[Quantitative study of the regeneration of bone marrow morphology after administration of high doses of benfluron to laboratory rats].
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Biomedical subjects
Publications and source records attributed to J Berger.
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In a randomized, endoscopically controlled double-blind trial the effectiveness of a single oral, morning dose of 40 mg omeprazole was compared with a twice daily oral dose of 150 mg ranitidine given to 334 ambulatory patients with duodenal ulcers. Under omeprazole 105 of 146 duodenal ulcers were demonstrated to have healed within 14 days (72%), compared with 95 of 160 (59%) on ranitidine. The difference is statistically significant (P = 0.0121). After 14 days smaller ulcers healed more quickly than large ones, regardless of the drug used: 80 of 110 with diameter 3-5 mm (73%); 48 of 90 with diameter more than 8 mm (53%). Smoking delayed healing [healing rate among non-smokers, 87 of 117 (74%); among smokers, 113 of 189 (60%)]. Healing rates among smokers receiving omeprazole and non-smokers receiving ranitidine were nearly identical. After 4 weeks, at 96 and 92% respectively, there was no difference in regard to healing rate. Both drugs had a similar influence on the symptoms. Thus, for the first time it has been demonstrated that omeprazole is superior to ranitidine after 14-day treatment of duodenal ulcer.
The conversion of type I procollagen to type I collagen was studied by cleaving the protein with partically purified type I procollagen N-proteinase from chick embryos. Examination of the reaction products after incubation for varying times at 30 degrees C indicated that, during the initial stages of the reaction, pro alpha 1(I) and pro alpha 2(I) chains were cleaved at about the same rate. As a result, all the pro alpha 2(I) chains were converted to pC alpha 2(I) chains well before all the pro alpha 1 chains were cleaved. When the reaction products were examined by gel electrophoresis without reduction of interchain disulfide bonds, a distinct band of an intermediate was detected. The same intermediate was seen when the reaction was carried out at 35, 37, and 40 degrees C. The data established that over two-thirds of the type I procollagen was converted to the intermediate and that this intermediate was then slowly converted to the final product of pCcollagen. The kinetics for the reaction, however, did not fit a simple model for precursor-product relationship among substrate, intermediate, and product. Examination of the reaction products with a two-step gel procedure demonstrated that the intermediate consisted of three polypeptide chains in which the N propeptide was cleaved from one pro alpha 1 chain and one pro alpha 2(I) chain but the N propeptide was still present on one of the pro alpha 1(I) chains. In further experiments it was demonstrated that a similar intermediate was seen when a homotrimer of pro alpha 1(I) chains was partially cleaved by the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
Procollagen N-proteinase, the enzyme which cleaves the NH2-terminal propeptides from type I procollagen, was purified over 15,000-fold from extracts of chick embryos by chromatography on columns of DEAE-cellulose, concanavalin A-agarose, heparin-agarose, pN-collagen-agarose, and a filtration gel. The purified enzyme had an apparent molecular weight of 320,000 as estimated by gel filtration and a pH optimum for activity of 7.4 to 9.0. The enzyme was inhibited by metal chelators and the thiol reagent dithiothreitol. Addition of calcium was required for maximal activity under the standard assay conditions, and the presence of calcium decreased thermal inactivation at 37 degrees C. The purified enzyme cleaved a homotrimer of pro-alpha 1(I) chains, an observation which indicated that the presence of pro-alpha 2(I) chain is not essential for the enzymic cleavage of NH2-terminal propeptides. Previous observations suggesting that the enzyme requires a substrate with a native conformation were explored further by reacting the enzyme with type I procollagen at different temperatures. Type I procollagen from chick embryo fibroblasts became resistant to cleavage at about 43 degrees C. Type I procollagen from human skin fibroblasts, which was previously shown to have a slightly lower thermal stability than chick embryo type I procollagen, became resistant to cleavage at temperatures that were about 2 degrees C lower. The results suggested that the enzyme is a sensitive probe for the three-dimensional structure of the NH2-terminal region of the procollagen molecule and that it requires the protein substrate to be triple helical.
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A significant proportion of large lymphocytes in laboratory rats is stained with Sudan black B. The increase in the counts of sudanophilic blood lymphocytes over control values indicated reliably the recovery of lymphocytic function even when total lymphocyte, small or large lymphocyte counts were normal or reduced.
The maxillofacial trauma patient whose neurologic status undergoes a rapid and serious deterioration may have a severe hyponatremia secondary to the inappropriate secretion of antidiuretic hormone (SIADH). Other causes of hyponatremia must be ruled out, especially posttraumatic cerebral salt wasting, which necessitates a different mode of therapy. A case of SIADH is reported, and the work-up and differential diagnosis of posttraumatic hyponatremia are discussed.
To characterize the physicochemical properties of the mesangial IgA in primary IgA nephropathy, acid-eluates from percutaneous renal biopsies of 20 patients were examined. The acid-eluates were obtained from 1287 +/- 498 glomerular sections. The IgA content (mean 15 +/- 10 ng) represented 0.4% of the total eluted proteins. To analyze the molecular weight and the charge of eluted IgA, 11 eluates were subjected to high pressure liquid chromatography (at pH 6.8 and/or pH 3.5) and five eluates to isoelectric focusing on agarose. IgA was detected in the fractions by an IgA-RIA. Comparison of the elution profiles at different pH showed a statistically significant decrease of the excluded IgA peak (greater than or equal to 1,000,000 daltons), and a significant increase of polymeric IgA peaks (1,000,000-320,000 and 320,000 daltons) in acidic chromatography, as compared to non-dissociating conditions. Under acidic conditions, polymeric IgA represent 64% of total eluted IgA. Secretory component binding to polymeric IgA was demonstrated in four out of eight eluates tested. The isoelectric point (pI) of eluted IgA ranged from 4.5 to 5.6, contrasting with the broader and more neutral pI of normal serum IgA (4.5 to 6.8). This study shows that the multimeric nature of IgA, the formation of IgA complexes, and the anionic charge of IgA are likely to be involved in the mesangial IgA deposition in idiopathic IgA nephropathy.
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This is a longitudinal study of all patients seen in the first five years of a private psychiatric practice. At the present time, it is believed to be the only known complete study of patients in a typical private practice. The data from 486 patients has been collected and analyzed and some of the results have been compared to those obtained in other studies. Some significant findings emerged. Depression is the single commonest condition and its frequency was similar to that found in other studies. Psychoses were rare. A large category of patients was described as having a Personality Disorder. The implications of these and other findings are discussed. The data are relevant to aspects of clinical psychiatry, to the teaching of psychiatry, and to the financial insurance coverage of medical services.
In an attempt to give assistance in the search for a simple haematological system for the detection of toxic-haemolytic effects of chemical substances, we used a battery of simple tests and phenacetin as a reference substance. The drug was administered in a single dose or repeatedly for two or four weeks. Higher plasma haemoglobin levels and symptoms of anaemia (decreased blood haemoglobin levels, erythrocytic counts, haematocrit) and activated erythropoiesis (increased reticulocyte counts, MCV, marrow and splenic E:M ratios) were found to be best marked following administration of phenacetin in the very high dose of 1.0 g/kg per orally for two weeks. Our results suggest that plasma haemoglobin levels could provide information on the haemolytic potential of phenacetin if the experimental schedule included the optimal combination of suitable phenacetin dosage and duration of loading.
The DNA binding guanine specific antibiotic, chromomycin A3, has been evaluated for fluorescence intensity measurements of T. cruzi, T. brucei brucei and T. musculi. Optimal fixation and staining conditions have been determined. The fluorometry was performed with a microscope photometer equipped with electronic systems for short time excitation of 7 milliseconds and operation control. The trypomastigote bloodstream forms of these species have a different chromomycin specific DNA content. The total DNA content of T. cruzi was 2.1-fold higher than for T.b. brucei and 2.3-fold higher than for T. musculi. The nuclear DNA content also was higher in T. cruzi. The nuclear DNA values were recorded to be 1.6-fold greater than in T.b. brucei and 2.0-fold greater than in T. musculi. The amount of the kinetoplast DNA of T. cruzi was shown to be 3.2-fold higher than in T. musculi and 11.7-fold higher than in T.b. brucei. The higher total DNA of T.b. brucei in relation to T. musculi was based on the nuclear values because the content of the kinetoplast DNA of T.b. brucei was 3.7-fold smaller than of T. musculi. The kDNA comprised 25% in T. cruzi, 18% in T. musculi and only 4% in T.b. brucei of the total amount of the chromomycin specific DNA. The chromomycin fluorescence intensities of the DNA of trypanosomes were subjected to a statistical model of discriminant analysis. It was possible to get perfect separation of the three trypanosome species. The hit rate was 100%.
An increase of the plasma haemoglobin level was found to be a reliable characteristic of toxic-haemolytic anaemia induced by a single dose of phenylhydrazine in laboratory rats. Very high doses of the substance increased the changes in many other characteristics to an extent that was up to now observed only for haemolytic events.
In two double-blind, randomized German multicentre trials the effects of omeprazole 20 mg mane and ranitidine 150 mg b.i.d. were compared for the first time in 334 outpatients with duodenal ulcer and 184 outpatients with gastric ulcer. In patients with duodenal ulcer endoscopically controlled healing rates after two weeks were 72% with omeprazole and 59% with ranitidine (p = 0.012); after 4 weeks 96 and 92%, resp. were healed (n.s.). In patients with gastric ulcer the healing rates after two, four, and eight weeks were 43, 81, and 95%, respectively, with omeprazole and 45, 80, and 90%, respectively, with ranitidine (n.s.). Smoking impaired healing in duodenal, but not in gastric ulcer. Symptom relief was comparable with both drugs. Serious side effects or clinically relevant changes in laboratory screening results were not detected. - Our results demonstrate for the first time that omeprazole 20 mg mane is superior to ranitidine 150 mg b.i.d. in the short-term treatment of duodenal, but not gastric ulcer.
Single oral administration of a toxic dose of mercuric chloride (2.0 mg/kg) resulted in moderate reticulocytopenia and stress reaction in the white blood picture. A slight decrease in marrow cellularity followed the administration of 0.5 or 2.0 mg/kg. Repeated administration led to an elevated reticulocyte count and leukocytic stress reaction. An increase in marrow E: M ratio, proportion of erythroid nucleated cells in both femoral marrow and spleen was also found. The elevation of doses and prolongation of the time of treatment did not lead to a deterioration of marrow morphology; a diminution of the haemotoxicity for the rat marrow was revealed in the present experiments too.
Two systems were used to generate collagen fibrils in vitro by enzymic cleavage of intermediates in the conversion of procollagen to collagen. In one system fibrils were generated by using procollagen NH2-terminal proteinase to cleave pNcollagen, the intermediate which contains the NH2-terminal but not the COOH-terminal propeptides found in procollagen. When pNcollagen was incubated with procollagen NH2-terminal proteinase, the NH2-terminal propeptides were enzymically cleaved from the protein, and there was an increase in the turbidity of the solution over and above the turbidity observed with pNcollagen alone. Electron microscope examination of the samples demonstrated that the increase in turbidity was associated with the assembly of collagen fibrils. The fibrils had a mean diameter of 104 nm +/- 51.7 S.D. or about the same as fibrils formed from pNcollagen alone. However, the fibrils formed by enzymic cleavage of pNcollagen had a more distinct gap-overlap pattern and they appeared to be more tightly packed than fibrils of pNcollagen. Varying the concentration of enzyme varied both the rate of enzymic cleavage of the pNcollagen and the rate of fibril assembly, but there was no consistent effect on the diameter or morphology of the fibrils. In the second system, fibrils were generated with a recently described procedure (Miyahara, M., Njieha, F. K., and Prockop, D. J. (1982) J. Biol. Chem. 257, 8442-8448) in which procollagen COOH-terminal proteinase is used to cleave pCcollagen, the intermediate containing the COOH-terminal but not the NH2-terminal propeptides found in procollagen. When incubated with procollagen COOH-terminal proteinase, the COOH-terminal propeptides were cleaved and collagen fibrils assembled. The collagen fibrils were unusually thick with a mean diameter of 1184 nm +/- 291 S.D. The large diameters of the fibrils made it possible to demonstrate by scanning electron microscopy that each fibril was comprised of a bundle of subfibrils packed into a right-handed helix. The fibrils frequently had branch points which appeared to consist of subfibrils which separated from the main axis of the structure. Also, the surface of the fibrils was scalloped at 270- to 300-nm intervals, suggesting that some of the collagen molecules on the surface were in a 4D staggered array. The results suggested the hypothesis that the order in which the NH2-terminal and COOH-terminal propeptides are cleaved in the conversion of procollagen to collagen may provide a mechanism for controlling the diameter, or both the diameter and morphology, of collagen fibrils.
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The clinical entities of bacterial contamination, septicemia, and septic shock have been discussed, and an unusual case of septic shock has been presented. The associated risks of intravenous delivery of drugs or fluids are stressed.