneic tumours in experimental systems1. But, there is only scanty evidence to suggest that conventional immune reactions can provide resistance against such tumour cells when transplantation is made into normal individuals. Yet, it is frequently found that even long-transplanted syngeneic tumour cells may require comparatively high numbers of cells to ensure tumour take in normal recipients. Mice failing to succumb to small numbers of tumour cells can frequently be shown to reject a second graft of the same tumour with similar vigour2. Thus, natural resistance against tumours may occur with no display of classical, immunological memory. That such natural protective forces do exist against tumours has been claimed for many years3, but its underlying basis is poorly understood. Here, we present data indicating that naturally occurring killer cells may play a decisive part in providing resistance against syngeneic tumour cells in vivo.

A transplantable insulinoma in the rat.

Abstract: A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days folowing 1000 rads (10J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 months in the first generation to 2-5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96% versus 69%). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 mug of immunoreactive somato-statin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2-4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the beta cells in the pancreata of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal.

Costs, Risks, and Benefits of Surgery

Abstract: Human life has traditionally been regarded as priceless. Therefore, no cost should be spared if a life can be saved. However, life-saving methods have now been developed that may well be beyond the capacity of society to pay for them. Perhaps coronary artery bypass surgery and renal transplantation cost more for society as a whole than society is willing to purchase. This book, using the methods of decision theory and cost-benefit analysis aims to clarify thinking rather than to be merely critical. The first part, background and general principles, introduces the methods of conditional probability, decision trees, and economic analysis. A second section, entitled "Surgical Innovation," shows historically that surgical procedures were devised in the past on the basis of intuition and insight of singular individuals. Distinguished foreign visitors to this country had an enormous impact on surgical practice. For example, Arbuthnot Lane, in 1909, explained an elaborate pathology of abdominal bands and adhesions. Symptoms produced by these included headache, lassitude, mental distress, poor temper control, and diminution of libido. These, caused by autointoxication, could be relieved by lysis of adhesions and ileosigmoidostomy, with resection of all the colon proximal to this anasto¬ mosis. In surgery, before 1945, the concept of control in evaluation of methods seemed totally unknown to surgeons. In modern surgery, advances have been made in experimental design of clinical investigations, so that review of surgical innovations, al¬ though not perfect, is vastly improved. A third section of this book assesses risks and benefits of established proce¬ dures by decision analysis. For exam¬ ple, elective inguinal herniorrhaphy is critically assessed, as is life expectancy after cholecystectomy for silent gall stones and after hysterectomy for uterine dysfunction. Surprisingly, al¬ though the indications for inguinal herniorrhaphy are generally agreed on, the analysis in this volume casts doubt on the life-saving efficacy of the opera¬ tion as performed in the elderly. Wisely, the authors suggest that the unchallenged status of the operation is based on its effectiveness in improving quality of life, rather than the quantity of survival of the patient. The results of analysis of this operation show the difficulties of cost-benefit analysis in surgical decision-making. The fourth section focuses on costly procedures that have appeared recently on the medical scene. The data show, in general, that coronary artery bypass surgery is not particularly efficient in the use of scarce health resource funds. An exception to this generalization might be a young man with a strong heart with severe angina who under¬ goes this form of surgery. An estimate is made of the premium that might be paid each year by American men to

Thyroid Dysfunction in Chronic Renal Failure: A STUDY OF THE PITUITARY-THYROID AXIS AND PERIPHERAL TURNOVER KINETICS OF THYROXINE AND TRIIODOTHYRONINE

Abstract: Thyroid function was evaluated in 46 patients with end-stage kidney disease and 42 normal subjects. Patients were studied before and after the institution of maintenance hemodialysis (HD) and after renal transplantation (RT). Serum total triiodothyronine concentrations (TT(3), ng/100 ml, mean+/-SD) were 63+/-17 and 83+/-22 in the non-HD and HD groups, respectively. Values from normal subjects were 128+/-25 and from RT patients 134+/-20. The TT(3) was in the hypothyroid range (<78 ng/100 ml; 2 SD below normal mean) in 80% of non-HD and 43% of HD patients. Mean serum total thyroxine concentration (TT(4)), although within the normal range, was lower than the control value. T(4)-binding globulin capacity was also slightly lower but the difference was not statistically significant. Among patients whose TT(4) was 1 SD below the normal mean, the free T(4) index was equally depressed, suggesting that factors other than decreased binding capacity might be responsible for the low TT(4). In addition, there was a 37% incidence of goiter. Mean serum thyroid-stimulating hormone (TSH) was not elevated and the TSH response to thyrotropin-releasing hormone (TRH) was distinctly blunted, suggesting the possibility of pituitary dysfunction as well. In vivo (125)I-l-T(4) and (131)I-l-T(3) kinetics during 0.2 mg/day of l-T(4) replacement showed marked reduction in T(3) turnover rate in the uremic patients, both before and during HD; the values (mug T(3)/day, mean+/-SD) for the different groups were as follows: normal, 33.8+/-6.1; non-HD, 13.5+/-2.6; HD, 12.9+/-3.1; and RT, 30.3+/-7.1. The low T(3) turnover rate was due to impaired extrathyroidal conversion of T(4) to T(3). The mean percent+/-SD of metabolized T(4) converted to T(3) was 37.2+/-5.8 in normal subjects, 15.7+/-3.1 in non-HD, 12.8+/-1.7 in HD, and 34.0+/-14.7 in RT patients. In contrast, thyroidal T(3) secretion rate was not different between the control and the three patient groups. Thus, it appears that uremia affects thyroid function at several levels: (a) subnormal pituitary TSH response to TRH; (b) possible intrathyroidal abnormalities as suggested by slightly decreased TT(4) and high incidence of goiter; and (c) abnormal peripheral generation of T(3) from T(4). Restoration of renal function with RT resulted in normalization of all parameters of thyroid function with the exception of blunted or absent TSH response to TRH. The latter may be a direct consequence of glucocorticoid administration.

Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. II. An autoradiographic study.

Abstract: Myonuclei and satellite cell nuclei were differentially labelled with 3H-thymidine in uninjured skeletal muscle of young rats and then traced autoradiographically at intervals after mincing the radioactive hindlimb muscles to determine the source of regenerating presumptive myoblasts. Labelled nuclei were detected by light microscopic examination of 1-micron thick autoradiographs and identified by electron microscopic examination of an adjacent section. Repeated injections of 3H-thymidine during fetal and neonatal development, followed by a 4- to 5-week maturation period, resulted in labelling of 20% of the myonuclei. Satellite cells were not observed to be labelled in this series. Eight to sixteen hours after mincing, 20% of the pyknotic myonuclei were labelled, whereas none of the regenerating presumptive myoblasts appeared labelled. A single injection of 3H-thymidine administered to 18-day-old rats, followed by sacrifice within ten hours, resulted in labelling of 23% of the satellite cell nuclei. Myonuclei were not observed to be labelled in this series. Eight to sixteen hours after mincing, silver grains were detected over both pyknotic and regenerating cell nuclei. These experiments indicate that many satellite cells survive muscle injury and transplantation to become regenerating myogenic cells at a time when most, if not all, myonuclei are undergoing pyknosis.

The origin and mechanism of the allograft reaction.

Abstract: Previous explanations for the allograft reaction have been based on the concept that antigen causes immunocyte activation, following engagement of the immunocyte's specific receptor. This notion lead to the concept of immune surveillance, the idea that the evolutionary pressure responsible for the development of the vertebrate immune system involved in allograft rejection was a need to recognize and destroy tumor cells that carried novel antigens. Allografts were rejected because they were, in effect, mistaken for tumor cells. At the practical level, these ideas suggested that a solution to the allograft problem required treatment of the recipient in a way that would reduce or eliminate the recipient's immune response to the grafted tissue. We have rejected these ideas on the grounds that the basic premise, the notion that antigen alone drives T cell differentiation, is invalid. To explain the origin of the allograft response, we have developed a theory of allogeneic reactivity based on the concept that a stimulator cell is required for the activation of blood cells involved in both nonspecific inflammatory reactions and specific cellular immunity. This theory provides a conceptual link between invertebrate and vertebrate alloreactivity and explains why the MHC and factors controlling the expression of T cell activity map in the same region of the genome. According to this theory, it is blood cells carried within the transplanted tissue and not transplantation antigen on the surface of graft parenchymal cells, that constitute the major barrier to allotransplantation. Experimentally we have presented evidence for a two-signal mechanism for T cell activation. Both antigen and an inductive stimulus are required for T cell activation, and neither factor alone induces detectable T cell activation. Organ culture of thyroid tissue for 4 weeks renders it non-immunogenic without altering its antigenic composition. Furthermore, cyclophosphamide pretreatment of the thyroid donor, a procedure that does not destroy the vascular bed of the donor tissue, also reduces its immunogenicity. These findings are of both theoretical and practical importance. They show that transplantation antigen carried on the parenchymal cells of a transplant do not constitute the major barrier to allotransplantation and, at least in the case of thyroid and parathyroid transplantation, indefinite allograft survival can be achieved by treatments directed at the transplanted tissue and not the recipient.

Tumorigenicity of human hematopoietic cell lines in athymic nude mice

Abstract: Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.

Sjögren-Type Syndrome After Allogeneic Bone-Marrow Transplantation

Abstract: Four patients, treated for hematologic disorders with bone-marrow transplants from HLA-identical siblings, spontaneously complained of dry eyes 8 to 12 months after transplantation. Four a...

Heterotransplantation of a Human Prostatic Adenocarcinoma Cell Line in Nude Mice

Abstract: Nude mice of NIH/Swiss background were utilized for the heterotransplantation of a tissue culture cell line derived from a human prostate adenocarcinoma metastatic to the brain These cells, which had been grown in vitro for 13 passages, formed solid tumors when injected sc into nude mice The cell line DU 145 has been passaged 60 times in vitro over a period of 18 months Tumors removed from the mice were serially transplanted to additional mice and reestablished in vitro Light-microscopic analysis of the tumor grown in nude mice revealed a strong similarity to the patient's metastatic tumor The ultrastructure of the tumor cells propagated in nude mice was compared to that of the original human tumor cells and to the tissue culture cells, both before and after passage in nude mouse No major differences were detected Karyotypic analysis of the tumor cells grown in vitro before mouse passage, grown in nude mouse, and grown in vitro after mouse passage indicated chromosomal identity and consistent marker chromosomes: three large acrocentric chromosomes and metacentric minute chromosomes

The Diabetic pancreas

Abstract: 1 Historical Review- 2 Comparative Morphology of Pancreatic Islets in Animals- 3 Growth Pattern of Pancreatic Islets in Animals- 4 Histology, Cell Types, and Functional Correlation of Islets of Langerhans- 5 Quantitative Studies of the Islets of Nondiabetic Patients- 6 Histochemistry and Electron Microscopy of Islets- 7 Morphology of Membrane Systems in Pancreatic Islets- 8 The Physiology of Insulin Release- 9 Idiopathic Diabetes- 10 Pathogenic Considerations of Idiopathic Diabetes- 11 Hormonal Diabetes- 12 Pancreatitis, Pancreatic Lithiasis, and Diabetes Mellitus- 13 Cancer and Diabetes- 14 Hemochromatosis and Diabetes- 15 The Pathology of Juvenile Diabetes- 16 The Islets of Infants of Diabetic Mothers- 17 Spontaneous Diabetes in Animals- 18 Chemically and Hormonally Induced Diabetes- 19 Viral Diabetes- 20 Effects of Sulfonylureas on the Pancreas- 21 Islet Transplantation- 22 Endocrine Tumors of the Pancreas

Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve

Abstract: SCHWANN cells can remyelinate axons normally myelinated by oligodendrocytes, after either primary demyelination1–3 or suppression of myelination by X irradiation at the time of myelination4,5. It has been suggested that the glial limiting membrane normally inhibits Schwann cell invasion of the CNS (ref. 2) and its reformation inhibits uncontrolled invasion by Schwann cells once this phenomenon has been initiated1,2. The Schwann cells in these situations are thought to arise from the nerve roots. I undertook experiments to determine whether it is possible to suppress remyelination following primary demyelination in an experimental animal. If so the resulting demyelinated axons would be similar to those present in the multiple sclerosis plaque, that is they would remain demyelinated unrepaired by glial or Schwann cells. Using such a lesion it would then be possible to establish if Schwann cells obtained from a source outside the central neuraxis would remyelinate these axons. In the past, attempts at transplanting peripheral nervous tissue into the central nervous system have shown very limited invasion of peripheral elements into the neuropil of the CNS (refs. 6,7) and it was hoped that the presence of large numbers of demyelinated axons would act as a stimulus for Schwann cell invasion8. In addition, intraspinal injections of lysolecithin facilitate Schwann cell invasion of the CNS from local sources2,9. By abolishing this intrinsic Schwann cell remyelination potential and by substituting an extrinsic source of Schwann cells it might be possible to determine if persistently demyelinated axons in the CNS, similar to those in multiple sclerosis plaques, can be repaired by outside interference. I report here the preparation of areas of demyelination in rats and cats which remyelinated only in the presence of added Schwann cells.

Cellular immunity and herpesvirus infections in cardiac-transplant patients.

Abstract: We observed severe infection with herpes simplex virus in cardiac-transplant patients despite their high serum antibody levels to this virus. Therefore, we sought to correlate clinical susceptibility to two herpesvirus (simplex and zoster) infections with specific cellular immunity, assessed by the transformation and interferon responses of peripheral blood mononuclear cells to heat-inactivated antigens. Transformation and interferon response to herps simplex virus was maximally depressed immediately after transplantation, the time when severe and prolonged infection with herps simplex virus occurred. Six months to six years after transplantation, both clinical susceptibility and cellular immunity to herpes simplex virus were normal. Herpes zoster infections were more frequent than normal at all times after cardiac transplantation; depressed or absent cellular responses to the varicella zoster virus paralleled that susceptibility. In these patients the risk of severe herpesvirus infections correlated with depressed cellular immune responses to the specific viral agent involved.

Severe combined immunodeficiency disease. Characterization of the disease and results of transplantation.

Abstract: Pretransplant and posttransplant data for 69 patients with severe combined immunodeficiency disease are presented Both B and T lymphocyte functions were absent in approximately 80% of the children and markedly depressed in the remainder Transplantation of marrow from HLA genotypically identical donors provided the highest six-month survival rate (63%); six-month survival rates for patients who received fetal tissue transplants (43%) or marrow from mixed leukocyte culture (MLC) negative donors (38%) were significantly higher ( P ( JAMA 238:591-600, 1977)

Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice.

Abstract: CBA/N mice have an X-linked B-cell maturation defect which is reflected in part in an absence or dysfunction of a subclass of mature B cells. We have immunized the defective male offspring of the mating (CBA/N female X BALB/c male) with BALB/c spleen cells. The resulting antiserum (alphaLyb3) selectively reacts with a component on the surface of a portion of B cells from a panel of H-2 different mouse strains. Binding of alphaLyb3 serum to this B-cell subclass results in substantial (10- to 20-fold) enhancement of the antibody response to low doses of SRBC. Both binding and enhancing activity are removed by absorption with B cells from B6 and BALB/c, but not CBA/N mice. Absorption of the serum with bone marrow cells, T cells, or thymocytes from Lyb3+ strains does not remove activity. Since the enhanced plaque-forming cell (PFC) responses are specific for the immunizing antigen, and since no PFC response is produced by injection of the antiserum alone, this enhancement probably reflects a second signal produced by specific interaction between antibody and the surface Lyb3 component. Moreover, this signal can partially replace the requirement for T cells in the production of antibody to a "thymus-dependent" antigen. These findings (taken in conjunction with the previously described immune defects in CBA/N mice and other studies of B-cell maturation) suggest to us that Lyb3 is a cell surface component expressed selectively on a mature B-cell subclass. This component is important in B-cell triggering by antigen and fails to develop in CBA/N mice, due to a dysfunction of a regulatory gene on the CBA/N X chromosome.