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Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 181 records · Page 10Linked to original sources
PubMed1990

On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.

Hyperandrogenic women appear to demonstrate an exaggerated 17-hydroxyprogesterone (17-HP) response to adrenal stimulation which is not due to the marked 21-hydroxylase deficiency of late-onset adrenal hyperplasia (LOAH). Furthermore, in hyperandrogenism the ovary also appears to secrete excessive amounts of 17-HP. It is not clear to what extent the elevated 17-HP levels after ACTH stimulation are due to extraadrenal production of the steroid. This investigation was undertaken to assess the adrenal contribution to the elevated 17-HP levels after ACTH stimulation observed in non-LOAH hyperandrogenism. One hundred and sixty consecutive unselected women with hirsutism and/or hyperandrogenic oligomenorrhea formed the clinical population. Excluded were 4 women with LOAH and all patients with hyperprolactinemia. For the purpose of investigating the relationship between adrenal response and clinical symptoms, hyperandrogenic patients were divided into 3 subgroups: hirsute only (n = 23), hirsute oligomenorrheic (n = 84), and oligomenorrheic only (n = 24). Subclassification for an additional 29 patients (18%) with hyperandrogenemia was not possible, since their symptomatology was not clearly stated in the record. However, these individuals were included in the patient group as a whole. Controls consisted of 21 healthy, regularly menstruating, nonhirsute female volunteers. Both patients and controls underwent acute adrenal stimulation with 1 mg ACTH-(1-24), and serum was obtained before and 30 min after ACTH administration. Hyperandrogenic patients had higher mean basal total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHS), 17-HP, and LH/FSH levels, but not cortisol (F), compared to normal subjects (P less than 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P less than 0.02). No correlation was noted between body mass index (BMI) and the levels of DHS, P, or A, while a weak positive association was noted between the BMI and the mean T (r = 0.31; P less than 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P less than 0.05). The mean 17-HP level 30 min after ACTH administration (17-HP30) was significantly higher in hyperandrogenic women than in normal subjects whether analyzed in separate subgroups or together and was due to the higher basal 17-HP levels. Basal 17-HP correlated with the circulating levels of T, A, and P, steroids largely of ovarian origin. Alternatively, the net increment in 17-HP from 0-30 min after ACTH (delta 17-HP30) was not significantly higher in hyperandrogenic women than normal subjects and did not correlate with the basal levels of T, A, and P. Neither the basal level of 17-HP nor its response to ACTH correlated with circulating DHS levels.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1990

Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase.

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Relationship between thyroid autoantibody spectrotype and IgG subclass.

The relationship between spectrotype and IgG subclass of autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO) has been investigated using sera from Hashimoto and Graves' patients. Isoelectric focussing (IEF) was carried out in gels over the range pI 3.5-9.5 followed by transblotting to nitrocellulose and probing the filters using 125I-labelled TPO and Tg. As has been shown previously for Tg antibodies, TPO antibody focussed over different pI values in different patients but the spectrotypes for individuals were constant over 2-5 years. Further, the pI values for TPO and Tg autoantibodies appeared to be related to IgG subclass, for example IgG1 Tg antibodies tended to focus nearer the cathode (pI 8.0-9.5) than IgG4 antibodies (pI 6.5-8.5) while antibodies of subclasses IgG1 + 2 + 4 produced spectrotypes covering a broad pI range (5.7-9.5). Consequently, it seems likely that the characteristic spectrotypes described by others for Tg autoantibodies, and those we now report for TPO antibodies, reflect the IgG subclass "fingerprints" which we suggest may be a measure of the ability of an individual to respond to different epitopes on these two thyroid antigens.

Autoantibodies↗
PubMed1990

Potential role of PHA in producing human monoclonal thyroid autoantibodies of different subclasses.

A human monoclonal autoantibody to thyroglobulin (Tg) of subclass IgG2 was developed by fusing a mouse myeloma with Tg antibody secreting Epstein-Barr virus (EBV)-infected B lymphocytes from a Hashimoto patient. Subsequent studies showed that EBV-infected B lymphocytes from this patient synthesized IgG2 Tg antibody while unfractionated blood lymphocytes cultured with pokeweed mitogen secreted IgG1, IgG2, and IgG4 Tg antibodies in amounts proportional to those present in the patient's serum. To investigate this discrepancy further, we cultured EBV-infected lymphocytes from blood, lymph nodes, and thyroid tissue in medium alone and with increasing concentrations of PHA. In individuals with thyroid autoantibodies predominantly of subclass IgG1, PHA enhanced the levels of total Tg antibody synthesis without affecting the IgG subclass distribution. However, in patients with serum autoantibodies of subclasses IgG1, 2, and 4, the increased levels of total Tg antibody synthesis were associated with increased amounts of thyroid autoantibodies of all of these subclasses; in some instances IgG1 and IgG4 autoantibodies were only synthesized in cultures containing PHA. These observations suggest that addition of the T-cell mitogen PHA to cultures of EBV-infected lymphocytes may ensure activation of B-cell precursors committed to synthesizing the IgG subclasses characteristic of serum antibody in the lymphocyte donor. Since Tg antibodies of subclasses IgG2 and IgG4 recognize different epitopes on Tg, the ability to produce human monoclonal antibodies of different IgG subclasses may simultaneously ensure the development of antibodies to different epitopes on the same antigen.

Animals↗
PubMed1989

Hematopoiesis in vitro coexists with natural killer lymphocytes.

The role of natural killer (NK) lymphocytes in the regulation of human hematopoiesis is controversial. NK-mediated inhibition of colony formation of hematopoietic progenitor cells has been irregularly reported for various cell lineages. In an effort to clarify such disparate findings, we studied the interaction of clearly defined NK and partially purified progenitor cell populations. Cell sorter purified CD16 positive blood NK cells and enriched autologous marrow progenitors were co-incubated at various lymphocyte to marrow cell ratios and then cultured in methylcellulose. There was no inhibition of myeloid, erythroid, or mixed colony formation. Similarly, activation of CD16 positive lymphocytes by interleukin-2 (IL-2) before co-incubation and co-culture did not result in inhibition of colony formation. Furthermore, in a newly designed assay system, we demonstrated that NK cells, which did not modulate colony-formation, remained capable of recognizing and killing rare K562 target cells seeded within the marrow cell population. Our results indicate that unstimulated and IL-2 activated isolated blood NK cells coexist with functioning autologous marrow progenitors in vitro.

Antigens, Differentiation↗
PubMed1989

Glutathione-coated cadmium-sulfide crystallites in Candida glabrata.

Cadmium-sulfide crystallites form in the yeast Candida glabrata cultured in the presence of cadmium salts. The particles function to sequester and detoxify intracellular cadmium ions. The crystallites are peptide-coated, but the coating peptide varies with the nutrient conditions of the growth medium. When cultured in rich nutrient broth the yeast forms intracellular CdS particles coated with a mixture of glutathione and the gamma-glutamylcysteine dipeptide. In contrast, cultures in synthetic minimal medium yield particles coated with polymerized gamma EC peptides of general structure (gamma-Glu-Cys)n-Gly. Glutathione/gamma-glutamylcysteine particles exhibit properties analogous to quantum, semiconductor-type crystallites. The optical properties are dependent on particle size, and irradiation results in photoluminescence and photoreduction not observed in bulk CdS mineral. Aerobic irradiation leads to particle decomposition presumably via oxidation of the sulfide ions within the crystallite.

Cadmium↗
PubMed1989

Flow cytometric surface light chain analysis of lymphocyte-rich effusions. A useful adjunct to cytologic diagnosis.

The cytologic diagnoses in 49 body cavity fluids from 46 patients, of whom 30 had a clinical diagnosis of lymphoma or lymphatic leukemia, and 16 patients with benign inflammatory or reactive conditions, were compared to flow cytometric surface immunoglobulin light chain analysis (kappa-lambda analysis [KLA]). The results of both tests were correlated with clinical outcome and all available information from biopsy, autopsy, and additional cell marker studies. When the diagnoses by both cytologic analysis and KLA were in agreement (57.1% of cases), there were no false-negative or false-positive results. Overall, false-positive and false-negative rates were, respectively, 6.1% and 12.2% with cytologic study, and 4.1% and 4.1% with KLA. Sixteen samples were from patients with small lymphocytic lymphoma (CLL) and small cleaved lymphoma, which had a false-negative rate of 37.5% by cytologic study, and only 6.2% by KLA. There was one false-positive result by KLA among the benign effusions. These findings indicate that KLA is a powerful adjunct to the cytologic evaluation of lymphocyte-rich effusions, especially in cases of lymphoproliferative disorders characterized by small lymphocytes, in which the cytologic diagnosis is frequently difficult.

Biomarkers, Tumor↗
PubMed1989

The effect of recombinant erythropoietin on intracellular free calcium in erythropoietin-responsive cells.

We have investigated whether recombinant erythropoietin (r-Epo) elicits a change in intracellular free calcium (IFC) in purified Epo-responsive cells in spleens of mice treated with phenylhydrazine. Colony-forming units (CFU-E) were prepared by negative selection through immunologic panning. Anti-Forssman, Mac-1, Ia, and HSA antibodies were used to eliminate nonhematopoietic progenitors. After two pannings, 29 +/- 1.5% (mean +/- 1 SD) of the recovered cells were CFU-E. IFC was measured by labeling cells with the fluorescent dye Indo-1 and analyzing them on a flow cytometer from 15 seconds to 30 minutes after the addition of agonist. At each step of the panning procedure, there was no effect of r-Epo (0 to 10 U/mL) on IFC even in the larger cells that are predominantly CFU-E. As a positive control, calcium ionophore (A23187) significantly increased IFC in greater than 90% of the spleen cells enriched in CFU-E. During growth of CFU-E in methylcellulose, the calcium ionophore did not affect the r-Epo-dependent formation of erythroid colonies. EGTA inhibited the formation of erythroid colonies. This inhibition appeared to be the result of a toxic effect of the chelator because the colony growth could not be restored when Ca2+ was added to the cultures in the presence of the EGTA. We conclude that the biologic action of Epo on responsive erythroid cells does not depend on acute changes in IFC.

Animals↗
PubMed1989

Vascular endothelial cells enhance T cell responses by markedly augmenting IL-2 concentrations.

Cultured human endothelial cells (EC), dermal fibroblasts (DF), and blood monocytes were compared for their effects on IL-2 concentration measured in the medium of both unfractionated peripheral blood mononuclear cells (PBMC) and highly enriched CD4+ T cell populations maximally stimulated by the polyclonal mitogen phytohemagglutinin (PHA). EC, but not DF or blood monocytes, could markedly augment IL-2 concentrations, up to 30-fold or more. This action of EC could not be replaced by fixed EC, EC-conditioned medium, or recombinant IL-1. Antibody to CD2 but not to CD18 blocked the EC effect. The augmented IL-2 concentrations generated in the presence of EC appeared biologically active in that the addition of living EC conferred a proliferative advantage to PBMC at suboptimal PHA concentrations, an effect which could be mimicked by exogenous IL-2. We propose that EC augmentation of IL-2 synthesis may contribute to the relatively unique ability of EC to stimulate a primary allogeneic response in vitro and may function in vivo to boost T cell responses to limiting quantities of antigen.

Adult↗
PubMed1989

Acquired immune deficiency syndrome presenting as a palatal perforation.

Head and neck manifestations are particularly frequent in the acquired immune deficiency syndrome. An unusual case of acquired immune deficiency syndrome in a female prostitute whose initial presentation included a palatal perforation is reported. This case is also noteworthy because the patient died of disseminated miliary tuberculosis, a disease only recently included in the Centers for Disease Control case definition of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Arteriovenous malformation of the mandible and its treatment: a case report.

Arteriovenous malformations (AVMs) can be life-threatening lesions and must be considered in the differential diagnosis of most radiolucent lesions of the jaws. The clinical and radiographic presentation of an AVM of the mandible and its treatment is reported. Diagnosis of the lesion was confirmed by arteriography, and the lesion was treated surgically by enbloc resection. The bony defect was successfully grafted with a porous hydroxyapatite block.

Arteriovenous Malformations↗
PubMed1989

Antibody valence and induced signal transduction: the role of antibody valence in anti-CD3-induced signal transduction in isolated normal T cells.

This report provides direct evidence that protein kinase C (PKC) is activated in isolated, rigorously accessory cell (AC)-depleted T cells when the T cell antigen recognition complex is stimulated by divalent anti-CD3 monoclonal antibody. Anti-CD3 monoclonal antibody-stimulated PKC activation alone does not, however, directly stimulate T cell proliferation in the absence of AC. A rise in cytosolic calcium is the second signal believed to be of paramount importance in T cell activation. While mitogenic concentrations of some divalent anti-CD3 antibodies do not cause a rise in cytosolic calcium, polyvalent anti-CD3 does evoke increased intracellular Ca2+ in rigorously AC-depleted resting human T cells.

Antibodies, Monoclonal↗
PubMed1989

Administration of a GABA antagonist selectively attenuates an ethanol-induced conditioned taste aversion.

Pretreatment with the GABA antagonist picrotoxin attenuated the development of an ethanol-induced conditioned taste aversion (CTA), while no effect of this compound was observed on the development of an amphetamine-induced CTA. These findings suggested some specificity of the effects of picrotoxin to the psychopharmacological properties of ethanol related to CTA. On the other hand, the benzodiazepine inverse agonist, Ro15-4513, purported to a specific ethanol antagonist, was shown to attenuate both an ethanol- and amphetamine-induced CTA. The results support the notion that ethanol intoxication may be mediated in part by GABAergic mechanisms. These GABA-mediated properties of ethanol may in fact underlie the development of an ethanol-induced CTA.

Amphetamine↗
PubMed1989

Similar effects of cyclosporine and verapamil on lymphokine, interleukin 2 receptor, and proto-oncogene expression.

Since calcium channel blocking agents and CsA exert an antiproliferative effect upon T cell mitogenesis, we have compared and characterized their immunosuppressive properties at the level of gene activation. Verapamil (greater than or equal to 30 microM), which blocks T cell mitogenesis and a rise in cytosolic calcium, was added to cultures of peripheral blood mononuclear cells stimulated with phytohemagglutinin (5 micrograms/ml) and phorbol myristate acetate (5 ng/ml). Northern blot analysis was performed using cDNA probes for the p55 interleukin 2 receptor (Tac; IL-2R), interleukin 2 and c-myc at 20 hr of culture. Accumulation of IL-2 encoding mRNA within the cytoplasm was completely abrogated by verapamil. However, IL-2R and c-myc encoding mRNA were clearly detectable in verapamil-treated cell cultures. Surface expression of the Tac protein in mitogen-activated T cells was also not blocked by verapamil as shown by FACS analysis. In companion experiments with CsA, verapamil only partially inhibits the intracellular processes leading to T cell activation. A calcium-independent pathway may exist for the expression of IL-2R and c-myc, while an increase of intracellular Ca2+ may provide the additional signal for IL-2 gene expression. Although the in vitro concentrations of verapamil used in these experiments are in excess of common clinically therapeutic levels, the results help clarify the mode of CsA action and may provide a new tool to dissect the early events of T cell activation.

Calcium↗
PubMed1989

A large proportion of T lymphocytes lack CD5 expression after bone marrow transplantation.

The lymphocyte cell surface molecule CD5 (T1, Leu 1, Tp67 in the human; Ly 1 in the mouse) is expressed on the majority of circulating T lymphocytes and a small population of B cells. We have analyzed CD5 expression on repopulating T cells in the peripheral blood of patients after allogeneic bone marrow transplantation (BMT). The frequency of CD3+ T cells that lack expression of CD5 is dramatically increased after BMT compared with the normal population. The percent of total CD3+ CD5- cells correlated with the presence of graft versus host disease and with time following transplant, but did not correlate with age, diagnosis, preparative regimen, T-cell depletion of the marrow, major histocompatibility complex compatibility, or the presence or absence of interstitial pneumonitis. Furthermore, the total number and percent of CD8+ CD5- cells was increased following BMT. CD3+ cells from BMT patients were sorted for the presence or absence of CD5 expression. CD3+ CD5- cells were capable of interleukin-2 production and of mediating cytolysis following lectin stimulation. We conclude that CD3+ CD5- T cells are functional and represent a significant proportion of circulating cells in patients after BMT.

Animals↗