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Biomedical subjects

W Ulrich

Publications and source records attributed to W Ulrich.

At least 37 records · Page 2Linked to original sources

Hereditary osteo-onycho-renal dysplasia with excess urinary pyridinoline cross-links and abnormal kidney collagen cross-linking.

HOOD syndrome is a rare genetic disorder also known as nail patella syndrome. Biochemical and molecular biological data are rare and not conclusive. Preliminary data suggest the involvement of collagen type IV. This would, however, not be enough to explain nail or bone involvement. As kidney pathology would be consistent with a cross-linking disorder, we tested collagen IV and kidney collagen cross-linking on SDS-PAGE. This method showed a remarkable reduction in high-molecular-weight collagen polymers. The patient's and his mother's urinary pyridinoline cross-link excretion was manifold increased. Disturbed cross-linking of connective tissue proteins would help to explain the multiorgan involvement.

Amino Acids↗

Antinociceptive properties of protein C in a model of inflammatory hyperalgesia in rats.

We investigated the role of human protein C in an animal model of inflammatory hyperalgesia. Pain was induced by intraplantar injection of carrageenan (3 mg) into the hind paw of rats. The pain threshold was measured by exerting increasing amounts of pressure (in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg) was administered intravenously immediately after carrageenan. Controls received either intraplantar injections of saline (100 microliters) instead of carrageenan or carrageenan alone. Effects on pain threshold were expressed in percent of the pretreatment value. Carrageenan alone lowered the mean pain threshold after 3 h to 33.2 +/- 2.2% of the pretreatment level. Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with saline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinociceptive effect. Protein C had no effect in animals not preconditioned with intraplantar carrageenan. Thus protein C clearly antagonized the inflammatory pain induced by carrageenan. The antinociceptive action of protein C was antagonized by injection of a monoclonal antibody against protein C, providing additional evidence that the effect was protein C-mediated.

Animals↗

High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure.

A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.

Acute Kidney Injury↗

Pattern of endothelin immunostaining during rejection episodes after kidney transplantation.

A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effects, we investigated intrarenal ET content in 82 kidney transplant biopsies and 10 normal control kidneys. ET-immunostaining, using a polyclonal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epithelium. Normal kidneys showed a strong staining of endothelial cells in all vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen. In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA toxicity, however, lead to a significant reduction of endothelial ET staining. Neither mean doses nor trough levels of CyA correlated closely with the immunostaining findings. Plasma big-ET levels were elevated during vascular rejection, but not in interstitial rejection and ATN. This study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these changes are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection and during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content.

Adult↗

Simultaneous measurement of DAPI-sulforhodamine 101 stained nuclear DNA and protein in higher plants by flow cytometry.

A 2-step staining procedure is presented for simultaneous measurement of nuclear DNA and protein content in higher plants by flow cytometry. To release nuclei, plant tissues were chopped and stirred in the presence of the DNA specific fluorochrome 4',6-diamidino-2-phenylindole (DAPI) and the nonionic detergent Triton X-100. Plant protoplasts were stirred in the DAPI dye solution with the detergent. After a short incubation period a second dye solution containing DAPI and the protein fluorochrome sulforhodamine 101 (SR 101) without detergent was added. Following another incubation, and after filtration through nylon gauze, the highly fluorescent nuclei were analyzed with an impulse cytophotometer. Accurate bivariate DNA-protein histograms were obtained with CV-values of about 2% or less for the 2C-peak of the univariate DNA parameter. The method presented here can be used for basic and applied cytogenetic studies of higher plants, for characterization of subcompartments of the cell cycle phases, or for examination of heterogeneity in plant tissues.

Cell Nucleus↗

[OKT 3 treatment of kidney transplant recipients].

Anti-rejection therapy with the monoclonal antibody OKT 3 was effective in the treatment of acute rejection episodes in 66% (47/71) of OKT 3 treated kidney graft recipients. The success of OKT 3 therapy, however, appeared to be dependent on certain variables. Reversal of rejection differed significantly according to the indication, namely if patients were treated first line, as opposed to rescue therapy. Vascular components of rejection and/or severe interstitial rejection, as well as acute tubular necrosis were associated with a worse reversal rate. Non-responders to OKT 3 presented with significantly lower serum OKT 3 trough levels during the first three days of the treatment course. The presence of more than one of these risk factors was shown to decrease the reversal rate of rejection significantly. The variables appeared to exert their influence in an additive fashion. Administration of OKT 3 led to the induction of an acute phase reaction, which could be detected within one day after start of therapy. The incidence of both bacterial and viral infection was increased dramatically in OKT 3 treated patients as compared with graft recipients who were not treated with monoclonal or polyclonal antilymphocyte antibodies. The findings demonstrate that OKT 3 is of value in the treatment of acute rejection episodes but provide evidence of differential indications for OKT 3 therapy, which must be taken into account to optimize control of rejection and avoid unnecessary side effects where the drug is not indicated.

Antibodies, Monoclonal↗

Cytoplasmic intermediate filament proteins of invertebrates are closer to nuclear lamins than are vertebrate intermediate filament proteins; sequence characterization of two muscle proteins of a nematode.

The giant body muscle cells of the nematode Ascaris lumbricoides show a complex three dimensional array of intermediate filaments (IFs). They contain two proteins, A (71 kd) and B (63 kd), which we now show are able to form homopolymeric filaments in vitro. The complete amino acid sequence of B and 80% of A have been determined. A and B are two homologous proteins with a 55% sequence identity over the rod and tail domains. Sequence comparisons with the only other invertebrate IF protein currently known (Helix pomatia) and with vertebrate IF proteins show that along the coiled-coil rod domain, sequence principles rather than actual sequences are conserved in evolution. Noticeable exceptions are the consensus sequences at the ends of the rod, which probably play a direct role in IF assembly. Like the Helix IF protein the nematode proteins have six extra heptads in the coil 1b segment. These are characteristic of nuclear lamins from vertebrates and invertebrates and are not found in vertebrate IF proteins. Unexpectedly the enhanced homology between lamins and invertebrate IF proteins continues in the tail domains, which in vertebrate IF proteins totally diverge. The sequence alignment necessitates the introduction of a 15 residue deletion in the tail domain of all three invertebrate IF proteins. Its location coincides with the position of the karyophilic signal sequence, which dictates nuclear entry of the lamins. The results provide the first molecular support for the speculation that nuclear lamins and cytoplasmic IF proteins arose in eukaryotic evolution from a common lamin-like predecessor.

Amino Acid Sequence↗

131I-metaiodobenzylguanidine (mIBG) for bronchial oat cell cancer and melanoma detection?

The neuroendocrine features of bronchial oat cell carcinoma and melanoma indicate the possibility of positive imaging by means of radiolabelled metaiodobenzylguanidine. However, only four out of seven patients with bronchial oat cell carcinoma and three out of seven with melanoma were correctly diagnosed. Only false negative and no false positive results were obtained. The findings demonstrate a limited diagnostic value of the tracer in the tumor types examined.

3-Iodobenzylguanidine↗

Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry and in situ DNA hybridization.

Brain tissues from 45 patients with AIDS and two brains with connatal cytomegalic inclusion body disease were investigated for a cytomegalovirus (CMV) etiology of encephalitic lesions. Nineteen brains showed evidence of CMV infection by histology, immunocytochemistry (ICC) using two different antibodies (mono- and polyclonal), and in situ hybridization (ISH). Fourteen cases with typical cytomegalic cells in conventional histology [eight with focally necrotizing encephalitis/ventriculitis including the two connatal infections and six with nodular encephalitis (NE)] revealed CMV with any method. In 5 of 15 AIDS cases of NE without cytomegalic cells, CMV infection was established by ISH, whereas ICC remained negative in these cases. Typical lesions of human immunodeficiency virus (HIV)-induced multi-focal giant cell encephalitis (HIV encephalitis) in 13 brains were never labeled for CMV. In necrotizing encephalitis/ventriculitis, cell types which labeled for CMV, with and without cytomegalic change, comprised neurons, astrocytes, oligodendrocytes, ependyma, choroid plexus, endothelia, and cells in peri- and endoneurium, and in leptomeninges. Both ISH and ICC were able to detect widespread non-cytomegalic CMV-infected cells in normal parenchyma, well beyond the necrotizing lesions, in two AIDS cases. Labeling patterns of nuclei versus cytoplasms varied between the three methods for CMV detection. We conclude that in CNS tissues with cytomegalic cells, ICC and ISH are of comparable sensitivity; however, a diagnosis of CMV disease is possible in such cases by conventional histology. For an in situ diagnosis of CMV infection in NE without cytomegalic cells in AIDS, ISH is the method of choice. A selective vulnerability to CMV infection of any specific cell type of the human CNS is absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Enhancement of human dental cyst PGI2 formation by platelet derived growth factor and its role in cyst growth and bone resorption.

Various prostaglandins, particularly PGE2 and PGI2, appear to play a major role in osteolytic processes. Radiochromatographic studies have demonstrated that 6-oxo-PGF1-alpha is a major product of exogenously added arachidonic acid in human dental cysts. As platelets may also act as inflammatory cells, platelet-derived growth factor might also have a PGI2-stimulating influence in such cysts. Eleven human dental cysts were examined by a radioimmunoassay and bioassay which can show PGI2 synthesis in human dental cysts without addition of PDGF. Incremental PDGF addition caused a highly significant increase in the rate of PGI2 synthesis. PGDF thus stimulates PGI2 synthesis in chronic inflammatory processes in vitro and may thereby elicit or accelerate osteolysis.

6-Ketoprostaglandin F1 alpha↗

Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A.

A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.

Adult↗

Optimal needle size for renal biopsy: in vitro and in vivo evaluation.

To evaluate the success and complication rates of small (16- and 18- gauge) needles in biopsy of the kidney, the authors performed in vitro biopsy in a cadaveric kidney and in vivo renal biopsy in 141 patients. Best results were obtained with a 16-gauge modified Menghini needle. In vitro, 9.7 +/- 5.7 (mean +/- standard deviation) glomeruli were retrieved, and the average length of tissue cores was 17.8 mm +/- 8.2. In vivo, 10.63 +/- 6.64 intact glomeruli were retrieved, and a definitive histologic diagnosis was achieved in 86% of patients. The frequency of major complications with this needle was 3.5%, and of minor complications, 5.8%. No major complications occurred after biopsy was performed with 18-gauge needles of the same design. However, the retrieval rate of glomeruli with these smaller needles was insufficient. An 18-gauge needle with two cutting edges yielded tissue cores of 11.0 mm +/- 3.5 in length. In vitro, 6.6 +/- 2.3 glomeruli were retrieved; in vivo, 9.92 +/- 6.65. A definitive histologic diagnosis was achieved with this needle in 75% of patients, and rates of 7.1% for major complications and 10.7% for minor complications were encountered.

Adult↗