Search PubMed⌕ Search

Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor suppressor gene, the entire MDR (approximately 347 kb) has been sequenced, and transcribed regions have been identified by exon trapping, EST-based full-length complementary DNA cloning, database homology searches, and computer-assisted gene prediction analyses. The MDR contains 2 pseudogenes and 3 transcribed genes: CAR, encoding a putative RING-finger containing protein; 1B4/Leu2, generating noncoding transcripts; and EST70/Leu1, probably representing another noncoding gene (longest open reading frame of 78 codons). These genes have been sequenced in 20 B-CLL cases with 13q14 hemizygous deletion, and no mutations were found. Moreover, no somatic variants were found in the entire MDR analyzed for nucleotide substitutions by a combination of direct sequencing and fluorescence-assisted mismatch analysis in 5 B-CLL cases displaying 13q14-monoallelic deletion. The nondeleted allele of the CAR and EST70/Leu1 genes was expressed in B-CLL specimens, including those with monoallelic loss, whereas no expression of 1B4/Leu2 was detectable in B-CLL, regardless of the 13q14 status. These results indicate that allelic loss and mutation of a gene within the MDR is an unlikely pathogenetic mechanism for B-CLL. However, haplo-insufficiency of one of the identified genes may contribute to tumorigenesis. (Blood. 2001;97:2098-2104)

Animals↗
PubMed2001

Quality of life in ALS is maintained as physical function declines.

OBJECTIVES: To study patients with ALS to determine how physical function, quality of life (QOL), and spirituality or religiousness change over time, and what relationship these changes have to one another. METHODS: Sixty patients with ALS were studied prospectively. They were assessed at baseline, 3 months, and 6 months, using questionnaires designed to measure general quality of life (McGill Quality of Life questionnaire), religiosity (Idler Index of Religiosity), ALS-specific health-related quality of life (SIP/ALS-19), and ALS-specific function (ALS functional rating scale). RESULTS: A two-way repeated measures multivariate analysis of variance revealed that both the passage of time and the specific QOL scales used were factors in predicting patient quality of life (F[1, 59]= 9.87, p < 0.003 and F[3, 177]= 16.90, p < 0.001) Despite a progressive decline in physical function as measured by the ALS-specific function score, the general QOL and religiosity scores changed little. In contrast, the ALS-specific health-related QOL score declined in parallel with the ALS-specific function score. CONCLUSIONS: QOL in patients with ALS appears to be independent of physical function, which agrees with a previous cross-sectional study. The ALS-specific health-related QOL score is primarily a measure of physical function. QOL instruments that assess spiritual, religious, and psychological factors produce different results than those obtained using measures of physical function alone.

Adult↗
PubMed2001

[Intima-media thickness in healthy probands without risk factors for arteriosclerosis].

BACKGROUND AND OBJECTIVE: Ultrasound examination of the intima-media thickness (IMT) is a well accepted, highly reproducible method for the evaluation of early atherosclerosis. However, for the exact interpretation of these measurements reference values for IMT should be determined. The present work provides for the first time normal values for IMT of the common carotid artery and the arteries of the lower limbs (common femoral, superficial and popliteal arteries) in a German population of healthy subjects without risk factors. SUBJECTS AND METHODS: A total of 112 subjects (50 men, 62 women), aged 40 to 70, were examined, according to the following inclusion criteria: no diabetes or marked elevation of postprandial plasma glucose; non-smokers; no hypertension, obesity, dys/hyperlipidaemia or albuminuria; no history of coronary heart disease, stroke and peripheral arterial occlusion. IMT was measured and standardized by the method of Pignoli. Total cholesterol, triglycerides, HDL-cholesterol, HbA1c, plasma glucose (fasting and postprandial) and albuminuria were examined by routine methods. RESULTS: The mean values of double measurements bilaterally in the distal part of the common carotid artery in men were 0.79 (0.73 ... 0.84) mm (40-54 years) and 0.87 (0.81 ... 0.93) mm (55-70 years). In women the values were: -0.70 (0.67 ... 0.75) mm and 0.82 (0.75 ... 0.90) mm, resp. In the group aged 40-54 years the men showed significantly higher IMT of all examined vessels in comparison to the women. In the group aged 55-70 years somewhat higher IMT of the common carotid artery and significantly higher IMT of the arteries of the lower extremity were observed in men. In multivariate analysis age was found to be a significant determinant of IMT of all examined vessels. CONCLUSION: Intima-media thickening of the common carotid artery in men aged 40-70 years is to be accepted if a single measurement of IMT exceeds > or = 1 mm. For women, aged 40-54 years, IMT is defined as pathological if one IMT is above 0.85 mm, and for those aged 55-70 years if IMT exceeds 1 mm.

Adult↗
PubMed2001

In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor.

Clinically, dexamethasone is known to reduce cerebral edema. To further investigate the mechanism of this neuroprotection, an in vitro model of brain-derived microvessel endothelial cells (BME cells) was used to investigate the effect of dexamethasone on hypoxia-induced hyperpermeability. Furthermore, the expression of vascular endothelial growth factor (VEGF), which is known to be the mediator of hypoxia-induced hyperpermeability, was evaluated. Dexamethasone (40 microg/ml=100 microM) decreased hypoxia-induced permeability and VEGF expression significantly during time periods of more than 3 h. The time dependence of the dexamethasone effect correlated with a changed mechanism by which hypoxia induced VEGF expression. This was deduced because hypoxia-induced hyperpermeability and VEGF mRNA level were decreased in the presence of an antisense oligonucleotide coding for a region which binds a mRNA stabilizing protein, but only up to 3 h of hypoxia. Furthermore, during this time period the half-life of VEGF mRNA was increased. Results suggest that dexamethasone only decreases transcriptional-induced VEGF expression and that this may be related to the efficacy of dexamethasone to treat brain edema.

Animals↗
PubMed2001

Mass-spectrometry-linked screening of protein fractions for enzymatic activities--a tool for functional genomics.

A simple and rapid strategy is described to screen protein fractions for defined enzymatic activity. A protein fraction from a porcine kidney extract was immobilized by covalent coupling to activated affinity beads. The immobilized proteins were incubated with probes specific for different enzyme activities. The reaction products were analyzed by matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry. The MALDI spectra indicate the presence of 5'-nucleotidase, phosphatase, kinase, glutathione reductase, and renin activities in the kidney protein extract. Furthermore, the method can be used to screen for inhibitors of enzymatic reactions. The method is adaptable to high-throughput sample handling and automated mass spectrometric analysis and therefore suited for functional genomics.

Animals↗
PubMed2001

Interaction of vibrational and visual cues in parasitoid host location.

Female parasitoids are guided by multisensory information during host finding. Individual cues are used in an interactive or a hierarchical manner according to the relative importance on the spatial scale of their effect. Unlike most studies that concentrate on single cues, the present paper investigates the interaction of two physical cues. The interaction of mechanosensory and visual cues was studied in the pupal parasitoid Pimpla turionellae (Hymenoptera: Ichneumonidae). This species uses, amongst other senses, vibrational sounding (echolocation in a solid substrate) to find its mainly endophytic hosts. Location and frequency of ovipositor insertions were scored on cylindrical plant stem models with single or combined cues. Single-cue experiments show that parasitoids use both visual and mechanosensory cues and achieve a similar precision of host location with either cue. The combination of vision and vibrational sounding increased the precision of host location by a factor of approximately two to three. We conclude that the two senses interact, resulting in an additive accuracy. Neither the visual nor the mechanosensory cue was favored when offered adjacent to each other on the same stem model. On the investigated spatial scale, both physical cues are used and seem to be equally important for host location in this species.

Animals↗
PubMed2001

Giant bronchial carcinoid tumors: a multidisciplinary approach.

BACKGROUND: Bronchial carcinoid tumors account for approximately 2% of all lung tumors. Although they were considered benign lesions, they are now categorized malignant, occasionally with poor prognosis. The clinical symptoms can be highly variable and are often present for many years before diagnosis. Whereas some carcinoids are entirely asymptomatic, others are accompanied by carcinoid or paraneoplastic syndromes. METHODS: We describe the multidisciplinary management of a 34-year-old female patient with a massive actively secreting bronchial carcinoid tumor of the right lung. Furthermore, we provide a review of the literature regarding the operative treatment and the perioperative management of pulmonary carcinoid tumors with respect to surgical, anesthetic, radiologic, and pathologic considerations. RESULTS: In the reported case, the first symptoms were chronic watery diarrhea, skin flushing, progressive shortness of breath, and increasing right shoulder pain. When the patient initially presented at our institution, the tumor had already reached an enormous size and it involved the right and left atrium as well as the atrial septum. Using an evidence-based, multidisciplinary approach the patient was treated successfully with extended surgical resection. CONCLUSIONS: Carcinoid tumors are potentially curable even if they reach a significant size and thus an aggressive strategy is warranted. The management of such cases requires careful investigation, planning, and treatment with collaborative expertise provided by a multidisciplinary team. We demonstrated that this approach can lead to a favorable outcome in what first appeared to be a formidable and unresectable tumor.

Adult↗
PubMed2001

Raffinose improves 24-hour lung preservation in low potassium dextran glucose solution: a histologic and ultrastructural analysis.

BACKGROUND: We have previously shown that the addition of raffinose to low potassium dextran (LPD) preservation solution improves transplanted rat lung function after 24 hours of storage. The mechanisms by which raffinose acts are unclear. The aim of this study was to examine the histologic and ultrastructural correlates of this enhanced pulmonary function after preservation with raffinose. METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C. Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in postpreservation edema were determined. In addition, lungs were flushed with a trypan blue solution to quantify cell death, and examined using both light and electron microscopy. RESULTS: The LPD lungs gained significantly more weight (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure, whereas LPD lungs showed a decreased number of intact type II pneumocytes and significant cellular necrosis. Interstitial and alveolar edema with interstitial macrophage infiltration was also observed. Alveolar capillaries were collapsed. In contrast, raffinose-LPD lungs showed only mild alterations such as minimal interstitial edematous expansion, fewer damaged cells, and minimal capillary injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts during preservation, which explains the previously documented improved function. This simple modification of LPD with raffinose may provide clinical benefit in extended pulmonary preservation.

Animals↗
PubMed2001

Localization of a new neutralizing epitope on the mumps virus hemagglutinin-neuraminidase protein.

Four protein fragments which span the entire hemagglutinin-neuraminidase protein (HN) of mumps virus were expressed in HeLa cells and cell extracts were tested for their capability to induce neutralizing antibodies in mice. Fragment HN3 (aa 213-372) was able to induce the production of hemagglutination-inhibiting and neutralizing antibodies. When a subfragment of HN3, the synthetic peptide NSTLGVKSAREF (aa 329-340 of HN) was used for immunization, hemagglutination-inhibiting and neutralizing antibodies against mumps wild type virus but not against the Urabe Am9 vaccine virus were raised. The peptide could, therefore, contain a new epitope, which may be critical for protective host humoral immune response.

Animals↗
PubMed2001

Glial cells mediate target layer selection of retinal axons in the developing visual system of Drosophila.

In the fly visual system, each class of photoreceptor neurons (R cells) projects to a different synaptic layer in the brain. R1-R6 axons terminate in the lamina, while R7 and R8 axons pass through the lamina and stop in the medulla. As R cell axons enter the lamina, they encounter both glial cells and neurons. The cellular requirement for R1-R6 targeting was determined using loss-of-function mutations affecting different cell types in the lamina. nonstop (encoding a ubiquitin-specific protease) is required for glial cell development and hedgehog for neuronal development. Removal of glial cells but not neurons disrupts R1-R6 targeting. We propose that glial cells provide the initial stop signal promoting growth cone termination in the lamina. These findings uncover a novel function for neuron-glial interactions in regulating target specificity.

Amino Acid Sequence↗
PubMed2001

Coronary artery bypass grafting surgery without the routine application of blood products: Is it feasible?

OBJECTIVE: Fresh frozen plasma (FFP) substitution is currently standard practise in cardiac surgery. In this study we investigate whether elective coronary artery bypass grafting (CABG) surgery is feasible without the administration of blood products compared to the substitution of fresh frozen plasma. PATIENTS AND METHODS: From September 1997 to April 1998, 120 consecutive patients underwent CABG surgery at our institution. In the FFP group patients (n=60; men, n=43; women, n=17; mean age: 64+/-8.5 years) received 4 units of fresh frozen plasma (FFP) intraoperatively. In comparison, patients in the control group (n=60; men, n=44; women, n=16; mean age: 65+/-7.5 years) did not receive FFP. Main endpoints included perioperative hematologic parameters, blood loss, and the amount of blood products that were administered. RESULTS: Intraoperatively, the substitution of packed red blood cells (pRBC) in the FFP group was significantly higher compared with the control group (0.63+/-0.94 units/patient vs. 0.12+/-0.38 units/patient, P=0.001). Postoperatively, patients in the FFP group required significantly more pRBC products than patients in the control group (0.78+/-1.09 vs. 0.42+/-0.77, P=0.024). There were no significant differences in hemoglobin (FFP group: 99+/-11.1 g/dl; control group: 105+/-13.5 g/dl) and hematocrit levels (FFP group: 30+/-3.39%; control group: 32+/-4%). Also, no significant differences regarding the postoperative blood loss was observed between groups (FFP group: 588+/-224 vs. control group: 576+/-272 ml/24 h). CONCLUSIONS: This study clearly demonstrates that the avoidance of routine intraoperative FFP administration does not lead to an increase in blood loss postoperatively compared to patients that received FFPs. Furthermore, we did not observe increased requirements for postoperative FFP infusion in patients that did not receive FFPs intraoperatively.

Aged↗
PubMed2001

Long-term survival after multiple resections of a fibrosarcoma involving the lung and chest wall.

We report on the case of a 61-year-old male patient who developed a giant fibrosarcoma involving both the lung and chest wall. This patient underwent three extended resections including the chest wall in each case. Radiotherapy was administered after the last resection, when the tumor was obviously not completely removed. The patient lives a normal life with no signs of recurrence 5 years after his last resection. Multiple extended resections of large and aggressive sarcomas can result in long-term survival, with good quality of life, in adequately selected patients.

Fibrosarcoma↗
PubMed2001

Ultraviolet-radiation-induced keratinocyte apoptosis in C1q-deficient mice.

Exposure to ultraviolet B radiation is an important trigger of both systemic and cutaneous disease flares in individuals with systemic lupus erythematosus. More than 90% of individuals with homozygous C1q deficiency develop a systemic-lupus-erythematosus-like illness, which is typically associated with a severe photosensitive rash. Apoptotic, human keratinocytes have been shown in vitro to bind C1q, in the absence of antibody. These observations, together with the hypothesis that a major source of the autoantigens driving the immune response in systemic lupus erythematosus comes from apoptotic cells, led us to investigate the effects of murine C1q deficiency on ultraviolet-radiation-induced keratinocyte apoptosis in vivo. In this work, we demonstrated C1q binding to apoptotic murine keratinocytes in vitro and showed for the first time that C1q is also present on sunburn cells in vivo. In addition to C1q, we detected C3 deposition on sunburn cells in both wild-type and C1q-deficient mice, suggesting activation of the alternative pathway. Following acute ultraviolet exposure in vivo, no difference in the rate of clearance of sunburn cells was found in C1q-deficient mice from three different genetic backgrounds, compared with strain-matched wild-type controls. Furthermore, chronic ultraviolet exposure did not result in the production of autoantibodies or the development of glomerulonephritis. Our findings suggest that C1q does not play a critical role in the physiologic clearance of apoptotic murine keratinocytes in vivo.

Acute Disease↗
PubMed2001

Apolipoprotein E polymorphism and lithogenic factors in gallbladder bile.

BACKGROUND: Associations between the polymorphism of apolipoprotein E, which plays an important role in cholesterol metabolism and cholesterol gallstone formation, have been reported recently. Patients with the apo E4 isoform showed increased numbers and cholesterol contents of their stones, a higher frequency of cholesterol crystals in bile, increased susceptibility to gallstone fragmentation by extracorporeal shock-wave lithotripsy and an increase in recurrence rate after dissolution. A recent study, however, showed that fast cholesterol crystallization in bile is associated with multiple stones but not with apo E4. Therefore the mechanism for an increased risk of gallstone formation in patients with the apo E4 isoform still remains under debate. DESIGN: To clarify this issue we investigated 37 patients with gallstones (10 with the apo E4 allele and 27 without the allele). Gallbladder biles were examined for total cholesterol and other lipids, cholesterol saturation index, crystal observation time, crystal mass, total protein and mucin. Moreover, number of gallstones and cholesterol in gallstones was compared in both groups. RESULTS: The crystal observation time (2.5 vs. 2.0 days, median) and the cholesterol saturation index (1.34 +/- 0.45 vs. 1.43 +/- 0.74) did not differ significantly between the apo E4 and the non apo E4 group. Total biliary lipids (11.6 +/- 3.8 vs. 9.3 +/- 3.9 g 100 mL-1, P = 0.126) and total biliary cholesterol (21.8 +/- 9.7 vs. 15.7 +/- 7 mmol L-1, P = 0.067) tended to be elevated in the apo E4 group. Crystal mass (3.60 +/- 4.10 vs. 2.38 +/- 2.70 mmol L-1), biliary total protein (8.6 +/- 3.5 vs. 8.3 +/- 6.6 mg mL-1) and mucin (0.55 +/- 0.38 vs. 0.66 +/- 0.67 mg mL-1), number (solitary/multiple) of gallstones and cholesterol in gallstones were not different in both groups of patients. CONCLUSIONS: In comparison to the non apo E4 patients the apo E4 group showed a trend to elevated biliary cholesterol whereas crystal observation time, cholesterol saturation index, crystal mass, number of gallstones, cholesterol content of gallstones and total protein and mucin were not different. These findings do not suggest an association of the apo E isoform and the formation of cholesterol gallstones

Apolipoproteins E↗