Biomedical subjects
Publications and source records attributed to J M Fowler.
Blunt needles have been developed that are easily used in fascial closures while limiting penetrating cutaneous injury to the surgeon and the operating staff. These needles offer the surgeon further protection from inadvertent exposure to blood borne pathogens.
Virulent cells of Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica are known to exhibit a low-calcium response in vitro characterized by restriction of growth and induction of V antigen at 37 degrees C in Ca2+-deficient media (Lcr+). A shared Lcr plasmid mediates these properties and encodes yersiniae outer membrane peptides (Yops) that are expressed in Lcr+ Y. pseudotuberculosis and Y. enterocolitica but not Y. pestis. We present direct evidence here verifying that synthesis of major Yops in the former two species is, like V, repressed by Ca2+ and that these structures are located primarily in the outer membrane. We also verified that rabbits infected with live Lcr+ Y. pestis can raise antibodies against V and Yops. Similar antisera, however, were recovered after immunization with sterile extracts of Ca2+-starved Lcr+ cells of Y. pestis. Results of immunoblots obtained with these antisera showed that restricted Y. pestis produced Yops of about 46 kDa (YopB) and 44 kDa (YopC) after shiftup by addition of Ca2+ at 37 degrees C or reduction of temperature to 26 degrees C. It is established that virulent cells of Y. pestis also possess a unique plasmid known to mediate pesticinogeny (Pst+). Restricted Lcr+, Pst- Y. pestis expressed YopB and YopC plus additional 76 kDa (YopF), 48 kDa (YopH), 36 kDa (YopD), 32.5 kDa (YopJ), and 27 kDa (YopE) outer membrane structures at concentrations comparable to those in Ca2+-starved Y. pseudotuberculosis and Y. enterocolitica. These findings indicate that carriage of the Pst plasmid prevents expression of the Lcr plasmid-mediated Yops in wild type Y. pestis.
Lcr-plasmids of yersiniae are known to mediate a unique low calcium response characterised by restriction of growth in vitro with induction of putative virulence factors including yersiniae outer membrane-peptides (YOPs) and V antigen (Lcr+). A medium was developed that permitted expression of high yields of V by Yersinia pestis KIM in large fermenter vessels. Immunoblots of specific precipitates prepared by prior molecular sieving showed that native unaggregated V exists as a monomeric 37,000 dalton peptide. Fractionation by precipitation with (NH4)2SO4 and chromatography on phenyl-Sepharose, DEAE cellulose, Sephacryl S200, calcium hydroxyapatite, and Sephadex G200 yielded highly purified antigen as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of parallel preparations from Lcr+ and Lcr- yersiniae. However, yields of V obtained by this process were unexpectedly low. As determined from immunoblots with monospecific polyclonal and monoclonal anti-V, this loss of activity occurred as a function of evident degradation at every step of purification yielding antigenic fragments of about 36,000, 34,000, 31,000, 30,000, and 28,000 daltons. Neutral or acidic pH favored hydrolysis; insignificant cleavage occurred in viable Lcr+ cells of Y. pestis or in culture supernatant fluids. V in neutral cytoplasm from Yersinia pseudotuberculosis or Yersinia enterocolitica did not undergo comparable degradation.
Hepatic encephalopathy (HE) is a syndrome of generalized neural inhibition, which complicates both acute and chronic liver failure. Since gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and HE is associated with increased responsiveness to certain drugs (benzodiazepines and barbiturates) that mediate neural inhibition by binding to the GABA receptor complex on postsynaptic neural membranes, the status of this receptor complex in HE was investigated. Fulminant hepatic failure was induced in rabbits by the intravenous injection of galactosamine hydrochloride. Neural membranes were isolated from the brains of normal rabbits, rabbits in hepatic coma, and rabbits with another type of metabolic encephalopathy, uremic coma. To characterize GABA and benzodiazine receptors, measurements were made of the specific binding to neural membranes of 3H-GABA and 3H-flunitrazepam, respectively. Computer-assisted Scatchard plot analysis of the binding data suggested the presence of two independent receptors for GABA and a single class of receptor for benzodiazepines. Hepatic coma was associated with no changes in the affinities of these receptors but with significant increases in their densities: 0.34 vs. 0.60; 1.1 vs. 2.2; and 4.6 vs. 7.3 pmol/mg of membrane protein for the high-affinity GABA, low-affinity GABA and benzodiazepine receptors, respectively. Uremic coma was associated with no changes in the affinities or densities of GABA receptors. On the basis of these findings, it is suggested that (1) increased numbers of GABA receptors in liver failure may potentiate neural inhibition by increasing the sensitivity of the brain to GABA and (2) increased responsiveness to the sedative-hypnotic effects of benzodiazepines in liver failure may be mediated by increased numbers of receptors for this class of drug, permitting increased drug effect.
The universal colicin-indicator strain Escherichia coli phi, unlike E. coli strain K-12, is sensitive to pesticin, a bacteriocin produced by wild-type Yersinia pestis. Eleven distinct phenotypes of E. coli phi mutants were obtained by selection for insensitivity to pesticin, group B colicins, the group A colicin S4, or coliphage T5. Representative isolates from eight of these classes closely resembled resistant receptor mutants (Cir-, Fep-, and TonA-) or tolerant mutants (TonB-, ExbB-, ExbC-, Ivt-, and Cmt-) described in Escherichia coli K-12. The remainder were unique; of these, one resembled TonB- but was also tolerant to colicin S4 (TonB/S4-), and the others exhibited specific resistance to either colicin S4 (Sfr-) or to pesticin (Psr-). All receptor mutants except Psr- remained sensitive to pesticin, whereas TonB/S4, TonB-, ExbB-, and ExbC- isolates were highly tolerant to this bacteriocin.
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In five rhesus monkeys surviving 'Peru strain' or 'strain 7' Trypanosoma cruzi infection for six to eight years, positive xenodiagnosis results and high indirect fluorescent antibody titres (4096 - 65536) persisted until the animals were killed. Abnormal electrocardiograph patterns in two monkeys (H and K) were possibly compatible with myocardial damage. Histopathological changes attributable to T. cruzi infection were minor in four monkeys but severe in one (R). In this animal, infected with what was judged previously to be the less virulent of the two T. cruzi stocks used ('strain 7'), there was severe myocarditis, with myofibre degeneration, and lesions of the oesophagus. Elevated serum levels of five enzymes were not detected in any of the chronically infected monkeys.
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Twenty-nine patients were given an intraperitoneal transfusion of blood. The procedure was found to be free of serious complications. Study of the absorption of an (51)Cr-labelled cells from the peritoneum in 14 patients showed that between 35 and 100% of the blood was absorbed intact in 6 to 10 days. Intraperitoneal transfusion may be indicated as an alternative or as an addition to exchange transfusion in severe hookworm anaemia.
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