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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 289 records · Page 16Linked to original sources

Functional characterization of the Staphylococcus carnosus SecA protein in Escherichia coli and Bacillus subtilis secA mutant strains.

The Staphylococcus carnosus secA gene was cloned using the Bacillus subtilis secA gene as a probe. The S. carnosus secA encodes a polypeptide of 844 amino acid residues which is homologous to other known SecA proteins. The S. carnosus SecA functionally complemented the growth and secretion defects of a temperature-sensitive B. subtilis secA mutant at the non-permissive temperature. In contrast, the growth defect of an Escherichia coli secA mutant could not be complemented by the S. carnosus SecA protein. Our results suggest that the interactions of SecA with precursor proteins and/or other components of bacterial preprotein translocase are optimized within each organism.

Adenosine Triphosphatases↗

Stereochemistry of the Aplysia neuronal 12-lipoxygenase: specific potentiation of FMRFamide action by 12(S)-HPETE.

Nervous tissue of the marine mollusc, Aplysia californica, generates arachidonic acid metabolites in response to neurotransmitters such as histamine or FMRFamide. In addition, identified neurons of Aplysia respond to the pharmacologic application of some of these products, particularly those of the 12-lipoxygenase pathway. We investigated the chirality of the initial Aplysia 12-lipoxygenase product, 12-HPETE, in preparation for more detailed metabolic studies and for the analysis of the physiological activity of the endogenous lipid. Neural homogenates and intact ganglia exclusively generate 12(S)-HPETE as do the better characterized mammalian lipoxygenases. The direct application of 12(S)-HPETE to cultured sensory neurons induced a hyperpolarization which averaged 2.6 mV. We did not find any difference between the response to the naturally-occurring 12(S)-HPETE and its diastereomer, 12(R)-HPETE which is not generated in Aplysia. Both isomers were significantly more effective than 15(S)-HPETE. In contrast, 12(S)-HPETE, but not 12(R)-HPETE, was a potent modulator of the action of the molluscan neuropeptide, FMRFamide. Prior application of 12(S)-HPETE to cultured sensory neurons increased the subsequent response to a submaximal dose of FMRFamide by 60%. On the other hand, 12(R)-HPETE reduced the subsequent response to the peptide by 30%. The lack of stereospecificity in the direct effect of the lipids differs markedly from their stereospecific effects as modulators of FMRFamide action. This suggests that there may be an important neurophysiologic role for these lipid modulators which is distinct from their direct effects, and also indicates that there are multiple sites and mechanisms by which lipid hydroperoxides act on neurons in Aplysia.

Animals↗

Prognostic impact of DNA content and AUER classification in primary fallopian tube carcinoma.

DNA ploidy has been studied in 61 primary fallopian tube carcinomas using image-cytometry. The investigation also included survival analysis, and ploidy classification according to AUER was performed in order to evaluate its prognostic impact for fallopian tube carcinoma. A high number of aneuploid cases were observed (79% aneuploid vs. 21% euploid tumors). The high incidence of aneuploid tumors was consistently observed among all FIGO-stages as well as all groups of histologic grading. There was no correlation between ploidy and FIGO-stage or histologic grading. Patients with euploid DNA content showed a median survival of 34 months compared to 24 months for aneuploid cases (log-rank, P = 0.83). No correlation between the AUER classification and FIGO-stage or histologic grading could be observed. Tumors with an AUER type I and II (75th quantile 41 months) showed a better outcome than tumors with AUER III and IV (75th quantile 19 months). Although these results did not reach statistical significance (P = 0.07), a trend could be observed. Therefore AUER classification may be useful as an objective prognostic parameter. The high incidence of aneuploid tumors could be an expression of the high biologic aggressiveness of primary fallopian tube cancer which has been repeatedly mentioned in the past.

Adenocarcinoma↗

A cell-free protein translocation system prepared entirely from a gram-positive organism.

A cell-free protein translocation system derived exclusively from a Gram-positive bacterium is described here for the first time. Highly efficient in vitro synthesis of plasmid encoded preprolipase of Staphylococcus hyicus is accomplished by coupled transcription/translation using either a cytosolic extract of S. carnosus alone or in combination with T7-RNA-polymerase. Addition of inside-out cytoplasmic membrane vesicles of S. carnosus leads to the partial conversion (processing) of preprolipase to prolipase. In addition, as shown in a protease protection assay, a significant part of preprolipase plus prolipase is translocated in vitro into the lumen of the vesicles. Translocation of preprolipase into the membrane vesicles requires the proton-motive force and the S. carnosus SecA protein.

Adenosine Triphosphatases↗

[TNF-alpha level in the vitreous body. Increase in neovascular eye diseases and proliferative diabetic retinopathy].

BACKGROUND: Deficient retinal capillary perfusion results in angioneogenesis of the eye. Its extension depends on the degree of ischemia. Mild stages are restricted to the retina, while marked ischemia results in neovascularization of the iris (rubeosis iridis). The neovascularization may be induced by the release of growth factors into the vitreous. Tumor necrosis factor alpha seems to be an important angiogenetic growth factor. PATIENTS AND METHODS: The patients were divided up into three groups with different retinal stages of ischemia, as judged by the extension of new vessel formation of the eye: a control group without angioneogenesis, a diabetes group with less severe to moderate angioneogenesis of patients with proliferative diabetic retinopathy and a rubeosis group with massive angiogenesis (rubeosis iridis) resulting from different causes. TNF-alpha was determined by immunological methods. RESULTS: The TNF-alpha level of vitreous in rubeosis (25.8 pg/ml; n = 6) was 2-fold elevated compared to controls (13.1 pg/ml; n = 10; p < 0.05) and 1.4-fold elevated compared to the diabetes group (18.2 pg/ml; n = 17). The values ranged from unmeasurable values to 41.25 pg/ml. Within the rubeosis group similar changes were observed independently of the causes of ischemia. There was no correlation between TNF-alpha-levels in the diabetes group and serum creatinine. CONCLUSIONS: 1. TNF-alpha is upregulated in ischemia. 2. TNF-alpha seems to be a mediator of angiogenesis in the eye. 3. Changes in diabetes may be secondary to local ischemia rather than being specific for diabetic retinopathy.

Adult↗

Coat protein of the Ectocarpus siliculosus virus.

Ectocarpus siliculosus virus, EsV, multiplies in sporangia and gametangia of the marine brown alga Ectocarpus siliculosus. We describe an improved method for the isolation of morphologically intact and infectious virus from diseased plants. We show that treatment of virus particles with high concentrations of CsCl results in a substantial loss of structural proteins. One of the proteins which resists CsCl treatment is glycoprotein-1, the largest of the three viral glycoproteins. We have isolated an EsV genomic fragment with an open reading frame encoding glycoprotein-1. The predicted amino acid sequence is rich in hydrophilic amino acids, but contains hydrophobic regions close to the amino and carboxy termini. A discrepancy between the molecular weight predicted from the coding region and the molecular weight determined by gel electrophoresis suggests that proteolytic processing is required for the maturation of the protein.

Amino Acid Sequence↗

DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer.

OBJECTIVE: Oncogene alterations are thought to be prognostic indices in patients with breast cancer. The present study was carried out to investigate the amplification of the HER-2/neu and INT-2 oncogenes in ovarian cancer. METHODS: In a retrospective study of 196 patients with epithelial ovarian cancer, the amplification of the oncogenes HER-2/neu and INT-2 in the DNA of paraffin-embedded tumor cells was determined by quantitative PCR. The purpose of this study was to analyze whether the two oncogenes correlated with such predictive factors as FIGO stage, histological grade, ascites, postoperative residual tumor mass, hormone receptor content, and preoperative CA 125 serum levels. The effect of HER-2/neu and INT-2 amplification on patient survival was also studied. RESULTS: The only correlation found in this study was between INT-2 and preoperative CA 125 levels (P = 0.03). No correlations were demonstrable between HER-2/neu (log-rank test; P = 0.67) and INT-2 (log-rank test; P = 0.75) amplifications and overall survival. CONCLUSION: Unlike the established prognostic factors, neither HER-2/neu nor INT-2 appears to be predictive for survival in patients with ovarian cancer.

Adolescent↗

Increased cancer screening behavior in women of color by culturally sensitive video exposure.

BACKGROUND: Electronic media have demonstrated efficacy in increasing knowledge and promoting health-protective behavior among individuals at high risk for chronic disease. In "Stimulating Cancer Screening among Women of Color through Video" (A. K. Yancey and L. Walden, 1994, J Cancer Educ 9:46-52) the development of a cost-effective documentary format for culturally sensitive health education videos was described. These videos could not be independently evaluated within the cancer control program for which they were developed. METHODS: A quasi-experimental study design tested the hypothesis that exposure to these videos increases cervical cancer screening behavior among samples of women from two clinic populations of predominantly low-income African-Americans and Latinos in New York City and Los Angeles. A 1-week-on-1-week-off design was utilized, in which the videos were continuously displayed in designated waiting rooms during on (intervention) weeks, with each facility serving as its own control during off weeks. RESULTS: The proportion of women seen as patients during the intervention weeks who subsequently obtained Pap smears was significantly higher than that of those seen during the control weeks at each site (P < 0.05). CONCLUSIONS: Culturally sensitive videos displayed in waiting rooms may be useful in health promotion efforts in communities of color. The similarity of results in both clinic sites suggests that Spanish-language tapes may be constructed to appeal to Latinos of different nationalities.

Black or African American↗

Characterization of a family of genes encoding a fruit-specific wound-stimulated protein of bell pepper (Capsicum annuum): identification of a new family of transposable elements.

Using a fruit-specific cDNA as a probe we isolated and sequenced the two corresponding homologous genes (Sn-1 and Sn-2) of the bell pepper (Capsicum annuum) genome. Both genes have a single intron and numerous unusual long inverted repeat sequences. The introns share 87% homology and Sn-2 contains one 450 bp additional sequence with structural features of a transposable element, which is highly repetitive in the bell pepper genome. Surprisingly, analysis in data banks showed that genes encoding the potato starch phosphorylase (EC 2.4.1.1) and patatin contain a similar element, named Alien, in their 5'-upstream region. Alien elements are characterized by a conserved 28 bp terminal inverted repeat (TIR), small size, high AT content, potential to form stable DNA secondary structures and they have probably been inserted in TA target sites. Interestingly, the TIR of the Alien elements shares high homology with sequences existing in the TIR of extrachromosomal linear pSKL DNA plasmid of Saccharomyces kluyveri. Northern blot analyses detected Sn-1 transcripts principally in the red fruit whereas no Sn-2 transcripts were detected in neither of the samples monitored. Western blot analyses detected a 16.8 kDa Sn protein principally in the ripe red fruit and wounded areas of green unripe fruit. A comparison of the deduced amino acid sequence of Sn-1 with protein sequences in data banks revealed a significant homology with proteins likely involved in the plant's disease resistance response. Analyses at the subcellular level showed that Sn-1 is localized in the membrane of vacuoles.

Amino Acid Sequence↗

The relation between depth of trophoblastic invasion and beta-HCG levels in tubal pregnancies.

beta-HCG (human chorionic gonadotropin) values of over 2500 I.U./l are associated with higher failure rates for therapy with prostaglandin F2 alpha in tubal pregnancies. The purpose of our study was to ascertain if the 2500 I.U./l limit correlates with histopathology. We therefore compared the pre-operative beta-HCG-values and intraluminal and extraluminal trophoblast growth in tubal pregnancy. Purely intraluminal trophoblast was significantly more frequent in patients of group I (beta-HCG < 2500 I.U./l), while group II patients (beta-HCG > 2500 I.U./l) almost exclusively had extraluminal growth (P = 0.0045). Since the efficacy of prostaglandin F2 alpha therapy depends on intact tubal musculature the correlation of the beta-HCG threshold level with histopathologic findings may explain the high failure rate in patients with beta-HCG values above 2500 I.U./l.

Chorionic Gonadotropin↗

The effects of prostacyclin on gastric intramucosal pH in patients with septic shock.

OBJECTIVE: To investigate whether infusing prostacyclin (PGI2) in patients with septic shock improves splanchnic oxygenation as assessed by gastric intramucosal pH (pHi). DESIGN: Interventional clinical study. SETTING: Surgical ICU in a university hospital. PATIENTS: 16 consecutive patients with septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine to maintain arterial blood pressure. INTERVENTIONS: All patients received PGI2 (10 ng/kg x min) after no further increase in oxygen delivery could be obtained by volume expansion, red cell transfusion and dobutamine infusion. The results were compared with those before and after conventional resuscitation. The patients received continuous PGI2 infusion for 33-32 days. MEASUREMENTS AND RESULTS: O2 uptake was measured directly in the respiratory gases, pHi was determined by tonometry. Baseline O2 delivery, O2 uptake and pHi were 466 +/- 122 ml/min.m2, 158 +/- 38 ml/min.m2, and 7.29 +/- 0.09, respectively. While O2 uptake remained unchanged, infusing PGI2 increased O2 delivery (from 610 +/- 140 to 682 +/- 155 ml/min.m2, p < 0.01) and pHi (from 7.32 +/- 0.09 to 7.38 +/- 0.08, p < 0.001) beyond the values obtained by conventional resuscitation. While 9 of 11 patients with final pHi > 7.35 survived, all patients with final pHi < 7.35 died (p < 0.01). CONCLUSIONS: Infusing PGI2 in patients with septic shock increases pHi probably by enhancing blood flow to the splanchnic bed and thereby improves splanchnic oxygenation even when conventional resuscitation goals have been achieved.

Adult↗

Munchausen syndrome by proxy and factitious illness: symptomatology, parent-child interaction, and psychopathology of the parents.

The term Munchausen syndrome by proxy is used to diagnose children presenting symptoms of an organic disorder resulting from manipulations initiated by their caretakers. Even in early infancy it happens that injuries are induced, and that drugs, poisons or medicine are administered in order to provoke and feign clinical symptoms of severe diseases. Exact data on prevalence are not available but it is obvious that Munchausen syndrome by proxy is a rare psychiatric disorder. There is a body of evidence that Munchausen syndrome by proxy is nothing but the extreme of a broader clinical entity for which the term factitious illness has been introduced. In this group children are included whose mothers invent a history of disease in order to produce symptoms without actually damaging their children. It is not well established whether such a distinction is necessary and whether there are differences in long-term outcome. Onset of symptoms is as early as three weeks up to twelve years, and mean age of diagnosis according to a more comprehensive study is 3 1/4 year. The estimated mortality rate of children with Munchausen syndrome by proxy is 9 percent. In three of the four cases of children reported here clinical presentations were dominated by symptoms of central nervous disorders. All mothers showed unsure and inconsistent parental behaviour and inefficient coping. None of them received support from their partners, if present. In interaction the children always wanted to dominate their mothers. The high amount of personality disorders observed in the caretakers might be the reason for the often reported failure of psychotherapeutic interventions.

Child↗

Case report: concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease.

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

Adolescent↗