The young lady with massive proteinuria, biopsy-confirmed steroid-resistant minimal change glomerulonephritis and episodes of turbid urine.
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Biomedical subjects
Publications and source records attributed to K Schubert.
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Four species of the newly proposed genus Macrococcus, namely macrococcus caseolyticus gen. nov., comb. nov. (formerly Staphylococcus caseolyticus Schleifer, Kilpper-Bälz, Fischer, Faller and Endl 1982, 19VP), Macrococcus equipercicus sp. nov., Macrococcus bovicus sp. nov. Macrococcus carouselicus sp. nov., are described on the basis of a phylogenetic analysis comparing 16S rRNA sequences, DNA-DNA liquid hybridization, DNA base composition, normalized ribotype patterns, macrorestriction pattern analysis and estimation of genome size using PFGE, cell wall composition, phenotypic characteristics and plasmid profiles. Compared with their closet relatives, members of the genus Staphylococcus, these organisms demonstrated significantly lower 16S rRNA sequence similarities (93.4-95.3%), higher DNA G+C content (38-45 mol%), absence of cell wall teichoic acids (with the possible exception of M. caseolyticus), unique ribotype pattern types and macrorestriction patterns, smaller genome size (approx. 1500-1800 kb) and generally larger Gram-stained cell size (1.1-2.5% microns in diameter). Macrococci can be distinguished from most species of staphylococci (except Staphylococcus sciuri, Staphylococcus vitulus and Staphylococcus lentus) by thier oxidase activity. The four Macrococcus species can be distinguished from one another on the basis of DNA-DNA hybridization, ribotype pattern types, macrorestriction patterns and their phenotypic properties, including colony morphology, cell morphology, haemolysins, Staphy Latex agglutination, acid production from a variety of carbohydrates, acetoin production, nitrate reduction, aesculin hydrolysis, and DNase and urease activities. The type species is M. equipercicus. The type strains of M. equipercicus, M. caseolyticus, M. bovicus and M. carouselicus are ATTCC 51831T (= DD 9350T) ATCC 13548T (= TDD 4508T) (Schleifer et al. 1982, ATCC 51825T (= DD 4516T) and ATCC 51828T (= DD 9348), respectively.
OBJECTIVE: To remotely test a stepwise framework of quality control measures, developed according to the 1997 European Society of Analytical Cellular Pathology consensus on diagnostic DNA image cytometry, in two series of measurements by means of the quantitation server EUROQUANT. STUDY DESIGN: In each of these series, 104 fine needle aspiration biopsies, imprints from breast cancer specimens and 28 rat liver imprints were measured twice at two different cytometry workstations. Further measurements on special rat liver specimens for evaluation of the stability of the machinery and of the preparation process were done at both workstations. Afterwards the measurement data from both machines were transferred to the quantitation server and analyzed automatically. Beside the classical DNA histograms, a set of further evaluations was performed to detect optical errors as well as inhomogeneities in the measurements. Running values for mean integrated optical density values, mean corrective factors and mean coefficients of variations of corrective factors were computed to control the stability of the entire methodology over time. RESULTS: The study demonstrated the preconditions and outcome of server-based quality control in DNA ploidy analysis. The results show that such a remote analysis is feasible and comparable to local DNA ploidy analysis. It is also demonstrated how quality control tests reflect the process performance of ploidy analysis at its different levels. CONCLUSION: Quality control must be an inherent part of the daily routine to allow a reliable diagnostic interpretation and ensure steadily high product quality.
OBJECTIVE: To compare the effect of two sequential hormone replacement regimens differing in the dose of levonorgestrel on climacteric symptoms, bleeding pattern and lipid metabolism in postmenopausal women. STUDY DESIGN: In a multicentre, randomized, double-blind, active-treatment-controlled study, 210 postmenopausal women were assessed at the end of treatment cycles 3 and 6. The high-levonorgestrel group was treated with 2 mg estradiol valerate (days 1-21) sequentially combined with 0.25 mg levonorgestrel (days 12-21). The low-levonorgestrel group received the same estrogen regimen (2 mg estradiol valerate, days 1-21), but levonorgestrel was administered sequentially in a dose of 0.15 mg during the last 12 days of the cycle (days 10-21). Statistical analysis by Student's t-test for dependent variables (measured values versus baseline) and independent variables (differences between groups), and the composite t-test method for comparison of both regimens with respect to efficacy, was performed. RESULTS: Both groups were statistically comparable. The trial was completed by 137 subjects. Protocol violations occurred in 38 cases. Thirty-five subjects dropped out during the study, 21 of them because of adverse events. Both treatments were equally effective in the treatment of climacteric complaints. There were no clinically significant changes in body weight, blood pressure, haematological tests, and parameters of clinical chemistry. There was a tendency towards a reduction in bleeding intensity in both groups in the second half of the treatment period. The treatment for six cycles with both regimens significantly (P < 0.05) decreased plasma concentrations of triglycerides (significant in the low-levonorgestrel group only), high-density lipoprotein cholesterol, high-density lipoprotein-3-cholesterol, lipoprotein(a) and apolipoprotein A1. In parallel, the serum concentration of total cholesterol increased significantly in both treatment groups, whereas low-density lipoprotein cholesterol increased significantly in the high-levonorgestrel group only. The changes in high-density lipoprotein-2-cholesterol, and apolipoprotein B did not reach statistical significance. CONCLUSIONS: It can be concluded that both sequential combined oral hormone replacement therapy (HRT) regimens were equivalent with respect to efficacy and tolerability in the treatment of women with climacteric complaints. The preparation with the lower dose of progestin showed a tendency towards a less unfavourable influence on the lipid profile.
Physiologically, an influence of sex steroids on the antioxidative capacity can be seen at least as a short-term effect. First of all the steroid effects are due to the estrogen component rather than the progestin component. The antioxidative potential of natural estrogens is several times higher than that of vitamin E. Long-term studies should be performed to verify this in perimenopausal hormone replacement.
Three subspecies of Staphylococcus sciuri, S. sciuri subsp. sciuri Kloos, Schleifer, and Smith 1976, 23AL emend. Kloos et al. 1997 [corrected], S. sciuri subsp. carnaticus subsp. nov., and S. sciuri subsp. rodentium subsp. nov., are described on the basis of their ribotype patterns, DNA-DNA liquid hybridization data, and phenotypic characteristics. Normalized ribotyping subdivided the S. sciuri patterns into three blocks of patterns, each corresponding to a subspecies. Each subspecies formed a separate, well-defined DNA similarity group when DNA-DNA hybridizations were conducted under stringent (70 degrees C) reassociation conditions. S. sciuri subsp. sciuri could be distinguished from the other subspecies on the basis of its ability to produce acid from D-cellobiose, alkaline phosphatase activity, and inability to produce either clumping factor or protein A. S. sciuri subsp. carnaticus could be distinguished by its ability to produce acid aerobically from D-xylose and maltose, inability to produce acid from D-melezitose, and smaller colony size on P agar. S. sciuri subsp. rodentium could be distinguished by its positive reaction in the latex agglutination test for clumping factor and/or protein A and generally higher frequencies and levels of oxacillin and methicillin resistance. All 40 strains of S. sciuri tested (including representatives of all three subspecies) hybridized with the mecA gene probe. All strains of S. sciuri subsp. sciuri, 79% of the strains of S. sciuri subsp. carnaticus and 89% of the strains of S. sciuri subsp. rodentium exhibited extracellular, staphylolytic enzyme activity. This activity was associated with an enzyme(s) that immunoblotted with a lysostaphin-specific monoclonal antibody; however, only three strains hybridized with a lysostaphin (end) gene probe. The type strain of S. sciuri subsp. carnaticus is DD 791 (= ATCC 700058), and the type strain of S. sciuri subsp. rodentium is DD 4761 (= ATCC 700061).
In the majority of cases, the mechanism underlying the resistance to acyclovir (ACV) of herpes simplex viruses (HSVs) is thymidine kinase (TK) deficiency. Plaque isolates from eight ACV-resistant (ACVr) clinical isolates from AIDS patients, of which five reactivated, were sequenced to determine the genetic lesion within the tk gene conferring resistance and whether this may have correlated with reactivation potential. Mutations were clustered within two homopolymer nucleotide stretches. Three plaque isolates (1737-14, 90-150-3, and 89-650-5) had insertion mutations within a stretch of 7 guanosines, while two isolates (89-063-1 and 89-353-1) had frameshift mutations within a stretch of 6 cytosines (a deletion and an insertion, respectively). Mutations resulted in premature termination codons, and the predicted 28- and 32-kDa truncated TK products were detected by Western blot analysis of virus-infected cell extracts. The repair of one homopolymer frameshift mutation (in isolate 1737-14) restored TK activity, demonstrating that this mutation is the basis of TK deficiency. Of the five reactivated isolates, four were TK deficient and contained frameshift mutations while the fifth retained TK activity because of its altered-TK or Pol- phenotype. These data demonstrate that the majority of ACVr clinical isolates contain frameshift mutations within two long homopolymer nucleotide stretches which function as hot spots within the HSV tk gene and produce nonfunctional, truncated TK proteins.
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The present study was designed to test the hypothesis that the descending pathway from the medial hypothalamus to the dorsal periaqueductal gray (PAG) is critical for the expression of defensive rage behavior in the cat and utilizes excitatory amino acids as a neurotransmitter. In the first phase of the study, monopolar stimulating electrodes were implanted into the medial hypothalamus from which defensive rage behavior could be elicited by electrical stimulation. For the entire study, the hissing response was used as a measure of defensive rage behavior. Cannula electrodes were implanted into the PAG from which defensive rage sites could be identified and were later used for microinfusion of the NMDA receptor antagonist, DL-2-amino-7-phosphoheptanoic acid (AP-7), into behaviorally identified sites within the PAG. Initially, intracerbral microinjections of the NMDA receptor antagonist, AP-7 (0.2, 2.0 nmol), which were placed directly into sites within the PAG from which defensive rage had been elicited, blocked the occurrence of hypothalamic hissing. Microinjections of similar doses of AP-7 into the PAG also blocked the facilitatory effects of medial hypothalamic stimulation upon hissing behavior elicited from the PAG. However, microinjections of 2 nmol into the PAG had no effect upon hissing that was also elicited from the region of the injection site. This finding indicates that AP-7 selectively blocks hissing elicited from the medial hypothalamus and that the suppressive effects of AP-7 cannot be the result of anesthetic or other nonselective properties of the drug. The next phase of the study, which employed immunohistochemical, receptor autoradiographic techniques, identified NMDA receptors to be present in highest concentrations in the dorsolateral aspect of the PAG where defensive rage is typically elicited. The final phase of the study, which employed a combination of retrograde labeling procedures following microinjections of Fluoro-Gold into defensive rage sites in the dorsal PAG and the immunocytochemical labeling of glutamatergic neurons, identified large numbers of neurons in the medial hypothalamus that were labeled positively for both Fluoro-Gold and glutamate. The overall findings of this study support the hypothesis that descending fibers of the medial hypothalamus that supply the dorsal aspect of the PAG mediate defensive rage behavior and utilize excitatory amino acids that act upon NMDA receptors within the dorsal PAG.
BACKGROUND/AIMS: The pathophysiological role of leukotrienes in liver disease is not well understood. Redistribution or enhanced formation in cholestatic states may result in increased hepatic concentrations that are expected to contribute to liver injury. To disclose the potential role of cysteinyl-leukotrienes in chronic liver diseases, we studied biliary and urinary secretion in the model situation of relief of bile duct obstruction. METHODS: Concentrations of cysteinyl-leukotrienes were determined in bile and urine of patients with extrahepatic biliary obstruction in the course of therapeutic decompression by endoscopic or transhepatic techniques. Leukotrienes were measured by radioimmunoassay after HPLC separation. Concentrations of bile acids in bile and serum were measured for comparison. RESULTS: Bile collected 2 h after decompression contained high concentrations of leukotrienes (57.5 +/- 22 microM). Biliary secretion decreased over 24 h reaching equilibrium values after 48-72 h (2.8 +/- 1.7 mM and 6.4 +/- 6.6 microM, respectively). Total bile acid concentration in serum followed a similar time course. In contrast, biliary bile acid concentration showed high interindividual variations. Bile contained all leukotriene C4, D4, E4 and NAc-LTE4, but LTC4 was predominant. Urinary leukotriene secretion in cholestasis (199.7 pmol/mmol creatinine) was less than 7% of maximal biliary secretion. It further decreased to 116.4 pmol/mmol creatinine within 72 h. Urine also contained all species of cysteinyl-leukotrienes, but the relative amounts of LTE4 and NAc-LTE4 were higher than in bile. CONCLUSIONS: Formation of cysteinyl-leukotrienes is increased in obstructive jaundice resulting in increased urinary excretion before and both biliary and urinary excretion after relief of the obstruction. Predominance of LTC4 suggests that the secreted leukotrienes are newly formed. Increased synthesis and retention of hepatic cysteinyl-leukotrienes may contribute to hepatic and extrahepatic consequences of cholestasis.
New species names, Brachybacterium alimentarium and Brachybacterium tyrofermentans, are proposed for two coryneform bacteria isolated from the surfaces of Gruyère and Beaufort cheeses. These two species are similar in their biochemical and chemotaxonomic characteristics but distinct from previously described bacteria. The most distinctive characteristics are the presence of meso-diaminopimelic acid-containing peptidoglycan with a D-Glu-D-Asp interpeptide bridge and the presence of erythritol teichoic acids that contain diaminoglucuronic acid (an uncommon substituent). The menaquinone pattern of these organisms is unique among coryneform bacteria. DNA-DNA hybridization experiments revealed that the level of hybridization between the two organisms is 15%, which indicates that they are distinct species. Despite the unique biochemical characteristics of these bacteria, a 16S rRNA sequence comparison revealed that they are unquestionably related to Brachybacterium faecium, Brachybacterium nesterenkovii, and Brachybacterium conglomeratum. DNA-DNA hybridization experiments performed with these three species, B. alimentarium, and B. tyrofermentans revealed that the levels of complementarity ranged from 11 to 38%, values that are similar to the values obtained for Brachybacterium strains described previously. With the inclusion of B. alimentarium and B. tyrofermentans the genus Brachybacterium becomes somewhat heterogeneous with respect to chemotaxonomic characteristics.
Previous studies have shown that, at certain dose levels, ethanol can exert a powerful, facilitatory effect on aggressive behavior in both animals and humans. In the cat, however, it was discovered that ethanol differentially alters two forms of aggression that are common to this species. Defensive rage behavior is significantly enhanced, whereas predatory attack behavior is suppressed by ethanol administration. One possible mechanism governing alcohol's potentiation of defensive rage behavior is that it acts on the descending pathway from the medial hypothalamus to the midbrain periaqueductal gray (PAG)-an essential pathway for the expression of defensive rage behavior that uses excitatory amino acids as a neurotransmitter. This hypothesis is supported by the finding that the excitatory effects of alcohol on defensive rage behavior are blocked by administration of the N-methyl-D-aspartate antagonist alpha-2-amino-7-phosphoheptanoic acid (AP-7) when microinjected into the periaqueductal gray, a primary neuronal target of descending fibers from the medial hypothalamus that mediate the expression of defensive rage behavior. Thus, the present study establishes for the first time a specific component of the neural circuit for defensive rage behavior over which the potentiating effects of ethanol are mediated.
Despite successful management of early complications in polytraumatized patients and obvious reduction of early death, lethality in the late course of the disease--frequently as a result of multiple organ failure (MOF)--remains generally unaffected. Concerning the pathogenesis of sepsis and MOF, there is some evidence that a central role is played by endotoxin. A series of 32 patients with severe polytraumatic injury (Hannover Polytrauma Score > 20 points) comprised the study group. Endotoxin was measured hourly over the first 24 hours. The first measuring point was four hours after injury at the latest. Endotoxin levels were determined by a quantitative turbidimetric limulus assay. The Goris MOF score reached between the 8th and 10th day after injury was used for evaluation of the severity of MOF. Thirty of the 32 patients showed episodes of endotoxemia during the measuring period. There was a strong correlation between observed endotoxin peak concentrations, on the one hand, and outcome as well as positive predictive value (PPV) concerning development of MOF, on the other hand. If the peak concentration was greater than 10 pg/ml, the PPV reached 100%. No patient survived a peak concentration greater than 12 pg/ml. Endotoxemia during the early phase after polytraumatic injury is a frequent phenomenon. It appears to be possible that measurement of endotoxin peak concentration during the early phase gives some indication of the development of MOF and the outcome of these patients.
A novel mouse L-cell mutant cell line defective in the biosynthesis of glycosaminoglycans was isolated by selection for cells resistant to herpes simplex virus (HSV) infection. These cells, termed sog9, were derived from mutant parental gro2C cells, which are themselves defective in heparan sulfate biosynthesis and 90% resistant to HSV type 1 (HSV-1) infection compared with control L cells (S. Gruenheid, L. Gatzke, H. Meadows, and F. Tufaro, J. Virol. 67:93-100, 1993). In this report, we show that sog9 cells exhibit a 3-order-of-magnitude reduction in susceptibility to HSV-1 compared with control L cells. In steady-state labeling experiments, sog9 cells accumulated almost no [35S]sulfate-labeled or [6-3H]glucosamine-labeled glycosaminoglycans, suggesting that the initiation of glycosaminoglycan assembly was specifically reduced in these cells. Despite these defects, sog9 cells were fully susceptible to vesicular stomatitis virus (VSV) and permissive for both VSV and HSV replication, assembly, and egress. HSV plaques formed in the sog9 monolayers in proportion to the amount of input virus, suggesting the block to infection was in the virus entry pathway. More importantly, HSV-1 infection of sog9 cells was not significantly reduced by soluble heparan sulfate, indicating that infection was glycosaminoglycan independent. Infection was inhibited by soluble gD-1, however, which suggests that glycoprotein gD plays a role in the infection of this cell line. The block to sog9 cell infection by HSV-1 could be eliminated by adding soluble dextran sulfate to the inoculum, which may act by stabilizing the virus at the sog9 cell surface. Thus, sog9 cells provide direct genetic evidence for a proteoglycan-independent entry pathway for HSV-1, and results with these cells suggest that HSV-1 is a useful reagent for the direct selection of novel animal cell mutants defective in the synthesis of cell surface proteoglycans.
The present study tested the hypotheses that: (1) defensive rage behavior elicited from the midbrain periaqueductal gray (PAG) in the cat is facilitated from the basal complex of amygdala; and (2) such facilitation from this region of amygdala is mediated via a pathway in which excitatory amino acids acting upon NMDA receptors within the PAG are utilized as a neurotransmitter. In the first phase of this study, cannula electrodes were implanted into PAG sites for the elicitation of defensive rage behavior as well as for drug delivery. Then, a second monopolar electrode was implanted into the basal nucleus of amygdala from which facilitation of defensive rage could be obtained. As a result of dual stimulation of the basal amygdala and PAG, response latencies for defensive rage were significantly lowered relative to PAG stimulation alone (P < 0.01). In the second phase of this experiment, 3 doses of a selective NMDA receptor antagonist, AP-7 (0.1, 0.5, 1.0 mg/kg), were peripherally (i.p.) administered in 5 animals. The results indicated a significant decrease in the facilitatory effects of amygdaloid stimulation in a dose and time dependent manner (P < 0.001). In the third phase, AP-7 was administered intracerebrally into PAG defensive rage sites in doses of 0.2 and 2.0 nmol. It was noted that intracerebral microinjections of AP-7 at the higher dose (2.0 nmol) also significantly suppressed the facilitatory effects of amygdaloid stimulation (P < 0.01); however, these effects were somewhat less potent then those observed following peripheral drug administration. A fourth phase of the study was conducted at the completion of the pharmacological experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Strains of a new species, Staphylococcus vitulus, were isolated from food and a variety of mammals. This species was recognized on the basis of the results of an analysis of genomic EcoRI fragments containing portions of the rRNA operons. The patterns of hybridized fragments obtained from strains belonging to the new taxon were sorted into a distinguishable cluster and were distinct from the Staphylococcus lentus and Staphylococcus sciuri patterns. The results of DNA-DNA hybridization reactions demonstrated that strains in this cluster were more closely related to S. lentus and S. sciuri than to other Staphylococcus species and yet were significantly different. While these strains had some of the phenotypic characteristics of the S. sciuri species group, the newly recognized taxon could be distinguished by its very small colonies on P agar, absence of alkaline phosphatase activity, and lack of acid production from L-arabinose, maltose, N-acetylglucosamine, D-mannose, and raffinose. The type strain of the new species is strain DD 756 (= ATCC 51145).
The primary structure of the peptidoglycan and the teichoic acids of two coryneform isolates from the surface flora of French cooked cheeses, CNRZ 925 and CNRZ 926, have been determined. In the peptidoglycan, meso-diaminopimelic acid was localized in position three of the peptide subunit. It contained an D-glutamyl-D-aspartyl interpeptide bridge, connecting meso-diaminopimelic acid and D-alanine residues of adjacent peptide subunits. The alpha-carboxyl group of D-glutamic acid in position two of peptide subunits was substituted with glycine amide. The teichoic acid pattern and composition differed between the strains: both contained an erythritol teichoic acid and strain CNRZ 925 also contained an N-acetylglucosaminylphosphate polymer. The erythritol teichoic acids differed in terms of the quality and quantity of substituents, but they both had N,N'-diacetyl-2,3-diamino-2,3-dideoxyglucuronic acid in common.
The performance of a membrane in renal failure therapy is determined by its structure, its overall mass transfer properties, and its blood compatibility. In this regard, removal of beta 2-microglobulin (beta 2M) has become a major objective of dialysis therapy. In the present study, a newly developed high-flux membrane composed of a polyester-polymer alloy (PEPA) with the components of polyarylate and polyethersulfone (dialyzer FLX-12 GW; Nikkiso Co., Japan) has been evaluated with regard to both biocompatibility and elimination capacity for beta 2M during hemodialysis of 8 stable chronic uremic patients. The clearance values of low molecular weight solutes were in the same range as those reported for high-flux dialyzers of comparable surface area. There was no drop in leukocyte counts and only a minimal fall in platelet counts nearly in the same range as has been observed by other investigators using polyamide membrane. C3a Des Arg generation was low, and C5a Des Arg formation was not significantly influenced. There was a sharp drop in the serum beta 2M level (-35%) during dialysis with a clearance between 59.7 +/- 5.6 ml/min (QB 200 ml/min) and 70.1 +/- 9.7 ml/min (QB 300 ml/min), respectively. Accordingly, the sieving coefficient was calculated to be 0.2 at 30 min after start of dialysis and 0.6 1 h later. The membrane was able to remove 184.0 +/- 22.3 mg/4 h due to an apparent rate of adsorption during the first hour of treatment in combination with high transmembrane transfer in the following time.