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Showing papers by "Karolinska Institutet published in 1973"


Journal ArticleDOI
TL;DR: The ACIF test was used as a tool to trace the Epstein‐Barr virus genome at the cellular level to study the complementfixing antigens of human lymphoblastoid cell lines.
Abstract: Anti-complement immunofluorescence (ACIF) was used to study the complementfixing antigens of human lymphoblastoid cell lines. These cell lines carry the Epstein-Barr virus (EBV) genome although only producer cultures synthetize EBV-specific antigens (virus capsid antigen, VCA and early antigen, EA) detectable by direct and indirect immunofluorescence, usually in less than 5% of the cells. The ACIF test revealed an antigen localized in the nucleus of the lymphoblastoid cells. In contrast to EA and VCA, this antigen was present in over 90% of the cells of both producer and non-producer cultures. The antigen was shown to be specific for EBV by comparing the reactions of 52 sera in the ACIF test. Sera giving the nuclear reaction contained antibodies to VCA, EA or antigens detectable by complement fixation tests on cell extracts, but sera without EBV antibodies failed to give the reaction. Weak, equivocal or discordant reactions occurred with six sera with low titres in VCA, EA or complement fixation tests. Cell lines derived by transformation of human and primate lymphocytes by EBV gave the nuclear reaction. Control cells with no known association with EBV were non-reactive. These included foetal lymphocytes transformed by phytohaemagglutinin, cell lines derived from breast cancer, glioma, normal glia, pleuritis maligna and myeloma, and two marmoset lymphoid lines carrying Herpesvirus saimiri (HVS). In preliminary experiments, the ACIF test was used as a tool to trace the EBV genome at the cellular level. Cells from two Burkitt lymphoma biopsies, one tested after biopsy and one after passaging in nude mice, contained an EBV-specific antigen. Three clones of cells derived from hybrids of mouse somatic cells and a human lymphoblastoid cell line also contained such an antigen, but the number of reactive cells varied from clone to clone. A fourth clone was non-reactive.

1,632 citations


Journal ArticleDOI
TL;DR: Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma and it was concluded that B lymphocytes, in contrast to T lymphocyte, have receptors for EBV.
Abstract: Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus (EBV) because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma. This was done by a cytoadherence technique where virus-producing cells, displaying fresh viral determinants in their cytoplasmatic membrane, were mixed with lymphocytes. Unfractionated lymphocytes were found to adhere to these cells in contrast to column-purified T lymphocytes. The specificity of the binding was confirmed by blocking experiments that showed that sera containing high titers of antibodies directed against the virus could partially inhibit the adherence in contrast to low-titer sera. It is concluded that B lymphocytes, in contrast to T lymphocytes, have receptors for EBV. In a second line of experiments it was found that established human lymphoblastoid lines that carry the EBV genome had receptors characteristic for B lymphocytes and did not form T-lymphocyte rosettes. In contrast, a line of known T-lymphocyte origin that did not carry the EBV genome had receptors characteristic for T lymphocytes. EBV-transformed simian lymphoblastoid lines had surface markers indicating a B-lymphocyte origin in contrast to HVS-transformed simian lines that lacked surface immunoglobulin but carried receptors for sheep red blood cells.

498 citations


Journal ArticleDOI
TL;DR: It is proposed that the function of iron in Protein B2 is the initial generation of radical from a protein-bound group, and that stability of the radical depends upon some continuing interaction with the iron center, which is apparently less stable than is metalloprotein structure.

357 citations


Journal ArticleDOI
TL;DR: The effect of 6-hydroxydopamine (6-OH-DA) on the central nervous system was studied with light, fluorescence and electron microscopy and it was concluded that this latter type corresponds to the nigral DA neurones.

292 citations


Journal ArticleDOI
TL;DR: The results suggest the possibility that the size of the dCTP pool may have a regulatory function for the rate of DNA synthesis, and show that allosteric mechanisms shown with a purified enzyme (ribonucleoside diphosphate reductase) operate in intact cells.

288 citations


Journal ArticleDOI
TL;DR: The ‘inspiratory-vagal’ cells showed inspiratory activity even when lung expansion in the inspiratory phase was prohibited, thus resembling the Rβ cells of von Baumgarten and Kanzow.

241 citations


Journal ArticleDOI
TL;DR: The data suggest that endogenous depression is a hiochemically heterogenous disease and there may be a subgroup of patients within the endogenous syndrome where indoleamine metabolism is disturbed, and treatment with drugs that influence indoleamines more directly than a typical noradrenaline uptake inhibitor like nortriptyline, may lead to better therapeutic results.
Abstract: Cerebrospinal fluid (CSF) levels of the indoleamine metabolites, 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) and indole‐3‐acetic acid (IAA) were measured by a specific mass fragmentographic method in 43 depressed psychiatric in‐patients. The mean level of 5‐HIAA was 19.7 ± 7.9 ng per milliliter. The 5‐HIAA concentration was positively correlated to age, and there was a tendency for women to have higher values than men. The distribution of 5‐HIAA concentrations appeared to be bimodal in the 27 patients with a depression of endogenous type. The bimodality could not be explained by differences in age or sex. The mean level of IAA was 6.4 ± 4.1 ng per milliliter. The distribution of IAA was unimodal. The correlation to age was not significant, and there was no sex difference. There was a positive correlation between the concentrations of the two metabolites. Twenty patients were treated with nortriptyline, 50 mg three times daily by mouth. After three weeks treatment, the concentrations of 5‐HIAA and IAA had decreased significantly. The mean decrease was 4.8 and 2.0 ng per milliliter, respectively. The magnitude of the decrease was not cormlated to the plasma level of nortriptyline. The data suggest that endogenous depression is a hiochemically heterogenous disease. There may be a subgroup of patients within the endogenous syndrome where indoleamine metabolism is disturbed. In these patients, treatment with drugs that influence indoleamines more directly than a typical noradrenaline uptake inhibitor like nortriptyline, may lead to better therapeutic results.

238 citations



Journal ArticleDOI
Erik Borg1
TL;DR: The relation of the middle ear reflexes to the olivochochlear efferent system and the extrapyramidal system was discussed and a parallel slower, pentobarbital sensitive pathway was found.

235 citations


Journal ArticleDOI
TL;DR: A marked proliferation and differentiation of the monoamine neuron systems took place between the 7th and 23rd week of gestation permitting a mapping of major cell groups, as well as several axon pathways and terminal innervation patterns.
Abstract: The distribution of monoamine neurons in the human fetal brain was studied by Falck-Hillarp fluorescence histochemistry. Catecholamine (CA)- and 5-hydroxytryptamine (5-HT)-neuron systems were found in the smallest brain studied, obtained from an embryo having a total length of 2.1 cm and a gestational age of 7 weeks. A marked proliferation and differentiation of the monoamine neuron systems took place between the 7th and 23rd week of gestation (the range covered in the present investigation) permitting a mapping of major cell groups, as well as several axon pathways and terminal innervation patterns.

234 citations


Journal ArticleDOI
TL;DR: The results demonstrate a clearcut dissociation between the sites of biosynthesis and metabolism in the kidney and the function of the cortical PGDH might be either to inactive prostaglandins formed in medulla or to protect medullary PG receptors from high levels of circulating prostag landins.

Journal ArticleDOI
05 Sep 1973-Nature
TL;DR: This work has shown that the structure of these molecules, characterized by repeating antigenic determinants, would make it possible for the molecules to establish multiple interactions with the immunoglobulin receptors of the B cells and thus cause their activation.
Abstract: CERTAIN antigens are known to be immunogenic in the absence of thymus-derived (T) lymphocytes1–5. One extreme explanation of this is that all antigens are fundamentally thymus-independent, whereas the contrary view is to deny the experimental evidence for the existence of this type of antigen6. Another explanation for thymus-independency is based on the structure of these molecules, which are characterized by repeating antigenic determinants. This special structure would make it possible for the molecules to establish multiple interactions with the immunoglobulin receptors of the B cells and thus cause their activation7.


Journal ArticleDOI
TL;DR: Guinea pig epiphyseal cartilage was studied ultrastructurally after staining with ruthenium red or Alcian Blue, and it was concluded that the matrix granules contain proteoglycans.

Journal ArticleDOI
TL;DR: The active form of ribonucleotide reductase consists of a 1:1 complex between proteins B1 and B2 of the type αα'β2, the type of which is strongly influenced by the presence of sucrose.

Journal ArticleDOI
TL;DR: The quantitative study revealed that the density of monoamine boutons is highest in the superficial, lateral parts of the median eminence, where about 33% of all boutons, corresponding to a density of about 120 such boutons/500 sq.μm area, belong to monoamine neurones.

Journal ArticleDOI
TL;DR: Although electron-microscopically observable changes in the microsomal membrane occurs only late in lipid peroxidation, chemical, physical and enzyme alterations are early phenomena during this process and can be ascribed to increased membrane permeability.
Abstract: Rat liver microsomes were peroxidized in vitro and chemical, physical and morphological changes in the membrane were related to the effects on certain membrane-bound microsomal enzymes. With increasing peroxidation, microsomal phospholipids revealed decreasing concentrations of 20:4 and 22:6 fatty acids. At a high level of peroxidation, where alterations in permeability and ultrastructural changes such as breakage and deformation of microsomal vesicles were apparent, there was also a decrease in the concentration of 18:2 fatty acids. Glucose-6-phosphatase, cytochrome P-450 and uridine-5′-diphosphate glucuronyltransferase (UDP glucuronyltransferase) (three microsomal enzymes known to be highly dependent on the integrity of the membrane for their function) responded differently to lipid peroxidation. Glucose-6-phosphatase showed an initial decrease in activity as well as in Km for glucose 6-phosphate, followed by a restoration to control values at an intermediate level of lipid peroxidation. At a high level of peroxidation, both kinetic parameters were again markedly decreased. Cytochrome P-450 concentration, on the other hand, revealed a continuous decrease with proceeding lipid peroxidation, which was only partly accounted for by a conversion to cytochrome P-420. The loss of cytochrome P-450 was paralleled by decreased rates of aminopyrine demethylation and 3,4-benzpyrene hydroxylation. Glucuronyltransferase activity, finally, was activated at low, but again normalized at high, levels of lipid peroxidation. It thus seems that although electron-microscopically observable changes in the microsomal membrane occurs only late in lipid peroxidation, chemical, physical and enzyme alterations are early phenomena during this process. The continuous loss of cytochrome P-450 and the final decrease in glucose-6-phosphatase late during peroxidation probably reflect damage to membrane lipids of vital importance for the integrity and function of these enzymes whereas the activation of UDP glucuronyltransferase early during peroxidation most likely can be ascribed to increased membrane permeability.

Journal ArticleDOI
TL;DR: It is suggested that PGE2 can modify but not stop the release of DA and NA from central CA nerve terminals and indicate that prostaglandins might act as modulators of central CA neurotransmission.


Journal ArticleDOI
TL;DR: The findings suggest that the intracellular restrictive mechanism that limits superinfection in the receptor‐positive, resistant lines, can also restrict the function of the activated genome, derived from within.
Abstract: Human, EBV-carrying lymphoblastoid lines show wide differences in their sensitivity to superinfection with EBV concentrates and also in their sensitivity to the activation of the resident viral genome by BUDR and IUDR. A significant correlation was found between sensitivity to superinfection and activation in 23 virus-receptor-positive lines. In 10 receptor-negative lines, there was no such correlation: they were resistant to superinfection since they could not adsorb the virus, but differed widely in their activatability. The findings suggest that the intracellular restrictive mechanism that limits superinfection in the receptor-positive, resistant lines, can also restrict the function of the activated genome, derived from within. Since some of the lines that were resistant to both superinfection and activation were spontaneous producers, however, it appears that the same mechanism does not necessarily affect the “spontaneous” function of the resident genome.

Journal ArticleDOI
TL;DR: The size of the dCTP pool was closely correlated to the rate of DNA synthesis while the other pools reached their highest values after DNA synthesis, and the pool of dGTP was the largest while the dTTP pool was the smallest.
Abstract: Cellular pools of all four deoxyribonucleoside triphosphates were determined in synchronized Chinese hamster cells obtained by mitotic selection or by the addition of complete medium to isoleucine-starved cells. Using either technique the degree of synchrony is high and a maximum of more than 80% of the cells incorporated labeled thymidine during a short pulse period. Cells not involved in DNA synthesis contained measurable pools of deoxyribonucleoside triphosphates, but the pools expanded when the cells entered S phase. At all time points the pool of dGTP was the largest while the dGTP pool was the smallest amounting to 1–5% of the size of the dCTP pool. The size of the dCTP pool was closely correlated to the rate of DNA synthesis while the other pools reached their highest values after DNA synthesis.


Journal ArticleDOI
TL;DR: In this article, a Burkitt's lymphoma was transferred to the congenitally athymic mouse mutant nude with biopsy material from a 7-year-old Kenyan girl.
Abstract: A Burkitt's lymphoma was transferred to the congenitally athymic mouse mutant nude with biopsy material from a 7-year-old Kenyan girl. The tumor grows locally at the site of inoculation with no distant metastases. The established tumor has been maintained for six passages so far with preservation of histological and cytological appearance. The mouse-passaged tumor has a normal human diploid female chromosome complement. Isozyme studies have shown tumor to be of the same glucose-6-phosphatedehydrogenase (G-6-PD) and phosphoglucomutase1 phenotype (B and 2-1 respectively) as tumor biopsy from the patient. The mouse-passaged line maintained surface IgM, similarly to the original tumor and the derived tissue culture line, but lost the IgG coating characteristic for the original tumor but absent from two subsequent biopsies and from the derived tissue culture line. This is in line with previous observations indicating that surface-associated IgG on Burkitt biopsies is due to coating from the outside, whereas surface-associated IgM is a cell marker. Whereas the biopsy cells of the patient were positive for EBV-associated membrane antigen (MA), but not for early antigen (EA) and viral capsid antigen (VCA), the mouse-passaged line was positive for all three. This suggests that the restrictive influence of the human host on the production of EA and VCA in the Burkitt tumor is raised in the mouse host. The serum of the tumor-bearing nude mice contained anti-human antibodies, but no detectable EBV (anti-MA, EA and VCA)-antibodies.

Journal ArticleDOI
TL;DR: Bacteria were found within dentinal tubules associated with inflammatory reactions within the pulp during preparation and restoration of cavities with citric acid and composite resin.
Abstract: Prepared cavities were treated with citric acid before restoring them with a composite resin. Subsequently, bacteria were found within dentinal tubules associated with inflammatory reactions within the pulp.

Journal ArticleDOI
TL;DR: Mouse spleen cells were successfully activated by mitogens in serum‐free medium and the T cell mitogen, concanavalin A (ConA), was found to activate DNA synthesis in the presence or absence of serum to the same extent, although the dose response curve was shifted.
Abstract: Mouse spleen cells were successfully activated by mitogens in serum-free medium. The T cell mitogen, concanavalin A (ConA), was found to activate DNA synthesis in the presence or absence of serum to the same extent, although the dose response curve was shifted. Thus, concentrations ten times lower were optimally stimulating in serum-free medium. The strain differences existing with regard to Con A activation were the same whether serum was present or not. B cell mitogens, such as lipopolysaccharide (LPS) and purified protein derivative (PPD) of tuberculin, were equally active in the presence or absence of serum with regard to dose response curves and kinetics for the induction of DNA synthesis. When added to normal spleen cells in culture in the absence of serum, Con A also activated antibody synthesis against a variety of antigens and haptens. It had no such effect on spleen cells from nude animals, indicating that it exerted its B cell-activating effect via T cells. It was also effective when DNA synthesis in the lymphocytes had been suppressed with mitomycin. LPS and PPD activated antibody synthesis to haptens in normal and nude spleen cells, the response in nude animals being markedly stronger. Since there is virtually no background antibody synthesis in unstimulated cultures in the absence of serum, but a substantial background in serum, it follows that the factor of activation caused by T and B cell mitogens is more pronounced in the absence of serum.

Journal ArticleDOI
TL;DR: The results are consistent with previously postulated pathways concerning biosynthesis of cholic acid and chenodeoxycholic acid in which 5/?-cholestane-3a,7a, 12n-trio1 and 5??-chollestane3a-7a-diol, respectively are the main substrates for the 26-hydroxylase.
Abstract: o-Hydroxylation (26-hydroxylation) of various C,,-steroids by the microsomal and mitochondrial fraction was studied Assay conditions for the microsomal 26-hydroxylation were determined with 5~-cholestane-3a,7a-diol as substrate NADPH was the required cofactor NADH stimulated the hydroxylation at suboptimal concentrations of NADPH The hydroxylation was inhibited markedly by carbon monoxide Treatment with phenobarbital inhibited the reaction whereas starvation or biliary drainage had no significant effect The rates of microsomal 26-hydroxylation of different C,,-steroids expressed in nmol/mg protein per 20 min were cholesterol, < 01 ; 5-cholestene-3#?,7a-diol, < 01 ; 7a-hydroxy-4-cholesten-3-one, 03 ; 7a,12a-dihydroxy-4-cholesten-3-one, 09 ; 5/?-cholestane-3a,7a-diol, 18 ; 5/?-cholestane-3a,7a,i2a-triol, 27 Assay conditions for the mitochondrial 26-hydroxylation were determined with cholesterol and 5~-cholestane-3a,7a-diol as substrates The rate of reaction was faster with an NADPHgenerating system than with NADPH The reaction was inhibited markedly with carbon monoxide Biliary drainage inhibited the reaction whereas starvation or treatment with phenobarbital had no significant effect The rates of mitochondrial 26-hydroxylation of different C,,-steroids expressed in nmol/mg protein per 20 min were : cholesterol, 03 ; 5-cholestene-3p,7adiol, 09 ; 7a-hydroxy-4-cholesten-3-one, 17 ; 7a,12a-dihydroxy-4-cholesten-3-one, 09 ; 5/?-cholestane-3a,7aw-diol, 09 ; 5~-cholestane-3a,7a,l2a-triol, 20 The results are consistent with previously postulated pathways concerning biosynthesis of cholic acid and chenodeoxycholic acid in which 5/?-cholestane-3a,7a, 12n-trio1 and 5/?-cholestane3a,7a-diol, respectively are the main substrates for the 26-hydroxylase The possibility is discussed that pathways involving intermediary formation of 7a,26-dihydroxy-4-cholesten-3-one and 7a,12a,26-trihydroxy-4-cholesten-3-one also are of importance in the biosynthesis of bile acids

Journal ArticleDOI
E. W. Lamon1, Hans Wigzell1, Eva Klein1, Birger Andersson1, H. M. Skurzak1 
TL;DR: Data demonstrate specific T cell and non-T cell activity in microcytotoxicity tests with a tumor-specific system and strongly suggest that the non- T cell activity described herein is a B cell function.
Abstract: Adult BALB/c mice were injected with Moloney sarcoma virus (MSV) after which the animals' lymphocytes were examined for activity against Moloney leukemia virus (MLV) antigen-bearing target cells at 5-day intervals for 30 days. Lymphocytes from these animals and appropriately matched controls were fractionated into B cell-deficient (primarily T cells) and T cell-deficient (primarily B cells) subpopulations. Macrophages were removed using iron powder and magnetism. The unfractionated lymphocytes, T cells, and non-T cells were then tested in microcytotoxicity tests. Antigen-specific activity was found in the unfractionated lymphocytes from animals that had not yet developed palpable tumors and from regressor animals. The T cells were active just before tumor development and just after regression; however, by day 30 after virus infection (8–10 days after regression) the T cell subpopulation was much less active. The non-T cell subpopulation was also active before tumor development and soon after regression. However, this activity continued to rise after regression and was highest at 30 days. At day 15 (peak tumor size) neither subpopulation was active. The activity was demonstrated to be specific for the MLV-determined cell surface antigen by testing on control target cells that were MLV antigen negative and by comparison of the inhibitory effects with lymphocytes immune to a nonpertinent antigen as well as normal lymphocytes. The non-T cells were tested for activity before and after removal of macrophages with iron powder and magnetism. Such cells were significantly more active after removal of the macrophages. These data demonstrate specific T cell and non-T cell activity in microcytotoxicity tests with a tumor-specific system and strongly suggest that the non-T cell activity described herein is a B cell function.

Journal ArticleDOI
TL;DR: Spectroscopic probes have become powerful tools in analysing the correlation between structure and function of biological macromolecules and have provided means to study the dynamics of structural changes and interactions in time domains spanning from nanoseconds and less up to infinite time.
Abstract: Spectroscopic probes have become powerful tools in analysing the correlation between structure and function of biological macromolecules. Though these spectral methods cannot give as circumstantial information about the anatomy of a biological structure as, for example, X-ray diffraction they can provide information on physical properties at defined loci in a macromolecule which are not accessible by other techniques. Most important, spectroscopic studies have provided means to study the dynamics of structural changes and interactions in time domains spanning from nanoseconds and less up to infinite time.

Journal ArticleDOI
TL;DR: A method was developed for the rapid isolation of liver microsomes by means of gel filtration, which has the main advantages over conventional techniques, the considerable decrease of time required for isolation of the microsome, the improved removal of solutes like hemoglobin, and the improved suspension stability of the preparation.

Journal ArticleDOI
TL;DR: It is the purpose of the present article to present some of the surface markers used in the analysis of human lymphocytes under varying clinical and experimental conditions and present views on human lymphocyte, their functional characteristics and distinguishing markers in healthy or diseased human beings.
Abstract: Lymphocytes of birds and mammals can be subdivided into two major groups according to origin and function. If classified according to dependence or origin they are called thymus-dependent or T lymphocytes and bursa-derived or B lymphocytes (Raff 1973). Whereas in animal model systems the functional role of these cells have been assessed under varying experimental conditions, analogies have been provided for by the experiment of nature in human beings suffering from immunodeficiency disorders (Gatti 1972, Cooper e al. 1973). Such comparisons have made it possible to state quite emphatically that the human T and B lymphocyte populations exist with similar functional characteristics as in the other mammals. Whereas especially in the mouse, progress into the functional characteristics of the subpopulations of lymphocytes have been made largely on the basis of development of surface markers allowing actual physical separation of the various groups of cells, less is known about such ptossibilities in the human system. It is the purpose of the present article to present some of the surface markers we have used in our analysis of human lymphocytes under varying clinical and experimental conditions. The present article has no ambition to make a complete review of this field but will merely cover our own results and present views on human lymphocytes, their functional characteristics and distinguishing markers in healthy or diseased human beings. The reader is referred to the other articles in this issue to receive a more complete and maybe more objective picture.