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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 235 records · Page 13Linked to original sources

Co-localization of beta-amyloid peptides, apolipoprotein E and glial markers in senile plaques in the prefrontal cortex of old rhesus monkeys.

Based on the homology of human and monkey amyloid precursor proteins and the derived beta-amyloid peptides (A beta) the investigation of brains from old monkeys might be useful for the understanding of beta-amyloidosis in the aetiology of Alzheimer's disease. In the present study, the prefrontal cortex, which is known to be highly susceptible to the deposition of A beta, was screened for the occurrence of senile plaques in perfused tissue of aged rhesus monkeys (Macaca mulatta). A beta deposits were immunocytochemically detected in five of six macaques aged about 28 years. Differently N-terminal truncated A beta species in the senile plaques were simultaneously detected by a carbocyanine double fluorescence method applying the bright red fluorescent Cy3 and the novel green fluorescent Cy2. In a few cases, immunoreactivity for the shortened fragment containing the amino acids 17-42 (A beta(17-42); p3 fragment with a molecular weight of 3 kDa) was demonstrated in deposits apparently devoid of A beta(8-17). Senile plaques were further characterized by carbocyanine double labelling of A beta and astrocytes, microglia and apolipoprotein E.

Aging↗

Cooperative and competitive interactions of regulatory elements are involved in the control of divergent transcription of human Col4A1 and Col4A2 genes.

The genes COL4A1 and COL4A2, coding for the two subunit chains alpha1(IV) and alpha2(IV) of collagen IV [alpha1(IV)2alpha2(IV)] are found closely linked on the human chromosome 13 in a unique head-to-head arrangement resulting in opposite strand transcription starting from a shared promoter region. Transient transfection experiments defined a shared promoter and two symmetrically arranged, downstream located and gene-specific activating elements in each gene. The shared promoter does not exhibit any transcriptional activity and efficient transcription depends on the cooperative effect of downstream elements. Mutual inhibitory effects between the two activating elements indicate competitive interactions with the shared promoter. Symmetry, cooperativity and competitivity of cis-elements are also reflected by the binding of transacting factors to the promoter and activating elements. From these data we propose a model for the coordination of divergent transcription of COL4 genes based on the cooperative and competitive interactions of the shared promoter and gene-specific regulating elements.

Binding, Competitive↗

Treatment of sebaceous gland hyperplasia with the pulsed dye laser.

BACKGROUND AND OBJECTIVE: Sebaceous gland hyperplasia may be treated by cryotherapy, cauterization, topical chemicals, or excision. The major disadvantage of these therapeutic strategies is a considerable risk of postoperative scarring or dyspigmentation. The pulsed dye laser may be an effective and safe alternative treatment option. STUDY DESIGN AND METHODS: Our report presents two patients with sebaceous gland hyperplasia who were treated with the pulsed dye-laser (585 nm, 6.5-8 J/cm2, 300-450/microsecond). RESULTS: After 2-3 treatment sessions, the lesions were completely gone. To data, no side effects have been observed. CONCLUSIONS: Based upon our experiences, we recommend the pulsed dye laser as a safe, fast, and minimal straining treatment alternative for hyperplasia of sebaceous glands.

Female↗

Combined myxoid liposarcoma and angiolipoma of the spermatic cord.

To date, only 14 cases of myxoid liposarcoma of the spermatic cord have been reported in the literature. The growth is a rare, usually highly differentiated malignancy that tends to recur locally, rarely metastasizes, and has a good prognosis following complete removal. We describe a new case of a highly differentiated myxoid liposarcoma of the spermatic cord, combined with an angiolipoma. Left inguinal orchiectomy with high ligation of the cord was performed. Staging revealed no evidence of regional or distal metastases. By the latest visit, at 30 months, the tumor had not recurred. The diagnosis, management, and prognosis of this oncologic entity are discussed in the light of the literature.

Angiolipoma↗

A predictive parameter in patients with brain related complications after cardiac surgery?

OBJECTIVE: The prognostic estimation of cerebral complications after cardiac surgery is a major problem in the early postoperative period. Neuron specific enolase (NSE) is an enzyme involved in glycolysis, which is localized in neurons and axonal processes. It escapes into the blood and cerebrospinal fluid at the time of neural injury. Therefore we focused the study on the question of how far serum levels of neuron specific enolase can predict the neurological and neuropsychological outcome after cardiac surgery. METHODS: We determined, with a prospective study design of NSE serum levels in 200 patients undergoing cardiac surgery preoperatively, right after the operation and 48 h later. The NSE was measured with a solid phase enzyme immuno assay which utilized a highly specific monoclonal antibody to NSE. We evaluated the neurological and neuropsychological status before and 72 h after surgical intervention. As a control group we recruited 50 patients undergoing general surgical treatment. RESULTS: The preoperative serum levels of NSE are constantly low in all patients with a mean value of 11.1 ng/ml (8.3-13.6) and a mean +/- S.D. of 3.12 in the main group and a mean value of 9.6 ng/ml (7.8-10.3) and a mean +/- S.D. of 1.84 in the control group. The early postoperative measurements indicated a significant increase to a mean value of 19.7 ng/ml (8.7-70.9) with a mean +/- S.D. of 2.89 in the main group. In contrast there is no increase of NSE serum levels after general surgery. The 48 h postoperative mean levels declined to 14.2 ng/ml (9.9-26.2), S.D. of 3.23. In 17 out of the 200 patients a neurological complication occurred. Elevated NSE levels were found in 16 of these 17 patients. The highest concentrations of NSE were measured in 7 patients with the most severe neurological complications being transient ischemic attack and stroke. CONCLUSIONS: The early serum levels of NSE after cardiopulmonary bypass, in those patients with severe neurological deficits, indicate that NSE is a suitable marker for the detection and quantification of cerebral injury after open heart surgery. Therefore, in addition NSE seems to be of predictive value for the clinical outcome and gives implications for the treatment and prognosis of patients with brain related complications in cardiac surgery.

Adult↗

Characterization of epoxide hydrolase activity in Alternaria alternata f. sp. lycopersici. Possible involvement in toxin production.

Using trans-diphenylpropane oxide (tDPPO) as a substrate, we measured epoxide hydrolase (EH) activity in subcellular fractions of Alternaria alternata f. sp. lycopersici (Aal), a fungus that produces host-specific toxins. The activity was mainly (> 99.5%) located in the soluble fraction (100,000 x g supernatant) with the optimum pH at 7.4. An increase of toxin production between days 3 and 9 found in a Aal liquid culture over a 15 days period was concomitant with a period of high EH activity. EH activity remained constant during the same period in an Alternaria alternata culture, a fungus which does not produce toxin. In vivo treatment of Aal culture with the peroxisome proliferator clofibrate stimulated EH activity by 83% and enhanced toxin production 6.3 fold. Both 4-fluorochalcone oxide (4-FCO) and (2S,3S)-(-)-3-(4-nitrophenyl)-glycidol (SS-NPG) inhibited EH activity in vitro with a I50 of 23 +/- 1 microM and 72 +/- 19 microM, respectively. The possible physiological substrate 9,10-epoxystearic acid was hydrolyzed more efficiently by Aal sEH than the model substrates trans- and cis-stilbene oxide (TSO and CSO) and trans- and cis-diphenylpropane oxide (tDPPO and cDPPO).

Alternaria↗

[Globus pharyngis and gastroesophageal equivalents].

BACKGROUND: Globus sensation is a phenomenon of largely unknown etiology. Dyskinesia of the upper esophageal sphincter is quite often evident without pathological ENT findings elsewhere. PATIENTS AND METHODS: One hundred ten patients were examined in a interdisciplinary approach. The investigation included videofluoroscopy, esophagogastroduodenoscopy with biopsy, pharyngoesophageal computer manometry, and esophageal pH monitoring. One hundred five cases were evaluated. RESULTS: In 13 cases (12.4%) there was no evidence for any organic or functional disorder. In 92 cases (87.6%) abnormal findings were seen with two constellations being predominant. These are primarily inflammatory lesions in the stomach or the duodenum in 69.5% of all patients (73/105) associated with helicobacter pylori colonization in 58% (42/73) as well as ulcera and/or erosions in 8.2% (6/73). Concurrent disorders of the lower esophageal sphincter play the second role. Sixty-one point nine percent of all patients (65/105) had an hiatal hernia, with gastroesophageal reflux in 36.9% (24/65). In 21.5% (14/65) a reflux esophagitis was evident. A cardiac sphincter insufficiency was found in 6.7% (7/105). CONCLUSIONS: Based on these findings a gastroenterologic diagnosis is recommended in all patients with globus sensation as the symptom may be associated with corresponding disorders.

Adolescent↗

Dominant cytotoxic T lymphocyte response to the immediate-early trans-activator protein, BZLF1, in persistent type A or B Epstein-Barr virus infection.

Five healthy human leukocyte antigen-B8 (HLA-B8)-positive virus carriers were studied to investigate the CD8+ cytotoxic T lymphocyte (CTL) response to an HLA-B8-restricted peptide, RAKFKQLLQ, located in the Epstein-Barr virus (EBV) immediate-early trans-activator protein, BZLF1. Of the 5 virus carriers, 4 were infected with type A and 1 with type B EBV. Using limiting-dilution analysis of peripheral blood mononuclear cells, a high RAKFKQLLQ-specific CTL precursor frequency was demonstrated after specific peptide or autologous lymphoblastoid cell line stimulation in both type A and type B EBV carriers. The RAKFKQLLQ-specific CTL precursor frequencies in all 5 persons were at least as dominant as those observed with two other EBV-associated, HLA-B8-restricted latent epitopes, FLRGRAYGL and QAKWRLQTL. These findings show that healthy virus carriers maintain a high frequency of BZLF1-specific memory T cells, potentially to control virus spread from lytically infected cells.

Antigens, Viral↗

The humoral immune response against human cytomegalovirus is characterized by a delayed synthesis of glycoprotein-specific antibodies.

An individual analysis of IgG antibodies against 12 known antigenic domains of human cytomegalovirus (HCMV)-derived structural phospho- and glycoproteins and nonstructural polypeptides was performed. In HCMV-seropositive healthy persons, the separate determination of antibody titers against the various antigens resulted in an antibody profile that was characteristic for each individual. Profiles were qualitatively stable over a period of >4 years. However, quantitative changes were observed in some persons. During primary HCMV infection, a delay of 50-100 days in the appearance of glycoprotein-specific antibodies was observed, whereas immunoglobulins directed against other HCMV-specific antigens were promptly synthesized. In contrast, during reactivation or reinfection, a synchronized production of antibodies was found. Levels of glycoprotein-specific antibodies and detection of viral DNA in peripheral blood inversely correlated. Precursor B cell analyses showed no significant differences between glycoprotein-specific and phosphoprotein-specific B cells.

Antibodies, Viral↗

Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting.

Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass (CPB) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses. We examined the effects of dopexamine on hemodynamic parameters, creatinine clearance, systemic and splanchnic oxygenation, gastric mucosal pH (pHi), and mixed and hepatic venous plasma levels of endotoxin, interleukin-6 (IL-6), serum amyloid A (SAA), and C-reactive protein (CRP) in 44 patients scheduled for coronary artery bypass grafting. Patients were randomized to receive continuous infusions of 0.5, 1.0, or 2 micrograms.kg-1.min-1 dopexamine (n = 10 per group) or placebo (n = 14) prior to surgery, intraoperatively, and postoperatively. Dopexamine infusion increased systemic oxygen delivery (P < or = 0.01). Hepatic venous oxygen saturation did not change, and pHi decreased during and after CPB in all patients (P < or = 0.01). Postoperative increases in IL-6 were smallest in patients who received 2.0 micrograms.kg-1.min-1 dopexamine (P < or = 0.02). SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study. Creatinine clearance was elevated in all dopexamine groups (P < or = 0.025). This elevation was higher with lower dopexamine doses (P < or = 0.025). We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation.

Acute-Phase Reaction↗

Chemotherapy of human malignant glioma: prevention of efficacy by dexamethasone?

Steroids are commonly administered for the control of edema, mass effect, and side effects from therapy to patients with malignant glioma who are receiving radiotherapy and chemotherapy. Here, we report that therapeutic concentrations of dexamethasone (DEX) attenuate cytotoxicity and growth inhibition of human malignant glioma cells induced by exposure to several chemotherapeutics, including ACNU, VM-26, vincristine, cytarabine, methotrexate, and adriamycin. DEX-mediated cytoprotection is not linked to DEX effects on glioma cell proliferation. However, the cytoprotective effects of DEX appeared to be more prominent in cell lines with wild-type p53 status (n = 2) than in p53 mutant cell lines (n = 3). Further, DEX-mediated rescue from chemotherapy does not directly involve Bcl-2 family proteins since DEX failed to change the expression of Bcl-2 or Bax proteins and since bcl-2 gene transfer-mediated cytoprotection was not redundant with the effects of DEX. DEX thus appears to control a common, bcl-2-independent death pathway in glioma cells that is not limited to specific drug actions. Chemotherapy is usually given as an elective, adjuvant treatment to glioma patients in stable condition who can tolerate steroid withdrawal. To maximize therapeutic efficacy, steroids should be withdrawn from glioma patients prior to chemotherapy.

Antibiotics, Antineoplastic↗

Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm.

Transgenic embryos expressing Cwnt8C under the control of the human beta-actin promoter exhibit duplicated axes or a severely dorsalised phenotype. Although the transgene was introduced into fertilised eggs all duplications occurred within a single amnion and, therefore, arose from the production of more than one primitive streak at the time of gastrulation. Morphological examination and the expression of diagnostic markers in transgenic embryos suggested that ectopic Cwnt8C expression produced only incomplete axis duplication: axes were always fused anteriorly, there was a reduction in tissue rostral to the anterior limit of the notochord, and no duplicated expression domain of the forebrain marker Hesx1 was observed. Anterior truncations were evident in dorsalised transgenic embryos containing a single axis. These results are discussed in the light of the effects of ectopic Xwnt8 in Xenopus embryos, where its early expression leads to complete axis duplication but expression after the mid-blastula transition causes anterior truncation. It is proposed that while ectopic Cwnt8C in the mouse embryo can duplicate the primitive streak and node this only produces incomplete axis duplication because specification of the anterior aspect of the axis, as opposed to maintenance of anterior character, is established by interaction with anterior primitive endoderm rather than primitive streak derivatives.

Actins↗

Dual-phase helical CT of the kidney: value of the corticomedullary and nephrographic phase for evaluation of renal lesions and preoperative staging of renal cell carcinoma.

OBJECTIVE: Our objective was to evaluate early-phase unenhanced and late-phase contrast-enhanced helical CT in revealing renal lesions and staging renal cell carcinomas. SUBJECTS AND METHODS: Contrast-enhanced helical CT of the kidneys was performed in 145 patients who also underwent unenhanced CT. Contrast-enhanced CT was performed in the corticomedullary phase (CMP) and nephrographic phase (NP). A total of 173 lesions in 96 patients were proven histologically or cytologically. The performance of helical CT in the three study groups was compared: unenhanced and CMP enhancement, group 1; unenhanced and NP enhancement, group 2; unenhanced, CMP enhancement, and NP enhancement, group 3. Among the parameters evaluated were the sensitivity for helical CT of all 173 renal lesions and the sensitivity and specificity for the 90 malignant tumors. Also, the preoperative CT staging of the 76 renal cell carcinomas was correlated with the pathologic specimens. RESULTS: The sensitivity for detection of all renal lesions in group 1 (84%) was significantly less than in groups 2 and 3 (97% and 100%). The specificity and accuracy of helical CT in revealing renal cell carcinomas were significantly higher (p < .05) in group 3 (95% and 95%, respectively) than in groups 1 (93% and 92%, respectively) and 2 (89% and 91%, respectively). Two renal cell carcinomas were overlooked by the interpreters of the helical scans in group 1. The accuracy of preoperative CT staging of renal cell carcinomas was significantly better (p < .05) in group 3 (91%) than in groups 1 (82%) and 2 (86%). CONCLUSION: When patients underwent unenhanced helical CT, CMP helical CT, and NP helical CT, we achieved a better rate of detection and characterization of renal lesions and better preoperative staging of renal cell carcinomas than when we used either CMP helical CT or NP helical CT alone.

Adult↗

Analysis of motile oligodendrocyte precursor cells in vitro and in brain slices.

Oligodendrocyte precursor cells are purported to migrate over long distances into the various brain regions where they differentiate into oligodendrocytes and fulfill their appropriate tasks, i.e., myelination of axons. Here we characterize motile oligodendrocyte precursor cells in detail. Video-time lapse analysis was performed on isolated precursor cells in single cell cultures, in co-culture with cerebellar microexplants, and in living brain slices. Motility analysis of individual cells was combined with electrophysiological, immunological, and morphological characterizations. Translocation of the cell bodies was not continuous but occurred in waves. All motile cells exhibited a simple morphology and most, but not all, of them expressed the A2B5 epitope in vitro. Patch clamp analysis of the motile cells confirmed that they belong to the O-2A lineage. The percentage of motile cells, as well as their velocities, were enhanced on substrate-coated laminin in comparison to poly-L-lysine. Motility was not influenced by the presence of cerebellar microexplants. O-2A progenitor cells did not migrate strictly along neurite fascicles which were projected from the microexplants. Glial progenitor cells in situ also did not strictly migrate along the main direction of the axonal fibers of the corpus callosum but rather traversed the fibers with an overall direction toward the cortex. After Lucifer Yellow filling of the motile progenitor cells in situ, we could demonstrate that they were dye-coupled to yet unidentified cells of the corpus callosum.

Animals↗

Differential responsiveness of murine T lymphomas to local growth and invasion factors may determine metastasis formation in the ovaries.

The murine T cell hybridomas BW-14 and BW-19, both derived from a fusion between the nonmetastatic BW 5147 lymphoma and a cytotoxic T cell line, differ in their capacity to metastasize to the ovaries. While ovary colonization by BW-19 cells is marginal and limited to the ovary follicles, BW-14 cells extensively colonize the complete ovary. The present study shows that the two T cell hybridomas respond differentially to ovary-derived migration and growth-modulating factors, in a way that correlates with their differential capacity to metastasize to the ovaries. More specifically, we observed that conditioned medium from cultured ovary fragments or from the ovary-derived granulosa cell line GRMO1V inhibited the migration of BW-19 cells in vitro, but stimulated the migration of BW-14 cells. Likewise, the local hormone prostaglandin E2 (PGE2) and the steroid hormone progesterone, both known to be secreted by GRMO1V cells, stimulated the migration of BW-14 cells, indicating that the stimulatory effect of the conditioned medium can be at least partially ascribed to the action of these two hormones. In contrast, the migration of BW-19 cells was inhibited by PGE2. In addition to the modulatory effect on hybridoma cell migration, conditioned medium from the granulosa cell line GRMO1V inhibited the proliferation of BW-19 cells in vitro, an effect that is likely to be mediated at least partially by PGE2. The proliferation of BW-14 cells, on the other hand was, depending on the dilution used, stimulated or inhibited by GRMO1V-conditioned medium. Our findings indicate that the differential capacity of the T cell hybridomas BW-14 and BW-19 to metastasize to the ovaries is mediated by the differential action of granulosa-cell-derived factors, in particular the sex hormone progesterone and the local hormone PGE2, on both the migration and proliferation of the T cell hybridomas.

Animals↗

A liver-specific isoform of the betaine/GABA transporter in the rat: cDNA sequence and organ distribution.

We report the cloning of a 2.2 kb cDNA encoding a Na(+)-and Cl- dependent betaine/GABA (gamma-aminobutyric acid) transporter from rat liver poly(A+) RNA. 5'-RACE revealed an additional 355 bases 5' to the 2.2 kb cDNA sequence. Northern analysis demonstrated two (2.2 kb and 2.6 kb) mRNA isoforms in rat liver. Betaine transporter mRNA was also detected in the brain, spleen, lung, and kidney using the 2.2 kb cDNA clone as a probe. Only the 2.6 kb mRNA from the liver hybridized with the 5'-RACE product.

Amino Acid Sequence↗

Beta-endorphin and catecholamine concentrations during chronic and acute stress in intensive care patients.

BACKGROUND: Only little information is available on the effects of acute and chronic stress on the opioid and adrenergic systems in patients at intensive care units. Animal models showed a stimulation of beta-endorphin and catecholamines. METHODS: In the present study, in 12 patients who were intubated and were receiving artificial respiration because of cardiopulmonary resuscitation or primary respiratory failure, venous plasma concentrations of adrenaline, noradrenaline and beta-endorphin immuno-reactive material (IRM) were determined by a radioimmunoassay. In these patients, regular endobronchial suctioning was necessary. For inducing acute stress patients underwent three different methods of endobronchial suctioning or lavage. RESULTS: In all patients concentrations of both adrenaline (529 +/- 117 pg/ml) and noradrenaline (2694 +/- 262 pg/ml) were increased above normal resting values. In 5 patients plasma beta-endorphin IRM concentration was below the detection limit, the other patients had beta-endorphin IRM concentrations above normal (26.65 +/- 3.80 pg/ml). Epinephrine (227 +/- 33 vs. 743 +/- 189 pg/ml; p < 0.01) and norepinephrine (1673 +/- 161 vs. 3423 +/- 368 pg/ml; p < 0.001) were significantly lower in the group with undetectable beta-endorphin IRM concentrations than in the group with detectable beta-endorphin IRM whereas heart rate was significantly higher (120/min vs. 99/min; p < 0.0003). beta-endorphin IRM concentrations were correlated negatively to heart rate (-0.55; p < 0.0005) and positively to the noradrenaline concentration (0.56; p < 0.0004). Artificially ventilated patients showed increased levels of beta-endorphin (19.27 +/- 3.16 pg/ml) as compared to the spontaneously breathing patients (13.29 +/- 4.34 pg/ml). Following acute stress due to endobronchial suctioning or lavage, blood pressure (150/70 mmHg vs. 172/81 mmHg; p < 0.01) and heart rate (107/min vs. 119/min; p < 0.005) increased in all patients, the other parameters did not. CONCLUSION: It is concluded that beta-endorphin IRM concentration in the plasma is linked to epinephrine and norepinephrine concentrations under intensive care conditions. Endobronchial lavage or suctioning does not influence beta-endorphin IRM levels in plasma.

Acute Disease↗