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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 505 records · Page 28Linked to original sources

Evidence for the production of high amounts of interleukin-6 in the peritoneal cavity of patients with ascites.

The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites.

Adult↗

The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation.

Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure. In the present study, the molecular nature of the defect in Alport glomerular basement membrane (GBM) was explored using anti-GBM alloantibodies (tissue-bound and circulating) produced in three Alport patients subsequent to renal transplantation. The alloantibodies bound to the alpha 3(IV)NC1 domain of type IV collagen and not to any other basement membrane component. In tissue sections, the alloantibodies bound specifically to peripheral GBM in normal kidney and the affected renal transplant but not to that of Alport kidney. These results establish that: the alpha 3 chain in type IV collagen molecules, the Goodpasture autoantigen, is the target alloantigen in post-transplant anti-GBM nephritis in patients with Alport syndrome, and that a molecular commonality exists in the pathogenesis of anti-GBM nephritis causing loss of renal allografts in patients with Alport syndrome and renal failure in patients with Goodpasture syndrome. These findings implicate: (1) defective assembly of type IV collagen molecules containing the alpha 3(IV) chain in Alport GBM; and (2) the existence of a mechanism linking the assembly of molecules containing the alpha 3(IV) chain with those containing the alpha 5(IV) chain.

Adult↗

Deletions of the COL4A5 gene in patients with Alport syndrome.

Mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen have been found in linkage with X-chromosomal Alport syndrome (AS). To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting. By using full length alpha 5(IV) cDNA probes, large COL4A5 deletions could be detected in two patients. In one case, a 34 kb deletion affecting the 14 most 3' exons of the gene was observed. The second patient harbored a complete COL4A5 deletion. In both cases, functional alpha 5(IV) mRNA was unlikely to be present. Clinically, both patients developed end-stage renal failure before age 30. Furthermore, they had characteristic retinal flecks, and sensorineural hearing loss with typical changes on the audiogram. The patient with the complete deletion of COL4A5 lost the renal allograft due to an anti-GBM mediated glomerulonephritis.

Adolescent↗

Erythropoiesis in multiple myeloma: defective red cell production due to inappropriate erythropoietin production.

We investigated the pathophysiology of erythropoiesis in 62 patients with multiple myeloma and examined whether it would establish a rational basis for the treatment of their anaemia with recombinant human erythropoietin. Erythropoietin (Epo) production was evaluated by serum levels and erythropoiesis was quantitated by serum transferrin receptor (TfR) levels, both assessed relative to the degree of anaemia. Instead of the expected stimulation of erythropoiesis in response to anaemia, haematocrit correlated positively with marrow erythropoietic activity, indicating that the mechanism of anaemia was primarily defective red cell production. Erythropoiesis decreased and anaemia worsened significantly with advancing clinical stage. 25% of the patients had inadequate Epo production and this proportion increased to 50% in stage 3. Inappropriate Epo production was seen in 60% of patients with renal impairment but was also observed in a number of patients with normal renal function. Erythropoiesis correlated strongly with the adequacy of Epo production, particularly in advanced disease. We conclude that most myeloma patients have defective red cell production even in the absence of massive marrow infiltration and that inappropriate Epo production contributes to their anaemia.

Adult↗

Different immunologic properties of the globular NC1 domain of collagen type IV isolated from various human basement membranes.

The C-terminal globular domain NC1 of collagen IV, which carries the epitopes recognized by anti-GBM antibodies in Goodpasture's syndrome, was isolated from human basement membranes (BM) of glomeruli (GBM-NC1), tubules (TBM-NC1), lung (ABM-NC1), placenta (PBM-NC1), and small intestine (IBM-NC1). All NC1 hexamers were of globular size on electron microscopy. On SDS-PAGE, the hexamers dissociated into monomeric and dimer-sized subunits of similar molecular weights. The following monomer:dimer relationships were identified: GBM-NC1, and PBM-NC1 = 1:3; ABM-NC1 = 1:4; and IBM-NC1 = 1:32. On immunoblot, all dimers of the various NC1 globules showed binding of anti-GBM antibodies. However, monomers stained differently, with three monomers demonstrable in GBM-NC1 and no monomer staining in PBM-NC1. In addition, studies with monoclonal antibodies showed that the C-terminus of the alpha 1(IV) collagen chain was demonstrable in all different NC1 hexamers. In contrast, the alpha 3(IV) chain, to which Goodpasture sera preferentially bind, showed a restricted distribution. One monomer and dimers were demonstrable in GBM-NC1 and ABM-NC1, only a weak dimer staining was seen in TBM-NC1, while no evidence for alpha 3(IV) was found in IBM-NC1 and PBM-NC1. Dissociation by 6 M guanidine-HC1 or treatment by acid increases the apparent number of accessible epitopes for anti-GBM antibodies. In addition, dose-response curves, which were obtained by incubation of increasing concentrations of NC1 with anti-GBM antibody positive sera, indicated that for GBM-NC1 and ABM-NC1 the lowest NC1 protein concentrations were necessary to bind 50% of the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Glomerular Basement Membrane Disease↗

Epicardial sites for vagal mediation of sinoatrial function.

The posterior atrial fat pad (PAFP) has been described as the probable anatomic location of parasympathetic ganglia mediating sinoatrial (SAN) and atrioventricular nodal function in the mammalian heart. This contrasts with recent localizations of such control elements in the pulmonary vein fat pad (PVFP) and in fatty tissues overlying the junction of inferior vena cava-inferior left atrium (IVC-ILA), respectively. Short bursts (5-8 pulses/burst, 3 bursts/train) of electrical current (1-16 Hz, 400 ms, 1-5 mA) applied directly to the ventral right atrial epicardium via a concentric bipolar electrode (separation 0.3-0.6 mm) during the atrial muscle refractory period, activated subepicardial postganglionic pathways from PVFP and entering the SAN; identical stimulation of dorsal right atrial epicardium between PAFP and SAN excited few or no fiber pathways controlling SAN discharge rate or patterns. In a second series of experiments, injection of a neuronal marker (Fast Blue) into and around SAN, with time (5-10 days) allowed for retrograde transport, resulted in staining of many soma in PVFP but none in IVC-ILA or PAFP. These data strongly affirm the primary, and perhaps exclusive, localization of ganglia that mediate parasympathetic regulation of SAN function in PVFP of the dog's heart, with little or no such participation by ganglia within PAFP or IVC-ILA.

Adipose Tissue↗

Cell cycle modification during the transitions between meiotic M-phases in mouse oocytes.

When metaphase II-arrested mouse oocytes (M II) are activated very soon after ovulation, they respond abortively by second polar body extrusion followed by another metaphase arrest (metaphase III, M III; Kubiak, 1989). The M II/M III transition resembles the natural transition between the first and second meiotic metaphases (M I/M II). We observed that a similar sequence of events takes place during these two transitions: after anaphase, a polar body is extruded, the microtubules of the midbody disappear rapidly and a new metaphase spindle forms. The MPM-2 monoclonal antibody (which reacts with phosphorylated proteins associated with the centrosome during M-phase) stains discrete foci of peri-centriolar material only in metaphase arrested oocytes; during both transitional periods, a diffuse staining is observed, suggesting that these centrosomal proteins are dephosphorylated, as in a normal interphase. However, the chromosomes always remain condensed and an interphase network of microtubules is never observed during the transitional periods. Incorporation of 32P into proteins increases specifically during the transitional periods. Pulse-chase experiments, after labeling of the oocytes in M phase with 32P, showed that a 62 kDa phosphoprotein band disappears at the time of polar body extrusion. Histone H1 kinase activity (which reflects the activity of the maturation promoting factor) drops during both transitional periods to the level characteristic of interphase and then increases when the new spindle forms. Both the M I/M II and M II/M III transitions require protein synthesis as demonstrated by the effect of puromycin. These results suggest that the two M-phase/M-phase transitions are probably driven by the same molecular mechanism.

Animals↗

Interactions between glomerular mesangial cells, cytokines, and extracellular matrix.

This brief overview summarizes recent information on the interactions of glomerular mesangial cells (MC) with soluble cytokines and nonsoluble extracellular matrix (ECM). The presently available knowledge stems largely from glomerular cell culture studies and from experimental work with laboratory animals. ECM production by MC appears to be regulated primarily by the paracrine or autocrine effects of cytokines, such as interleukin 1, platelet-derived growth factor, and transforming growth factor beta. However, ECM itself also affects the behavior of cultured MC, e.g., with regard to cell replication and the production of ECM components and other proteins. At present, little is known about the recognition of ECM and cytokines by MC that allows these interactions to take place. First results indicate that MC, like other cell types, possess surface proteins belonging to the beta 1 integrin family, which serve as specific receptors for ECM molecules. Receptors for the cytokines platelet-derived growth factor, insulin-like growth factor 1, epidermal growth factor, and transforming growth factor beta have also been demonstrated on MC. The expression of various receptors on MC appears to be affected by the ECM substratum. Thus, it is becoming apparent that mesangial ECM is not only important as a mechanical scaffold of the glomerular capillary tuft but that it also contains and conveys information relevant for the regulation of the MC phenotype, e.g., by modulating the MC response to cytokines. The available evidence suggests that alterations of ECM composition in glomerular disease can directly or indirectly affect MC behavior, e.g., by promoting cell replication and further accumulation of ECM, eventually resulting in progressive mesangial and glomerular sclerosis.

Animals↗

[Urinary tract infections during the 1st month after kidney transplantation].

The incidence and the predisposal factors of urinary tract infections (UTI) in the first month post-transplant were studied in 255 kidney transplantations (252 patients). UTI episodes were demonstrated in 73.7% of the grafts. The most common organisms were: Escherichia coli (35.8%), Staphylococcus (33.6%), Streptococcus D (11.2%), Klebsiella (5.3%). The infectious episodes were recurrent in 39% of the cases. The majority of the UTIs were asymptomatic but 7% of the infections led to septicaemia. Etiology of end-stage renal disease, pre-graft binephrectomy, asymptomatic vesicoureteral reflux into the patient's own kidneys, type of immunosuppressive treatment, acute tubular necrosis, rejection episodes, urological complications, coexistent other infections were not predisposal factors. Bacteriuria was more frequent in female than in male patients. The incidence of UTI was found to be statistically increased with history of UTI preoperatively (p = 0.039) and the use of ureteral catheter (p = 0.018). Occurrence of UTI was less common when the donor was treated by antibiotics before brain death (p-0.025). These results provide additional support for regular monitoring of urine cultures in the first month post-transplant. They should help to identify means of reduction of this infectious risk.

Adult↗

[Rotational stability of angiography catheters].

Rotatory stability is a parameter that reflects the ability of a catheter to transmit a rotation applied at the outer end to the catheter tip for the purpose of selective probing. A method for measuring the rotatory stability is described, and the results of rotatory stability measurements of 70 different commercially available catheters are reported. There is an almost linear correlation between the rotatory stability and the difference between the respective fourth power of the external and internal diameter or, approximately, to the fourth power of the external diameter for catheters without wire reinforcement. With the same cross-sectional dimensions, the rotatory stability of teflon, polyethylene, and nylon catheters has an approximate ratio of 1:2:4. Wire reinforcement increases rotatory stability by an average factor of about 3. For catheters of calibers 5 F and 6 F, a correlation between the rotatory stability and the weight of the reinforcing wire mesh is apparent.

Biomechanical Phenomena↗

[Current treatment of poisoning by ingestion of caustic substances].

Lesions by ingestion of corrosive substances had so far been treated at the time of sequelae. In the seventies several events modified deeply the epidemiology and the early care of these poisonings. At that time household products like highly concentrated basic and acid substances and oxidizing agents were distributed and led to an increase of the number and the severity of these intoxications. In the same time, fiberoptic endoscopy of the digestive tract played a leading part to evaluate the diagnosis and the prognosis of these poisonings at an early stage, and thus, with accurate intensive care and digestive surgery contributed to generate appropriate guidelines, according to the severity. The first step of the treatment is fasting, fluid replacement and analgesic if required. A full examination must be performed, especially in the throat even if there is no strong correlation between early clinical signs and the severity of the lesions; blood samples must be obtained to look for metabolic acidosis, hyperleukocytosis hemolysis and consumption coagulopathy which could be better indicators of the severity. Fiberoptic endoscopy of the upper digestive tract should be performed as soon as the physical and psychological patient's condition is stable; if possible before the twelfth hour and no more late than the twenty-fourth hour. It should determine the lesions: type, range and grade according to Quincy's classification modified by Mongon and Di Constanzo. Survival and healing of "extremely severe" grade intoxication can only be obtained through a surgical intervention within the first hours; a laparotomy will indicate the depth of the lesions, which is not determined by endoscopy, and will consist of Celerier's stripping method and if necessary a gastrectomy, more seldom a cephalic duodeno-pancreatectomy. Only the surgical excision of necrotic tissues can prevent the occurrence of lethal complications like oesophageal or gastric perforations and septic shocks. The analysis of the literature from 1975 up to now gives us information on the methods and the results of these different therapeutic approaches.

Adult↗

[Current status of poisoning by ingestion of caustics: apropos of a series of 49 cases].

The authors report the history of 49 patients, admitted to an intensive care unit after a caustic or corrosive ingestion. This series follows a similar one, related in 1979. An update is made for early evaluation and management, based on patients classification in three groups: severe cases, moderate cases, mild cases. Clinical and biological data, treatment and outcome for the three groups are related. The frequency and gravity of these poisonings appear to be the same as in the first series, with poor prognosis for extreme emergencies and high risk of oesophageal or gastric stricture for important forms. In this population, 20% of extreme emergencies have favorable outcome with early major surgical procedure.

Adolescent↗

[Antibiotic sensitivity of forty-four strains of group EF4 bacteria: study of minimum inhibitory concentrations using the agar dilution method].

EF4 bacteria are found in animal saliva and may contaminate bite wounds. Minimum inhibitory concentrations of 36 antimicrobials against 44 EF4 strains were determined using dilution in Mueller-Hinton agar. EF4 bacteria were susceptible to aminopenicillins, carboxypenicillins, ureidopenicillins, third-generation cephalosporins, fluoroquinolones, rifampicin, and trimethoprime-sulfamethoxazole. Susceptibility was intermediate for penicillin G, low for macrolides and variable for aminoglycosides. EF4 bacteria were resistant to lincomycin and trimethoprime. Routine prophylactic treatment of bite-induced Pasteurella infections using an aminopenicillin or a cycline also protects against EF4 infection of the wound.

4-Quinolones↗