[What is reliable in the treatment of glomerulonephritis?].
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Glomerulonephritis↗
Biomedical subjects
G Stein
Publications and source records attributed to G Stein.
[Electron microscopic evidence of aluminum in lysosomes of kidney cells by electron energy loss spectroscopy].
Aluminium effects have increasing attention in long term dialysis of kidney patients and in a number of cerebral diseases. At present, however, there are still many open points concerning its localization and actions in the cell. If using electron spectroscopic imaging (ESI), aluminium could be directly demonstrated in the lysosomes of the kidney cells of uraemic rats experimentally loaded with aluminium. These findings were corroborated by means of electron energy loss spectroscopy (EELS).
Aluminum↗
[Serum level and organ deposits of beta 2-microglobulin in dialysis patients].
In radioimmunological estimation of beta 2-microglobulin (beta 2m) significant higher serum values were found in 36 dialysis patients (44.4 +/- 20.3 mg/l) in comparison with healthy probands (1.5 +/- 0.2 mg/l). A significant relation to the duration of dialysis, diuresis, symptoms of the musculo-skeletal system, but not to radiologic changes or bone biopsy findings could be seen. Post mortem examinations carried out in 21 dialysis patients revealed AB-amyloid deposits in synovial tissue of different joints (particularly shoulder and hip joint) or intervertebral discs in eight patients (age 48 to 73 years, dialysis duration less than four years) without correlation to serum beta 2m level or radiographically suspect areas. In the tissue of cervical spine or intervertebral discs of two patients suffering from destructive spondylarthropathy no amyloid could be detected. These results suggest that AB-amyloid may occur in elderly patients early in the course of hemodialysis and may be asymptomatic in most cases.
Aged↗
[Possibilities for increasing the elimination rate of Bonnecor].
Bonnecor is excreted in rats both via urine (3/4) and bile (1/4). It was the aim of this study to find out suitable methods for detoxication of a poisoning with this antiarrhytmic drug. In vivo methods intended to enhance the renal excretion of Bonnecor (forced diuresis, changes in urinary pH-values, peritoneal dialysis) are not qualified for therapeutically relevant increase of Bonnecor elimination. Relating to this Bonnecor is quite comparable with other antiarrhythmic drugs or dibenzazepine derivatives. The hemoperfusion can be recommended for the therapy of a Bonnecor overdosage as a propping up of symptomatic methods of intensive care, which are precendentally indicated. Therefore the therapy of a Bonnecor poisoning seems to be more promising compared to intoxications with other antiarrhythmics. Among the adsorbents tested, the resin Wofatit UH91 is most suitable to remove Bonnecor from the organism. If hemoperfusion equipments are not available, hemodialysis can also be used for acceleration of Bonnecor elimination, although its effectivity is only one third of that of hemoperfusion.
Animals↗
[Clinical signs and diagnosis of hyperkalemia].
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Acute Disease↗
[Therapy of hyperkalemia].
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Adrenergic beta-Agonists↗
[Comparative studies of the effectiveness of 1-day treatment and 7-day treatment with sulfamerazine/trimethoprim (Berlocombin) of patients with urinary tract infection].
Insights into the pathogenesis of urinary tract infections warrant reflections on new therapeutic strategies. Of particular interest is the phenomenon of bacterial adherence to cells, as the adhesion of microorganisms to uroepithelial cells plays an important role in the development of the disease. In 21 women with an acute episode of lower urinary tract infection who were known of having chronic pyelonephritis, we studied the influence of a one-day (n = 7) and a seven-day treatment by administering the regular sulfamerazine/trimethoprime (Berlocombin) dose (2 X 2 tablets from the 2nd day, n = 7) or a reduced amount (2 X 1 tablet from the 2nd day, n = 7). All treatment regimes led to a disappearance of the clinical symptoms; however, in one case of the group receiving one-day treatment, dysuric complaints recurred as early as on day 3 after therapy. Only when employing the regular schedule of therapy, the controls of the urine cultures revealed sterility of the urine for all cases still on the 21st day after treatment. This treatment regimen most clearly influenced the ability of the microorganisms to adhere to the uroepithelial cells of the probands (in-vivo adherence). The one-day treatment was not able to reduce the rates of bacterial adherence to the cells. In all patients, the acute disease resulted in an increase in microorganisms coated with antibodies; on day 21 following therapy, however, the findings registered were as before onset of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multiple types of mRNA-cytoskeleton interactions.
Nearly all actively translated mRNAs are associated with the cytoskeleton in HeLa cells and the nature of this association is poorly understood. To gain insight into this association, we have examined and compared the cytoskeleton-mRNA interactions of a signal peptide-histone fusion mRNA (membrane-bound polysomal mRNA) to those of endogenous histone mRNA (nonmembrane-bound polysomal mRNA). We report here the detection of a cytoskeleton attachment site within the signal peptide-histone fusion mRNP/mRNA nucleotide sequence that is not present in wild-type histone mRNA or in HLA-B7 and chorionic gonadotropin-alpha membrane-bound polysomal mRNAs. These results support the possibility that there are multiple mechanisms for the attachment of specific classes of mRNAs to the cytoskeleton.
Base Sequence↗
Role of messenger RNA subcellular localization in the posttranscriptional regulation of human histone gene expression.
Histone mRNAs are naturally localized on non-membrane-bound polysomes and selectively destabilized during inhibition of DNA replication. Targeting histone mRNA to membrane-bound polysomes, by incorporating sequences coding for a signal peptide into the message, results in the stabilization of the histone fusion mRNA when DNA synthesis is interrupted (Zambetti et al.: Proceedings of the National Academy of Sciences of the United States of America 84:2683-2687, 1987). A single nucleotide substitution that abolishes the synthesis of the signal peptide results in the localization of the histone fusion mRNA on non-membrane-bound polysomes to the same extent as endogenous histone mRNA and fully restores the coupling of histone fusion mRNA stability to DNA replication. Signal peptide-histone fusion mRNAs containing two point mutations that result in the incorporation of two positively charged amino acids into the hydrophobic domain of the signal peptide are partially retained on non-membrane-bound polysomes and are partially destabilized during inhibition of DNA synthesis. These data indicate that the degree to which the signal peptide-histone fusion mRNAs are associated with non-membrane-bound polysomes is correlated with the extent to which the mRNAs are degraded during inhibition of DNA synthesis. These results suggest that the subcellular location of histone mRNA plays an important role in the posttranscriptional regulation of histone gene expression.
Amino Acid Sequence↗
Effects of calcium channel blockers on the development of early rat postimplantation embryos in culture.
Rat embryos (9.5-day-old) were cultured for 48 h in the presence of nifedipine (NIF), nimodipine (NIM), nitrendipine (NIT), gallopamil HCl (GAL), verapamil HCl (VER) and diltiazem HCl (DIL). The effects on growth and morphogenetic differentiation in vitro were monitored. Dose-response relationships were evaluated, including an assessment of the "no-observed-effect-level" (NOEL) or the "lowest-observed-effect-level" (LOEL), and the lowest concentration tested inducing abnormalities in 100% of the embryos ("100% EL"). The morphological alterations observed at the highest concentrations were very similar for all six drugs. The abnormalities concerned yolk sac circulation and morphology, as well as heartbeat, the morphology of the heart, head, neural tube, or forelimbs, and the shape of the embryo. The abnormal embryos were also growth retarded (decrease in protein content and crown-rump length). Interference with calcium channel functions seems to represent an interesting model for studying a special kind of abnormal prenatal development, especially the differentiation of certain mesenchymal structures. The concentration ranges between NOELs and 100% ELs were found to be: NIM = 0.1-1 microgram/ml; NIT and VER = 1-10 micrograms/ml; DIL = 1-30 micrograms/ml, and LOELs-100% ELs were: GAL = 1-10 micrograms/ml; NIF = 10-30 micrograms/ml.
Abnormalities, Drug-Induced↗
Differential association of membrane-bound and non-membrane-bound polysomes with the cytoskeleton.
We report here a differential release of specific mRNAs from the cytoskeleton by cytochalasin D treatment. Non-membrane-bound polysomal mRNAs, such as histone mRNA and c-fos mRNA, are readily released from the cytoskeleton of HeLa cells during cytochalasin D treatment. Over 90% of H3 and H4 histone mRNA is associated with the cytoskeleton in control cells and only 25% in cells treated with cytochalasin D (40 micrograms/ml). In contrast, the membrane-bound polysomal mRNAs for HLA-B7 and chorionic gonadotropin-alpha are inefficiently released from the cytoskeletal framework by cytochalasin D alone; approximately 98% of the HLA-B7 mRNA in control cells is associated with the cytoskeleton, whereas approximately 65% of the HLA-B7 mRNA is retained on the cytoskeleton in cells treated with cytochalasin D (40 micrograms/ml). Disruption of polysome structure with puromycin during cytochalasin D treatment results in the efficient release of HLA-B7 mRNA from the cytoskeleton. Under these conditions, only 25% of the HLA-B7 mRNA remains associated with the cytoskeletal framework. Thus, membrane-bound polysomes appear to be attached to the cytoskeleton through a cytochalasin D-sensitive site as well as through association with the nascent polypeptide and/or ribosome. These results demonstrate a complex association of polysomes with the cytoskeleton and elements of the endoplasmic reticulum.
Actin Cytoskeleton↗
Responses and toxic deaths in phase I clinical trials.
This review analysis consists of the antitumor activity and toxic deaths reported in single agent Phase I clinical trials using cytotoxic compounds published from 1972 to 1987. A total of 6639 patients with a variety of solid tumors and hematological malignancies were accrued in 211 trials studying 87 compounds. The median number of patients per trial was 28 (range: 7-111) and the median of the median ages reported in the individual trial was 56 (range of individual age: 2 to 93 years). Ten percent of the trials enrolled pediatric patients (less than 18 years), but the exact numbers of children were not always given or separated from the adult patients. Nine percent of the patients had received no prior treatment, 75% were pretreated either with chemotherapy alone (50%) or radio- plus chemotherapy (25%). Radiotherapy alone was administered to 11% of the patients and the remaining 5% of the patients received prior treatments which was not specified. The most frequent tumor types were those of the gastrointestinal tract (22%) and the respiratory tract (19%). The frequency of the remaining malignancies was less than 10% of all patients. There were 23 (0.3%) complete responders and 279 (4.2%) partial responders for an overall response rate of 4.5% among all entries. Toxic deaths were rare and reported in only 31 patients (0.5% of the entire population). Responses were usually observed in chemosensitive tumor types. Despite a low response rate reported during the first phase of cytotoxic drug development, the present analysis shows that some therapeutic benefit can be achieved.
Antineoplastic Agents↗
Malaria presenting as atypical depression.
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Adult↗
[In vitro studies of the adsorption behavior of Wofatit Y 88 in relation to various drugs].
The adsorber Wofatit Y 88 (VEB Chemiekombinat Bitterfeld) was tested regarding its adsorption properties in comparison with Hämoresin (B. Braun, Melsungen, FRG) Hemosorbent SKN-2K (USSR) and the own product Wofatit UH 91. As adsorptives the hypnotics Metaqualon, Pyrithyldion, Crotylbarbital and Phenobarbital were used. The investigation have been performed in a single-pass system in a relation of 1:25 to the clinical practice conditions. The concentration measurements to the estimation of adsorbed amounts were made by UV-VIS spectrometry. It was found that Wofatit Y 88 is superior to Hämoresin with regard to adsorbed amounts and adsorption speed. For all drugs Wofatit Y 88 was superior to UH 91.
Adsorption↗
[Use of calcium carbonate (CaCO3) as phosphate binder in dialysis patients in long-term follow-up over 3 years].
In 26 dialysis patients (age 46 +/- 47.8 years, dialysis 20.1 +/- 57 months) calcium carbonate was introduced to phosphate reduction for 3 years. The use of CaCO3 (4.4-9 g/d) for 9 months did reduce the phosphate level from 2.51 to 1.51 mmol/l in 77% of the patients and increase the calcium from 2.23 to 2.47 mmol/l. The long-term use use up to 3 years did'nt reduce the phosphate level effectively (mean value 2.24 mmol/l). In 77% of the patients a progression and in 42% new calcifications could be observed. The percentage of patients with soft tissue calcification within the 3-year CaCO3 therapy was increased from 43% to 67%. Therefore, CaCO3 alone in unsuitable for long-term use as phosphate binder in dialysis patients.
Aluminum↗
Natriuresis-pressure relationship in polycystic kidney disease.
We studied, under outpatient conditions, nine patients with autosomal dominant polycystic kidney disease who were hypertensive on their usual diet, and nine normotensive healthy probands. The subjects were examined in random order on the 7th day after equilibration on a low-sodium diet (20 mmol/day) and again on the 7th day after equilibration on the same diet but with added sodium to yield a final intake of 200 mmol/day (or vice versa). Blood pressure was monitored non-invasively for 2 h at 4-min intervals using an automatic system. In healthy probands, mean arterial pressure (MAP) was similar on the low- and the high-sodium diets (92.7 versus 91.9 mmHg). In hypertensive patients, a significant (P less than 0.02) increase in mean MAP (107.2 versus 111.2 mmHg) and in systolic blood pressure (140.6 versus 148.7 mmHg) was observed irrespective of whether the glomerular filtration rate (GFR) was normal or reduced. The natriuresis pressure curve showed an upward shift (resetting) and a positive slope (sodium sensitivity). Patients with a reduced GFR as shown by inulin clearance differed from probands and patients with a normal GFR, by showing greater proportional changes in GFR and body weight. In hypertensive patients, atrial natriuretic factor (ANF) levels were higher at baseline and showed an exaggerated response to sodium loading. Changes in angiotensin II (Ang II) or in Ang II binding sites on platelets were similar in patients and controls and changed appropriately with the sodium intake. These data show a resetting of the natriuresis-blood pressure relationship and an increased blood pressure sensitivity to sodium in hypertensive patients with adult, dominant, polycystic kidney disease.
Adult↗
Influence of membranes on generation of beta 2 M and release of leukocyte lysosomal enzymes.
Normal leukocyte functional capacity was investigated by evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. After incubation with dialysis membranes (different cellulosic membranes, polysulfon membrane (PS), polymethylmetacrylate membrane (PMMN), the phagocytosis index, expressed as percent decrease with respect to initial values without membrane, decreased by 10%-25%. The most pronounced effect was observed with PS, cuprophane, modified cellulose and PMMA. The results are not related to differences in the viability of PMN during the test procedure; dead PMN amounted to about 4-6.5%. A significant increase in beta-NAG and beta-Gluc activities was released in the supernatants of the phagocytosis suspensions. This increase activity can be explained by the phagocytosis of PMN but it was not influenced by membrane contact. There was no influence of membrane contact or phagocytosis activity of PMN on the beta 2 M concentration in the supernatant demonstrating that no in vitro generation during incubation with either membrane exists.
Acetylglucosaminidase↗
Down-regulation of histone H3 and H4 gene transcription in differentiated L6 myotubes.
The core histone mRNA levels in terminally differentiated L6 myotubes decrease to less than 5% of the amount present in proliferating myoblasts in parallel with the cessation of DNA synthesis (Bird, RC., Jacobs, F.A., Stein, G., Stein, J. and Sells, B.H. (1985) Biochim. Biophys. Acta 824, 209-217). The role of gene transcription in the down-shift of histone mRNA levels was assessed using a cell-free system. The level of transcription from the differentiation-independent adenovirus major late promoter was directly related to the RNA polymerase II activity of myoblast and myotube nuclear extracts. In addition, both extracts actively transcribed the histone H4 gene template containing only the 5 proximal promoter region (-210 bp). In contrast, inclusion of the distal-proximal promoter region (-410 to -210 bp) in the template resulted in a 60% decrease in transcription by the myotube extract. A similar down-shift in transcription of the histone H3 gene template (containing 900 bp 5 of the initiation site) by myotube nuclear extracts was also observed. The decrease in histone mRNA levels in myotubes may therefore be controlled in part by a transcriptional mechanism involving a negative regulatory factor.
Animals↗