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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 181 records · Page 10Linked to original sources
PubMed1991

Thyrotropin-releasing hormone degradation in patients with insulin dependent diabetes mellitus. Effects of metabolic control.

We investigated thyrotropin releasing hormone (TRH) degradation in terms of half-life (t1/2) and metabolic clearance rate (MCR) in eight subjects with insulin dependent diabetes mellitus (IDDM) before and after strict metabolic control. The results were compared with those of six healthy control subjects. The basal plasma TRH-IR levels (31 +/- 9 fmoles/ml) were on the lowest normal limit in the IDDM patients and were not considerably changed (24 +/- 10) after strict metabolic control. The basal and delta max rise of TSH to TRH (200 micrograms i.v.) were not significantly different before or after improved metabolic control in IDDM and as compared to controls. The TRH-degradation curves showed similar exponential decay before and after improvement of metabolic control (t1/2: 7.6 +/- 0.4 min and 7.3 +/- 0.3 respectively; 6.5 +/- 0.4 min for the controls). The MCR of exogenously administered TRH in IDDM before (65.5 +/- 8.6 l/m2/day) and after (65.0 +/- 8.9) control was not different compared to the normals (76.5 +/- 9.6). The area under the plasma concentration-time curve (AUC) in IDDM before (52.193 +/- 6.773 fmoles.ml-1.min) and after improvement of metabolic control (53.186 +/- 7.856) was slightly higher than in the healthy subjects (40.151 +/- 3.741, n.s.). These findings demonstrate that a) the degradation of exogenous TRH is not dependent on the glucose metabolic state, b) insulin deficient diabetes mellitus does not affect the enzymatic system responsible for TRH degradation and, c) the hypothalamic-pituitary axis appears to be intact in IDDM.

Adolescent↗
PubMed1991

Generation of free radicals during the reductive metabolism of the nitroaromatic compound, nilutamide.

Incubation of the antiandrogen nilutamide with rat liver microsomes and NADPH, under anaerobic conditions, led to the formation of the nitro anion free radical, as indicated by electron spin resonance spectroscopy. The steady-state concentration of the nitro anion free radical was not decreased by SKF 525-A, carbon monoxide or metyrapone (3 inhibitors of cytochrome P-450) but was decreased by NADP+ or p-chloromercuribenzoate (2 inhibitors of NADPH-cytochrome P-450 reductase). Under aerobic conditions, the nitro anion free radical was reoxidized by oxygen, and the electron spin resonance signal was not detected. This redox cycle was associated with NADPH oxidation, consumption of oxygen, and formation of superoxide anion, hydrogen peroxide and glutathione disulfide. Under anaerobic conditions, nilutamide was further reduced to chemically reactive metabolites. Anaerobic incubation of [3H]nilutamide (0.1 mM) with rat liver microsomes and a NADPH-generating system resulted in the in vitro covalent binding of [3H]nilutamide metabolites to microsomal proteins; covalent binding required NADPH; it was decreased in the presence of NADPH-cytochrome P-450 reductase inhibitors (methylene blue, 2'-adenosine monophosphate) or in the presence of the nucleophile glutathione, but was unaffected by cytochrome P-450 inhibitors (SKF 525-A, CO). Covalent binding was decreased markedly under aerobic conditions. We conclude that nilutamide is reduced by microsomal NADPH-cytochrome P-450 reductase into a nitro anion free radical. In the presence of oxygen, this nitro anion free radical undergoes redox cycling with oxygen, and forms reactive oxygen species. In anaerobiosis, it is reduced further to covalent binding species.

Androgen Antagonists↗
PubMed1991

[How do breast cancer patients experience participation in a psycho-oncologic follow-up study?].

62 breast cancer patients participating in a prospective psychooncological research project were asked about their attitude toward the study after a one year follow-up period. 40 percent of the women had an indifferent opinion about the study. They felt neither burdened nor unburdened by their collaboration on the study. 32 percent had a positive and 28 percent a negative attitude toward the study. Patients with a positive attitude were more often singles and were more often in unfavourable stages of their cancer when entering the study. However they felt the interviews and rating scales rather helpful for coping with their disease. The women with a negative attitude were more often burdened by psychological problems already before the diagnosis of cancer was made and showed more signs of depression, distrust and cognitive withdrawal in their coping strategies. The results indicate that in psychooncological prospective studies the development of patients' attitude toward the study should be considered more carefully.

Adaptation, Psychological↗
PubMed1990

Single-compartment model analysis of thyrotropin-releasing hormone kinetics in hyper- and hypothyroid patients. Kinetic studies using a combined system of RIA and FPLC.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were assessed following an i.v. injection in blood of ten hyperthyroid, ten hypothyroid, and six normal subjects. A single-compartment model was employed. After methanol extraction, TRH concentrations were analyzed using a specific radioimmunoassay technique combined with fast protein liquid chromatography (FPLC). As for the basal levels of TRH, no differences were observed in either study group. Peak concentrations were always present two min after the injection of TRH. In the euthyroid subjects, TRH blood levels had a half-life (t1/2) of 6.5 +/- 0.41 min, mean +/- SD, while t1/2 was 7.2 +/- 0.62 min in the hyperthyroid and t1/2 was 12 +/- 1.67 min (p less than 0.001) in the hypothyroid patients. The metabolic clearance rate (MCR) (82.2 +/- 15.3 liters/m2/day vs. 89.8 +/- 17.2) and the volume of distribution (Vd) (7.1 +/- 4.2 liters vs. 7.3 +/- 3.4) were approximately the same in the normal subjects and in the hyperthyroid group. MCR (66.2 +/- 15.3 liters/m2/day) and Vd (6.2 +/- 3.3 liters) were found to be lower in the hypothyroid patients. In FPLC, when TRH was added to plasma, it eluted in one peak. Blood samples taken 5 min after TRH i.v. injection had an elution profile of 9.94 ml. These data indicate that 1) TRH has a very short half-life, 2) hypothyroidism can prolong the t1/2 of exogenous TRH, and 3) when TRH should be used in clinical studies, the function of the thyroid gland has to be taken into consideration.

Chromatography, Liquid↗
PubMed1990

hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.

Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.

Amino Acid Sequence↗
PubMed1990

[Postoperative course and endocrine stress reaction of geriatric patients with para-articular hip fractures. Prospective randomized study comparing spinal anesthesia and halothane intubation narcosis].

During a period of one year, all patients above the age of 60 with surgical repair of fractured neck of femur were investigated in a prospectively randomized design. A follow-up study included a total number of 56 patients, 32 were allocated to halothane anaesthesia with intubation, 24 received spinal anaesthesia. In addition, 15 patients of the halothane group and 17 patients with spinal anaesthesia were investigated with regard to endocrine stress response. Total mortality was 12.5%, and different anaesthetic management had no influence on the postoperative course. During the operation, adrenaline and ADH increased in both groups. This increase was attenuated by spinal anaesthesia. Noradrenaline was markedly increased even before the operation, and concentrations increased in the halothane group in the course of the operation. There was a linear correlation to time between accident and the beginning of the operation. With regard to endocrine parameters, prompt surgical treatment is beneficial.

Adrenocorticotropic Hormone↗
PubMed1990

A species and organ specific glomerular basement membrane antigen.

By the use of a monoclonal antibody reacting with the human glomerular basement membrane exclusively we have been isolating a specific glomerular antigen. The antibody failed to react with other renal structures and other basement membranes and extracellular matrix constituents of other organs or plasma proteins. It did not react with glomerular basement membranes of other species as mice and rats. For the isolation of the antigen we applied affinity chromatography, on Sepharose beads coupled to the monoclonal antibody PM II 34 G3. From this column the antigen was eluted under acid conditions. In 8% polyacrylamide gel electrophoresis the approximate molecular weight was estimated with 14400 daltons, which was confirmed on high pressure liquid chromatography using the Bio-Sil TSK method. The antigen was temperature sensitive in that at high temperatures (60 degrees C) several bands on SDS-PAGE and several peaks on HPLC could be noted. This could be responsible for the crystal formation after treatment/concentration on the rotary vacuum pump at 60 degrees C. Preliminary data of amino acid analysis showed a high glycine content pointing towards a collageneous molecule. But cross reactivity with many connective tissue proteins could be ruled out by immuno-histochemical techniques and affinity chromatography. A major point of interest is that this antigen can be detected in human urine under physiological conditions. We are herewith reporting the first species and organ specific glomerular basement membrane antigen.

Amino Acids↗
PubMed1989

Binding of two spin-labelled derivatives of chlorpromazine to human erythrocytes.

The binding to human intact erythrocytes of two different spin-labelled derivatives of chlorpromazine has been studied. The influence of the positively charged side chain of the drug has been the focus of our attention. The positively charged amphiphilic compound (spin derivative I) is water-soluble up to 80 microM at pH values below 5.9. The apolar analogue (spin derivative II) aggregates in aqueous buffer from the lowest concentration tested. Both spin derivatives undergo a slow reduction inside the erythrocyte. The reduced nitroxides are readily reoxidized by adding a low, non-quenching, concentration of potassium ferricyanide to the intact erythrocytes. The fractions of spin label I and II bound to the erythrocyte membrane or to the erythrocyte-extracted lipids remain constant as a function of the temperature (3-42 degrees C) and as a function of the concentration of the spin label up to 150 microM. E.s.r. spectra of both spin labels show a two-component lineshape when they are bound to intact erythrocytes. Below 35 degrees C for the positively charged spin probe, and below 32 degrees C for the apolar spin probe, the simulation of the lineshape shows that more than 50% of the spectrum originates from a slow-motion component. This slow-motion component is also found in erythrocyte-extracted lipids probed by the positively charged spin label below 25 degrees C. In contrast, no slow-motion component is detected in the range 4-40 degrees C for the apolar spin label in erythrocyte-extracted lipids. In this environment the apolar probe experiences a single fast anisotropic motion with an exponential dependence on 1/temperature. Detailed lineshape simulations take into account the exchange frequency between binding sites where the probe experiences a fast motion and binding sites where it experiences a slow motion. The exchange frequency is strongly temperature-dependent. Characterization of the different motions experienced inside the different locations has been achieved and compared for whole erythrocytes and for the extracted lipids. The biochemical nature of the binding sites (membrane protein/acidic phospholipid) giving rise to the slow-motion component is discussed as a function of the polarity of the spin-labelled drug and as a function of the temperature controlling the fluidity of the lipid bulk and influencing the distribution of the drug inside the membrane.

Chlorpromazine↗
PubMed1989

Effects of calcium and calcium analogs on calmodulin: a Fourier transform infrared and electron spin resonance investigation.

Fourier transform infrared (FTIR) and electron spin resonance (ESR) spectroscopies have been used to monitor changes in the conformation of calmodulin induced by Ca2+ and Ca2+ analogs. Using FTIR spectroscopy we observe that Ca2+: (i) favors the alpha-helical conformation and decreases the flexibility of the molecule; (ii) multiplies the intramolecular hydrogen bonds (the ratio of freely vibrating NH/hydrogen bound NH groups decreases); (iii) induces changes in the C-terminal tyrosine environment; and (iv) increases compactness of the molecule (less NH groups in the peptide bonds can be deuterated). As proved by ESR, Ca2+ binding induces exposure of hydrophobic domains allowing binding of a spin-labelled phenothiazine on calmodulin. When the experiments are performed in the presence of increasing amounts of Ca2+, both ESR and FTIR provide evidence that major conformational changes result after the filling of only two Ca2+-binding sites. But achievement of the spectroscopical changes is only observed when the four binding sites are filled (Ca2+/calmodulin = 4). The effects of analogs are monitored with the same spectroscopical parameters. Zn+ does not induce structural modifications of calmodulin but all other analogs studied mimic the calcium effects to some extent. As regards the amplitude of the spectroscopical effects, analogs rank in the following order: Ca2+ greater than Cd2+ greater than Tb3+ = Eu3+ greater than Gd3+ greater than La3+ greater than Zn2+ = cation depleted. Except for Zn2+, ranking for their activating potency of MLCK, the analogs can be arranged in a similar order.

Animals↗
PubMed1989

Influence of PAF-acether on lecithin-oriented multibilayers monitored by ESR: interaction of PAF-acether with cholesterol.

The influence of PAF-acether on natural ovolecithin oriented multibilayers is detected by ESR of intercalated 5 doxyl stearic acid. Simulation of lineshapes demonstrates an enlarged orientational distribution of the local director of the phospholipid phase and a small increase of the order parameter. The amount of PAF-acether required to destabilize the ovolecithin lamellar phase depends on the degree of hydration. By contrast, cholesterol displays an organizing effect on the PAF-acether phase. Simulation establishes a sharp orientational distribution of the local director when cholesterol reaches stoichiometric ratio relative to PAF-acether. At the same time, cholesterol increases the order parameter.

Cholesterol↗
PubMed1989

Simultaneous determination of thiopental and its metabolite, pentobarbital, in blood by high-performance liquid chromatography and post-column photochemical reaction.

A novel approach for the simultaneous high-performance liquid chromatographic (HPLC) analysis of thiopental and its major metabolite, pentobarbital, in blood plasma is described. On-line irradiation of the column eluate with UV-light leads to a significant bathochromic shift in the absorbance spectrum of pentobarbital, allowing now sensitive UV-detection of both barbiturates at 270 nm. At this longer wavelength, plasma matrix constituents are less interfering in the analysis, thus less sample preparation is necessary and blood plasma can be directly injected into the HPLC system only after protein precipitation with acetonitrile. Because of the minimal sample handling, the described HPLC method has good accuracy and reproducibility and thiopental and pentobarbital can be determined in small plasma volumes down to 0.2 micrograms ml-1.

Chromatography, High Pressure Liquid↗
PubMed1989

Episodic angioedema with eosinophilia.

A 40-year-old woman had monthly episodes of angioedema, eruption of pruritic papules and plaques and fever. During acute episodes white blood cell counts increased to 31,000/mm3 with 75% eosinophils, body weight increased to 10% of baseline weight, and urine excretion decreased to 40 ml/24 hours. No evidence was found for cardiac or other visceral organ involvement. Extensive diagnostic evaluations revealed no evidence for parasitic infestation, connective tissue disease, or neoplastic disorders. Results of immunologic studies revealed increased serum IgM and IgE levels and showed elevated levels of circulating activated T-helper cells. Biopsy specimens of lesional skin showed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil granule major basic protein in the extracellular matrix within the dermis. Immunophenotyping of the dermal infiltrate with monoclonal antibodies revealed the predominance of T-helper cells, many of them expressing the human leukocyte antigen (HLA)-DR, suggesting that angioedema with eosinophilia may be a T-helper cell-mediated disease.

Adult↗