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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 379 records · Page 21Linked to original sources
PubMed1990

Targeting of a lysosomal membrane protein: a tyrosine-containing endocytosis signal in the cytoplasmic tail of lysosomal acid phosphatase is necessary and sufficient for targeting to lysosomes.

Lysosomal acid phosphatase (LAP) is synthesized as a transmembrane protein with a short carboxy-terminal cytoplasmic tail of 19 amino acids, and processed to a soluble protein after transport to lysosomes. Deletion of the membrane spanning domain and the cytoplasmic tail converts LAP to a secretory protein, while deletion of the cytoplasmic tail as well as substitution of tyrosine 413 within the cytoplasmic tail against phenylalanine causes accumulation at the cell surface. A chimeric polypeptide, in which the cytoplasmic tail of LAP was fused to the ectoplasmic and transmembrane domain of hemagglutinin is rapidly internalized and tyrosine 413 of the LAP tail is essential for internalization of the fusion protein. A chimeric polypeptide, in which the membrane spanning domain and cytoplasmic tail of LAP are fused to the ectoplasmic domain of the Mr 46 kd mannose 6-phosphate receptor, is rapidly transported to lysosomes, whereas wild type receptor is not transported to lysosomes. We conclude that a tyrosine containing endocytosis signal in the cytoplasmic tail of LAP is necessary and sufficient for targeting to lysosomes.

Acid Phosphatase↗
PubMed1990

Phosphorylation of microtubule-associated protein tau: identification of the site for Ca2(+)-calmodulin dependent kinase and relationship with tau phosphorylation in Alzheimer tangles.

The microtubule array in neuronal cells undergoes extensive growth, dynamics and rearrangements during neurite outgrowth. While little is known about how these changes are regulated, microtubule-associated proteins (MAPs) including tau protein are likely to perform an important role. Tau is one of the MAPs in mammalian brain. When isolated it is usually a mixture of several isoforms containing between 341 and 441 residues that arise from alternative splicing. Tau can be phosphorylated by several protein kinases. Phosphorylation at certain sites results in major structural and functional changes, as seen by changes in electrophoretic mobility, interaction with microtubules, molecular length and elasticity. Here we show that the sites of phosphorylation by four kinases (PKA, PKC, CK and CaMK) all lie in the C-terminal microtubule-binding half of tau, but only the phosphorylation by CaM kinase shows the pronounced shift in electrophoretic mobility characteristic for tau from Alzheimer neurofibrillary tangles. By using a combination of limited proteolysis, protein sequencing and protein engineering we show that a single phosphorylation site is responsible for this shift, located at Ser 405 in the C-terminal tail of the protein outside the region of internal repeats. Phosphorylation at this site not only reduces the electrophoretic mobility of tau, it also makes the protein long and stiff, as shown earlier. The site is likely to be phosphorylated in tau from Alzheimer neurofibrillary tangles.

Alzheimer Disease↗
PubMed1990

Muscle biopsy in AIDS and ARC: analysis of 50 patients.

We report a large spectrum of histological muscle abnormalities in 50 homosexual men with AIDS and ARC. We encountered moth-eaten fibers in 76%, angulated fibers in 76%, type groupings in 62%, type 2 fiber atrophy in 58%, mononuclear endomysial and/or perimysial and/or perivascular infiltrates in 36%, necrosis and phagocytosis in 30% and target fibers in 6%. Two patients showed vasculitis and two others showed perifascicular atrophy. On the whole, 96% of the biopsies showed substantial abnormalities. Muscle involvement in AIDS seems more common than previously suspected.

AIDS-Related Complex↗
PubMed1990

Desmin and actin associated with cytoplasmic bodies in skeletal muscle fibers: immunocytochemical and fine structural studies, with a note on unusual 18- to 20-nm filaments.

In a fine structural and immunocytochemical study, the latter performed on semithin sections of epoxy resin embedded skeletal muscle fibers, three types of cytoplasmic bodies were identified in a case of cytoplasmic body myopathy: (1) The first type, the classical type, showed a central core and a light halo with radiating actin filaments at the periphery. (2) The second type, the spheroid body was characterized by irregularly arranged granular masses associated with intermediate filaments. Desmin immunoreactivity occurred in the central and peripheral parts, where filaments of intermediate size were visualized by electron microscopy. Desmin immunoreactivity was noted also at the Z-bands of striated annulets, within areas of disordered myofibrils, such as sarcoplasmic masses, and in atrophic muscle fibers. (3) The third type of the cytoplasmic body was composed mainly of large masses of uneven granularity and electron density. The center of this type reacted to anti-actin antibody suggesting that the 5- to 6-nm filaments, which ultrastructurally proved to be a major component, were of the actin type. By contrast, neither intermediate filaments nor actin microfilaments were found by electron microscopy in cytoplasmic bodies in a second case where no immunoreaction to desmin or actin occurred. Anti-vimentin antibody stained only the cytoplasm of endomysial cells, but not the inclusion bodies. Some other, unusual inclusions with 18- to 20-nm tubulo-filamentous structures have to be distinguished from the various types of filaments in cytoplasmic bodies. It is concluded, that pleomorphism and heterogeneity of "cytoplasmic bodies" have to be taken into consideration when classifying cytoplasmic body myopathies.

Actins↗
PubMed1990

Indications for radioisotope bone scanning in staging of cervical cancer.

The total of 160 patients with newly diagnosed invasive cancer of the cervix had whole body radioisotope bone scanning during staging of their disease. 51 patients had cancer of the cervix stage I, 63 had stage II, 34 stage III and 12 stage IV (FIGO). Only in 8 of 160 patients did the bone scans indicate possible metastases and this was confirmed by X-ray examination in only one patient with stage IV disease and liver metastases. We conclude that patients with stage I and stage II carcinoma of the cervix do not need to have bone scans.

Bone Neoplasms↗
PubMed1990

Evaluation of phagocytic cell function in an ex vivo model of hemodialysis.

An ex vivo model of hemodialysis was used to evaluate the effect of dialysis membranes on phagocytic cell function. Blood was withdrawn continuously from healthy, non-uremic donors, heparinized, and pumped, single pass, through membrane modules under conditions which simulated normal dialysis conditions. The membrane modules contained membranes of cellulose, DEAE-substituted cellulose, or polysulfone. Blood was obtained from the module outlets for determination of complement activation, phagocyte elastase release, zymosan-induced phagocyte chemiluminescence, and monocyte interleukin-1 production. Significantly less complement activation occurred with the polysulfone and DEAE-substituted cellulose membranes than with cellulose membranes. Normal monocyte interleukin-1 production was not stimulated by any of the membranes used. In contrast, the cellulosic, but not the polysulfone, membranes primed the oxidative burst of the phagocytes and caused them to release elastase. DEAE-substituted cellulose had a lesser effect on elastase release than did cellulose and elastase release correlated significantly with the degree of complement activation. However, the correlation between complement activation and priming of phagocyte oxidative burst was weak, suggesting that membranes affect phagocyte oxidative metabolism through more than one mechanism. We conclude that some dialysis membranes stimulate the bacteriacidal functions of normal phagocytic cells, in part through complement-dependent mechanisms.

Humans↗
PubMed1990

The incidence of injuries in young people: I. Methodology and results of a collaborative study in Brazil, Chile, Cuba and Venezuela.

Injuries and accidents are acknowledged as leading causes of mortality among children and adolescents in the developing countries of the world. However, little is known of the extent of non-fatal injuries and of their potential risk factors. The Pan American Health Organization sponsored the first collaborative study to examine morbidity incidence in specified areas of four selected countries in Latin America, and to test the feasibility and practicality of the developed methodology for application in other regions of the world. The study subjects were injured children and adolescents (0-19 years of age) presenting at the study hospitals in the chosen urban centres, as well as injured that were surveyed in households in the catchment area of the hospitals. Falls constituted the most common (40-52%) cause of injury in all areas, and tended to occur in the younger age groups. Motor vehicle injuries were not as frequent (5-24%) as expected from mortality studies. Males outnumbered females 2:1. The home was the most frequent (37-57%) site of injuries, especially for younger ages. Few received medical care at the site of the injury or en route to a hospital, if they went at all. The results found are consistent with those found in other studies in the developed world. The study methodology provides initial valid information for investigating the injury situation in countries with limited resources.

Adolescent↗
PubMed1990

Respiratory response and pharmacokinetics of intravenous salbutamol in infants with bronchopulmonary dysplasia.

The effects of iv salbutamol on respiratory mechanics were studied in six infants with bronchopulmonary dysplasia. Salbutamol was infused at a dose of 30 micrograms/kg over 30 min in five infants; a sixth infant received 66.7 micrograms/kg over 4 min. Salbutamol caused improvement in total respiratory system compliance and in airflow resistance. There was no correlation between salbutamol serum concentration and pulmonary function. Elimination half-time appears to be dictated in these infants more by the distribution volume (Vd) than by clearance (Cl). The area under concentration-time curve of salbutamol correlated inversely to the change in heart rate (HR). There was a significant positive correlation between Vd and percent HR change. These data provide evidence that preterm infants have measurable activity of bronchiolar beta 2 receptor responsive to salbutamol.

Airway Resistance↗
PubMed1990

Differential activation of monocytes in haemodialysis patients exposed to different types of membranes.

Peripheral blood mononuclear cells (PBMC) from haemodialysis patients treated with different types of membranes were isolated, incubated in vitro, and extracellular and cell-associated interleukin I (IL-1) assayed by radioimmunological methods. Extracellular IL-1 was low and not different from controls, regardless of the dialyser used. In contrast, cell-associated IL-1 was increased in patients treated with dialysers containing low-flux Cuprophan (CU, n = 5) and polyacrylonitrile sheet membrane (AN69, n = 5). Patients treated with dialysers containing high-flux polysulphone (PS, n = 7), and polymethylmethacrylate (PMMA, n = 8), exhibited no increase in cell-associated IL-1 under these conditions. To elucidate the mechanism of the activation, aqueous extracts of dialysers containing CU, PS, and AN69 were tested for their ability to induce IL-1 generation in PBMC from healthy donors. Extracts from unrinsed CU-containing dialysers caused significant IL-1 synthesis and release, whereas incubation with extracts from dialysers containing PS and AN69 sheet membranes did not. Hence, although both CU and AN69 sheet-type dialysers result in activation of blood monocytes the mechanism of action appears to be different. We speculate that functional signs of PBMC activation as evidenced by increased spontaneous IL-1 production observed in some patients on long-term haemodialysis may result from extractable dialyser membrane material while in other instances direct cell membrane interactions or endotoxin transfer from the dialysate may be relevant.

Adult↗
PubMed1990

Purification of NADPH-dependent electron-transferring flavoproteins and N-terminal protein sequence data of dihydrolipoamide dehydrogenases from anaerobic, glycine-utilizing bacteria.

Three electron-transferring flavoproteins were purified to homogeneity from anaerobic, amino acid-utilizing bacteria (bacterium W6, Clostridium sporogenes, and Clostridium sticklandii), characterized, and compared with the dihydrolipoamide dehydrogenase of Eubacterium acidaminophilum. All the proteins were found to be dimers consisting of two identical subunits with a subunit Mr of about 35,000 and to contain about 1 mol of flavin adenine dinucleotide per subunit. Spectra of the oxidized proteins exhibited characteristic absorption of flavoproteins, and the reduced proteins showed an A580 indicating a neutral semiquinone. Many artificial electron acceptors, including methyl viologen, could be used with NADPH as the electron donor but not with NADH. Unlike the enzyme of E. acidaminophilum, which exhibited by itself a dihydrolipoamide dehydrogenase activity (W. Freudenberg, D. Dietrichs, H. Lebertz, and J. R. Andreesen, J. Bacteriol. 171:1346-1354, 1989), the electron-transferring flavoprotein purified from bacterium W6 reacted with lipoamide only under certain assay conditions, whereas the proteins of C. sporogenes and C. sticklandii exhibited no dihydrolipoamide dehydrogenase activity. The three homogeneous electron-transferring flavoproteins were very similar in their structural and biochemical properties to the dihydrolipoamide dehydrogenase of E. acidaminophilum and exhibited cross-reaction with antibodies raised against the latter enzyme. N-terminal sequence analysis demonstrated a high degree of homology between the dihydrolipoamide dehydrogenase of E. acidaminophilum and the electron-transferring flavoprotein of C. sporogenes to the thioredoxin reductase of Escherichia coli. Unlike these proteins, the dihydrolipoamide dehydrogenases purified from the anaerobic, glycine-utilizing bacteria Peptostreptococcus glycinophilus, Clostridium cylindrosporum, and C. sporogenes exhibited a high homology to dihydrolipoamide dehydrogenases known from other organisms.

Amino Acid Sequence↗
PubMed1990

Changes in anterior pituitary hormone levels after serotonin 1A receptor stimulation.

Although the role of serotonin (5HT) in the regulation of anterior pituitary hormone secretion is well documented, the involvement of specific 5HT receptor subtypes in this action is not yet fully elucidated. In the present work we attempted to determine the neuroendocrine role of the 5HT1A receptor subtype. This was chosen mainly because highly selective pharmacological tools are available for that subtype. 8-Hydroxy-2-(di-n-propylamino)tetralin (8OHDPAT) and ipsapirone were injected iv in conscious, freely moving male rats cannulated in the jugular vein. For the sake of comparison, a 5HT receptor agonist with preference for the 5HT1B and 5HT1C receptor subtypes 1-(m-trifluoromethyl-phenyl)piperazine (TFMPP) was also administered. Plasma PRL, ACTH, and beta-endorphin levels increased in a dose-dependent manner after 8-OHDPAT (0.01-1 mg/kg) or ipsapirone (0.5-7.5 mg/kg) injection. Maximal effects were obtained between 7-15 min. Only the highest dose of 1-(m-trifluoromethyl-phenyl)piperazine (5 mg/kg) resulted in the same response. In contrast, none of the drugs used affected plasma GH, TSH, or LH levels at any dose tested. The results indicate that 5HT1A receptors are involved in the regulation of PRL as well as ACTH and beta-endorphin secretion. 8OHDPAT was almost 40 times more potent than ipsapirone. The maximal effects of the two drugs on PRL release were comparable. In contrast, ipsapirone behaved as a partial agonist only on ACTH and beta-endorphin secretion, thus suggesting that different neuronal targets are involved in the stimulation of the three hormones by 5HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

[Distribution pattern of chemical in surface waters as a reflexion of entry pattern--nonvolatile halogenated hydrocarbons].

The concentrations of some nonvolatile halogenated hydrocarbons in surface waters of an industrialized city and its surroundings are given. About 80% of the ballast isomers of hexachlorocyclohexane (alpha, beta and delta BHC) and of DDT and its metabolites are in the range of less than 5 micrograms l-1, whereas ca. 50% of lindane (gamma BHC) were found to be between 5 and 100 micrograms l-1. Starting form the remarks about the differential-diagnostic assessment of environmental concentrations conclusions as to the origin of hexachlorocyclohexane isomers are drawn with the help of their distribution pattern. A high part of the gamma isomer, compared with the ballast isomers means an application (e.g. against mosquitos). This fact may be supported if it coincides with the months typical for such an application. in contrast to this if you have high percentages of alpha, beta and delta hexachlorocyclohexane, it indicates a point source or diffuse inputs of technical BHC. If all four isomers are present on a comparable and very low level this may reflect a remobilization from the sediment.

DDT↗
PubMed1990

[Psychosocial management of glioma patients treated with combined therapy].

Based on an empirical study it is pointed out that psychosocial care of patients with glioma differs in some points from that of other cancer patients. The first essential difference is that the emotional involvement of the care staff is not as intensive as those of other cancer patients. Other differences concern some illness- and therapy related effects such as family problems or monotony problems resulting from the longterm therapy. These specific problems are described in detail.

Brain Neoplasms↗
PubMed1990

Growth parameters and attention to faces at 4 to 6 months of age.

Duration of attention to faces and response decrement were studied in 57 full-term infants between 15.1 and 28.5 weeks of age during a health maintenance clinic visit. Six measures of growth, obtained from the medical record, included weight, length, and head circumference at birth, and weight, length, and head circumference at the time of the clinic visit. Correlation analysis revealed that longer average initial fixation time was associated with male sex, shorter birth length, and larger ponderal index. Multiple regression analysis indicated that together these three variables accounted for 17% of the variance in average initial fixation time (p less than 0.05). Length at the time of the health maintenance visit and male sex also were associated with longer average initial fixation time and, together, accounted for 13% of the variance (p less than 0.05). Response decrement was larger in children with larger head circumference at birth, in girls, and in infants with a larger ponderal index at birth. Together, these three variables accounted for 27% of the variance (p less than 0.001). Results suggest that more efficient processing of visual information may be related to neurophysiological maturity at term, and raises the possibility that neurophysiological maturity may account for a substantial portion of the correlation between attention behavior and later intelligence.

Arousal↗
PubMed1990

[Psychophysiologic particularities in patients with functional syndromes].

Patients with gastroenterological or cardiovascular functional syndromes (n = 109) were examined by means of an extensive psychological standardized diagnostic programme and psychological strain analysis was carried out under psychogenic stress in laboratory. The results were compared with healthy probands (n = 51) likewise examined. Patients with functional syndromes significantly discriminated of healthy probands by more psychosocial risk constellation under strain caused by more distress and in parameters of performance and in psychophysiological field in some strain variables (heart rate, blood pressure, acral vasomotricity) and their dynamics.

Adult↗
PubMed1990

[Management of elderly citizens in a residential setting].

On the basis of demographical and social developments as well as of the "demand" for nursing resources in the GDR, the medical and social care situation for the elderly is discussed with special emphasis on the responsibilities of the family practitioner. Concluding from our own investigations we propose to use the Classification of Disabilities for deducing indications of care activities and standards. Examples are given, in particular, in respect of differing forms of protected lodging of care-needing elderly citizens.

Aged↗