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F Gudat

Publications and source records attributed to F Gudat.

At least 19 recordsLinked to original sources
PubMed1992

Radiation-induced lymphoid tumors and radiation lethality are inhibited by combined treatment with small doses of zinc aspartate and WR 2721.

Combined small doses of zinc aspartate and WR 2721 provided additive protection against radiation lethality in mice. Survival obtained with a small dose of WR 2721 which was ineffective alone could be enhanced to 83% by combining the drug with zinc aspartate, which on its own also displayed no effect. The survival of 25% provided by a higher dose of WR 2721 was increased significantly by adding zinc aspartate. Additivity was also tested in a model of radiation carcinogenesis. For this purpose, lethality and occurrence of lymphoid tumors induced by fractionated total-body irradiation were studied in C57B1/6 mice treated with zinc aspartate and WR 2721. In order to reveal additive effects, both agents were used at sub-optimal dosages. In mice subjected to 5 daily exposures of 1.9 Gy, the combination of zinc aspartate and WR 2721 was effective and enhanced the survival to 83% as compared with 25% afforded by WR 2721 alone (p < 0.005). Similarly, histological assessment of organ involvement with lymphoma revealed that zinc aspartate and WR 2721 alone did not bring about a significant reduction of lymphoma incidence. On the other hand, the combined agents diminished organ involvement with lymphoma to 9.1% as against 90% in the controls (p < 0.0005) and 62.5% with WR 2721 alone (p < 0.025). Thus, combined treatment with zinc aspartate and WR 2721 also inhibited radiation-induced lymphoid tumors.

Amifostine↗
PubMed1992

Polymerase chain reaction detects hepatitis B virus DNA in paraffin-embedded liver tissue from patients sero- and histo-negative for active hepatitis B.

The polymerase chain reaction (PCR) was used to analyse tissues from paraffin blocks of liver needle biopsies retrospectively. Biopsies of 29 patients with proven HBsAg and HBcAg expression in liver tissue and of 8 healthy volunteers served as positive (group 1) and negative tissue controls (group 2), respectively. These were compared with 16 patients with proven HBsAg expression in liver but lack of HBcAg (group 3), with 23 patients with anti-HBc as the only hepatitis B virus (HBV)-related marker (group 4) and with 21 patients with liver disease and without HBV markers in tissue or serum (group 5). PCR detected HBV sequences in all cases of the positive control group and in 94% of group 3, in 65% of group 4, and in 71.4% of group 5, whereas all healthy volunteers were negative. Our data show that PCR is able to detect HBV-DNA sequences in virtually all patients with active viral antigen expression but also in a high proportion of hepatitic patients who are silent for active HB but may or may not show signs of a contact with the HBV. Thus, PCR for HBV-DNA in paraffin sections might become a useful tool for identifying patients carrying HBV-DNA but not expressing HBV antigens.

Base Sequence↗
PubMed1992

Localization of thromboxane synthase in human tissues by monoclonal antibody Tü 300.

Using the monoclonal antibody Tü 300 we localized thromboxane synthase, a secondary enzyme of the arachidonic acid cascade, employing the alkaline phosphatase anti-alkaline phosphatase method and indirect double labelling immunofluorescence in frozen sections of human tissues. Aside from platelets, the source of the antigen, all cells of the mononuclear phagocytic system were positive, including epithelioid cells and associated giant cells, starry sky macrophages, dendritic cells of T-cell areas, Langerhans cells and Kupffer cells. In addition, some epithelial cells such as epithelia of tonsillar crypts, reticular epithelia of the thymic cortex and ductular epithelia in liver, pancreas, female breast and salivary glands showed occasional focal reactivity for thromboxane synthase. We suggest that the mAb Tü 300 is a key marker for the macrophage system and the thromboxane generating system in normal and pathological conditions. It may detect functional activities of as yet unknown significance in some specialized epithelial cells.

Blood Platelets↗
PubMed1992

Mouse/human chimeric anti-HIV-1 gp120 antibody to the principal neutralizing determinant: tolerability and pharmacokinetics in cynomolgus monkeys, Macaca fascicularis.

In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47,439 in HIV-1 infected individuals, it was administered to Macaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47,439/kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 alpha of 14.2 h (range 11.8-19.3 h) and a mean T1/2 beta of 172.6 h (range 137.2-220.5h). Following four successive antibody infusions serum concentrations of CGP 47,439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients.

Animals↗
PubMed1992

Hepatitis B X-gene expression in hepatocellular carcinoma.

A RNA-PCR method and different sets of primers were used to investigate the expression of different hepatitis B (HB) virus genes at the RNA level. We tested paired samples (tumor and non-tumor) from the liver tissues of 48 Taiwanese patients with primary hepatocellular carcinoma (HCC). By using a set of primers which spanned the sequences of the S-gene, we found expression in only 2 patients. In one HBs-RNA was only detected in the tumor tissue and in the other only in the surrounding non-tumor tissue. Using primers covering the C-gene, expression was found in 7 patients. In 2 of these RNA was detected in both the tumor and the surrounding tissue, in 2 in the tumor tissue, and in 3 in the surrounding tissue only. Finally, when primers spanning the X-gene sequences were used, RNA was detected in 40/48 patients. In 33 of these cases HBx-RNA was detected in both tumor and non-tumor tissue, in 3 patients in tumor tissue only, and in 4 in the surrounding tissue. Among the cases in which HBc and HBs-RNA was expressed, all showed HBx expression also. These data indicate that the expression of the HBx gene in HCC may play an important role in hepatocarcinogenesis.

Base Sequence↗
PubMed1992

Extranodal multilobated B-cell lymphoma: diagnosis by fine needle aspiration.

Malignant lymphoma with multilobated nuclei is a rare variant of follicle centre cell lymphoma. We describe a 34-year-old patient who initially presented with enlarged cervical and inguinal lymph nodes due to a histologically proven centroblastic-centrocytic lymphoma. Two years later, she developed a soft tissue mass in the gluteal area and malignant lymphoma with multilobated nuclei was diagnosed on fine needle aspiration.

Adult↗
PubMed1992

Renal graft rejection or cyclosporin toxicity? Early diagnosis by a combination of Papanicolaou and immunocytochemical staining of urinary cytology specimens.

A method is described for distinguishing between graft rejection and cyclosporin nephrotoxicity in renal allograft recipients by analyzing fresh morning urine samples. The technique combines classic Papanicolaou with immunocytochemical staining and was performed in urine specimens from a series of 42 patients. Early-stage cyclosporin toxicity was usually associated with increased numbers of proximal tubular cells only, whereas in rejection and late-stage toxicity there were increases in both tubular cells and in lymphocytes and monocytes (greater than 2000 cells/ml urine). Differentiation between these two clinical conditions was achieved by immunostaining, which revealed that increased numbers of CD25+ and CD8+ cells, as well as an increase in the HLA-DR/Lu5 ratio, were typical of rejection. CD25 positivity proved to be the best indicator of rejection, with a sensitivity and specificity of more than 90%. A cytodiagnostic algorithm is presented that is based on cell numbers and types, including immunophenotypes. The proposed method has the advantage of being noninvasive and appears to represent a reliable and rapid adjunct for the monitoring of graft function, especially in high-risk patients on cyclosporin immunosuppression.

Adolescent↗
PubMed1992

Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts.

Cyclosporine (CSA)-associated arteriolopathy (CAA) is the second most frequent morphological diagnosis in renal allografts and its final outcome remains unclear. The present study was performed to clarify the morphological outcome of CAA by follow-up histological analysis after stopping CSA. Furthermore, the clinical management of patients showing CAA is discussed. Most of the patients came from our early experience with CSA between 1981-1983 when CSA doses and trough levels were high. Twenty recipients were divided into two groups according to the presence of CAA after stopping CSA: group A (n = 9) showed persistent CAA and group B (n = 11) showed no CAA. The majority of the patients, including five incomplete remission in group A, showed obvious improvement of CAA even if the arterioles were severely affected. Improvement of CAA was noted a few months after stopping CSA or after lower dose CSA therapy. There were no significant differences in CSA blood levels or duration of CSA therapy between the groups. The severity of preexistent CAA was significantly greater in group A. Only two patients who died from malignant tumor showed exacerbation of CAA. Eight patients died and eight grafts were lost, seven due to vascular rejection and one to hemolytic uremic syndrome-like CAA. Poor renal function was also noted in four cases with functioning graft owing to vascular rejection even though the improvement of CAA was evident. The complete regression of CAA and the remodelling of arterioles showing well preserved vascular patency were frequently found after stopping or reducing the dose of CSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cardiac myxomas: immunohistochemical study of benign and malignant variants.

Immunohistochemical investigation of 11 cardiac myxomas (CMs) including one malignant metastasizing CM showed a co-expression of epithelial (lu-5 and CAM 5.2), mesenchymal (vimentin) and neuroendocrine antigens (neuron-specific enolase) in all tumour cells. Factor VIII was found in the endothelial cells of capillaries only. In the subendocardium of fetal heart tissue close to the foramen ovale myofibroblasts reacting with the panepithelial antibody lu-5 were detected. We conclude that CMs are neoplasms that may develop from embryonic cell remnants.

Adult↗
PubMed1991

Collagen type III glomerulopathy: a new idiopathic glomerular disease.

A new type of idiopathic glomerular disease is reported in a 49-year-old Italian woman who presented with uncharacteristic renal symptoms, i.e., hypertension and slight proteinuria. Clinical investigation excluded a familial renal disease and more specifically nail-patella syndrome. Diagnostic renal biopsy by light microscopy showed a picture similar to membranoproliferative glomerulonephritis. The enlarged glomeruli were lobulated, the peripheral basement membranes were thickened by the deposition of light-microscopically undefined material, cell proliferation was lacking. By electron microscopy, the material was nonhomogenous, partly granular partly fibrillar, containing typical collagen fibers. The latter were identified as collagen type III, to a lesser extent collagen type I. Review of the literature resulted in 12 similar or identical cases reported from Japan and one additional case reported in a white American female. Evidence of systemic disease is lacking. Etiology and pathogenesis are elusive. A progressive deterioration of renal function must be expected. Collagen type III glomerulopathy is suggested as term of this new type of idiopathic glomerular disease.

Biopsy↗
PubMed1991

Tumor necrosis factor receptors in lymphoid tissues and lymphomas. Source and site of action of tumor necrosis factor alpha.

Tumor necrosis factor alpha (TNF alpha), which is produced by germinal center dendritic reticulum cells (DRC) in lymphoid tissue, plays a regulatory role in a local immune response. However no information is available on the nature and location of cells responding to this cytokine. Thus TNF receptor distribution was investigated in situ by immunohistochemistry using monoclonal antibodies directed against the p75 and p55 receptor proteins. Receptor expression was unique and restricted to the lymphoreticular tissue. The p75 receptor was found on activated lymphocytes and interdigitating reticulum cells of the T-cell area, whereas the p55 receptor was confined to the germinal center DRCs, which are the main site of TNF alpha production. The two receptor proteins were expressed on distinct cell populations of the lymphoid system and no coexpression was observed. Preliminary results indicate that TNF receptor (TNFR) expression is regulated; Upregulation of TNFR proteins was found in reactive hyperplasia together with increased TNF alpha expression. In lymphoproliferative disorders, expression of the p75 receptor and TNF alpha was found mainly in high-grade malignant non-Hodgkin lymphomas. In summary, TNF alpha produced by germinal center DRCs might regulate an in vivo immune response through autocrine and paracrine pathways. Thus TNF alpha might signal, through the distinct TNFR proteins, the p55 and p75 receptor, which are expressed on different cell types in lymphoid tissue.

Humans↗
PubMed1991

Tumour necrosis factor receptor distribution in human lymphoid tissue.

The nature and location of cells responding to tumour necrosis factor-alpha (TNF-alpha) were investigated in situ by immunohistochemistry using monoclonal antibodies (mAb) directed against the p75 and p55 proteins of the TNF receptor. Receptor expression was found in the thymus and secondary lymphoid tissues. In the thymus the p75 receptor was confined to medullary lymphoblasts and dendritic cells, which co-stain with the Tac protein of the interleukin-2 (IL-2) receptor. In lymph nodes and other secondary lymphoid tissues, the p75 receptor was expressed on activated lymphocytes and interdigitating reticulum cells of the T-cell area, whereas the p55 receptor was confined to the germinal centre dendritic reticulum cells (DRC), which is the main site of TNF-alpha production. TNF receptor (TNFR) proteins were up-regulated in reactive hyperplasia together with increased TNF-alpha expression. Surprisingly, no TNFR was detectable on non-lymphoid tissues. The species specificity of these TNFR antibodies was high: whereas the antibodies cross-reacted with epitopes in non-human primates, no immunoreactivity was detected in lower animal species, e.g. dog, rabbit and rodents. The data presented suggest that TNF-alpha, which is produced by germinal centre DRC, might regulate an in vivo immune response through autocrine and paracrine pathways, e.g. through the p55 and p75 receptor proteins, which are expressed at different sites of the lymphoid tissue.

Animals↗
PubMed1991

Immunohistochemical studies on human pituitary gland and adenomas.

To study coexpression patterns in normal and adenomatous pituitaries, frozen (n = 4) and paraffin-embedded (n = 10), normal human glands and 34 pituitary adenomas were investigated, using immunoperoxidase and double-labeling immunofluorescence methods. Broad range monoclonal antibodies (mAB) against cytokeratins (CK) (lu-5, A45-B/B3, AE1/3, CAM 5.2) as well as anti-CK18 (DC10) and anti CK19 (A53-B/A2) were compared with mAB's against vimentin, epithelial membrane antigen (EMA), epithelial sialomucin (ESM 140 C1), GFAP (GF-2), neurofilament (2F11), Leu-7 (HNK-1) and polyclonal AB's against pituitary hormones (ACTH, FSH, LH, TSH, GH, PRL). CK and vimentin coexpressing endocrine cells, mainly of the ACTH type, were observed in the pars intermedia in 5 of 14 normal pituitaries. All hormone producing cells expressed CK. The mAB A53-B/A2 (CK19) stained selectively the folliculo-stellate cells in frozen and paraffin sections. EMA, sialomucin and Leu-7 antigen localized to different structures of normal pituitaries. 25 of 34 pituitary adenomas exhibited CK positive tumor cells. Coexpression of vimentin or neurofilament protein was rare (2 cases of each). 9 CK negative adenomas were also negative for other intermediate filament proteins. 6 hormone producing adenomas showed unusual positivity for CK19. Whereas EMA and sialomucin reactivity disappeared in adenoma tissues, an enhanced Leu-7 antigen expression in the GH and prolactin adenoma group was noted. The heterogeneity of antigen expression seen in normal and neoplastic pituitary cells calls for further functional studies and usage of a broad range of mAB's against intermediate filaments in immunohistochemical studies of the pituitary.

Adenoma↗
PubMed1979

[Hepatitis B markers in paediatric patients (author's transl)].

372 children with suspected liver disease were examined for serum HBsAg. Six (three boys, three girls) were found to be positive (1.6%). Further studies of these patients for up to three and a half years revealed elimination of HBsAg in one case only. Biopsies were performed in five patients. Three showed mild chronic hepatitis (two chronic persistent hepatitis, one unspecific reactive hepatitis). Chronic aggressive hepatitis was diagnosed in one patient. One child seemed to be normal on light microscopy, but the findings on electron microscopy were abnormal, the liver cell nuclei being filled with core particles. Two thirds of the family contacts of these children showed hepatitis B marker. Two pregnancies were observed in HBsAg-positive mothers. An infection of the babies was not demonstrable.

Carrier State↗
PubMed1979

Pathological cell aggregates in bone marrow cultures from patients with various hematological diseases.

Non-clonal growth of macroscopic cell aggregates in methylcellulose cultures of abnormal marrow is described. They were seen in all patients with Graft-versus-Host Disease, graft rejection, and autoimmune disease presumably directed against hemopoietic cells, we found them in 35% of patients with primary hematological neoplasias and rarely in patients with solid tumors. They were never encountered in 80 healthy controls. The aggregates originated from small cell clumps which sedimented with the "buffy coat" in contrast to normal bone marrow particles. They contained tumor cells, grafted myeloid cells, or target cells of autoimmune disease in association with a widely varying amount of macrophages. Preliminary results suggest that the frequency of macrophages within the aggregates correlates inversely with the aggressiveness of the clinical condition. We propose that appearance of such aggregates in an indicator of immune activation; we expect that further quantitation of the phenomenon will reveal important clinical correlations and provide a model for the study of host defense to "foreign" cells.

Anemia, Hemolytic, Autoimmune↗