Search PubMed⌕ Search

Biomedical subjects

R E Schmidt

Publications and source records attributed to R E Schmidt.

At least 145 records · Page 8Linked to original sources
PubMed1997

Thyroid and adrenal function in HIV-infected outpatients.

We investigated parameters of thyroid and endocrine functions in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 44% increase in plasma TBG and a 15% increase in plasma CBG, while the T4/TBG ratio was decreased by 20%, plasma DHEAS was lowered by 30% and urinary aldosterone excretion fell by 70%. Plasma T4, T3 and TSH and urinary excretion of cortisol and catecholamines was not influenced by the disease. A weak, but significant negative correlation was found between plasma CBG and the body mass index of the patients. Significant positive correlations were observed between CD-4 cell count and the T4/TBG-ratio or plasma DHEAS levels. TBG was inversely correlated with CD-4 cell count and DHEAS. Thus, an increase in plasma TBG and a shift from adrenal androgen and mineralocorticoid steroid secretion towards cortisol secretion may be endocrine markers for progression of the disease in patients with HIV-infection.

Adrenal Glands↗
PubMed1997

Functional characterization of receptor-type protein tyrosine phosphatase CD148 (HPTP eta/DEP-1) in Fc gamma receptor IIa signal transduction of human neutrophils.

Activation of the 40-kDa low-affinity receptor for IgG (Fc gammaRIIa, CD32) leads to tyrosine phosphorylation, increase of cytosolic free calcium concentration ([Ca2+]i), and production of superoxide anions (O2-) in neutrophils (PMN). It has been established that protein tyrosine kinases (PTK) and phosphatases (PTP) are essential for the regulation of intracellular signaling. CD45 is a type I receptor-type protein tyrosine phosphatase (RPTP) with two PTP domains. Recently it has been demonstrated that co-cross-linking of CD45 modulates the signal transduction pathway of Fc gammaRIIa in PMN. In contrast, the functional characteristics of CD148 (HPTP eta/DEP-1), a new RPTP with only one PTP domain, is unknown. CD148 is expressed on PMN in slightly lower density than CD45, and in higher density than on lymphocytes. [Ca2+]i measured with fluo-3-loaded PMN by flow cytometry and O2- production determined by lucigenin-dependent chemiluminescence were inhibited by co-cross-linking of CD45 with Fc gammaRIIa in comparison to isotype control monoclonal antibody (mAb). In contrast, pre-incubation with CD148 mAb 143-41 abolished O2- generation, but did not inhibit [Ca2+]i rise. In summary, both clustered human RPTP, CD45 and CD148, inhibit Fc gammaRIIa-induced O2- production in PMN, but they differ in regulation of [Ca2+]i. Therefore, it is suggested that co-cross-linking of Fc gammaRII with CD45 and CD148 leads to dephosphorylation of different substrates. These distinct functional capacities may be important for differential regulation of Fc gammaR signaling by currently unknown ligands.

Humans↗
PubMed1997

Adrenergic control of natural killer cell circulation and adhesion.

Natural killer (NK) cell circulation is subject to adrenergic regulation. Exactly how NK cells are released into the circulation is unknown. In an attempt to identify some of the mechanisms, the present report focuses on aspects of adhesion regulation of NK cells. Results demonstrate that interactions between NK and endothelial cells (EC) in vitro can be reduced by beta 2-adrenoceptor stimulation for as long as the receptor stimulation occurs. The level of soluble adhesion molecules (sICAM-1, sE-selectin, sVCAM-1) in vivo remained unchanged during adrenaline infusion. In vitro analyses further reveal the requirement for Ca2+/Mg2+ in NK-EC adhesion. Blocking studies indicate the involvement of several members of the beta 1(CD29)- and beta 2(CD18)-integrin family, reducing NK cell adhesion by 28 to 39%. Stimulation of beta 2-adrenoceptors in the presence of these blocking antibodies further reduced NK adhesion by an average of 22%. Analysis of NK cell adhesion to various extracellular matrix components demonstrates significant NK cell adhesion to fibronectin but much less to laminin or collagens I and IV. NK cell adhesion to fibronectin was reduced by 50% upon beta 2-adrenoceptor stimulation, independent of the VLA-4/VLA-5 binding site on fibronectin. Together these results contribute to understanding the influences of beta-adrenoceptor stimulation on NK cell circulation and adhesion.

Cell Adhesion↗
PubMed1997

Histology and function of the internal anal sphincter after injection of botulinum toxin.

BACKGROUND: Children with Hirschsprung's disease may have persistent obstructive symptoms due to internal anal sphincter hypertonicity, even after definitive surgery. Anal myectomy is not universally effective and may result in permanent sphincter injury. Botulinum toxin injection has been used to selectively weaken a variety of muscles and could theoretically represent a less invasive option for children with this difficult problem. We evaluated the efficacy and safety of botulinum toxin in an immature porcine model. MATERIALS AND METHODS: Six-week-old piglets underwent four-quadrant intrasphincteric injection of botulinum toxin or saline. Under ketamine sedation, internal sphincter resting pressure was measured using a water-perfused system before injection and 4 weeks later. Animals were sacrificed 4 weeks after injection. Histological evidence of neuromuscular changes or inflammation in the internal sphincter was documented. All analysis was done blindly. RESULTS: Internal anal sphincter pressure increased in control animals, likely due to growth over the 4-week period. Conversely, botulinum toxin injection was associated with a significant decrease in internal sphincter pressure. There were no significant differences between the botulinum toxin and control groups with respect to histologic evaluation of neuronal size and number, nerve bundle size and number, inflammation, or muscle atrophy. CONCLUSIONS: These data suggest that botulinum toxin is effective in decreasing internal anal sphincter pressure without histologically evident adverse effects. A clinical trial using botulinum toxin for persistent obstructive symptoms following surgery for Hirschsprung's disease is therefore justified.

Anal Canal↗
PubMed1997

G-CSF and cyclosporin induce an increase of normal cells in hypoplastic paroxysmal nocturnal hemoglobinuria.

Four paroxysmal nocturnal hemoglobinuria (PNH) patients with severe thrombocytopenia, hemolytic anemia and neutropenia were treated using a combination of filgrastim (G-CSF) and cyclosporin. In all patients a trilineage response of hematopoiesis was achieved. In addition, the proportion of glycosyl-phosphatidylinositol (GPI)-deficient granulocytes decreased. All patients mobilized CD34+ hematopoietic progenitors into peripheral blood after starting treatment with G-CSF. The majority of early progenitors (CD34+ CD38-) after mobilization into peripheral blood was found to be unaffected by the GPI-anchoring defect. No patient developed leukemia while under therapy. We conclude from these data that the combination of G-CSF and cyclosporin represents an efficient option for the treatment of hypoplastic PNH.

Adult↗
PubMed1997

Expression and in-vivo modulation of alpha- and beta-adrenoceptors on human natural killer (CD16+) cells.

Expression and in-vivo modulation of beta- and alpha-adrenoceptors on peripheral human natural killer (CD16+) cells was investigated. Ligand binding studies revealed that CD16+ lymphocytes express beta2, alpha1-, alpha2- but not beta1-adrenoceptors. Infusion of adrenaline, but not noradrenaline, significantly decreased beta2- and alpha1-adrenoceptor numbers on NK cells. Both catecholamines did not appreciably alter alpha2-adrenoceptor numbers. Additional analyses showed that adrenaline administration increases alpha2-adrenoceptor numbers on peripheral mononuclear blood cells (PBMC) and T-cell subsets (CD4+, CD8+) in contrast to decreased receptor numbers on CD16+ cells. These data demonstrate a specific effect of increasing levels of circulating catecholamines on beta2-adrenoceptors on NK cells.

Adrenergic Agonists↗
PubMed1997

Hepatitis B and C in HIV-infected patients. Prevalence and prognostic value.

BACKGROUND/AIMS: There is only limited information on the prevalence and influence of coinfection with either hepatitis B or C on the clinical course in patients infected with the human immunodeficiency virus (HIV). METHODS: Follow-up was available in 232 HIV-infected patients (age 37+/-8 years, CD4 count 167+/-167 microl; 46% had AIDS). Samples were investigated for markers of HBV and HCV infection (HBsAg, HBeAg, HBV-DNA, Anti-HBs, anti-HBc, anti-HCV, HCV-RNA). RESULTS: 60/232 patients (23%) were anti-HCV positive. 78% of these sera were positive for HCV-RNA. 22/232 patients (9%) suffered from chronic HBV infection (HBsAg positive), 18/22 (82%) of these sera had detectable HBeAg and 19/22 (86%) HBV-DNA. Presence of HCV-RNA, HBeAg and amount of HBV-DNA were related to the degree of immunodeficiency. In contrast to the control group without HBV or HCV infection, patients infected with HIV and either HBV or HCV showed a direct correlation between a reduction in CD4 counts and decreased cholinesterase activity. In patients with AIDS, coinfection with HBV or HCV was associated with a reduced survival compared to controls (HBV: 212 days, 95%CI, 106-317; HCV: 267, 95%CI, 112-396; controls: 439 days, 95%CI, 364-513). CONCLUSIONS: Coinfection of HIV and HBV or HCV is frequently observed. Our results suggest that with prolonged survival of HIV-infected patients, coinfection with either HBV or HCV correlates with a reduced survival rate.

Acquired Immunodeficiency Syndrome↗
PubMed1997

MHC-I antigen expression determines sensitivity of hematopoetic progenitor cells as targets for NK cells.

Hybrid resistance is suggested to be mediated by NK lymphocytes as effector cells. NK cytotoxicity is triggered by specific NK cells receptors. One group of receptors recognizing MHC-I antigens is predominantly transmitting an inhibitory signal into the cell. However, NK cells have not been shown to recognize hematopoetic progenitor cells directly. In these studies we demonstrate that hematopoetic progenitor cells are sensitive targets for NK recognition. NK cytotoxicity is shown to depend on MHC-I antigen expression on these target cells. Bone marrow-derived hematopoetic progenitor cells from a beta 2-microglobulin-deficient mouse strain exhibit a significant increase of cytotoxic susceptibility compared with the wild type control. CFU-assays reveal an almost complete loss of proliferation after coincubating MHC-I-deficient bone marrow cells with NK cells from the wildtype mouse strain. The examination of H-2K in allorecognition of hematopoetic progenitor cells reveals an increased cytotoxicity after treatment of resistant syngeneic hematopoetic progenitor cells with H-2Kb F(ab)2-antibodies. Also masking of allogeneic hematopoetic progenitor cells with anti-H-2Kd F (ab)2-antibodies results in enhanced NK killing. Thus, hematopoetic progenitor cells are sensitive targets for NK cells and MHC-I antigen complex is the critical structure in NK recognition of hematopoetic progenitor cells. This complex mediates resistance of NK-specific lysis of hematopoetic progenitor cells.

Animals↗
PubMed1997

The high-affinity Fc gamma RI on PMN: regulation of expression and signal transduction.

In this paper we report that interferon-gamma (IFN-gamma) maintains and enhances functional properties of terminally differentiated polymorphonuclear cells (PMN). Such effects are obvious when compared with untreated PMN declining in their functional response. Culture for 18 hr with 100 IU/ml of recombinant IFN-gamma resulted in the expression of about 15,000 Fc gamma RI per PMN. IFN-gamma maintained viability of PMN and prevented reduction of Fc gamma RIIIb caused by apoptosis. No alterations were found in the level of Fc gamma RIIa. Next, functional properties of Fc gamma RI were evaluated. Calcium mobilization was detected in fura-2/acetoxymethylester (AM)-loaded PMN using a spectrophotometer and the respiratory burst was measured as luminol-dependent chemiluminescence. Cross-linking of an F(ab')2 fragment of monoclonal antibody (mAb) 22.2 to Fc gamma RI gave similar results to those obtained with intact monomeric human immunoglobulin G (mhIgG) when subsequently cross-linked. Moreover, after blocking Fc gamma RIIa and Fc gamma RIIIb with respective mAb fragments, mhIgG was still effective in triggering a calcium flux demonstrating that second messenger generation was caused by Fc gamma RI engagement. Even though Fc gamma RI expression was lower than that of Fc gamma RIIa, Fc gamma RI induced a higher increase of the respiratory burst. In addition, the protein tyrosine phosphatase CD45 was able to inhibit both responses when it was co-cross-linked with CD64, suggesting involvement of tyrosine phosphorylation in early signalling steps.

Adult↗
PubMed1997

Dystrophic axonal swellings develop as a function of age and diabetes in human dorsal root ganglia.

Neuroaxonal dystrophy, characterized by swollen axon terminals and, to a lesser degree, enlarged initial segments of axons or perikaryal projections, develops in human dorsal root sensory ganglia as a function of aging and diabetes. Lesions are typically located within the satellite cell capsule and are intimately applied to sensory neuronal perikarya, which are compressed and distorted but are otherwise normal. Swollen axons contain large numbers of neurofilaments that are immunoreactive with antisera to highly phosphorylated neurofilament epitopes but fail to stain with antisera directed against hypophosphorylated neurofilament epitopes. Other dystrophic swellings contain collections of tubulovesicular profiles admixed with neurotransmitter granules. Neuroaxonal dystrophy involves subpopulations of intraganglionic axons and apparent terminals, notably those containing CGRP, while apparently sparing others, including noradrenergic sympathetic axons. Diabetic subjects develop lesions prematurely and in greater numbers than in aged subjects. Individual dystrophic axons in diabetics and aged human subjects are identical in their light microscopic, immunohistochemical and ultrastructural appearance, suggesting the possibility of shared pathogenetic mechanisms.

Adolescent↗
PubMed1997

IgG binding sites on human Fc gamma receptors.

The structure for the three human Fc gamma receptors classes Fc gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16) has been well characterized. Here the IgG binding sites on Fc gamma RII and Fc gamma RII with their responsive FG, BC and C'/E loops on the membrane proximal domains are described in detail. For Fc gamma RI the second extracellular domain is suggested as a key structure of IgG binding. The lower hinge regions of human and murine IgG binding to these Fc receptors and their structural relationship in Fc gamma R-IgG interactions are discussed. The potential of inhibiting the pathophysiological effects of Fc gamma receptors by blocking studies are considered for future therapeutic modalities.

Binding Sites, Antibody↗
PubMed1997

Clear cell neoplasms and pseudoneoplastic lesions of the central nervous system.

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Alkaline Phosphatase↗
PubMed1997

[Coinfection of hepatitis B and C in HIV-infected patients].

There is only limited information on the prevalence and influence of coinfection with either hepatitis B or C on the clinical course in patients infected with the human immunodeficiency virus (HIV). Samples of 232 HIV infected patients were investigated for markers of HBV and HCV infection (HBsAg, HBeAg, Anti-HBs, anti-HBc, anti-HCV, HCV-RNA). 60/232 patients (23%) were anti-HCV positive. 78% of these sera were positive for HCV-RNA. 22/232 patients (9%) suffered from chronic HBV-infection (HBsAg positive), 18/22 (82%) of these sera had detectable HBeAg. Presence of HCV-RNA, HBeAg was related to the degree of immunodeficiency. In patients with AIDS coinfection with HBV or HCV was associated with a reduced survival compared to controls (HBV: 212 days, 95% CI, 106 to 317; HCV: 267, 95% CI, 112 to 396; controls: 439 days, 95% CI, 364 to 513). Coinfection of HIV and HBV or HCV is frequently observed. Our results suggest that in HIV-infected patients with AIDS coinfection with either HBV or HCV was associated with a reduced survival rate.

AIDS-Related Opportunistic Infections↗
PubMed1996

Separate promoters from proximal and medial control regions contribute to the natural killer cell-specific transcription of the human FcgammaRIII-A (CD16-A) receptor gene.

The molecular events governing the differentiation pathway of natural killer (NK) cells are not well understood. The phenotype of mature NK cells is specified by the expression of the low affinity Fc receptor for IgG (human FcgammaRIII, CD16) encoded by the FcgammaRIII-A gene. Here we report that the Pprox promoter (-198/-10) of FcgammaRIII-A stimulated by its own intron enhancer (+10/+712) was only one of the cis-elements that target the expression of a reporter gene in the immature NK cell line, YT. The transcription start sites of the FcgammaRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial -1817/-850 FcgammaRIII-A control region. Two promoters, Pmed1 (-942/-850) and Pmed2 (-1376/-1123) resided in this region and controlled for the initiation of these transcript classes encoding the known FcgammaRIII-A receptor protein. Deletion mapping studies demonstrated that the 93 base pairs -942/-850 Pmed1 sequence was sufficient to confer cell type-specific expression in YT cells. The 5' end of Pmed1 (-942 to -921) was required for full promoter function indicating the presence of an important sequence motif recognized by a YT-specific factor. Our data suggest that this motif might be a useful tool for subsequent identification of putative transcription factors uniquely active in YT and NK cells.

Alternative Splicing↗
PubMed1996

Neuropathology of human sympathetic autonomic ganglia.

The neuropathologic alterations which underlie autonomic nervous system dysfunction in aging and in a variety of diseases have been systematically examined in the sympathetic ganglia of a series of 347 autopsied adults and in a review of previously published studies. Markedly swollen terminal axons containing neurofilamentous aggregates were found immediately adjacent to the neuronal cell bodies of prevertebral sympathetic ganglia in aging, in diabetes, and, to a lesser extent, in alcoholism. Dystrophic axons appeared to involve subpopulations of intraganglionic nerve fibers, chiefly those containing neuropeptide Y (NPY), and were more frequent in males than females. Neither aging nor diabetes resulted in significant numbers of actively degenerating neurons or a substantial decrease in neuronal density. Parenchymal aggregates of lymphocytes in the ganglionic neuropil and perivascular regions represented a frequent histologic finding in both prevertebral and paravertebral ganglia; however, they were not selectively increased in frequency or intensity in diabetic subjects or in any other disease entity. Many dilated clear "vacuoles," apparently located within the neuronal cell bodies of paravertebral and prevertebral ganglia according to light microscopy, were subsequently shown by electron microscopy to represent vacuolated or fluid-filled neurites, most likely terminal axons or synapses. Vacuolated neurites were more frequent in, although not confined to, diabetic patients. Similar pathologic findings have been reported in studies of sympathetic ganglia in various human diseases. The frequency of some pathologic lesions in control populations as a function of age or gender necessitates the careful selection of a relatively large, appropriately matched, control population for comparison with presumed disease-induced ganglionic neuropathology, and emphasizes the importance of quantitative comparisons.

Adolescent↗
PubMed1996

The binding epitopes of human CD16 (Fc gamma RIII) monoclonal antibodies. Implications for ligand binding.

Numerous mAbs have been generated against Fc gamma RIII (CD16), the low-affinity receptor for the Fc part of IgG. Most of the mAbs recognize both the receptor isoforms, transmembranous Fc gamma RIIIA, and glycosylphosphatidylinositol-linked Fc gamma RIIIB. Binding epitopes of some of the mAbs that differentiate between the two neutrophil Ag (NA) alleles of Fc gamma RIIIB (CLB-Gran11 against NA1; GRM1, BL-LGL/1 against NA2 allele) have been mapped on the first, membrane-distal domain of CD16. We demonstrate that mAbs 3G8, B88-9, CLB-Gran1, MEM-154, and LNK16 almost completely block the receptor's interaction with IgG. Using chimeric Fc gamma RIIIB/Fc epsilon RI receptors and molecular modeling, we localized the epitopes of 3G8 and B88-9 on the putative FG loop of the membrane-proximal Ig-like domain, which we have previously identified as the major binding site for IgG. The epitopes of CLB-Gran1 and MEM-154 are shown to reside in proximity to the FG loop (probably BC or C'E loop). The blocking mAb LNK16 was detected to be directed against the putative C' beta-sheet of the membrane-proximal domain, suggesting that additional residues may be involved in IgG binding of Fc gamma RIII.

Antibodies, Monoclonal↗
PubMed1996

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School].

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

Adolescent↗