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Biomedical subjects

B Schulz

Publications and source records attributed to B Schulz.

At least 73 records · Page 4Linked to original sources

Molecular structure of microtubule-associated protein 2b and 2c from rat brain.

Full length cDNA clones encoding microtubule-associated proteins (MAP) 2b and 2c from rat brain have been isolated and sequenced. The cDNA fragments spanning the coding regions for both MAP2b and MAP2c were assembled and expressed in Escherichia coli. The mobility of these bacterial expressed proteins in sodium dodecyl sulfate gels is identical to that of MAP2b and MAP2c from rat brain. The protein sequence of rat MAP2b has been compared to the full length sequence from mouse and the partial sequence from human high molecular weight MAP2. This comparison has revealed that MAP2b is composed of several highly conserved domains flanked by domains with extensive sequence divergence. Two of the conserved domains, found either at the NH2 or COOH terminus, overlap with the binding domain for the regulatory subunit of the cAMP-dependent protein kinase II and the microtubule-binding domain, respectively. A third homologous domain of unknown function lies in a central region of MAP2b. Secondary structure prediction suggests that the portion of MAP2b which extends from the microtubule surface is composed of an extensive number of alpha-helices separated by small turns which may account for the extended yet flexible structure of MAP2. Interestingly, the 4000-base pair deletion from the middle of MAP2b which generates MAP2c not only removes these helices, but also this third highly conserved MAP2b domain.

Amino Acid Sequence↗

The b alleles of U. maydis, whose combinations program pathogenic development, code for polypeptides containing a homeodomain-related motif.

U. maydis is a fungal pathogen of corn with two forms: one is yeast-like and nonpathogenic; the other is filamentous and pathogenic. The b locus, with 25 different alleles, regulates this dimorphism: any combination of two different alleles triggers pathogenic development, whereas the presence of identical alleles results in the yeast-like form. We have cloned four b alleles (b1, b2, b3, and b4) and show that the b locus contains a single open reading frame (ORF) of 410 amino acids with a variable N-terminal region and a highly conserved C-terminal region (60% and 93% identity, respectively). Mutational analysis confirms that this ORF is responsible for b activity. The b polypeptides appear to be DNA binding proteins because they contain a motif related to the homeodomain in their constant region. We propose that combinatorial interactions between b polypeptides generate regulatory proteins that determine the developmental program of the fungus.

Alleles↗

The effect of antihypertensive treatment on kidney function in insulin-dependent (type I) diabetics with renal failure.

Diabetic nephropathy is the dominant cause of hypertension in insulin-dependent diabetics, and long-term rigid antihypertensive treatment inhibits the progression of nephropathy, probably even when there is renal insufficiency. In our clinical study 14 insulin-dependent diabetics with diabetic nephropathy and renal failure (glomerular filtration rate [GFR] 0.39 +/- 0.12 ml/sec) underwent rigid blood pressure treatment. Antihypertensive therapy included furosemide, propranolol, dihydralazine and nifedipine. The whole group showed a lowering in mean blood pressures from 150.1 +/- 2.3/91.3 +/- 1.4 mm Hg to 139.8 +/- 3.1/86.5 +/- 2.0 mm Hg (p less than 0.01). During the observation period the mean decline in glomerular filtration rate decreased from -0.022 +/- 0.003 ml/sec per month to -0.010 +/- 0.007 ml/sec per month. In 10 out of 14 patients with very advanced nephropathy the further decline of GFR halted markedly. Thus, vigorous blood pressure control is able to postpone endstage renal disease even in advanced diabetic nephropathy.

Acute Kidney Injury↗

Autoimmune reactions in a patient with malignant insulinoma treated by multiple low dose streptozotocin.

A 66-year-old female patient with a malignant insulinoma was treated with streptozotocin (STZ; Zanosar) in 5 cycles every 4 weeks as 5 day courses with an intravenous dosage of 850 mg per day. Under this treatment hypoglycemic episodes decreased continuously in number as well as severity and - after a delay of 12 months after the last treatment - an overt diabetes mellitus appeared. Plasma insulin concentrations dropped immediately after starting of STZ therapy. On the other hand, islet cell surface antibodies and their complement-dependent cytotoxicity increased continuously, being at their highest 6 months after termination of STZ treatment. Thus, STZ is able to induce a specific immune response against islet cells with a progressive damage of malignant insulin producing cells.

Adenoma, Islet Cell↗

Red blood cells bearing CD4 bind to gp120 covered plates and aggregate with cells expressing gp120.

Full-length recombinant CD4 (rCD4) was bound to human red blood cell membranes using a low-pH incubation procedure. The red blood cells bearing recombinant CD4 (RBC-rCD4+) specifically bound to gp 120-covered plates. The binding showed a threshold effect at low rCD4 concentrations per RBC. The binding of RBC-rCD4+ to gp120 plates was not inhibited by plasma proteins (incubation in human blood plasma). Preincubation of the RBC-rCD4+ with monoclonal anti-CD4 antibodies blocked the binding to the gp120-covered plates. Incubation of chinese hamster ovary (CHO) fibroblasts, which constitutively express the HIV envelope protein gp120 with RBC-rCD4+, resulted in the formation of large cell aggregates. These in vitro data suggest that RBC-rCD4+ retain affinity for gp120 and thus could have potential therapeutical value in AIDS treatment.

Animals↗

[Postoperative ventilation in non-intubated patients with iron lung versus conventional ventilation].

Postoperative ventilation using a steel lung is an alternative to conventional ventilation through an endotracheal cannula. Both methods were compared in two groups of patients undergoing major abdominal surgery. Group A was ventilated using a Servo Ventilator 900C, whereas group B was ventilated using a newly designed steel lung. The duration of ventilation using the steel lung and that of postoperative intubation were significantly shorter than those used in group A, in spite of a higher anesthesiological and surgical risk in patients in group B. pO2 was significantly increased during ventilation with the steel lung in comparison to conventional ventilation. An automatic classification of EEG activity was used to estimate depth of anesthesia. This showed a close correlation between clinical signs and anesthesiological levels. The spectroanalytical evaluation of ventilation curves allowed the early recognition of spontaneous breathing and determined tidal volumes using steel lung ventilation.

Aged↗

[Knowledge and ability of patients concerning the administration of nasal drops].

The study tried to find out what patients know on the application of nose drops when leaving the pharmacy. As could be shown knowledge and ability were not satisfying. Two third of the patients applied their nose drops in a correct single dose but in too long intervals. Almost the half did not know the correct technique of application. Only 2% of the patients mentioned the pharmacist as source of their information. The results require a more effective information about the application of drugs by the pharmaceutical staff.

Administration, Intranasal↗

[Occupational medicine outpatient management of workers with responsibilities involving great psychological stress].

Some selected results from regular medical occupational fitness evaluations, the statistic of unfitness for work, the disablement of teachers and the occupational referred mortality were demonstrated in special consideration of workers with particular psychic load. From it conclusions were drawn for the development of methods for occupational medical fitness examinations and check ups, prophylactic and therapeutic programmes. The necessarity of scientific dealing with this problems was emphasized.

Adult↗

Dextran protection of erythrocytes from low-pH-induced hemolysis.

Low-pH-induced hemolysis of erythrocytes is inhibited by dextrans. The protective effect was observed with dextrans larger than 40 kDa. Electron microscopy showed dextrans of 150 kDa in a tight association with the erythrocyte membrane. These results indicate that dextrans stop the low-pH-induced hemolysis by interacting with the acid-induced defects in the erythrocyte membrane [(1989) Biochim. Biophys. Acta, in press].

Dextrans↗

Low-pH association of proteins with the membranes of intact red blood cells. I. Exogenous glycophorin and the CD4 molecule.

Glycophorin and CD4 proteins are tightly associated with intact human erythrocyte membranes after a short-time incubation at low pH (1-2 min, pH lower than 5, 37 degrees C). Flow cytometry and epifluorescence microscope observations showed that after incubation of red cells with fluorescein isothiocyanate (FITC) labeled glycophorin at pH values lower than 5, the erythrocyte membrane and subsequently formed ghost membranes were fluorescent. Unlabeled glycophorin was reacted with mouse erythrocytes using the same low-pH conditions. Flow cytometry and fluorescence microscopy showed that anti-glycophorin monoclonal antibodies were able to recognize the epitopes of glycophorin associated with the mouse erythrocytes. Kinetic experiments showed that the interaction of FITC-glycophorin with red cell membranes can be monitored by a decrease in the fluorescence intensity. Erythrocyte associated glycophorin was not removed from the membranes after 24 h incubation in human plasma (in vitro, 39 degrees C). A glycoprotein extract containing CD4 was isolated from a T4-lymphoma cell line (CEM). This protein extract was incubated with erythrocytes using the same low-pH conditions. Fluorescently labeled monoclonal antibodies against CD4 stained the red cells after association of CD4 with the membranes. Electron microscopy showed 10 nm immunoglobulin G-coated gold beads associated with CD4-bearing erythrocyte membranes after incubation with anti-CD4 antibodies and then with the gold beads. The potential use of the CD4-erythrocyte complex as a therapeutical agent against acquired immune deficiency syndrome (AIDS) is suggested.

Acquired Immunodeficiency Syndrome↗

Low-pH association of proteins with the membranes of intact red blood cells. II. Studies of the mechanism.

The low-pH interaction of proteins with erythrocyte membranes has been found to be correlated with pH-induced changes in the erythrocyte membrane. Using a 90 degree lightscattering method it was shown that red blood cell hemolysis was slow between pH 5.8 and 5 (t1/2 above 1 h) but became fast at and below pH 4.7 (t1/2 less than 20 min). At pH 4.7, the presence of glycophorin in the incubation medium inhibited the hemolysis of erythrocytes and this protective effect was found to be dependent on the glycophorin concentration. Electron microscope experiments showed the presence of membrane defects after 10 s incubation at pH 4.6 in the absence of glycophorin in the incubation medium. These defects could further develop into openings with average widths of 14 nm after 1.5 min incubation under the acidic conditions. Fluorescence and flow cytometry studies showed that at pH 4.7, but not at pH 7.4, glycophorin tightly associates with phosphatidylcholine liposomes, and that liposome associated glycophorin molecules are recognized by anti-glycophorin monoclonal antibodies.

Cell Communication↗

Importance of cardiovascular autonomic dysfunction in IDDM subjects with diabetic nephropathy.

Diabetic nephropathy (DNP) is associated with increased cardiovascular mortality. This may be contributed to by associated cardiovascular autonomic dysfunction (CAD). The aim of this study was to investigate the prevalence of CAD in patients with insulin-dependent diabetes mellitus (IDDM) at different stages of DNP. We studied patients with incipient DNP (group 1, n = 10), overt DNP (group 2, n = 20), renal insufficiency (group 3, n = 27), and end-stage renal failure (group 4, n = 12) and compared them with 30 IDDM patients without clinical signs of DNP (group 5) and with 17 nondiabetic controls (group 6). All groups were matched for age and diabetic groups were matched for duration of diabetes. Assessments of CAD included beat-to-beat variation during forced respiration, heart-rate response to standing, heart-rate response to Valsalva maneuver, basal heart rate, and blood pressure response to standing. Clinical evaluation included assessment of the history and an examination for peripheral polyneuropathy. We found mean impairment of heart-rate variation during respiration, in response to Valsalva maneuver, and in heart-rate response to standing in all diabetic groups compared with nondiabetic controls (P less than .01). Heart-rate responses differed significantly between patients with renal insufficiency (groups 3 and 4) and with other patient groups (group 5; P less than .01). CAD was shown to be more prevalent in patients with DNP, more so as DNP progresses. To some extent, it is already present in the early stages of DNP. CAD may be a contributory factor for increased cardiovascular mortality in patients with DNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inhibition of nuclear accumulation of karyophilic proteins in living cells by microinjection of the lectin wheat germ agglutinin.

The lectin wheat germ agglutinin (WGA), which has been reported to inhibit nuclear protein uptake in vitro by isolated nuclei (Finlay et al. (1987) J. Cell Biol. 104, 189), also blocks, on microinjection into living cells, the migration of proteins into the cell nucleus. Radioactively labeled nuclear proteins were injected into the cytoplasm of Xenopus oocytes and their reentry into the nucleus was analyzed in the presence or absence of WGA by two-dimensional gel electrophoresis. In another set of experiments, fluorescently labeled nucleoplasmin was injected, alone or together with WGA, into the cytoplasm of rat hepatoma cells, and its nucleocytoplasmic distribution was studied by quantitative laser fluorescence microscopy. The results indicate that WGA inhibits the uptake of karyophilic proteins in general, independent of their sizes. Since the nucleocytoplasmic flux of a dextran with Mr 10,000 was not affected it can be excluded that WGA acts by a general blockade or constriction of the functional pore channel. At reduced WGA concentrations, the rate but not the final extent of nuclear protein accumulation was decreased. These findings support the concept that the O-glycosidically bound carbohydrates of certain nuclear pore complex proteins are exposed to the pore interior and that these regions are probably involved in nucleocytoplasmic translocation processes.

Animals↗

The effect of mixing regular- and intermediate-acting insulins on their absorption and biological activity.

Many insulin-dependent diabetics are now treated with different regimens of short- and intermediate-acting insulins. The new L-insulin S.N.C. (Berlin-Chemie) is thought to be appropriate for a combination with regular insulin. We investigated whether or not absorption kinetics and biological activity changes when L-insulin S.N.C. is mixed with regular insulin S.N.C. Eight non-obese healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.1 U of insulin S.N.C. and 0.3 U per kg b.w. of L-insulin S.N.C. or Monotard MC insulin (NOVO) were administered either in a mixture or separately. Injecting L-insulin S.N.C. and insulin S.N.C. in a mixture there was some, but not a statistically significant, delay in absorption of insulin. A mixture of insulin S.N.C. and Monotard provoked a marked delay of absorption during the first two hours. To examine biological activity we used the BIOSTATOR (glucose controlled dextrose infusion system). Glucose infusion rate necessary to keep blood glucose steady state concentration was taken as a measure of insulin action. Whereas mixing of insulin S.N.C. and L-insulin S.N.C. only slightly changed the profile of biological activity, a mixture of insulin S.N.C. and Monotard has a clear-cut higher potency during the late phase when compared with separately injected insulins. Therefore, insulin S.N.C. and Monotard should not be mixed. A mixture of insulin S.N.C. and L-insulin S.N.C. is also not recommended but can be done in exceptional cases.

Absorption↗