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Biomedical subjects

W Ulrich

Publications and source records attributed to W Ulrich.

At least 55 records · Page 3Linked to original sources

Severe sublimate intoxication in the rat. Influence of thyroxine on renal enzymes of fatty acid degradation and on the survival rate of intoxicated rats.

1. The influence of thyroxine pretreatment on prognosis and some renal enzymes of fatty acid degradation of mercuric chloride intoxicated rats was studied. 2. Survival rates as observed over 10 d after 1.5 to 6.0 mg mercuric chloride/kg i.p. were not influenced by thyroxine pretreatment. 3. A quarter of survivors of both groups developed renal hypertrophy more pronounced in animals not treated with thyroxine. 4. Fatty acyl-CoA oxidase, the rate limiting enzyme of peroxisomal beta-oxidation was found to be depressed by about 50% 2 d after intoxication. This effect was prevented by thyroxine pretreatment. The other enzyme activities (carnitine acetyltransferase, carnitine-palmitoyltransferase and crotonoyl-CoA dependent NAD+ reduction) are essentially not influenced neither by intoxication nor by thyroxine pretreatment. 5. It is concluded that the prognosis of the intoxication is not correlated with fatty acid degradation enzymes.

Acute Kidney Injury↗

Medullary thyroid carcinomas express chromogranin A and a novel neuroendocrine protein recognized by monoclonal antibody HISL-19.

PURPOSE AND METHODS: A number of endocrine peptides and proteins are expressed by medullary thyroid carcinoma (MTC). The expression of two newly appreciated neuroendocrine tumor markers, chromogranin A (CgA) and the endocrine antigen defined by monoclonal antibody HISL-19, was determined in 14 MTCs by immunohistology to evaluate the clinical utility of these markers in the diagnosis of MTC. Papillary, follicular, and undifferentiated thyroid tumors were also evaluated along with an MTC cell line. The same tissues were evaluated with antibodies to human calcitonin. RESULTS: All human calcitonin antibodies were found to react with the MTCs. In addition, all MTCs were reactive for CgA and the antigen detected by antibody HISL-19. CgA was generally present in the human calcitonin-containing cells, whereas the HISL-19 antigen had a more distinctive distribution. The other thyroid tumors failed to show reactivity with any of the three antibodies. CONCLUSION: Our results demonstrate that, in addition to human calcitonin, MTCs commonly express CgA and the antigen defined by antibody HISL-19. Our observations thus add to the repertoire of endocrine substances produced by MTC. These studies also demonstrate the clinical value of immunohistologic procedures for two novel antigens in distinguishing MTCs from other thyroid tumors.

Adenocarcinoma↗

Acute vascular toxicity after combination chemotherapy with cisplatin, vinblastine, and bleomycin for testicular cancer.

Twenty-one consecutive patients with testicular cancer treated with bleomycin, vinblastine, and cisplatin (PVB) were evaluated for acute vascular ischaemic events during chemotherapy. Angina pectoris occurred in 8/21 (38%) patients, a median 5.6 weeks after initiation of chemotherapy and persisted for 2-7 days. Raynaud's phenomenon was detected in seven (33%) subjects, transient ischaemia of the toes was found in six (29%) patients, one patient complained of migraine, but none had major cerebrovascular accidents. Patients with and without angina pectoris and/or Raynaud's phenomenon did not differ in respect of age, histology of tumor or medication. Ischaemia occurred at any time during the course of chemotherapy. No correlation was found between dosage of drugs and time of onset of ischaemic reactions. However, arterial occlusive event is a frequent and common toxicity and a result of treatment with PVB.

Adult↗

Cytomegalovirus infection after kidney transplantation using cyclosporin A and low-dose prednisolone immunosuppression.

The incidence and clinical relevance of cytomegalovirus (CMV) infection has been investigated in 120 consecutive renal allograft recipients receiving cyclosporin A and low-dose steroid (CsA/LDS) immunosuppression. Forty patients (33.3%) showed serological evidence of recent CMV infection; 21 patients (17%) developed clinically symptomatic infection. A seronegative recipient status and an aggressive additional immunosuppressive therapy were significant risk factors for the development of serological infection. There was, however, no difference with regard to these or any other relevant parameters (HLA matching; pretransplant history) between the symptomatic and asymptomatic group. Furthermore there was no influence of CMV infection, whether symptomatic or not, on graft outcome. During the study CMV infection prophylaxis consisted of single-shot CMV hyperimmunoglobulin in 72 patients immediately before grafting, recombinant interferon alpha 2 in 28 patients, and placebo in 20 patients. There was no beneficial effect of either interferon or hyperimmunoglobulin on the incidence and severity of CMV infection. However, steroid-resistant vascular rejections were much more common in the interferon group. We conclude that the incidence of CMV infection after kidney transplantation using CsA/LDS immunosuppression is lower when compared to kidney grafting with conventional immunosuppression. Prophylactic treatment with single-shot hyperimmunoglobulin is not effective, and recombinant interferon alpha 2 prophylaxis may even exert deleterious effects on graft survival by inducing steroid-resistant vascular rejection.

Adult↗

Acute oliguria associated with chlorprothixene overdosage.

The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis.

Acute Disease↗

Immunochemical characterization of a novel secretory protein (defined by monoclonal antibody HISL-19) of peptide hormone producing cells which is distinct from chromogranin A, B, and C.

In this study we have investigated the biochemical properties as well as the subcellular localization of a 67 kD (35/32 kD dimer) polypeptide detected by a monoclonal antibody (HISL-19), which was generated after immunization of BALB/c mice with human islet cell preparations. This protein is expressed by neuronal and peptide hormone producing cells and shares many biochemical and molecular key features with the chromogranin proteins. As demonstrated by one-dimensional and two-dimensional gel electrophoresis, immunoblotting, monoclonal antibody HISL-19 immunoaffinity chromatography, and immunoelectron microscopy, it is a water-soluble, acidic protein stored within secretory granules of peptide hormone-producing cells, and it is released in detectable amounts into the serum of patients bearing neuroendocrine carcinomas. Differences of the HISL-19 protein and chromogranins A, B, and C are indicated by their different tissue distribution, the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels and isoelectric points, and by the lack of cross-reactivity of their specific antibodies. The protein detected by monoclonal antibody HISL-19 represents therefore a novel component of the soluble compartments of neurosecretory granules, which is distinct from chromogranin A, B, and C.

Adrenal Medulla↗

[Diffuse xanthogranulomatous pyelonephritis in childhood].

Xanthogranulomatous pyelonephritis is a rare disease and rare cause of suppurative proliferative pseudotumor in children. An accurate diagnosis is difficult because of its clinical, radiological, sonographical and pathologic-anatomical similarities to renal tuberculosis. After removing the diseased kidney the prognosis is excellent. A 6-year old boy with xanthogranulomatous pyelonephritis is reported.

Child↗

Pathology of renal cancer and its metastases.

The pretherapeutic classification of renal carcinomas includes the assessment of the tumor stage, the histological gross pattern, the cytological features, and the histopathological grading. As to the local tumor extension the perinephric invasion and renal vein involvement are the most important prognostic features. The presence of metastases dramatically alters survival. Histologically, compact, tubular, and papillary growth patterns are differentiated. Furthermore, the verification of the cell types in renal carcinomas is of prognostic significance. The clear cell carcinomas are opposed to the granular cell and spindle-shaped/pleomorphic types with poor prognosis. Rarely tumors consist of so-called "chromophobe" cells with finely reticular cytoplasms. They closely resemble clear cell carcinomas and exhibit a similar biological behaviour. According to the grade of atypia in renal carcinomas three grades of malignancy are distinguished. Conclusively, the tumor grade and the tumor cell type are the most reliable indicators of the malignant potential of renal carcinomas.

Carcinoma, Renal Cell↗

Identification of a 400-kd protein in the brush borders of human kidney tubules that is similar to gp330, the nephritogenic antigen of rat Heymann nephritis.

The nephritogenic antigen of Heymann nephritis (HN)--a well-studied experimental rat model disease of human membranous glomerulonephritis (MGN)--was recently shown to be a 330-kd glycoprotein (gp330) which is present in the membranes of both the rat tubular brush borders and of podocytes. Because the pathogenic antigen(s) of MGN are unknown, the authors have searched for a gp330-like molecule in human kidney and for its role in MGN. The authors here report that a membrane protein (apparent molecular weight 400 kd) is present in human kidney which is immunologically cross-reactive with rat gp330. By immunoelectron microscopy (using rabbit anti-rat gp330 IgG or a monoclonal anti-400-kd IgG) this molecule is similarly localized in human proximal tubules, but it is absent from the podocytes of human glomeruli. The 400-kd molecule is not detected in the glomerular immune deposits of 30 biopsies of MGN. It is proposed that this is due to the lack of the 400-kd protein in human glomeruli which prevents the formation of initial 400-kd anti-400-kd IgG immune complexes in situ.

Animals↗

[Familial juvenile nephronophthisis--a cause of chronic renal failure in childhood].

Familial juvenile nephronophthisis (FJN) represents an important cause of chronic renal insufficiency in the first two decades of life. Its frequency is reported to vary between 7 and 20% of all cases of terminal renal failure in childhood. Usually the onset is insidious, with polyuria, polydipsia and anaemia being the main clinical features. The diagnosis is based on clinical, laboratory and pathological findings. The purpose of our report is to emphasize the importance of this pathological entity with respect to the clinical symptoms and signs and diagnostic approach on the basis of the case reports of four patients.

Adolescent↗

Immunohistochemical detection of 6-oxo-PGF1 alpha and PGE2 in radicular cysts.

Prostaglandin synthesis in the wall of radicular cysts was determined by immunohistochemistry and radiothinlayer chromatography. PGE2 is predominantly produced by plasma cells and histiocytic elements, whereas much less is synthesized by fibroblasts and endothelial cells as estimated using immunohistochemistry. 6-oxo-PGF1 alpha, however, was primarily found to be generated by endothelial cells and fibroblasts; only small amounts seem to be derived from histiocytic elements and plasma cells. The response of the cystic epithelium to anti-PGE2 and anti-6-oxo-PGF1 alpha antibodies was negative or showed only minimal staining. It can thus be concluded that the granulation tissue and its cellular components modulating the inflammatory process are the main source of prostaglandin synthesis in the wall of radicular cysts and may therefore be responsible for the resultant osteolytic activity.

6-Ketoprostaglandin F1 alpha↗

The histopathologic identification of CMV infected cells in biopsies of human renal allografts. An evaluation of 100 transplant biopsies by in situ hybridization.

In order to determine the incidence and significance of CMV infected cells within human renal allograft biopsies 100 transplant biopsies were examined for the presence of CMV DNA within the renal tissue specimens using the in situ hybridization technique. In 41 cases CMV infected cells were predominantly found within proximal tubular epithelial cells, although typical nuclear inclusion ("owl eyes") were absent. In only one case was CMV detected within a few glomerular cells. The presence of CMV infected cells within allograft biopsies does not correlate with active CMV infection of the patients at the time of biopsy. There are no significant differences in the distribution of primary and secondary CMV infections between patients with positive and negative biopsy findings. No significant differences as to the histological alterations between CMV infected and non-infected biopsies could be found. The data give evidence that the renal allograft is more often affected by CMV than is generally appreciated. The in situ hybridization technique may be useful for the fast detection of latently CMV infected cells in renal transplants and thus may influence the choice of therapeutic steps early after transplantation. Furthermore, it may facilitate the diagnosis of interstitial nephritis due to virus infection if typical nuclear inclusions in routinely stained tissue sections are absent.

Biopsy↗

Limited value of 111-indium platelet scintigraphy in renal transplant patients receiving cyclosporine.

Since the differential diagnosis between cyclosporine (CyA) nephrotoxicity and acute graft rejection is still a problem in clinical routine, we studied retrospectively the value of 111-indium (In) platelet scintigraphy in 53 patients immunosuppressed with CyA and prednisolone. Autologous platelets were labeled once per week. After daily gamma camera imaging, the platelet deposition in the graft was expressed as platelet-uptake ratio (PUR). The patients were monitored during the first 4-6 weeks after surgery. PUR values measured during an episode of graft dysfunction were compared to the histological diagnosis. The PUR of well-functioning and stable grafts measured 1.07 +/- 0.11 (mean +/- SD). The 111-In platelet scintigraphy failed to register acute interstitial rejection. The PUR values in episodes of chronic vascular rejection, of acute tubular necrosis due to prolonged ischemia times, of tubular CyA nephrotoxicity and of cytomegalovirus (CMV) infection did not differ from the PUR of well-functioning and stable grafts as well. The PUR was significantly increased to 1.48 +/- 0.26 because of a marked platelet deposition in the graft in episodes of acute vascular rejection. In 4 cases of microvascular CyA nephrotoxicity the same phenomenon of significantly increased PUR (1.33 +/- 0.18), could be encountered, too. Two of these 4 cases resembled the hemolytic uremic syndrome (HUS). The value of PUR measurement for diagnosis of acute vascular rejection and microvascular CyA nephrotoxicity together, was: sensitivity 0.62, specificity 0.95, predictive value of positive result 0.64, predictive value of negative result 0.94.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Monoclonal antibody HISL-19 as an immunocytochemical probe for neuroendocrine differentiation. Its application in diagnostic pathology.

The monoclonal islet cell antibody HISL-19 was generated after immunization of BALB/c mice with human islet cell preparations. Besides reactivity with all cells of the human pancreatic islet, MAb HISL-19 also reacted with other cells of the diffuse neuroendocrine system, including anterior pituitary cells, C cells of the thyroid, endocrine cells of the gut and bronchus, the adrenal medulla, and central and peripheral neurons. In this study the authors screened a series of 53 neuroendocrine and 71 nonneuroendocrine tumors for their reactivity with MAb HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and Paraplast-embedded sections. MAb HISL-19 reacted strongly with all insulomas (10), carcinoids (8), C-cell carcinomas of the thyroid (8), pituitary adenomas (6), neuroendocrine carcinomas of the skin (4), paragangliomas of the carotid body (3), and pheochromocytomas (2) tested. Neuroblastomas (3), oat-cell carcinomas of the lung (2), and melanomas (4) exhibited only very few immunoreactive cells scattered throughout the tumor or remained unstained with MAb HISL-19. With the exception of one lobular carcinoma of the breast (1/3), one adenocarcinoma of the endometrium (1/4), and one adenocarcinoma of the stomach (1/6), nonneuroendocrine tumors were negative with MAb HISL-19. Biochemical findings obtained by SDS-PAGE, "Western" immunoblotting, immunoaffinity chromatography, and absorption experiments indicate that the MAb HISL-19-defined antigen is not related to neuron specific enolase. Because the epitope recognized by MAb HISL-19 is well preserved in formalin-fixed and routinely processed tissues, this monoclonal antibody finds potential applications in diagnostic pathology as an indicator for neuroendocrine cells and their neoplasms.

Antibodies, Monoclonal↗

Organisation of experimental thrombosis by blood cells. Evidence of the transformation of mononuclear cells into myofibroblasts and endothelial cells.

To clarify whether thrombus organisation was carried out by local cell activity or by elements of the circulating blood we developed an artificial prosthesis, made of an impermeable polyurethane material with an athrombogenic surface but with a central part consisting of a DACRON velour ring which was thrombogenic. We implanted these devices into the aorta of 10 sheep. In these animals, organisation of the central thrombus by local aortic cells could be excluded. After varying periods of time (2-84 days), the device was removed and the organized thrombus investigated by light and electron microscopy. From our investigations the organisation process with the development of mesenchymal cellular elements proceeded in 3 steps: The activation of the mononuclear macrophage system, the appearance of myofibroblastic cells and endothelial formation. The activation of the mononuclear macrophage system is probably induced by chemospecific products of metabolism arising from aging thrombotic material. Apart from mononuclear elements such as monocytes, macrophages, and giant cells we observed fibroblast-like and myofibroblast-like cells. The matrix contained collagen. Endothelium developed on the surface of the organizing thrombus. The final stage was characterized by the formation of a pseudovessel wall, which followed the pattern of the vascular model. Our findings support the hypothesis that a thrombus may be organized by cells derived from the circulating blood.

Animals↗