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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 199 records · Page 11Linked to original sources
PubMed1990

Heat-shock protein 65 as a beta cell antigen of insulin-dependent diabetes.

The primary beta-cell antigen of insulin-dependent diabetes is thought to be a protein with a molecular weight of approximately 64 kD. Hyperthermic incubation and cytokines such as interleukin 1 beta, gamma interferon, and tumour necrosis factor induce synthesis of 64 kD protein by insulinoma cells. By western blot techniques, cross-reactivity was found between this 64 kD protein and monoclonal antibodies directed against Mycobacterium tuberculosis heat-shock protein 65, but not with antibodies directed against a similar epitope of M leprae heat-shock protein 65. Binding of M tuberculosis heat-shock protein 65 antibodies to interleukin-1 beta-treated cells was inhibited by prior addition of serum from insulin-dependent diabetic patients which contained antibodies to 64 kD beta-cell antigen. It is suggested that heat-shock protein 65 may be the 64 kD beta-cell antigen and that autoreactivity to an epitope of heat-shock protein 65 may confer susceptibility to insulin-dependent diabetes mellitus.

Animals↗
PubMed1990

Percutaneous exposure of medical students to HIV.

A preliminary survey of 42 fourth-year medical students at Cornell University Medical College found that 21% of the students (95% confidence interval, 9% to 34%) reported being stuck by an HIV-contaminated needle during the third and fourth years of medical school. Seventy-four percent believed their school had not adequately taught them what to do after a needle-stick injury, and half of them would not seek the services of the school's student health clinic. If the risk of infection following percutaneous exposure to HIV approaches seroconversion rates seen in prospective studies, then medical students are experiencing a serious occupational exposure. More research in this area is clearly necessary, but immediate steps should be taken by medical colleges to address the risks among medical students and implement appropriate training and safeguards.

Body Fluids↗
PubMed1990

Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase.

An avidin-biotin enhanced immunoperoxidase procedure using monoclonal antibodies (AA1, AA3, and AA5) prepared against human mast cell tryptase resulted in intense staining of mast cells in paraffin-embedded tissue. The distribution of mast cells observed was similar to that seen when adjacent serial sections were stained using a standard procedure with toluidine blue, though the immunoperoxidase technique permitted the identification of significantly more mast cells. With monoclonal antibody AA1, immunostaining was entirely specific for mast cell granules, and there was negligible background staining in a range of tissues including lung, tonsil, colon, gastric mucosa, skin, and pituitary. There was no staining of antibody on basophils or on any other normal blood leukocyte. The technique was effective with tissue fixed in either Carnoy's or neutral buffered formalin, though the internal mast cell structure was better preserved with formaldehyde fixation. The immunoperoxidase staining procedure with monoclonal antibody AA1 is a highly specific and sensitive means for the detection of mast cells in routinely processed tissues.

Antibodies, Monoclonal↗
PubMed1990

Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms.

This study attempts to define histologic patterns in 1039 consecutive cases of basal cell carcinoma and to correlate these patterns with adequacy of margins of surgical excision. Five major histologic patterns were identified: nodular, 218 cases (21%); superficial, 181 cases (17%); micronodular, 151 cases (15%); infiltrative, 77 cases (7%); and morpheic, 11 cases (1%). A mixed pattern (two or more major histologic patterns) was present in 401 cases (38.5%). Our study indicates that nodular and superficial basal cell carcinomas can be completely removed by simple surgical excision in a high percentage of cases (93.6% and 96.4%, respectively) whereas the micronodular, infiltrative, and morpheic basal cell carcinomas have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision. Mixed patterns that consisted of combinations of the nodular, micronodular, or infiltrative types exhibited a behavior similar to the pattern that resulted in a greater chance of incomplete surgical removal.

Basal Cell Carcinoma↗
PubMed1990

Immunoenzymatic assessment of interferon-gamma in Hodgkin and Sternberg-Reed cells.

The typical histological picture seen in Hodgkin's disease is consistent with the release of cytokines and other active mediators by the malignant cells, i.e., Hodgkin and Sternberg-Reed cells. Since interferon-gamma is regarded as an important regulator of the cytokine cascade, we have undertaken an immunohistological assessment of this mediator in Hodgkin's disease tissue biopsies. In approximately 50% of the cases investigated we found Hodgkin and Sternberg-Reed cells to be positive with antibodies against interferon-gamma. These in situ findings were substantiated by immunostaining of Hodgkin's disease-derived cell lines L428 and L540. L540 was consistently positive, whereas L428 was negative. It is noteworthy that L428 exhibit a B-cell pheno- and genotype, whereas L540 is of T-cell origin. These data are consistent with theories that propose that cytokine production by tumour cells is central to the pathogenesis of Hodgkin's lymphoma.

Antibodies, Monoclonal↗
PubMed1990

Bilateral keloid-like myofibroblastic proliferations of the cornea in children.

Two 6-month-old white boys developed localized multifocal white nodules of the anterior corneal stroma without evidence of antecedent trauma, inflammatory disease, or familial occurrence. The first patient had bilateral lesions initially; the second patient initially had unilateral involvement followed by a corneal nodule in the second eye at 11 years of age. Light and electron microscopic studies of the lesions in both patients were similar and disclosed stromal nodules composed of proliferating myofibroblasts, activated fibroblasts, and haphazardly arranged fascicles of collagen. Immunohistochemical studies revealed that the spindle cells within the nodules expressed immunoreactivity for vimentin and alpha-smooth muscle actin. Management options for these slowly progressive corneal lesions include lamellar versus penetrating keratoplasty and topical corticosteroids.

Child, Preschool↗
PubMed1990

What's new in the lymphocyte phenotype?

It is a relatively short period of time since the demonstration of surface immunoglobulin by immunofluorescence and the technique of cell surface rosetting first enabled in the identification of lymphocyte subsets. When we now examine the range of monoclonal antibodies which are available to lineage specific and lineage related epitopes the early methods used for the characterisation of normal or abnormal lymphocyte populations seem amazingly crude. The initial development by Kohler and Millstein of techniques for hybridising antibody producing cells to establish continuous lines and their development by large numbers of workers worldwide have provided a vast array of reagents available for cell phenotyping, ranging from the simplest diagnostic determinations to the sophisticated analysis of lymphocyte subsets in development. Indeed, so great is the array of monoclonal antibodies available that the nomenclature has been standardised at four international workshops. The basic aim of these workshops has been to establish a standardised system for the identification of the different monoclonal antibodies available for staining lymphocytes and also to officially allocate antibodies to these groups. A wide range of techniques are employed by the many groups who contribute to these workshops in order to achieve these results. Despite these basic aims, it is also clear that a considerable amount of functional and molecular biological information has come from these large group studies. At the Oxford Workshop, held in 1986, the number of identified "Clusters of Differentiation" (CD) reached the figure 45.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1990

The interaction of vitamin A deficiency and rotavirus infection in the mouse.

Weanling mice were fed on a control diet ad lib., a vitamin A-deficient diet ad lib. or pair-fed to the intake of the vitamin A-deficient group. Vitamin A deficiency was induced by 63-70 d of age. On day 77 mice were given 30 microliters rotavirus/mouse orally and examined histologically 1 week later. There were no changes in relative liver weight in any of the groups, but following infection animals deficient in vitamin A showed a significant increase in spleen weight compared with the other groups. The relative weight of the thymus was reduced by vitamin A deficiency, in both non-infected and infected animals. The histology of the spleen, thymus and small intestine was similar in all three dietary groups before infection. The number of goblet cells per duodenal villus in vitamin A-deficient animals was significantly lower than that of control and pair-fed animals. In the small intestine of vitamin A-deficient animals, rotavirus infection caused dramatic changes to the mucosa, with almost complete destruction of the tips of the villi, but control and pair-fed animals had normal villi. It is concluded that although rotavirus infection and vitamin A-deficiency cause few changes alone, in their action together there is significant destruction of the mucosal barrier of the small intestine.

Animals↗
PubMed1990

Monoclonal antibody MAC 387 recognizes a myelomonocytic antigen shared by epithelial cells in inflammatory skin diseases.

The monoclonal antibody MAC 387 recognizes an antigen expressed by human macrophages and granulocytes. Normal epidermis does not react with the antibody, but the inflamed epidermis may react. In this immunocytochemical study we have investigated the intracytoplasmic expression of the MAC 387 antigen in biopsies of a variety of skin disorders. In lichen planus the basal cells were usually negative, whilst suprabasal cells were positive. In the majority of other inflammatory dermatoses studied, there was positive staining of basal and suprabasal cells. A parallel frozen- and paraffin-section study of biopsies of cutaneous T-cell lymphomas and inflammatory conditions failed to demonstrate HLA Class II expression in the cytoplasm of keratinocytes. Expression of the MAC 387 antigen in the epidermis is directly associated with cell-mediated activity in the papillary dermis, but is not related to HLA Class II expression.

Antibodies, Monoclonal↗
PubMed1990

Clonality of T cell and phenotypically undefined lymphoid neoplasms: the value of genotypic analyses.

The value of genotypic analysis for routine assessment of leukaemia and lymphoma was shown by the findings in a selected series of 30 cases. T cell receptor (TcR) gene rearrangements were observed in six out of nine cases of CD3+ CD8+ lymphocytoses and provided clear evidence for clonality in this group. The T cell proliferations in two of the remaining cases masked B cell lymphocytic leukaemia and hairy cell leukaemia, while in the third case no cause was found for the polyclonal proliferation. Heterogeneity of phenotype and genotype were observed in peripheral T cell lymphomas: one out of six cases showed TcR gene rearrangement, one case retained its germline configuration, a further case masked B cell lymphoma and the remainder were polyclonal. Genotypic analysis was helpful in the analysis of a tumour of mixed T cell and myeloid phenotype which was shown to be germline for TcR and immunoglobulin genes, consistent with a myeloid origin. Two histiocytic tumours were found to have clonal rearrangement of TcR genes. Nine out of 11 B cell tumours showed immunoglobulin gene rearrangement. It is concluded that genetic analyses are useful in the analysis of T cell, histiocytic, and B cell tumours in which an immunoglobulin phenotype cannot be defined.

Antigens, CD↗
PubMed1990

Percutaneous pediatric renal biopsy: use of the biopsy gun.

A recently developed biopsy gun was used in the ultrasound (US)-guided biopsy of native kidneys in seven children. The biopsy gun employs a needle (18 gauge) smaller than that usually used for renal biopsies. In all seven cases it provided a core biopsy specimen that contained enough glomeruli to make a definitive histologic diagnosis of renal parenchymal disease. Use of the biopsy gun eliminated the more complicated movements needed to obtain samples with the conventional manual biopsy techniques. No major complications occurred, and in only one case a minor complication, trace hematuria determined by means of dipstick analysis, was found. The time required to obtain the tissue samples was decreased with use of this technique. Because of the advantages of the biopsy gun, the authors now use it exclusively in percutaneous US-guided biopsy of native pediatric kidneys and recommended that this method be considered by other institutions performing similar biopsies.

Adolescent↗
PubMed1990

Cyclosporin A and vehicle toxicity in primary cultures of rabbit renal proximal tubule cells.

The capability of cyclosporin to produce direct injury to primary proximal tubular renal cells was studied. These cells, when grown on Millicell inserts, retain the functional polarity of the proximal tubule, i.e., generate a transepithelial pH gradient (apical compartment acidic) that is reversibly blocked by amiloride addition only if it is added to the apical compartment. Administration of ouabain to the basal compartment also blocks the generation of the transepithelial pH gradient. Additionally, the cells were more responsive to parathyroid hormone (PTH), a proximal tubule characteristic, than to arginine vasopressin (AVP), a distal tubule characteristic. The following substances were tested for their effect on the capacity of these cells to generate a pH gradient: Sandimmune, the commercial form of cyclosporin A; the free form of the drug; Cremophor EL, the vehicle used in the commercial preparation; and ethanol, the vehicle used to dissolve the free form. Sandimmune, at 25-50 microM, inhibited the generation of the pH gradient within 24 h. Surprisingly, Cremophor also blocked the development of a pH gradient, although somewhat less effectively. In contrast, 10 microM cyclosporin, regardless of the form tested, had no effect for up to 96 h. These findings show that cyclosporin, in the form of Sandimmune, has a direct toxic effect on these cells; they also suggest that the vehicle, Cremophor, may contribute to the well-established nephrotoxicity of cyclosporin A.

Amiloride↗
PubMed1990

Effect of undernutrition on the immune response to rotavirus infection in mice.

The effect of moderate and severe undernutrition on the immune response to EDIM rotavirus was studied in mice. A moderate state of undernutrition was produced by feeding weanling mice either 15 or 30% less diet than the control group had eaten on the previous day, for 7 weeks. After 6 weeks, mice were given 30 microliters/mouse of EDIM rotavirus orally and the antibody production was measured 1 week later. The delayed-type hypersensitivity (DTH) response to picryl chloride (PC) was measured as an index of cell-mediated immunity. For severe undernutrition, weanling mice were fed either 30 or 50% less diet than the control group had eaten on the previous day, for 12 weeks. After 11 weeks of feeding, animals were given 30 microliters/mouse of EDIM rotavirus either orally or intramuscularly and the antibody production was measured 1 week later. In moderate undernutrition, the serum antibody levels specific to rotavirus and the DTH response to PC were normal in all dietary groups compared with the control group. In severe undernutrition, the antibody levels following oral challenge of rotavirus were similar in all dietary groups. There was a significant impairment of serum antibody levels following intramuscular challenge in the group fed 50% less than the control group. It is concluded (1) that a balanced reduction in food intake does not impair the immune response, unless severe restriction is maintained for a long period of time, and (2) that the antibody response varies with the route of immunization.

Animals↗
PubMed1990

Distribution of LCA protein subspecies and the cellular adhesion molecules LFA-1, ICAM-1 and p150,95 within human foetal thymus.

The distribution of leucocyte common antigen (LCA) protein subspecies and the cellular adhesion molecules LFA-1 (CD11a), ICAM-1 (CD54) and p150,95 (CD11c) has been established within frozen sections of human foetal thymus. Whereas over 95% of foetal cortical thymocytes and approximately 85% of medullary thymocytes were CD45RO positive, CD45RA was only expressed by approximately 29% of medullary thymocytes. The majority of foetal thymocytes also expressed CD11a, whereas CD54 was expressed by thymic epithelial and accessory cells and also apparently by some cortical thymocytes adjacent to epithelial cells. The distribution of CD54 and the major histocompatibility complex (MHC) class II molecule HLA-DR, demonstrated with a monoclonal antibody to a monomorphic determinant, was similar. The CD11c molecule was present on a population of dendritic-type accessory cells, but was absent from the large, scavenger, KiM8-positive macrophages occurring throughout the thymic cortex.

Antibodies, Monoclonal↗
PubMed1990

Phenotypic changes in a CD4+ lymphocyte subset correlate with a conversion from suppressor to helper inducer function.

The monoclonal antibodies WR16 (CD45RA) and WR19 were used to isolate two reciprocal subsets of CD4 lymphocytes by negative selection. The CD4+/WR16-/WR19+ subset exhibited helper-inducer activity in a pokeweed mitogen (PWM)-driven Ig secretion assay, whereas the CD4+/WR16+/WR19- subset showed suppressor activity. When the CD4+/WR16+/WR19- subset was cultured in phytohaemagglutinin (PHA) or purified protein derivative (PPD) there was increased expression of the antigen binding WR19 but the cells remained WR16 negative. Cultures of CD4+/WR16+/WR19- lymphocytes with PHA or PPD induced a phenotypic change that resulted in a population which was CD4+/WR16-/WR19+. Investigation of the functional activity of the CD4+/WR16+/WR19- subset, before and after activation and phenotypic change to WR16-/WR19+, indicated that the change in phenotype correlated with a functional conversion from suppressor to helper-inducer activity. These results suggest that the CD4+/WR16+/WR19- suppressor subset comprises cells that differentiate to WR16-/WR19+ helper-inducer cells after exposure to antigen or mitogen.

CD4 Antigens↗
PubMed1990

[Autoradiography determination of the GABA(A) receptor density in the brain of rats with portacaval shunt].

Quantitative autoradiography was used to assess the densities of gamma-aminobutyric acid (GABAA) receptors in the brains of rats with a portacaval end-to-side shunt (PCA). The shunt alone induced only mild encephalopathy with ataxia and decreased locomotion. Aggravation of the encephalopathy was achieved by gavage feeding of packed erythrocytes or by induction of severe hyperammonemia by intraperitoneal injection of urease. Gavage feeding of erythrocytes led to severe encephalopathy in about 50% of the animals with PCA. The combination of PCA and urease treatment caused severe encephalopathy in every animal. The serum ammonia concentration increased 5 times normal by PCA alone, 20 times normal by gavage feeding of erythrocytes and more than 30 times normal by urease-treatment of the PCA-animals. For autoradiography, coronal slices were cut at the level of the hippocampal formation and through the cerebellum. Radioligand binding was measured using as a ligand 3H-muscimol, a specific GABAA receptor agonist. The specific binding of 3H-muscimol was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellar cortex. No significant differences were observed between the magnitude of ligand binding to specific microregions of brains from normal animals, animals with PCA without overt encephalopathy and animals with severe encephalopathy induced by a combination of PCA and gavage feeding of erythrocytes or urease treatment.

Ammonia↗