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Biomedical subjects

J Winter

Publications and source records attributed to J Winter.

At least 199 records · Page 11Linked to original sources
PubMed1988

Primary histiocytosis X of the parieto-occipital lobe.

Immunohistochemical and ultrastructural evidence support the concept that histiocytosis X is the result of proliferation of pathological Langerhans' cells. Central nervous system involvement by histiocytosis X has been commonly described in multisystem disease and in association with lytic skull lesions. Unifocal brain involvement by histiocytosis X without concomitant osseous involvement is rare, with only 14 cases reported in the literature to date. Ten of these cases have involved the hypothalamus; the remaining four have involved the frontal lobe (two cases) and the temporal lobe (two cases). The fifth case of extrahypothalamic unifocal histiocytosis X, the first female case, and the first case with parieto-occipital lobe involvement, is reported. Pathology demonstrated infiltration of brain parenchyma by clusters of characteristic histiocytosis X cells with an admixture of morphologically related giant cells, eosinophils, and lymphocytes. Langerhans' granules were identified in the histiocytosis X cells by electron microscopy. Immunohistochemistry showed strong S-100 protein, HLA-DR, and T6 antigen positivity by the histiocytosis X cells. Therapy included complete surgical excision and postoperative radiation therapy for the incompletely excised lesion. Patients with unifocal extrahypothalamic histiocytosis X may have a better prognosis than patients with localized hypothalamic disease.

Adult↗
PubMed1988

Heterogeneity of phenotypic expression in normal and neoplastic B-cell proliferations detected by monoclonal antibodies LN-1 and DLC-48.

Recently developed monoclonal antibodies DLC-48 and LN-1 have been shown to be effective reagents for complement-mediated cell lysis of human B-cells. The authors have initially found that these reagents are useful in elimination of malignant lymphomas cells from human bone marrow for autologous bone marrow transplantation. In the current study, the authors have further characterized the reactivity of these antibodies in B-cell neoplasia and have analyzed the heterogeneity of antigenic expression among benign and neoplastic lymphoid cells for B-cell monoclonal antibodies. With the use of quantitative flow cytometric techniques to assess heterogeneity of antigen expression, the findings indicate that phenotypic heterogeneity within neoplasms from individual patients exists for a number of B-cell-related monoclonal antibodies, including B1, common acute lymphocyte leukemia antigen (CALLA), Ia, Ba-1, DLC-48, and LN-1. Within a given histologic class of lymphoid neoplasia, phenotypic heterogeneity was found to be a property of some individual cases and not others for all B-cell monoclonal antibodies examined. This heterogeneity was not consistently expressed in patients with similar tumors, nor was it a consistent property of a given antigen. Using cell lines derived from large cell lymphomas, the authors were able to find phenotypic heterogeneity within neoplastic cell lines that can be used to develop models for dealing with phenotypic heterogeneity in the context of complement-mediated cell lysis. They also established that for DLC-48 and LN-1, the heterogeneity was not related to the phase of the cell cycle of the proliferating cells. The results suggest that single monoclonal antibody treatment for bone marrow depletion of neoplastic cell may be insufficient to overcome phenotypic heterogeneity of B-cell neoplasms.

Antibodies, Monoclonal↗
PubMed1988

The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis.

We selected murine coronavirus JHM variants specifically changed in defined antigenic sites of the peplomer protein E2. Variants were isolated from the supernatants of monoclonal antibody hybridoma cell cultures which continued to secrete neutralizing antibodies after being infected with JHM. Comparative antigenic analysis and biological tests were performed in order to refine an operational epitope map and to characterize functional domains important for pathogenicity. The reaction patterns (neutralization, inhibition of cell fusion, immunofluorescence and binding in ELISA) between the variant viruses and the panel of monoclonal antibodies were very similar. Four groups of variants were characterized each of which revealed distinct changes affecting one defined antigenic site. These observations indicated that at least four independently mutable antigenic sites were associated with domains involved in cell fusion, neutralization and pathogenicity (E2-Aa, -Ab, -Ba and -Bb). JHM variants with alterations in the E2-Aa, -Ab or -Bb sites were similar to wild-type virus. These variants caused acute hepatitis and encephalomyelitis in mice. In contrast, JHM variants with changes in site E2-Ba had a strong propensity to induce chronic disease accompanied by demyelination persisting for several months.

Animals↗
PubMed1988

Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture.

Capsaicin is a pungent pain-producing compound found in plants of the capsicum family; it exerts excitatory, desensitizing, and toxic effects on a subset of sensory neurons, including the polymodal nociceptor population. We have carried out a quantitative study of capsaicin-induced fluxes of sodium, guanidine, calcium, rubidium, and chloride ions in cultures of neonatal and adult rat DRG neurons, in conjunction with the use of a histochemical stain that identifies capsaicin-sensitive neurons by means of cobalt uptake. Those cells that take up cobalt in a capsaicin-dependent manner (EC50 = 0.2 microM) represent about 50% of the total neuronal population derived from neonatal DRGs on short-term culture. Overnight treatment of cultures with 2 microM capsaicin leads to the loss of the cobalt-staining subpopulation. The capsaicin-insensitive neurons contain immunoreactive neurofilament epitopes that are present in fewer than 10% of capsaicin-sensitive neurons. This observation provides indirect evidence that the sensitive cells correspond to the small, dark B-type neurons, which are negative for neurofilament immunoreactivity in vivo. A capsaicin-dependent calcium uptake (EC50 = 0.2 microM), as measured by 45Ca incorporation, is shown by a DRG neuronal subpopulation that, like the cobalt-staining population of DRG neurons, is lost after overnight capsaicin treatment (2 microM). Capsaicin application leads to the accumulation of millimolar levels of calcium within a few minutes. Cadmium and other divalent cations block capsaicin-induced calcium uptake, but little or no inhibition is seen with organic calcium channel antagonists. Mitochondria, rather than the endoplasmic reticulum, are the probable destination of the internalized calcium, because ruthenium red inhibits calcium uptake (IC50 = 0.05 microM), whereas methylxanthines are inactive. The subset of sensory neurons that takes up calcium also releases 86Rb when exposed to capsaicin (EC50 = 0.06 microM). No efflux of 36Cl ions could be induced by capsaicin. These cells also show a capsaicin-induced uptake of 22Na or 14C guanidine (EC50 = 0.06 microM). In contrast, chick DRG cells in culture showed no capsaicin-induced calcium or cobalt uptake. Primary cultures of rat superior cervical ganglion neurons and Schwann cells, and a number of neuronal cell lines, also failed to respond to capsaicin, as judged by the calcium, cobalt, or guanidine uptake assays.

Animals↗
PubMed1987

Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans.

Rutin and quercitrin are hydrolysed to quercetin, and robinin is hydrolysed to kaempferol, by faecal flora from healthy subjects. The enzymes required for these hydrolyses, namely alpha-rhamnosidase and beta-galactosidase, were produced by some strains of Bacteroides distasonis; other strains, however, synthesized beta-glucosidase. The last-named enzyme was also elaborated by Bacteroides uniformis and Bacteroides ovatus. All the enzymes were produced constitutively. A cell-free extract of B. distasonis containing beta-glucosidase displayed an enzymic activity of 1 mumol/10 min per 10 mg of protein.

Bacteroides↗
PubMed1987

Characterization of capsaicin-sensitive neurones in adult rat dorsal root ganglion cultures.

Two populations of neurones can be distinguished in sections of dorsal root ganglia (DRG) by light microscopy and immunofluorescence techniques: large light (neurofilament-positive) and small dark (neurofilament-negative) neurones. This paper shows that corresponding populations can be seen in cultures of adult rat DRG, as judged by cell body size distributions and neurofilament content. None of the large light neurones, which are strongly positive for neurofilament immunoreactivity, show capsaicin sensitivity, which is detected histochemically by a cobalt uptake stain.

Animals↗
PubMed1987

Mode of inhibition of the DNA polymerase of Methanococcus vannielii by aphidicolin.

The mode of action of aphidicolin on DNA synthesis catalysed by the DNA polymerase of Methanococcus vannielii is competitive for dCTP, noncompetitive for dATP, dGTP and dTTP and uncompetitive for activated DNA. The kinetic data are accounted for by a mechanism in which dCTP and aphidicolin compete for the dCTP-specific binding site on the DNA polymerase. The dissociation constant for the aphidicolin--DNA-polymerase complex is 0.04-0.07 microM. Similar modes of inhibition of DNA synthesis exist for DNA polymerase alpha of higher eucaryotes but not for eubacteria or viruses and suggests a close functional relationship between the DNA polymerase of eucaryotes and of the archaebacterium M. vannielii.

Aphidicolin↗
PubMed1987

Coronavirus JHM induced demyelinating disease: specific domains on the E2-protein are associated with neurovirulence.

Infections of rodents by murine coronaviruses can lead to chronic diseases of the central nervous system. These infections are interesting systems to study mechanisms which could be relevant for the pathogenesis of certain human diseases. One major factor influencing the outcome of infection is related to the virus. To understand the virological basis for neurovirulence we compared JHM-virus isolates with different biological properties. JHM-Wt causes only acute disease, JHM-Ts43 a demyelinating encephalomyelitis and a virus shedded from persistently infected cells (JHM-Pi) is not virulent at all. The spread of these viruses in glial cell cultures reflects their different neurovirulence for animals. The peplomer E2 of these viruses reveals structural and antigenic differences. We characterised the epitopes of E2 with a panel of monoclonal antibodies. Four epitopes are associated with regions important for neutralisation, cell fusion and attachment. More than five epitopes are not related to such functions. Epitopes differ in their location and accessibility on the E2 protein subunits between JHM-Wt, JHM-Ts43 and JHM-Pi. To identify epitopes in regions important for pathogenesis, we performed animal studies with variants selected by monoclonal antibodies. Variants changed in a defined epitope (E2-Ba) induce in Balb/c mice a chronic disease. Variants changed in only one of the other three neutralisation epitopes induce acute disease. These results support and extend the observation that the peplomer protein E2 is a major determinant for virulence and antigenic variability of coronaviruses 1,4,5,6,8,10,17,19,22,23. Increasing evidence had been obtained that certain structural features of this protein are important for the cell tropism of the virus. Furthermore, this protein influences strongly the type and specificity of immune responses against viral and host antigens. The highly advanced knowledge on structure and replication of coronaviruses will be of great value to analyze further mechanisms leading to inflammatory demyelinating diseases associated with a persistent virus infection.

Animals↗
PubMed1987

The role of laminin and the laminin/fibronectin receptor complex in the outgrowth of retinal ganglion cell axons.

Chick embryo retinal ganglion cell (RGC) axons grow to the optic tectum along a stereotyped route, as if responding to cues distributed along the pathway. We showed previously that, in culture, RGCs from embryonic Day 6 retina are responsive to the neurite-promoting effects of the extracellular matrix glycoprotein laminin and that this response is lost by RGCs at a later stage of development. Here we report that, before axon outgrowth is initiated in vivo, laminin, is expressed along the optic pathway at nonbasal lamina sites that are accessible to the growth cones of RGC axons. The distribution of laminin within the pathway is consistent with its localization at the end-feet of neuroepithelial cells that line the route, and it continues to be expressed at these marginal sites during the first week of embryonic development. At later stages, concomitant with the loss of response by RGCs in culture, laminin becomes restricted to basal laminae at the retinal inner limiting membrane and pial surface of the optic pathway. Neurofilament-positive RGC axons bind a monoclonal antibody, JG22, which recognizes the laminin/fibronectin receptor complex, and continue to do so throughout embryonic development. We show that, in vitro, the JG22 antigen expressed by RGCs appears to function as a laminin receptor, by demonstrating that JG22 antibody blocks neurite outgrowth on a substrate of laminin. These findings are consistent with the possibility that laminin defines a transient performed pathway specifically recognized by early RGC growth cones as they navigate toward their central target.

Animals↗
PubMed1987

Cofactor requirements of steroid-17-20-desmolase and 20 alpha-hydroxysteroid dehydrogenase activities in cell extracts of Clostridium scindens.

Two neutral steroid-transforming activities were demonstrated in cell extracts of Clostridium scindens. Steroid-17-20-desmolase and 20 alpha-hydroxysteroid dehydrogenase were found to be inducible in cells cultured in the presence of cortisol. Both activities required manganese ions and NAD+ or NADH for activity. Cortisol, cortisone and 11-desoxycortisol were substrates as well as inducers of steroid-17-20-desmolase and 20 alpha-hydroxysteroid dehydrogenase activities. 17 alpha-Hydroxyprogesterone was an effective inducer but did not serve as a substrate for either enzyme activity. C. scindens is the first bacterial species of the normal human intestinal flora reported to elaborate inducible steroid-17-20-desmolase and 20 alpha-hydroxysteroid dehydrogenase activities. The results of cofactor, substrate specificity and induction studies suggest that these two activities may reside in the same enzyme complex.

20-Hydroxysteroid Dehydrogenases↗
PubMed1987

Bacterial metabolism of natural and synthetic sex hormones undergoing enterohepatic circulation.

Steroids undergoing enterohepatic circulation are exposed to bacterial metabolism particularly by obligate anaerobes which account for 99.99% of the fecal flora. The most common transformation is hydrolysis of conjugated steroids. The glucuronidases are synthesized by Escherichia coli and Bacteroides species. The bacterial catabolism of unconjugated steroids may be considered under several headings: 1. Reduction of ring-A due to clostridia species synthesizing specific enzymes; C. paraputrificum, 3 alpha,5 beta-reductase; C. innocuum, 3 beta,5 beta-reductase; and a new species C.J-1, 3 beta,5 alpha-reductase. 2. Reduction of the delta 5 bond by human fecal flora. The specific strain(s) synthesizing the enzyme have not yet been identified. 3. Reduction of 17-keto estrogens by the above mentioned ring-A reducing clostridia and by Eubacterium lentum. 4. Reduction of 17-keto androstenes by Bacteroides fragilis. 5. Desmolase mediated side chain cleavage at C17-C20 position of 17 alpha-hydroxysteroids by two new species Clostridium scindens and Eubacterium desmolans isolated from human and cat fecal flora respectively and by Clostridium cadavaris isolated from New York City sewage. 6. And 16 alpha- and 21-dehydroxylase by E. lentum a normal inhabitant of the human gut; it is the only organism known to synthesize 16 alpha- or 21-dehydroxylases. Due to the high specificity of the enzymes and the simplicity of extracting the metabolites, biosynthesis of reference compounds and radioimmunoassay reagents is practical and inexpensive. The enzymes can also be used for titration of specific bacterial strains in fecal flora and as markers for bacterial identification in particular for the strains difficult to be defined by regular biochemical reactions.

17-Ketosteroids↗
PubMed1987

Radiation dose enhancement therapy with iodine in rabbit VX-2 brain tumors.

Loading tissue with iodine enhances the radiation dose absorbed from low energy X-rays. In order to test whether this is a useful procedure for treating brain tumors, we infused radiographic contrast media into rabbits carrying VX-2 brain tumors and delivered 15 Gy of 120 kVp X-rays in 3 fractions to the tumor. From CT scans we estimated that the dose enhancement was approximately 30%. The median survival times, after tumor detection on CT, of untreated rabbits, treated with radiation alone, and treated with radiation plus contrast media were 3, 25.5, 38.5 days, respectively. The repeated infusion of contrast media, 3.5 g of iodine per kg of body weight, did not affect kidney function as measured by serum creatinine levels. This method of enhancing radiation dose in brain tumors therefore appears promising.

Animals↗
PubMed1987

Leksell stereotactic radiosurgery in the treatment of eye melanoma.

Current experiments indicate that a focussed single radiation treatment with a dose of 6000 to 9000 rads delivered to the 90% zone through a collimator of the Leksell stereotactic radiosurgical unit or 'gamma knife' to the rabbit eye melanoma model is capable of destroying the cancer totally and thus effecting a cure. The beneficial effect in these rabbit eye melanoma experiments appears to be similar to the results obtained by physicians using the Harvard and Berkeley cyclotrons in treating malignant neoplasms in the human eye. Therefore, it is proposed that a properly designed stereotactic radiosurgical unit can be used in patients with eye tumours similar to those selected for the cyclotron systems.

Animals↗
PubMed1987

Purification and use of Methanobacterium wolfei pseudomurein endopeptidase for lysis of Methanobacterium thermoautotrophicum.

The pseudomurein-degrading enzyme from autolysates of Methanobacterium wolfei was purified approximately 500-fold to electrophoretic homogeneity by ion-exchange chromatography under anaerobic conditions. Analysis of the soluble cell wall fragments produced by the pure enzyme from a cell wall preparation of M. thermoautotrophicum indicated that it is a peptidase hydrolyzing the epsilon-Ala-Lys bond of pseudomurein. A partially purified preparation of pseudomurein endopeptidase was free of nuclease activity and thus proved useful for the preparation in high yields of undegraded chromosomal and plasmid DNA from M. thermoautotrophicum. The partially purified enzyme was also used for the preparation of protoplasts, which were stabilized by 0.8 M sucrose. Under growth conditions the protoplasts produced methane and increased up to 100-fold in size, but failed to regenerate a cell wall.

Endopeptidases↗
PubMed1987

21-Deoxyaldosterone excretion in patients with primary aldosteronism and 21-hydroxylase deficiency.

21-Deoxyaldosterone appears in urine in free and conjugated forms. Total excretion is best determined after acid hydrolysis (pH 1) of urine, followed by extraction, repeated chromatographic purification, and quantitation of the steroid by RIA. 21-Deoxyaldosterone excretion was normal in 70% of patients with essential hypertension (n = 18), while 30% (n = 8) had more or less elevated values. In patients with primary aldosteronism (n = 21) elevated as well as normal values of urinary 21-deoxyaldosterone were found, indicating that in some patients aldosterone may be formed not only from corticosterone but also from the 21-deoxy compound. In patients with 21-hydroxylase deficiency (n = 21) urinary 21-deoxyaldosterone was invariably elevated, whether the patients had the virilizing or salt-losing form of the disease. Although the clinical manifestations of the salt-losing form seem unrelated to the inability to convert 21-deoxyaldosterone to aldosterone, the determination of 21-deoxyaldosterone adds insight into the biosynthesis of aldosterone in primary aldosteronism and 21-hydroxylase deficiency.

Adolescent↗
PubMed1987

MR imaging of the cervical spine: neurovascular anatomy.

High-resolution surface-coil MR imaging reveals intricate anatomic detail of the cervical spinal canal and its neurovascular contents. Appreciation of the normal neurovascular anatomy provides a scientific foundation for the detection of disease. Sagittal, axial, and oblique MR images of normal subjects were correlated with comparable anatomic sections obtained with a cryomicrotome whole-organ sectioning technique. The anterior epidural venous plexus is a prominent structure in the cervical spinal canal and was consistently identified both with cryomicrotomy and with MR in sagittal and axial planes. Epidural veins can be displaced and distorted in patients with cervical disk disease. Nerve roots including dorsal and ventral rootlets were consistently identified on axial images coursing through the subarachnoid space. Oblique-plane imaging showed nerve roots "en face" in their respective foramina; this may be a useful imaging technique in the diagnosis of nerve root impingement.

Cadaver↗