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Biomedical subjects

H Wexler

Publications and source records attributed to H Wexler.

At least 19 recordsLinked to original sources

Isolation and characterization of heat-modifiable proteins from the outer membrane of Porphyromonas asaccharolytica and Acinetobacter baumannii.

Active porins were isolated and purified from the outer membranes of the gram-negative anaerobic rod Porphyromonas asaccharolytica and the aerobic coccobacillus Acinetobacter baumannii. The porins from both bacteria appear to be monomers when isolated and purified. Both porins exhibited decreased mobility on SDS-PAGE after boiling for 10 min in the sample buffer. After heating, their molecular weight is estimated at 43 kDa while without heating they run as proteins with a molecular weight of approximately 37 kDa. Due to their characteristic heat-modifiability, these proteins were named HMP (heat-modifiable protein)-P. asaccharolytica and HMP-A. baumannii. Amino acid analysis revealed both porins to be hydrophilic proteins. These proteins have been shown to be active in transporting sugars when incorporated into liposomes. The permeability of both porins for L-arabinose was less than that produced by the porin of Escherichia coli B. Permeability to high molecular weight disaccharides was lower than for small monosaccharides. Western blot analysis did not reveal any antigenic cross reaction between HMP-A. baumannii and the HMP-P. asaccharolytica. The results obtained in this study confirm that although these heat-modifiable proteins are pore forming proteins and have similar activity they differ in their antigenicity.

Journal Article↗

In vitro antibacterial properties of pexiganan, an analog of magainin.

Pexiganan, a 22-amino-acid antimicrobial peptide, is an analog of the magainin peptides isolated from the skin of the African clawed frog. Pexiganan exhibited in vitro broad-spectrum antibacterial activity when it was tested against 3,109 clinical isolates of gram-positive and gram-negative, anaerobic and aerobic bacteria. The pexiganan MIC at which 90% of isolates are inhibited (MIC90) was 32 micrograms/ml or less for Staphylococcus spp., Streptococcus spp., Enterococcus faecium, Corynebacterium spp., Pseudomonas spp., Acinetobacter spp., Stenotrophomonas spp., certain species of the family Enterobacteriaceae, Bacteroides spp., Peptostreptococcus spp., and Propionibacterium spp. Comparison of the MICs and minimum bactericidal concentrations (MBCs) of pexiganan for 143 isolates representing 32 species demonstrated that for 92% of the isolates tested, MBCs were the same or within 1 twofold difference of the MICs, consistent with a bactericidal mechanism of action. Killing curve analysis showed that pexiganan killed Pseudomonas aeruginosa rapidly, with 10(6) organisms/ml eliminated within 20 min of treatment with 16 micrograms of pexiganan per ml. No evidence of cross-resistance to a number of other antibiotic classes was observed, as determined by the equivalence of the MIC50s and the MIC90s of pexiganan for strains resistant to oxacillin, cefazolin, cefoxitin, imipenem, ofloxacin, ciprofloxacin, gentamicin, and clindamicin versus those for strains susceptible to these antimicrobial agents. Attempts to generate resistance in several bacterial species through repeated passage with subinhibitory concentrations of pexiganan were unsuccessful. In conclusion, pexiganan exhibits properties in vitro which make it an attractive candidate for development as a topical antimicrobial agent.

Anti-Bacterial Agents↗

Renal cell carcinoma with acrometastasis: report of two cases and review of the literature.

Metastases to the small bones of the hands and feet are rare. Although acrometastasis is usually a late manifestation of disseminated disease, it may be the primary manifestation of an occult carcinoma. Clinically it may be confused with benign disease and be treated improperly. We report two cases of renal cell carcinoma metastatic to the distal phalanx of a finger in Case 1 and the proximal phalanx of a toe in Case 2. The lesion was discovered following trauma in Case 1. In Case 2 there was no history of trauma. These acrometastases were the first evidence of metastatic disease in these two patients who had undergone a nephrectomy for Stage II renal cell carcinoma 2 yr and 1 yr prior to the development of acrometastases, respectively. Additional visceral metastases developed over the following months in Case 1, and the patient expired 7 mo after the discovery of the acrometastasis. In Case 2, the acrometastasis was the only site of metastases, and the patient is alive and well without evidence of disease as of the latest follow-up in January 1990. Review of the literature, including our cases, revealed 22 cases of renal cell carcinoma metastatic to the bones of the hand, nine cases to the bones of the foot, and three cases to the bones of both hand and foot. The clinical characteristics, pathogenetic mechanisms, and treatment are reviewed.

Bone Neoplasms↗

Bilophila wadsworthia, gen. nov. and sp. nov., a unique gram-negative anaerobic rod recovered from appendicitis specimens and human faeces.

Strongly catalase-positive Gram-negative anaerobic rods were isolated from approximately half of all intra-abdominal specimens received from patients with gangrenous and perforated appendicitis, and subsequently also from normal faecal specimens. The organism was originally detected on Bacteroides-bile-aesculin (BBE) agar, and grew slowly on non-selective anaerobic media containing blood. It was stimulated by bile and differed from other known genera by being urease- and catalase-positive, and by reducing nitrate. It did not reduce sulphate. Other anaerobic Gram-negative rods showed no homology by DNA dot-blot hybridization. The thermal melting profile of chromosomal DNA showed 39-40 mol% G + C. The whole-cell fatty acid methyl ester profile included cyclic and branched long-chain acids, and differed from those of all other anaerobes that have been tested. beta-Lactamase was not detected. The name Bilophila wadsworthia gen. nov., sp. nov. is proposed for this organism.

Appendicitis↗

Microbial flora in the bypassed jejunum of patients with biliopancreatic bypass for obesity.

The microbial flora in the bypassed biliopancreatic intestinal segment was studied after obesity surgery. This procedure causes less diarrhea than jejunoileal bypass and appears to avoid extraintestinal complications. This report concerns type and quantity of bacteria colonizing the biliopancreatic segment and changes occurring after oral metronidazole treatment. Twelve specimens were aspirated in 10 patients via catheter inserted percutaneously during surgery. The specimens were plated immediately on selective and nonselective media under aerobic and anaerobic conditions. Essentially equal numbers of aerobes and anaerobes were recovered from the biliopancreatic segment with average counts of 10(4) cfu/mL and median counts of 10(5) cfu/mL. Four patients had counts of 10(7) cfu/mL. The most common aerobes were E. coli, Klebsiella, Gram-positive cocci, and Candida; among anaerobes, Clostridium and the Bacteroides fragilis group were most common. In three patients treated with metronidazole because of diarrhea, anaerobes were eliminated and diarrhea cleared.

Adult↗

Bowel flora changes in humans receiving cefixime (CL 284,635) or cefaclor.

Twelve healthy young male subjects received either cefixime, a new oral cephalosporin (CL 284,635), or cefaclor (six subjects on each drug) orally for 2 weeks. In the case of cefixime, single daily doses of 400 mg were taken; with cefaclor, the dosage was 250 mg three times daily. Modest changes in the fecal flora were noted in both drug groups, but the changes were of different types. In the case of cefixime, there was more of an impact on the indigenous flora, and in the case of cefaclor, there was more ingrowth of new flora. With cefixime, Enterobacteriaceae were usually decreased (the decrease in Escherichia coli count was statistically significant), as were counts of clostridia and sometimes Bifidobacterium spp.; the Bacteroides fragilis group was eliminated in one subject. Coincident with these decreases, four subjects had increases in counts of group D streptococci of 3 logs or more. There was new appearance of Clostridium difficile in four subjects and of Staphylococcus aureus in one; four new strains of Enterobacteriaceae appeared. With cefaclor, there was no decrease of E. coli counts; two subjects had elimination of Bifidobacterium spp. There was little change in counts of group D streptococci. On the other hand, there were 13 new strains of Enterobacteriaceae, two of S. aureus, and three of C. difficile.

Bacteria↗

Comparative activity of SCH 34343 against anaerobic bacteria.

The in vitro activity of SCH 34343 was compared with that of imipenem, clindamycin, cefoxitin, and metronidazole against 78 strains of anaerobic bacteria in the presence and absence of blood. Wilkins-Chalgren agar was used. SCH 34343 and imipenem were the most active agents, inhibiting all strains at less than or equal to 8 micrograms/ml. The addition of blood had little effect on the activity of any of the agents. Seven strains were unable to grow on Wilkins-Chalgren agar. Even with the addition of blood, one strain each of Bacteroides asaccharolyticus and Bacteroides bivius and two strains of Fusobacterium were unable to grow. Sixty-eight of the strains were tested against SCH 34343 and imipenem on Brucella lysed blood agar. Minimal inhibitory concentrations tended to be somewhat higher on Brucella lysed blood agar than on Wilkins-Chalgren agar, and all strains were able to grow on Brucella lysed blood agar.

Anti-Bacterial Agents↗

In-vitro activity of Sch 34343 against anaerobic bacteria.

The in-vitro activity of Sch 34343, was compared with that of imipenem against 226 strains of anaerobic bacteria. Sch 34343 was identical in activity to imipenem, inhibiting 99.5% of the organisms tested at 16 mg/l (the breakpoint for both drugs). Imipenem was slightly more active than Sch 34343 against Bacteroides, Fusobacterium and Veillonella, although both drugs inhibited all organisms in these groups below breakpoint levels.

Anti-Bacterial Agents↗

In vitro activity of cefbuperazone against anaerobic bacteria.

The in vitro activity of cefbuperazone was compared with that of cefoxitin, moxalactam, and piperacillin against 305 strains of anaerobic bacteria. Piperacillin was the most active overall, inhibiting 97% of all anaerobes tested at 128 micrograms/ml. Cefbuperazone had poor activity against the Bacteroides fragilis group and Clostridium difficile (43 and 0% susceptible, respectively) but good activity (90.5%) against all other anaerobic bacterial species tested.

Anti-Bacterial Agents↗

Comparative in vitro activities of cefpiramide and apalcillin against anaerobic bacteria.

The in vitro activities of two new antimicrobial agents, apalcillin and cefpiramide (SM-1652), were evaluated against 324 strains of anaerobic bacteria. Apalcillin (a penicillin derivative) and cefpiramide (a semisynthetic cephalosporin) were compared with piperacillin, moxalactam, and cefoxitin. Organisms studied included the Bacteroides fragilis group, other Bacteroides species, fusobacteria, clostridia, nonsporeforming gram-positive rods, and anaerobic cocci. Piperacillin was found to be the most active overall, inhibiting 96% of the strains tested at its achievable level in serum (128 micrograms/ml). Apalcillin was comparable in activity to piperacillin, inhibiting 93% of anaerobes tested at this concentration. The other antibiotics inhibited ca. 80% of the strains at 32 micrograms/ml. In terms of activities against particular species, apalcillin was active against 75% of B. fragilis group strains and 97 to 100% of all other anaerobes. Cefpiramide inhibited 37% of B. fragilis group strains at 32 micrograms/ml and 68% at 64 micrograms/ml (a level that may be achievable with this drug). Cefpiramide inhibited 92% of all other anaerobes at 32 micrograms/ml and 95% at 64 micrograms/ml. The clostridia other than Clostridium perfringens were the most resistant (84% inhibited at 32 micrograms/ml and 95% inhibited at 64 micrograms/ml).

Ampicillin↗

Studies on the induction and expression of T-cell-mediated immunity. XIII. Membrane-associated antigens of cytotoxic T lymphocytes involved in cytotoxicity.

An xenogeneic rat anti-mouse T-cell serum, designated RAT*, has been shown to block the cytolytic activity of cytotoxic T lymphocytes (CTL) at a postbinding step. RAT* serum or the IgG fraction was extensively absorbed with the target cell, P815, a DBA mastocytoma, and used with or without further absorption to immunoprecipitate specific molecules from radiolabeled membrane extracts of CTL derived from either in vivo-allosensitized mice or from cytotoxic clones maintained in in vitro cultures. Cell surface sialic acid residues were labeled by oxidation with sodium periodate (NaIO4) and reduction with tritiated sodium borohydride ([3H]NaBH4). Alternatively, cell surface proteins were labeled with 125I by lactoperoxidase-catalyzed iodination. Nonidet P-40 (NP-40)-solubilized radiolabeled membranes were then immunoprecipitated with RAT* serum and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Three membrane-associated molecules of 95,000, 140,000 and 180,000 Mr were found by such analysis. The sensitivity of these three molecules to trypsinization and their susceptibility to labeling with [3H]NaBH4 suggested that they are glycoproteins. Moreover, when RAT* serum or the IgG fraction was absorbed with various cell types, its ability to immunoprecipitate the three molecules correlated with its ability to block cytolysis. Adsorption of RAT* serum with CTL, but not with nonimmune thymocytes, significantly reduced the ability of RAT* serum to inhibit cytotoxicity and to immunoprecipitate the 95k, 140k, and 180k molecules. Thus, these findings suggest that one or more of these cell surface molecules of CTL may be involved in the cytolytic process.

Animals↗

Etiological aspects of double monsters.

Four cases of double monsters are reported, including a rare case of craniofacial duplication (diprosopus). Based on the findings observed, etiological factors of these malformations are discussed. We suggest that exogenous (environmental) factors such as habits, way of life or religious practices of certain populations can influence the development of double monsters.

Abnormalities, Severe Teratoid↗

A case of fibrous hamartoma of infancy.

An instance of fibrous hamartoma of infancy (FHI) in the perianal region of an 8-mo-old infant, a hitherto unreported location, is described. The majority of the reported cases occur in the torso and upper extremities. The differential diagnostic features which aid differentiating FHI from other conditions is discussed. Although the tumor may recur after excision, a conservative surgical management appears adequate since all reported cases ultimately have proven to have an excellent prognosis.

Anus Neoplasms↗

Isolation, characterization, and biological properties of an endotoxin-like material from the gram-positive organism Listeria monocytogenes.

The bacterial component responsible for the induction of transient cold agglutinin syndrome in rabbits after intravenous injection of heat-killed Listeria monocytogenes type 4B has been purified and biologically and chemically characterized. A purified immunoglobulin M cold agglutinin was prepared from high-titer sera resulting from the immunization of rabbits with heat-killed L. monocytogenes type 4B and was subsequently used to monitor the purification of the bacterial component responsible for its induction. The bacterial component was isolated from a hot phenol-water extract of lyophilized L. monocytogenes type 4B by multiple molecular sieve chromatography. Upon chemical analysis the purified material was found to be strikingly similar in chemical composition to gram-negative lipopolysaccharide endotoxins. The material contained 15% total fatty acid (of which 50% was beta-hydroxymyristic acid), 40 to 45% neutral sugar (glucose, galactose, and rhamnose), 11.5% amino sugar, 12% uronic acid, 2.5% 2-keto-3-deoxyoctonic acid, 2% heptose, 0.87% phosphorus, and 1.6% amino acid, thereby accounting for 85 to 90% of the weight of the component. Electron micrographs of the purified material were similar to those of lipopolysaccharide preparations from gram-negative organisms. The purified material exist in aqueous solutions as large aggregates, but can be dissociated into a single smaller subunit (3.1S) by dialysis against sodium dodecyl sulfate buffer. The listerial component was toxic and pyrogenic to rabbits, producing symptoms typical of gram-negative endotoxins. Activity in the limulus lysate gelation assay and in the carbocyanine dye assay provides a further link of this material with classical gram-negative endotoxins.

Agglutinins↗

Pulmonary metastases from autochthonous 3-methylcholanthrene-induced murine tumors.

In three experiments, 87%, 75%, and 85% of female C57BL/6N mice developed pulmonary metastases by 50 days after amputation of legs having autochthonous 3-methylcholanthrene-induced sarcomas. No difference in the incidence of pulmonary metastases was observed when autochthonous tumors of short (49--94 days) and longer (95--119 days) latency periods were compared. These metastasizing autochthonous tumors may provide a useful model for studies of metastases and for the evaluation of cancer therapy in a minimal residual disease setting.

Amputation, Surgical↗