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Biomedical subjects

G Paul

Publications and source records attributed to G Paul.

At least 19 recordsLinked to original sources

APP RNA splicing is not affected by differentiation of neurons and glia in culture.

Amyloid precursor protein (APP) gene expression was investigated in primary cultures of neurons, astrocytes, microglial cells and oligodendrocytes. Neurons from various rat brain regions, as well as oligodendrocytes, contained RNA encoding APP695, while astrocytes and microglial cells expressed high levels of RNAs for APP770 and APP751. It was studied whether the cell type-specific regulation of APP gene expression could be modified by induction of cellular differentiation in vitro. While neuronal differentiation of PC12 cells has been shown to correspond with an altered pattern of APP splicing, in the primary cultures neither the time in culture nor a treatment of the cells with appropriate differentiation factors affected this pattern.

Amyloid beta-Protein Precursor

Two variants of transferrable extended-spectrum TEM-beta-lactamase successively isolated from a clinical Escherichia coli isolate.

In a leukaemic patient presenting a septicaemia treated with ceftazidime and amikacin, two clinical Escherichia coli isolates distinguished by their level of resistance to oxyimino-beta-lactams were isolated at an interval of 24 h. The isolates were identified by biotyping and esterase electrophoretic typing and the two host strains were shown to be identical. However, each of these strains exhibited a different transferrable extended-spectrum beta-lactamase. These enzymes had different pI values (5.25 and 5.58), but were both blaTEM-1 mutants. The enzyme with pI 5.25 was identical to TEM-101 (TEM-12) (serine 162 substitution). The enzyme with pI 5.58 showed an additional amino acid substitution (lysine residue instead of an arginine at position 237) and was denominated TEM-23. These data indicate that point-mutations can be successively cumulated in vivo by blaTEM mutants, leading to expression of beta-lactamases with increased hydrolysis rates.

Bacterial Typing Techniques

Clinical isolates of Escherichia coli producing TRI beta-lactamases: novel TEM-enzymes conferring resistance to beta-lactamase inhibitors.

Two different strains of Escherichia coli exhibiting unusual patterns of resistance to beta-lactam antibiotics were isolated from patients at Cochin Hospital. Both isolates showed a low level of resistance to amoxycillin, ticarcillin and ureidopenicillins but were susceptible to cephalosporins, aztreonam and imipenem; beta-lactamase inhibitors potentiated the activities of the beta-lactams to only a limited extent. All resistance characteristics of the strains were transferable by conjugation to E. coli K12. Resistance was shown to be due to beta-lactamases of pI 5.20 and relative molecular masses of 24,000. The hydrolytic and inhibition profiles of these enzymes were similar to each other but differed from those of broad-spectrum beta-lactamases (TEM-1). The rates of hydrolysis (Vmax) of amoxycillin (c. 200%) were higher than that for TEM-1 (84%). Ticarcillin, ureidopenicillins and cephaloridine were hydrolyzed slowly. However, as for TEM-1, no hydrolysis was observed with cefoxitin, third generation cephalosporins, aztreonam and imipenem. The high Km values demonstrated the poor affinity of these enzymes for their substrates. Unlike TEM-1, they were poorly inhibited by beta-lactamase inhibitors. These two enzymes differed from each other as follows: (i) the concentrations of clavulanic acid required for 50% beta-lactamase inhibition were 31 mumol/L for one enzyme (E-SAL) and 9.4 mumol/L for the other (E-GUER); (ii) p-chloromercuribenzoate was a more active inhibitor of E-SAL then E-GUER. The titration curve method and DNA-DNA hybridization studies demonstrated that both enzymes were structurally related to TEM-1. The novel plasmid-encoded enzymes produced by the two isolates of E. coli appeared to be almost identical and to be derived from TEM-enzymes. On the basis of their presumed phylogeny and their biological properties, we propose that these beta-lactamases be given the generic name TRI (TEM Resistant to beta-lactamase Inhibitors).

Anti-Bacterial Agents

Cyanide dermatosis or a post-mortem artefact?--A case report.

A case of a chronic alcoholic, found dead in the afternoon after consuming an intoxicant early in the morning and showing post-mortem skin slippage with a blackened charred-like appearance, is reported. Viscera chemical analysis gave a positive test for significant quantities of cyanide. However, on histopathological examination, since no evidence of blister formation or vital reaction in the skin tissues were found, this was thought to be a very short duration, accelerated postmortem change phenomenon, due to local heating from contact with the sun-baked terrace.

Adult

[Neonatal cervical cord compression by a staphylococcal abscess].

In a small for date premature newborn infant, septicemia caused by Staphylococcus aureus was observed on day 16. In spite of an appropriate antimicrobial therapy, proteins of inflammation serum levels remained elevated for 2 weeks. The occurrence of cervical cord compression which could be related to a staphylococcal abscess explained the persisting inflammatory process. After puncturing of the abscess, immobilization and prolonged antibiotic treatment, outcome was favorable. This case demonstrates the difficulty of preventing abscesses related to staphylococcal septicemias and reports a very unusual site of abscess which could be well localized using MRI.

Abscess

[The distribution of avian enteroviruses in Germany].

Sera from chicken flocks of different regions in Germany were examined for antibodies to avian nephritis virus (ANV) by indirect immunofluorescence. There was no evidence of a wide distribution of ANV, at least in chicken parent flocks, in contrast to results from investigations in England, Northern-Ireland and Japan.

Animals

[Liver abscess and appendicular foreign body].

We report a case of liver abscess secondary to appendicitis which was due to a wire within the appendix. Appendicitis was asymptomatic, probably because of its retrocaecal position and/or previous antibiotic treatment. The abscess was treated with broad-spectrum antibiotics and percutaneous drainage, followed by a second stage appendicectomy. This case illustrates the value of gastrointestinal radiological investigations before considering the abscess as cryptogenetic.

Adult

[Infectious disease factors in poultry].

The increased importance of multicausal diseases of poultry in the present time is due to a better control and prevention of the monocausal diseases and epidemics predominant in the past. This development is supported by the intensive methods of modern poultry husbandry, the high stocking densities and the improved performance of the poultry by genetic selection. Opportunistic as well as pathogenic organisms can be involved in the development of infectious factorial diseases. A variety of clinical signs can be observed. Above all immunosuppression accompanied by mixed infections and other factors causes health problems of great economical importance. Frequently series of events take place in the development of infectious factorial diseases, in the course of which a preceding disturbance acts as factor of further diseases. Some examples of diseases and syndroms are given to substantiate the multiple involvement of different factors and infections in the development of series of events.

Animal Husbandry

Biochemical, immunological and physicochemical comparisons between OHIO-1 and four SHV-type beta-lactamases.

The biochemical, immunological and physicochemical properties of the beta-lactamase OHIO-1 were compared to those of four beta-lactamases commonly found in Klebsiella pneumoniae: SHV-1, SHV-3 and the beta-lactamases of strains GN 11-03 and GN 422. The substrate profile of SHV-1, OHIO-1 and of the beta-lactamases GN 11-03 and GN 422 were similar, while that of SHV-3 appeared comparable to that of the extended spectrum SHV-2. Moreover, anti-TEM-1 serum inactivated OHIO-1 as well as SHV-1 and the beta-lactamases of strains GN 11-03 and GN 422. Analysis of the electrophoretic mobilities, isoelectric points and titration curves demonstrated that OHIO-1 and the 4 other beta-lactamases examined were closely related variants. From these findings it appears that OHIO-1 could be classified among the SHV-type beta-lactamases.

Electrophoresis

The analysis of five carbenicillin-hydrolysing enzymes by electrophoretic methods.

Five carbenicillin-hydrolysing enzymes (carbenicillinases, or CARB), PSE-4 (CARB-1), PSE-1 (CARB-2), CARB-3, CARB-4 and CARB-5, and the beta-lactamase PSE-2 were compared by analysing their isoelectric points (pI), electrophoretic mobilities (mR) and titration curves (pH gradient electrophoresis). The pI determined by isoelectric focusing were 4.3 (CARB-4), 5.3 (PSE-4/CARB-1), 5.7 (PSE-1/CARB-2), 5.75 (CARB-3), 6.1 (PSE-2) and 6.35 (CARB-5). Their mR were estimated by zone electrophoresis as congruent to 26 for PSE-1 (CARB-2), CARB-3 and CARB-5, congruent to 30 for PSE-2, congruent to 33 for PSE-4 (CARB-1) and congruent to 61 for CARB-4. Titration curve analyses indicated that (1) PSE-4 (CARB-1), PSE-1 (CARB-2), CARB-3 and CARB-5 are closely related variants differing by a few amino acid substitutions; (2) the qualitative titration curve of CARB-4 is different from those of PSE-4 (CARB-1), PSE-1 (CARB-2), CARB-3 and CARB-5, although their patterns are somewhat similar; and (3) PSE-2 has no structural relationship with any of the other carbenicillin-hydrolysing enzymes or carbenicillinases (CARB) studied. Electrophoretic methods, and in particular titration curve determination combined with other physicochemical and enzymatic data, allowed a rapid comparison of the molecular structures of the beta-lactamases, and hence their classification.

Acinetobacter

Analysis of the molecular relatedness of four extended spectrum beta-lactamases (SHV-2, SHV-3, SHV-4 and SHV-5) by comparative protein titration curves.

Six beta-lactamases from Klebsiella pneumoniae, five of which (SHV-1, SHV-2, SHV-3, SHV-4 and SHV-5) were plasmid-encoded and one which (beta 1a GN 11-03) was chromosomally-encoded, were compared by analysis of their isoelectric points (pI), electrophoresis mobilities (MF) and titration curves or pH gradient electrophoresis. Four groups were defined by their pI and MF, namely SHV-1 and SHV-2 (pI = 7.6, MF approximately 14), SHV-3 and beta 1a GN 11-03 (pI = 7.0, MF approximately 20), SHV-4 (pI = 7.8 MF approximately 12) and SHV-5 (pI = 8.2, MF approximately 5). The titration curves of SHV-1 and SHV-2 enzymes on the one hand, and SHV-3 and beta 1a GN 11-03 on the other were completely superimposable for the whole of the pH gradient (3.5-10), indicating strongly similarity. Conservative amino-acid substitutions could account for the differences in the substrate spectra of the purified enzymes. The differences observed between the titration curves of the enzymes SHV-1/SHV-3, SHV-1/beta 1a GN 11-03, SHV-2/SHV-3 and SHV-5/SHV-4 pairs were consistent with the replacement of a basic amino-acid residue in the former enzyme of each pair by an acidic residue in the latter. Similarly, the titration curves of SHV-1/SHV-4 and of SHV-2/SHV-4 pairs may suggest the replacement of an acidic amino-acid in the former beta-lactamases by a neutral amino-acid in the latter of each pair. However, the presence of several self-cancelling or neutral substitutions is also possible. In contrast, when SHV-1 and TEM-1 (pI = 5.4 MF approximately 45) were titrated together, no structural relationship could be inferred.

Chromosomes, Bacterial

Novel carbenicillin-hydrolyzing beta-lactamase (CARB-5) from Acinetobacter calcoaceticus var. anitratus.

A strain of Acinetobacter calcoaceticus var. anitratus highly resistant to ticarcillin but susceptible to ticarcillin in combination with clavulanic acid (2 mg/l) was found to produce a constitutive beta-lactamase. This enzyme was periplasmic with a characteristic substrate profile of a carbenicillin-hydrolyzing enzyme. Enzyme inhibition was detected with antiserum (anti-CARB-3), pCMB, cloxacillin, clavulanic acid and sulbactam. This novel enzyme with a molecular mass of 28,000 resembles other plasmid-mediated carbenicillinases (CARB) but differs in its apparent isoelectric point estimated as 6.3 and has been designated CARB-5 on this basis.

Acinetobacter

Injury Severity Score (ISS) as a yardstick in assessing the severity and mortality of various abdomino-pelvic trauma hospitalized victims--a clinical vis-à-vis autopsy study.

A summary of 51 cases of vehicular accident showing abdomino-pelvic trauma, along with associated other regional injuries, were studied at the Department of Forensic Medicine at MAM College and Associated Hospitals in New Delhi during 1986. A detailed Injury Severity Score (ISS) was done in all the cases and the relationship of ISS during their clinical treatment phase and after death was studied, keeping in mind factors such as age, survival periods, etc.

Abdominal Injuries