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J Otte

Publications and source records attributed to J Otte.

At least 37 records · Page 2Linked to original sources
PubMed1996

Molecular characterization of human zyxin.

Zyxin is a component of adhesion plaques that has been suggested to perform regulatory functions at these specialized regions of the plasma membrane. Here we describe the isolation and characterization of cDNAs encoding human and mouse zyxin. Both the human and mouse zyxin proteins display a collection of proline-rich sequences as well as three copies of the LIM domain, a zinc finger domain found in many signaling molecules. The human zyxin protein is closely related in sequence to proteins implicated in benign tumorigenesis and steroid receptor binding. Antibodies raised against human zyxin recognize an 84-kDa protein by Western immunoblot analysis. The protein is localized at focal contacts in adherent erythroleukemia cells. By Northern analysis, we show that zyxin is widely expressed in human tissues. The zyxin gene maps to human chromosome 7q32-q36.

Amino Acid Sequence↗
PubMed1996

Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma.

We describe molecular and clinical findings in an immunocompetent patient with an oligoastrocytoma and the concomitant presence of the human papovavirus, JC virus (JCV), which is the etiologic agent of the subacute, debilitating demyelinating disease, progressive multifocal leukoencephalopathy. Histologic review revealed a glial neoplasm consisting primarily of a moderately cellular oligodendroglioma with distinct areas of a fibrillary astrocytoma. Immunohistochemical analysis revealed nuclear staining of tumor cells with antibodies against the viral oncoprotein [tumor antigen (T antigen)], the proliferation marker (Ki67), and the cellular proliferation regulator (p53). Using primers specific to the JCV control region, PCR yielded amplified DNA that was identical to the control region of the Mad-4 strain of the virus. PCR analysis demonstrated the presence of the genome for the viral oncoprotein, T antigen, and results from primer extension studies revealed synthesis of the viral early RNA for T antigen in the tumor tissues. The presence of viral T antigen in the tumor tissue was further demonstrated by immunoblot assay. To our knowledge, this is the first report of the presence of JCV DNA, RNA, and T antigen in tissue in which viral T antigen is localized to tumor cell nuclei and suggests the possible association of JCV with some glial neoplasms.

Antigens, Neoplasm↗
PubMed1996

Evidence that the soluble factors secreted by activated immune cells suppress replication of human neurotropic JC virus DNA in glial cells.

Coordination of the immune response to viral infection and disease in the brain is believed to involve bidirectional interaction between the immune system and the central nervous system (CNS). Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the CNS that generally affects patients exhibiting an immunocompromised condition due to various illnesses. The human polyomavirus, JCV, which infects greater than 70% of the adult population is the etiological agent of this disease. Infection with JCV occurs during childhood and the virus remains in the latent state with no apparent clinical signals. However, under immunocompromised conditions, the virus enters the lytic cycle, and upon cytolytic destruction of glial cells, causes PML. To understand the molecular mechanism underlying immune regulation of JCV replication, we have developed a cell culture system and have investigated the effect of soluble factors from T-cell cultures on replication of JCV DNA in glial cells. Our data demonstrate that replication of JCV DNA in the presence of PMA-stimulated T-cell supernatant is substantially decreased in transfected glial cells. Heat-inactivation and size-fractionation studies revealed participation of a heat labile factor(s) which loses its maximum activity at 60 degrees and ranges between 30 and 100 kDa in size. The unfractionated T-cell supernatant and the fraction enriched in 30- to 100-kDa proteins reduced the level of viral DNA replication during the early phase of the lytic cycle. These observations suggest that regulatory factors which are secreted by immune cells may modulate the level of JCV DNA replication in glial cells. The importance of these observations in reactivation of JCV in immunocompromised individuals and development of PML is discussed.

Antigens, Polyomavirus Transforming↗
PubMed1995

Differential regulation of plasminogen activator and inhibitor gene transcription by the tumor suppressor p53.

The ability of p53 to activate or repress transcription suggests that its biological function as tumor suppressor is in part accomplished by regulating a number of genes including such required for inhibition of cell growth. We here give evidence that p53 also may regulate genes responsible for the proteolytic degradation of the extracellular matrix, which is considered a crucial feature for local invasion and metastasis of neoplastic cells. An important and highly regulated cascade of such proteolytic events involves the plasminogen activator system. We show that wild-type p53 represses transcription from the enhancer and promoter of the human urokinase-type (u-PA) and the tissue-type plasminogen activator (t-PA) gene through a non-DNA binding mechanism. Oncogenic mutants lost the repressing activity. In contrast, wild-type but not mutant p53 specifically binds to and activates the promoter of the plasminogen activator inhibitor type-1 (PAI-1) gene. Interestingly, one of the p53 mutants (273his) inhibited PAI-1 promoter activity. Our results suggest that altered function of oncogenic forms of p53 may lead to altered expression of the plasminogen activators and their inhibitor(s) and thus to altered activation of the plasminogen/plasmin system during tumor progression.

Base Sequence↗
PubMed1994

Micellar electrokinetic capillary chromatography for determination of indolyl glucosinolates and transformation products thereof.

Micellar electrokinetic capillary chromatography based on dodecyltrimethylammonium bromide as a surfactant has been developed for the qualitative and quantitative determination of indolylic compounds. Indolyl glucosinolates (indol-3-ylmethylglucosinolates), its degradation products, and further transformation products thereof have been included in the studies. The influence of various parameters on the separation has been investigated, resulting in efficient separation, even for structurally closely related compounds, with theoretical plate number per meter of capillary of up to 370,000 for some compounds. Repeatability and linearity of the method have been determined giving relative standard deviations for the migration times of the compounds between 0.5 and 0.9% and linear correlation coefficients between 0.9924 and 0.9996, respectively. The method can be successfully applied to follow the degradation of indolyl glucosinolates in detail.

1-Propanol↗
PubMed1993

Ets transcription factor binding site is required for positive and TNF alpha-induced negative promoter regulation.

Thrombomodulin (TM) is expressed on vascular endothelial cells and plays an important role in the anticoagulant pathway by maintaining the thrombo-resistance of the blood vessel wall. We show that in primary human endothelial cells TM gene expression is repressed at the transcriptional level by Tumour necrosis factor (TNF alpha) through a protein kinase C independent pathway. The TM promoter is highly active in endothelial cells and is inhibited by TNF alpha. The -76/-56 region mediates both specific high basal activity and TNF alpha-repression. It binds a nuclear factor specific to endothelial cells, that appears to belong to the Ets-family by various criteria. The -76/-56 region contains three direct repeats of the ets-core sequence GGAA that are important for specific high basal activity, TNF alpha repression and trans-activation by expression of Ets-1 and 2. Although human Ets-1 (h-Ets-1) and chicken c-Ets-1 and 2 stimulate the TM promoter through the -76/-56 element, their activity is not suppressed by TNF alpha. c-Ets-1 competes and overrides TNF alpha repression in a concentration dependent manner. We propose that either a different member of the Ets domain protein family, or an Ets-associated co-factor, is the target of the TNF alpha signalling cascade in endothelial cells.

Animals↗
PubMed1993

A mouse model for varicella-zoster virus latency.

Following primary infection with varicella-zoster virus (VZV), the virus establishes a latent infection in humans. The molecular pathogenesis of VZV latency is not well understood, mainly due to the lack of an adequate animal model. We report here that we have developed a mouse model for VZV infection that involves corneal inoculation of mice. Although infected animals showed no signs of disease, most of the animals could not eliminate the virus early after infection. By PCR, we demonstrated that at 33 days post-infection (p.i.), viral DNA was still present in more than 60% of the animals (14/21). VZV DNA was most frequently detected in the trigeminal ganglia (7/14) followed by the brain stem (10/21), kidneys (4/21), spleen (3/20), liver (2/21) and brain (1/21). By in situ hybridization, a few cells positive for VZV mRNA were detected in the trigeminal ganglia, brain stem, cerebellum and spleen of a small number of the infected animals as late as 33 days p.i. No viral proteins were detected at the site of inoculation or in any other tissue by immunostaining. Our results suggest that VZV spreads in mice by both viraemia and axonal transport and establishes a non-productive (latent) infection.

Animals↗
PubMed1992

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis.

PURPOSE: This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis. PATIENTS AND METHODS: Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit. RESULTS: Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events. CONCLUSIONS: Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.

Acute Disease↗
PubMed1992

Influence of intact and myrosinase-treated indolyl glucosinolates on the metabolism in vivo of metronidazole and antipyrine in the rat.

Induction of the cytochrome P-450 enzymes is a mechanism whereby cruciferous vegetables and their glucosinolates could influence the risk of cancer. The cytochrome P-450-inducing capacity of isolated intact broccoli glucosinolates and their degradation products, resulting from myrosinase-catalysed hydrolysis, has been assessed in studies of the metabolism of antipyrine (AP) and metronidazole (MZ) in the rat. The intact glucosinolates had no effect on the metabolism of MZ and AP as measured by the clearance and metabolite formation rates; however, the myrosinase-treated glucosinolates significantly increased the clearance of AP by two-thirds and the formation rates of the three major AP metabolites by 87-100%, and doubled the rate of oxidative metabolism of MZ to its hydroxy and acetic acid metabolites. Active myrosinase was thus essential for the capacity of glucosinolates from broccoli (mainly indolyl glucosinolates) to induce the activity of several cytochrome P-450 isoenzymes involved in the metabolism of AP and MZ. The data indicated that hydrolysis products of indolyl glucosinolates had an inducing effect on the activity, but not the total amount, of hepatic cytochrome P-450 isoenzymes. The effect of these products on the oxidative metabolism of AP and MZ was similar to that of phenobarbital. The significance of this induction pattern in relation to cancer risk depends primarily on the activation/inactivation mechanism of the relevant carcinogen.

Animals↗
PubMed1991

The HSV-1 latency associated transcript (LAT) variants 1704 and 1705 are glycoprotein C negative.

The latency associated transcripts (LAT) of herpes simplex virus type 1 (HSV-1) are encoded by diploid genes that are expressed during latent infections. Two LAT variant viruses, 1704 and 1705, were compared with the parental strain 17+. Variant 1705 has a deletion affecting one copy of the LAT genes, expresses LATs during latent infection and reactivates normally. Variant 1704 has deletions affecting both LAT gene copies, does not express LATs during latent infection, and its reactivation is impaired (Steiner et al., 1989). Comparison of infected cell proteins by immunoprecipitation and Western blot analysis revealed one significant difference between HSV-1 strain 17+, 1704 and 1705; glycoprotein C (gC) was not synthesized by 1704 or 1705. Since both 1704 and 1705 are gC minus, the reactivation defect of 1704 is most likely related to the absence of the LATs, and not to the absence of gC.

Animals↗
PubMed1990

Proteinase-antiproteinase imbalance in meningitis: determination of alpha 1 proteinase inhibitor (alpha 1PI), elastase-alpha 1PI complex, and elastase inhibition capacity in cerebrospinal fluid.

Mortality and long-term neurologic sequelae are still frequent complications of meningitis despite effective antibiotic treatment. This suggests that pathogen-independent inflammatory mechanisms may play an important role in the course of this illness. Neutrophil granulocytes form the primary immune defense in meningitis. Once activated, these cells release elastase into the cerebrospinal fluid (CSF). Elastase may induce tissue damage if local antiproteinase capacity is low as under normal conditions. To define the relevance of this mechanism we studied 22 patients with meningitis. Concentrations of elastase in complex with the main antiproteinase alpha 1-proteinase inhibitor (elastase-alpha 1 PI), alpha 1-proteinase inhibitor (alpha 1PI), and elastase inhibition capacity (EIC) were measured in CSF of 9 patients with bacterial meningitis (BM), aged 1 month-14 years; 13 patients with non-bacterial meningitis (NBM), aged 1 month-15 years; and 20 patients in whom meningitis was excluded after spinal tap (control group), aged 6 months-15 years. The concentration of elastase-alpha 1PI in the BM group (median 552 micrograms/l) was significantly higher than in either the NBM group (median 30 micrograms/l, p less than 0.01) or the control group (median 30 micrograms/l, p less than 0.01). Similarly, the alpha 1PI-concentration in the BM group was significantly higher (median 113 mg/l) than either the NBM group (median 13.7 mg/l, p less than 0.025) or the control group (median 6.3 mg/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Enhanced transport in a therapeutic transdermal system.

Ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. A variety of control membrane laminates were examined for swelling and adhesion strength following equilibration with ethanolic solutions to identify a mechanically stable control membrane laminate. In vitro skin permeation analysis of the control membrane laminate showed that ethanol flux was linearly related to the ethanol volume fraction. A reservoir-type therapeutic transdermal system incorporating ethanol was developed to provide constant release of drug and ethanol through skin for 24 h. In vitro ethanol skin permeation rates were constant for 24 h and adhesion was stable over 16 wk at 40 degrees C using a transdermal reservoir device.

Adhesiveness↗
PubMed1990

[Determination of C-reactive protein (CRP) in capillary blood--a comparison with the CPR level in venous serum].

C-reactive protein (CRP) has served as a reliable indicator of infectious and inflammatory diseases for a long time. Sequential CRP determinations offer a useful means of monitoring clinical courses and therapeutic effects in patients of any age as its serum concentrations correlate well with clinical symptoms. Especially in pediatric patients, however, venous blood sampling causes many problems. Thus, in our study a new method of CRP analysis from capillary plasma samples was tested and compared with CRP determinations from venous serum samples. 101 pairs of samples simultaneously obtained from 64 pediatric and neonatal patients (mean age of 5.8 months: min. 1 day, max. 5.5 years) were analyzed and compared. A good correlation (r = 0.967) was found for the whole range of measured CRP-concentrations (5-175 mg/l), showing a linear relationship between both methods. Results were analyzed by chi 2-test. Using a cutoff level of 5 mg/l, a sensitivity of 96%, a specificity and a positive predictive value of 98% each and an efficiency of 97% was found. Thus, the CRP determination from capillary blood samples offers a reliable method and a useful alternative for conventional analysis from venous serum.

C-Reactive Protein↗
PubMed1990

[Acute renal failure with high-dose combination therapy with penicillin G and amoxicillin].

A 3 year old girl was admitted with suspected bacterial meningitis. The patient's history concerning renal and cerebral function and known allergies had been uneventful until that time. 36 h after initiation of a high dose antibiotic therapy with Penicillin G (0.5 Mega IE/kg/day) and Amoxicillin (400 mg/kg/day) macrohematuria and consecutive anuria was observed. Prerenal cardiocirculatory failure, a Schwartz-Bartter-reaction as well as coagulatory failure could be ruled out. There were no symptoms of hypersensitivity. Sonographic examinations of the kidneys and the urinary tract as well as urinanalysis suggested an acute tubular obstruction and papillary necrosis caused by amoxicillin. After changing the antibiotic regimen to chloramphenicol and induction of diuresis by furosemide and dopamine renal failure could be resolved within 39 h. The patient recovered completely. High dose therapy with amoxicillin (greater than 300 mg/kg/day) includes the risk of tubular obstruction due to cristalluria. Solubility of ampicillin in aqueous fluids (6.5 mg/ml at pH 7) should be supported by sufficient diuresis and urine alkalization.

Acute Kidney Injury↗
PubMed1989

Specificity of a cysteine proteinase of Entamoeba histolytica against various unblocked synthetic peptides.

The activity of highly purified cysteine proteinase of Entamoeba histolytica against different peptides of the sequence X-Gly-Phe-Phe was compared. The synthetic peptide Arg-Gly-Phe-Phe of the insulin B-chain was readily hydrolyzed yielding Arg-Gly and Phe-Phe as split products. Lys-Gly-Phe-Phe and Tyr-Gly-Phe-Phe were cleaved at rates of 20 and 4%, respectively. Val-Gly-Phe-Phe, Gly-Gly-Phe-Phe, Glu-Gly-Phe-Phe, and Ser-Gly-Phe-Phe were hydrolyzed at rates far below 1%. Gly-Arg-Phe-Phe, Gly-Phe-Phe, and Gly-Phe were completely resistant to the enzyme. Another good substrate was found in Arg-Gly-Leu-Hyp, which represents a model compound of a scissile site in collagen type I. Furthermore, peptide Arg-Arg-Phe-Phe was attacked by the enzyme releasing Arg-Arg and Phe-Phe. Compared with Arg-Gly-Phe-Phe at substrate concentrations of 2 mM the rates of hydrolysis of Arg-Arg-Phe-Phe and Arg-Gly-Leu-Hyp were 37 and 127%. The enzyme exhibited dipeptidyl peptidase activity against the nonapeptide Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala releasing Arg-Gly.

Animals↗