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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 163 records · Page 9Linked to original sources
PubMed1998

Prion protein expression in muscle cells and toxicity of a prion protein fragment.

The prion protein (PrP) is a cell surface glycoprotein normally associated with neurones. Expression of the prion protein in cultured mouse myoblasts and myotubes suggests that the prion protein may play a physiological role in skeletal muscle. When myotubes differentiate from myoblasts prion protein expression is upregulated. Accompanying this increase is an upregulation of Cu/Zn superoxide dismutase (SOD-1) in myotubes. Muscle cells derived from mice deficient in cellular PrP (PrPc) show little increase in SOD-1 after differentiation from myoblasts to myotubes. Myoblasts and myotubes are resistant to the toxicity of a neurotoxic prion protein peptide (PrP106-126). However, in the presence of murine microglia, PrP106-126 causes a reduction in cell number. This effect is greater on myotubes than myoblasts. Even in the presence of microglia PrP106-126 is not toxic to muscle cells derived from PrP-deficient mice. Our results suggest that PrPc expression is associated with regulation of cellular resistance to oxidative stress in skeletal muscle.

Animals↗
PubMed1998

The surgical anatomy of the nasolabial fold.

OBJECTIVE: The purpose of this cadaver dissection study was to investigate the anatomy of the nasolabial fold with a view to explaining the problems of surgical softening or elimination of the fold. STUDY DESIGN: Ten formalin-fixed cadavers and 6 fresh-frozen cadavers were used for this study. In 12 cadavers (8 formalin-fixed, 4 fresh-frozen), the nasolabial fold was sectioned at right angles to the fold for histologic examination, and in 4 cadavers (2 formalin-fixed, 2 fresh-frozen) the epithelium was dissected off the fold to allow for more detailed gross examination of the underlying musculature. RESULTS: The fold was clearly identified on 14 of the cadavers but was indistinct on 2 on gross examination. Beneath the fold were 2 muscle bundles. The more superficial muscle runs parallel to the fold whereas a deeper muscle runs at right angles to it. The buccal fat pad lies above the fold and appears to be retained by horizontal septae in the fat pad and also by the musculature of the fold. Cadavers showing a poorly defined nasolabial fold had fewer muscle bundles to support the fat and fewer fibrous septae running through the fat. CONCLUSIONS: The nasolabial fold is defined by structures that support the buccal fat pad and hold it above the fold. This appears to be a combination of muscle bundles that run both across and parallel to the fold and also by fibrous septae supporting the fat pad. This has implications for the development of surgical procedures to soften or eliminate the fold, which must separate the muscles from the dermis of the fold and allow the fat to descend and soften the fold.

Adipose Tissue↗
PubMed1998

Effects of copper on survival of prion protein knockout neurons and glia.

The N-terminal region of the prion protein (PrP) contains an octameric repeat region suggested to bind copper. A 32-amino acid peptide (PrPOcta) based on this region in the protein was tested for its effects on cultured cerebellar cells. Cerebellar cells from mice deficient in cellular PrP (Prnp0/0 mice) are more sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes the survival of Prnp0/0 cerebellar cells. However, PrPOcta also reduces the toxicity of CuSO4 on cerebellar cells and abolishes the difference in increased sensitivity of Prnp0/0 cells to both copper toxicity and also oxidative stress from xanthine oxidase. PrPOcta does not promote the survival or proliferation of astrocytes or microglia. The survival-promoting effects of PrPOcta on neurons may be due to its ability to effectively chelate copper. The octameric repeat region of PrP may represent a functional domain of the native protein.

Animals↗
PubMed1998

Dialysis neutropenia: the role of the cytoskeleton.

Dialysis neutropenia is the result of pulmonary sequestration of neutrophils after complement activation by the dialyzer membrane. Increased expression of neutrophil adhesion receptors, such as CD11b/CD18, suggests that neutrophil adhesion to the capillary endothelium is a possible mechanism. An alternative hypothesis is that the complement fragment C5a modulates neutrophil mechanical properties via the cytoskeleton-largely filamentous actin (F-actin)-stiffening them and thereby slowing their passage through the pulmonary capillaries. To investigate this hypothesis, we developed an assay to measure the F-actin content of neutrophils in whole blood using flow cytometry and the stain NBD-phallacidin. We measured neutrophil F-actin content during hemodialysis of patients with polysulfone (N = 6), Hemophan (N = 6), and Cuprophan membranes sterilized with either ethylene oxide (N = 5) or steam (N = 6). Cell counts, neutrophil and monocyte CD11b expression and plasma C5a concentrations were also measured. The results confirm the strong relationship between the degree of neutropenia, increases in CD11b expression and plasma C5a levels reported by previous researchers. Modulation of the F-actin content of neutrophils was also strongly related to C5a levels, indicating that the neutrophil cytoskeleton is active during dialysis. Modeling of cell counts suggests that with Cuprophan a substantial fraction of neutrophils and monocytes are sequestered before they even pass through the dialyzer, suggesting some form of systemic activation of these cells. Evidence for systemic activation was also seen in measurements of F-actin content, but not CD11b expression, a finding that strengthens the case for the involvement of the cytoskeleton in dialysis neutropenia.

Actins↗
PubMed1998

Expression of G1-->S transition regulatory molecules in human urothelial cancer.

Growth of cancer cells is characterized by accelerated passage through the cell cycle, which is often caused by deregulation of the G1-->S transition. In this study the expression of G1-->S transition regulatory molecules was analyzed in 32 transitional cell carcinoma specimens and fifteen normal tissues obtained by cystectomy or nephroureterectomy of mainly locally advanced tumors, as well as six bladder cancer cell lines. Expression of mRNAs for cyclins D1 and D2 and cyclin-dependent kinases (CDK) 2 and 4 was investigated by quantitative reverse transcription-polymerase chain reaction. Overexpression of cyclin D1 compared to normal mucosa was observed in 3 tumors (9.4%), but in neither of the cell lines. All tumors with overexpression were moderately differentiated (G2) pT1 or pT2 tumors, and thus among the less advanced specimens. Cyclin D2 was not expressed in normal bladder mucosa or in tumors. The expression of CDK4 mRNA varied within the same range in mucosa, tumors, and cell lines. CDK2 mRNA expression varied more strongly and was diminished in individual tumors and in four cell lines. It is concluded that cyclin D1 overexpression can play an important role in the early stage of urothelial tumorigenesis, driving cell proliferation. Ectopic expression of cyclin D2 or amplification of CDK4 does not occur at a significant frequency in urothelial carcinomas. Different expression patterns of cyclin D1 and CDK2 indicate heterogeneity in the mechanisms of G1-->S transition deregulation in individual bladder tumors which may elicit differences in their biological and clinical behavior.

Aged↗
PubMed1998

Review article: Antioxidant micronutrients and gastric cancer.

A review of the literature reveals a very consistent association between gastric cancer risk and low intake of fruits and vegetables. This observation has been documented in many countries with different epidemiological techniques: interpopulation correlations, case-control studies and follow up of several cohorts. Low serum levels of beta-carotene and alpha-tocopherol, but not vitamin C, have been reported in patients with gastric dysplasia. Helicobacter pylori infection has been associated with lower concentrations of vitamin C in the gastric juice. Detailed studies in Colombia and New Orleans have shown a gradient towards lower concentration in the gastric juice and lower ratios of gastric juice to serum concentration of vitamin C in the following comparisons: i) lower vs. higher gastric cancer risk; ii) mild vs. advanced gastric precancerous histopathologic lesions; iii) mild vs. advanced degree of atrophy; iv) mild vs. advanced damage to the surface gastric epithelium; v) lower vs. higher gastric pH. Such a gradient is not observed for serum levels of vitamin C. The role of infection with H. pylori in the metabolism of ascorbic acid is discussed, as well as the possible role of ascorbic acid in inhibiting cell damage by reactive oxygen species.

Antioxidants↗
PubMed1998

Diagnostic tests for bacterial infection from birth to 90 days--a systematic review.

AIM: To determine the clinical value of common diagnostic tests for bacterial infection in early life. METHODS: A Medline search (1966-95) was undertaken to identify studies that reported the assessment of a diagnostic "test," predicting the presence or absence of bacterial infection in infants up to 90 days of age. The quality of each selected study was assessed using defined criteria. Data were extracted twice to minimise errors. RESULTS: Six hundred and seventy articles were identified. Two independent investigators agreed that 194 studies met the inclusion criteria (kappa = 0.85), 52 of which met primary quality criteria; 23 studies reported data on (a) haematological indices, (b) C reactive protein evaluation, and (c) surface swab assessment. For haematological indices, the likelihood ratios for individual tests ranged from 20.4 (95% confidence interval 7.3 to 56.8) for a white cell count < 7000/mm3 to 0.12 (0.04 to 0.37) for an immature:total (I:T) white cell ratio < 0.2. For C reactive protein evaluation, the likelihood ratios ranged from 12.56 (0.79 to 199.10) for a value of > 6 mg/l to 0.22 (0.08 to 0.65) for a negative value. For surface swab assessment, the likelihood ratios ranged from 33.6 (2.1 to 519.8) for a positive gastric aspirate culture to 0.08 (0.006 to 1.12) for microscopy of ear swab material that did not show any neutrophils. Likelihood ratios for combinations of these individual tests ranged from 10.17 (3.64 to 28.41) to 0.47 (0.22 to 1.00). CONCLUSIONS: The methodological quality of studies assessing the accuracy of diagnostic tests is generally poor. Even in rigorous studies, the reported accuracy of the tests varies enormously and they are of limited value in the diagnosis of infection in this population.

Bacterial Infections↗
PubMed1998

A placebo-controlled randomized trial of antithrombin therapy in neonatal respiratory distress syndrome.

Neonatal respiratory distress syndrome (RDS) is associated with decreased plasma activity of antithrombin (AT) and increased formation of thrombin. We tested whether AT reduces thrombin formation, improves gas exchange, and decreases the duration of mechanical ventilation and supplemental oxygen. One hundred twenty-two infants were randomized to pasteurized AT concentrate or to placebo. Two ml/kg (equivalent to 100 IU AT/kg) were followed by 1 ml/kg (50 IU/kg) every 6 h for 48 h. Outcome measures included plasma AT activity, thrombin-AT (TAT) complex, prothrombin fragment (F1+2), the ratio of arterial to alveolar oxygen pressure [(a/A)PO2], and the ventilator efficiency index (VEI). In the AT group (n = 61), mean (SD) birth weight was 1,198 (301) g, mean (SD) gestational age (GA) was 28.3 (2.0) wk, 54% were male. In the placebo group (n = 61), mean (SD) birth weight was 1,201 (315) g, mean (SD) GA was 28.8 (2. 3) wk, 51% were male. In treated infants, AT activity was raised to means of 1.69 and 2.25 U/ml at 24 and 48 h, respectively. Corresponding means in control infants were 0.37 and 0.44 U/ml (p < 0.0001). F1+2, but not TAT, was significantly reduced by AT (p = 0. 004). VEI and (a/A)PO2 were similar in both groups throughout the first week of life. Median days receiving mechanical ventilation were 7.1 (AT) versus 4.8 (placebo), p = 0.0014. Median days receiving supplemental oxygen were 7.9 (AT) versus 5.5 (placebo), p < 0.0001. There were seven (11.5%) deaths in the AT group and three (4.9%) deaths in the placebo group. We conclude that treatment with AT cannot be recommended in premature infants with RDS.

Antithrombin III↗
PubMed1998

Heparin improves gas exchange during experimental acute lung injury in newborn piglets.

Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).

Analysis of Variance↗
PubMed1998

Centronuclear myopathy. Histopathological aspects in ten patients with childhood onset.

Centronuclear myopathy is a rare congenital myopathy. According to the period of onset of signs and symptoms and the degree of muscular involvement three clinical forms are distinguished: severe neonatal; childhood onset; and adult onset. We describe herein the muscle biopsy findings of ten patients with the childhood onset form of the disease including three cases with ultrastructural study. The biopsies disclosed increased nuclear centralization that varied from 25 to 90% of the fibers, type I predominance, great variability in fiber diameters, involvement in the internal fiber's architecture, and focal areas of myofilament disorganization. The main histopathologic differential diagnoses included type I fiber predominance, congenital fiber type disproportion, and myotonic dystrophy. The histologic abnormalities in centronuclear myopathy may be due to an arrest of maturation on the fetal myotubular stage. The cause of this arrest remains elusive.

Adolescent↗
PubMed1998

Histochemical study of the skeletal muscle in children with chronic renal failure in dialysis treatment.

Among the modifications occurring in the uremic organism, in addition to the consequences of dialysis, myopathy and peripheral neuropathy are very significant. Children are particularly affected, as their growth and development are jeopardized. Histochemistry of muscular biopsy was used to study eighteen children with end-stage renal failure under dialysis during a ten-month period. According to our results, the skeletal muscular tissue presented the following types of alterations: atrophy, type grouping, lipidosis, glycogen depletion and mitochondrial proliferation.

Adolescent↗
PubMed1998

Characterization of the aminomethylchroman derivative BAY x 3702 as a highly potent 5-hydroxytryptamine1A receptor agonist.

The aminomethylchroman derivative BAY x 3702 (R-(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d] isothiazolone hydrochloride) is a new high affinity 5-hydroxytryptamine (5-HT)1A receptor ligand [calf hippocampus: Ki: 0.19 nM; reference compounds 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and ipsapirone: 0.98 and 2.56, respectively; rat cortex: 0.24 nM; rat hippocampus: 0.58 nM; human cortex and recombinant 5-HT1A receptors: 0.25 and 0.4 nM, respectively]. BAY x 3702 bound also with relatively high to moderate affinity to the following receptors: alpha-1 and alpha-2 adrenergic (Ki: 6 and 7 nM, respectively); 5-HT7- and 5-HT1D (7 and 36 nM); dopamine D2- and D4 (48 and 91 nM); sigma sites (176 nM) and 5-HT2C (310 nM); others: > 10 microM, as obtained in more than 50 different binding assays. In the forskolin-stimulated adenylate cyclase assay in rat hippocampal tissue, a model of postsynaptic 5-HT1A receptor function, BAY x 3702 was a potent 5-HT1A receptor full agonist (IC50: 1.9 nM; 8-OH-DPAT: 25.3 nM, full agonist; ipsapirone: partial agonist) and its effects could be completely blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide trihydrochloride (WAY-100635). At those receptors where BAY x 3702 bound with lower affinity, the compound appeared to be either an agonist (5-HT1D receptors) or an antagonist (alpha-1, alpha-2 and D2 receptors). In a rat brain slice preparation containing the dorsal raphe nucleus (DRN), a model of somatodendritic 5-HT1A receptor function, BAY x 3702 inhibited potently (1 nM) neuronal firing. Also in vivo, BAY x 3702 (0.5 microgram/kg, i.v.) was found to suppress 5-HT neuronal firing in the DRN of anesthetized rats. In both electrophysiological assays BAY x 3702 was more potent than 8-OH-DPAT and ipsapirone; the potency difference being about 1 and 2 orders of magnitude, respectively. In rats trained to discriminate 8-OH-DPAT (0.1 mg/kg, i.p.) in a drug discrimination procedure, complete generalization was obtained with BAY x 3702 (ED50: 0.022 mg/kg, i.p. and 0.38 mg/kg, p.o.; 8-OH-DPAT: 0.028 mg/kg, i.p. and ipsapirone: 0.44 mg/kg, i.p.). In the rat hypothermia model BAY x 3702 induced a WAY-100635-reversible effect and the compound had a higher potency and intrinsic activity than 8-OH-DPAT and ipsapirone (ED50: 0.25 mg/kg, i.p. and 5.4 mg/kg, p.o., respectively; 8-OH-DPAT: 1.1 mg/kg, i.p. and ipsapirone: 6.2 mg/kg, i.p.). BAY x 3702 induced a stimulation of plasma ACTH levels in the rat; the effect being again more pronounced than that of ipsapirone (ED50: 7.5 and 25.3 mg/kg, p.o., respectively). It is concluded that BAY x 3702 is a relatively selective 5-HT1A receptor agonist with high potency and intrinsic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

[Dynamic splinting after flexor tendon injuries of the hand in childhood].

Ninety severed flexor tendons were repaired in 24 boys and 14 girls in a four-year-period at the Department of Pediatric Surgery in Graz. Mean age was 4.9 years. In 16 patients (42%) additional lesions were found. Direct repair was performed with modified techniques of Kirchmayr (23) or Kleinert (8). In four fingers, flexor tendon reconstructions were carried out. Postoperatively, the dynamic Kleinert splint was used for early nonresistive motion, beginning on average on the second postoperative day. Intensive training of motion was performed in physiotherapeutic sessions during a mean period of five months, postoperatively. In five cases tenolysis was performed; in one case a rupture of a sutured tendon had to be corrected. 27 patients (71%) with 42 injured fingers were followed-up on average 2.7 years after the operation. In accordance with the Buck-Gramcko classification, very good results were achieved in 37 cases (88%), and a poor result in one patient (2%). Atraumatic technique, dynamic splinting, consequent physiotherapeutic training by experienced physiotherapists, and well informed parents will yield excellent results after flexor tendon repair in the paediatric age group.

Child↗
PubMed1998

[Endoscopic interventions in the tracheobronchial system].

Therapeutic bronchoscopy is widely used in the treatment of airway stenosis, fistula, and pulmonary bleeding. Recanalisation of tracheobronchial stenoses can be treated by Nd: YAG-laser or stent implantation. While the use of laser irradiation is limited to intraluminal obstruction, stenting is also effective in stenoses due to extraluminal compression. Stent implantation has also become the method of choice in the treatment of tracheobronchial fistulas. A more specific strategy in the treatment of malignant lesions is photodynamic therapy. By use of photosensitizers and subsequent irradiation tumor cells can be destroyed selectively. Gene therapy represents a promising new approach in tumor therapy. After retrovirus-mediated gene transfer of a suppressor gene an increase of tumor cell apoptosis was observed. Altogether interventional pneumology has experienced substantial enlargement of therapeutic possibilities.

Bronchial Diseases↗
PubMed1997

Effects of metrifonate on radial arm maze acquisition in middle-aged rats.

The efficacy of metrifonate, a well-tolerated cholinesterase (ChE) inhibitor, in attenuating the normal aging- and corticosterone-induced impairments of radial maze performance of rats was compared. Middle-aged Fischer 344 rats were screened for their spatial orientation performance in the Morris water escape task. Good and bad performers were selected: good performers (N= 22) were treated with subcutaneous sustained-release corticosterone pellets, resulting in hippocampal cell damage and impaired spatial orientation in the radial maze; age-induced bad performers (N = 20) were tested without additional pharmacological intervention. Metrifonate (MFT), administered daily during radial maze testing, 30 min before training, at a dose of 15 mg/kg p.o., facilitated the acquisition of the task in age-impaired rats, but not in corticosterone-impaired rats.

Age Factors↗
PubMed1997

Conversion of cysteine to formylglycine: a protein modification in the endoplasmic reticulum.

In sulfatases a Calpha-formylglycine residue is found at a position where their cDNA sequences predict a cysteine residue. In multiple sulfatase deficiency, an inherited lysosomal storage disorder, catalytically inactive sulfatases are synthesized which retain the cysteine residue, indicating that the Calpha-formylglycine residue is required for sulfatase activity. Using in vitro translation in the absence or presence of transport competent microsomes we found that newly synthesized sulfatase polypeptides carry a cysteine residue and that the oxidation of its thiol group to an aldehyde is catalyzed in the endoplasmic reticulum. A linear sequence of 16 residues surrounding the Cys-69 in arylsulfatase A is sufficient to direct the oxidation. This novel protein modification occurs after or at a late stage of cotranslational protein translocation into the endoplasmic reticulum when the polypeptide is not yet folded to its native structure.

Alanine↗
PubMed1997

Oxygen-independent oxidases: a new class of enzymes for application in diagnostics.

Some years ago, a new class of enzymes, the quinoproteins, were described. They are oxygen-independent oxidases. Common to this class of enzymes is the content of pyrroloquinoline quinone, which acts as a redox centre. These enzymes can transfer electrons from substrates such as glucose to electron acceptors such as cytochromes. They do not transfer electrons to oxygen. This property is very interesting with respect to the use of these enzymes in clinical chemistry, especially in assays where oxygen may have an influence on the results. Several examples of newly designed tests including biosensors for glucose and cholesterol will be discussed. The application of this type of enzyme has led to diagnostic tests that are superior in performance and reliability of test results.

Biosensing Techniques↗