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Biomedical subjects

B D Jones

Publications and source records attributed to B D Jones.

At least 19 recordsLinked to original sources
PubMed1992

Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants.

Salmonella typhimurium penetrate intestinal epithelial cells during infection. In vitro studies reveal that the availability of oxygen during bacterial growth decreases their capacity to adhere to and enter cultured epithelial cells. To identify S. typhimurium genes involved in epithelial cell entry, mutants were selected that entered HEp-2 cells when grown under repressing, aerobic culture conditions. Two types of transposons were used to generate bacterial mutations--transposons that disrupt genes (Tn10 and Tn5) and one transposon (Tn5B50) that, in addition to disrupting genes, can cause constitutive expression of genes from the neo promoter at one end of the transposon. Three classes of mutations were found that increased the ability of aerobically grown S. typhimurium to enter HEp-2 cells. One class of mutations disrupts the che operons and results in a nonchemotactic phenotype. The second class of mutations revealed that defects in rho, which encodes an essential transcription termination factor, result in hyperinvasiveness. The third class of mutations was obtained only from mutagenesis with Tn5B50, suggesting that their increased invasiveness is due to constitutive expression of a gene(s) from the exogenous neo promoter. Analysis of this third class of mutations identified a S. typhimurium locus hil (hyperinvasion locus), which is essential for bacterial entry into epithelial cells. The results suggest that hil encodes an invasion factor or an activator of invasion factor expression. hil maps between srl and mutS near minute 59.5 of the S. typhimurium chromosome, a region adjacent to other loci that have been identified as required for S. typhimurium invasiveness and virulence.

Anaerobiosis↗
PubMed1992

Invasion by Salmonella typhimurium is affected by the direction of flagellar rotation.

When grown aerobically, Salmonella typhimurium exhibits a low level of entry into tissue culture cells. We have isolated an S. typhimurium Tn10 mutant which, when grown under aerobic conditions, efficiently invades HEp-2 cells. Sequencing of S. typhimurium DNA adjacent to the site of the Tn10 element showed that the insertion disrupted transcription of the aspartate receptor gene, tar. Polar effects of the transposon on downstream genes also eliminated chemotaxis. Isogenic nonchemotactic (Che-), as well as nonmotile (Mot-) and nonflagellated (Fla-), S. typhimurium strains were examined for their ability to invade HEp-2 cells. "Smooth" swimming Che- mutants (cheA, cheW, cheR, and cheY) were found to possess increased invasiveness for cultured mammalian cells. In contrast, a "tumbly" cheB mutant and Mot- (flagellated) strain were found to have decreased levels of tissue culture invasiveness. A Fla- strain was found to be as invasive as the wild-type strain if centrifugation was used to facilitate contact with the monolayer surface. In addition, the observed hyperinvasiveness of the smooth swimming tar::Tn10 mutant was suppressed when the strain was paralyzed by the introduction of a mot or fla mutation. A murine infection model was used to demonstrate that the mutant invasive phenotypes were also observed in vivo. These data are most consistent with the idea that the rotation and physical orientation of flagella around the bacteria affect the ability of salmonellae to enter host cells.

Animals↗
PubMed1992

Clozapine in the treatment of refractory schizophrenia: Canadian policies and clinical guidelines.

Clozapine is an atypical neuroleptic agent that has recently become available in Canada with potential clinical efficacy in the treatment of refractory schizophrenia, and in patients with schizophrenia neurologically intolerant to conventional neuroleptics. Although it causes few extra-pyramidal symptoms, the drug has a number of other adverse effects including a risk of agranulocytosis in one to two percent of all patients. Because of this, the use of the drug is permitted only if the white blood count is monitored weekly. The monitoring system, outlined in this article, requires a coordinated effort between clinical staff, pharmacy, laboratory and the Clozaril Support and Assistance Network. Clinical guidelines are proposed, detailing the indications and contraindications for treatment and the pharmacokinetics, dosing, adverse effects, and drug interactions with clozapine. In addition, the economics, government policies and implications for future research are considered. Although there are administrative and clinical difficulties associated with its use, clozapine represents an advance in therapeutic research. Patients and family members will be inquiring about the drug and may deserve a trial. This article aims to inform Canadian mental health professionals about the safe and beneficial use of clozapine.

Clozapine↗
PubMed1990

Introduction to endoscopy.

Endoscopy is an area of rapidly growing interest within veterinary medicine. This is understandable, because it is a relatively noninvasive procedure in which a tremendous amount of diagnostic data may be obtained. The purpose of this article is to introduce the novice to the equipment and potential uses of endoscopy.

Anesthesia↗
PubMed1990

Endoscopy of the lower gastrointestinal tract.

Colonoscopy is an extremely valuable diagnostic technique. It allows the veterinarian to visualize the lower gastrointestinal tract and obtain tissue for a definitive diagnosis with a noninvasive approach. This article reviews the indications, contraindications, instrumentation, and technique of endoscopy of the lower gastrointestinal tract.

Animals↗
PubMed1990

Laparoscopy.

Laparoscopy is a relatively noninvasive technique that provides a view of the abdominal contents and peritoneal surfaces. This article reviews the indications, limitations, contraindications, equipment, and technique of laparoscopy.

Abdomen↗
PubMed1990

Construction of a urease-negative mutant of Proteus mirabilis: analysis of virulence in a mouse model of ascending urinary tract infection.

Proteus mirabilis, a urease-producing uropathogen, causes serious urinary tract infections in humans. To specifically evaluate the contribution of urease to virulence, a mutation was introduced into P. mirabilis HI4320 by homologous recombination. Virulence was assessed in the CBA mouse model of ascending urinary tract infection. Twenty mice each were challenged transurethrally with P. mirabilis HI4320 and its urease-negative derivative (1 x 10(9) to 2 x 10(9) CFU). At 48 h animals were sacrificed and the mean log10 CFU per milliliter of urine (parent, 6.23; mutant, 4.19; P = 0.0014) or per gram of bladder (parent, 6.29; mutant, 4.28; P = 0.0002), left kidney (parent, 4.11; mutant, 1.02; P = 0.00009), and right kidney (parent, 4.11; mutant, 2.43; P = 0.036) were all shown to be significantly different. These data demonstrate a role for urease as a critical virulence determinant for uropathogenic P. mirabilis.

Animals↗
PubMed1990

Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains.

Acute pyelonephritis, a complication of Escherichia coli bacteriuria, must represent a bacterial invasion through the kidney epithelium. To study this process, we overlaid bacterial suspensions onto monolayers of cultured human kidney proximal tubular epithelial cells and measured cytotoxicity by release of lactate dehydrogenase (LDH). Thirty-four isolates cultured from patients with acute pyelonephritis were screened for the ability to cause pyelonephritis in CBA mice by transurethral challenge. The eight most virulent strains (greater than or equal to 70% of mice challenged developed greater than or equal to 10(3) CFU/g of kidney after 48 h) were selected for study. Each strain displayed mannose-resistant hemagglutination of human O erythrocytes; three strains were phenotypically and genotypically hemolytic. Pyelonephritogenic strains were significantly more cytotoxic (30.1 +/- 9.5% LDH release after 18 h) than eight fecal control strains (13.5 +/- 11.5% LDH release; P = 0.0068). We selected the most cytotoxic strain, CFT073, for further study. Sterile filtrate from this hemolytic strain was significantly more cytotoxic than was the filtrate of the fecal control strain, FN414. Transposon mutagenesis of CFT073 with TnphoA abolished hemolytic activity and cytotoxicity by both whole cells and sterile filtrate. Southern blot analysis revealed that the Tnphoa insertion mapped to the E. coli chromosomal hly determinant within a 12-kilobase SalI restriction fragment. Transformation of a nonhemolytic strain, CPZ005 with plasmid pSF4000, which carries a cloned hemolysin determinant, resulted in highly elevated cytotoxicity. Light micrographs of proximal tubular epithelial cell cultures demonstrated cell damage by pyelonephritogenic strains that was not induced by a fecal strain or the hemolysin-deficient mutant. Results indicate that pyelonephritogenic E. coli strains are more frequently cytotoxic for a putative target, that is, human renal tubular epithelium, than are fecal isolates. Hemolysin, in some strains, is apparently responsible for this cytotoxicity.

Bacterial Toxins↗
PubMed1990

Morganella morganii urease: purification, characterization, and isolation of gene sequences.

Morganella morganii, a very common cause of catheter-associated bacteriuria, was previously classified with the genus Proteus on the basis of urease production. M. morganii constitutively synthesizes a urease distinct from that of other uropathogens. The enzyme, purified 175-fold by passage through DEAE-Sepharose, phenyl-Sepharose, Mono-Q, and Superose 6 chromatography resins, was found to have a native molecular size of 590 kilodaltons and was composed of three distinct subunits with apparent molecular sizes of 63, 15, and 6 kilodaltons, respectively. Amino-terminal analysis of the subunit polypeptides revealed a high degree of conservation of amino acid sequence between jack bean and Proteus mirabilis ureases. Km for urea equalled 0.8 mM. Antiserum prepared against purified enzyme inhibited activity by 43% at a 1:2 dilution after 1 h of incubation. All urease activity was immunoprecipitated from cytosol by a 1:16 dilution. Antiserum did not precipitate ureases of other species except for one Providencia rettgeri strain but did recognize the large subunits of ureases of Providencia and Proteus species on Western blots (immunoblots). Thirteen urease-positive cosmid clones of Morganella chromosomal DNA shared a 3.5-kilobase (kb) BamHI fragment. Urease gene sequences were localized to a 7.1-kb EcoRI-SalI fragment. Tn5 mutagenesis revealed that between 3.3 and 6.6 kb of DNA were necessary for enzyme activity. A Morganella urease DNA probe did not hybridize with gene sequences of other species tested. Morganella urease antiserum recognized identical subunit polypeptides on Western blots of cytosol from the wild-type strain and Escherichia coli bearing the recombinant clone which corresponded to those seen in denatured urease. Although the wild-type strain and recombinant clone produced equal amounts of urease protein, the clone produced less than 1% of the enzyme activity of the wild-type strain.

Amino Acid Sequence↗
PubMed1990

Tardive dyskinesia: legal and preventive aspects.

Tardive dyskinesia is a complication associated with long term neuroleptic drug treatment that can be the object of litigation. Such litigation has occurred recently in the United States, where awards of considerable value have been granted to plaintiffs. Circumstances that can lead to TD litigation are presented as well as guidelines for the prescription of neuroleptics, the prevention of litigation and of the syndrome itself. Five lawsuits associated with TD serve as a backdrop for the discussion.

Antipsychotic Agents↗
PubMed1989

Proteus mirabilis urease: nucleotide sequence determination and comparison with jack bean urease.

Proteus mirabilis, a common cause of urinary tract infection, produces a potent urease that hydrolyzes urea to NH3 and CO2, initiating kidney stone formation. Urease genes, which were localized to a 7.6-kilobase-pair region of DNA, were sequenced by using the dideoxy method. Six open reading frames were found within a region of 4,952 base pairs which were predicted to encode polypeptides of 31.0 (ureD), 11.0 (ureA), 12.2 (ureB), 61.0 (ureC), 17.9 (ureE), and 23.0 (ureF) kilodaltons (kDa). Each open reading frame was preceded by a ribosome-binding site, with the exception of ureE. Putative promoterlike sequences were identified upstream of ureD, ureA, and ureF. Possible termination sites were found downstream of ureD, ureC, and ureF. Structural subunits of the enzyme were encoded by ureA, ureB, and ureC and were translated from a single transcript in the order of 11.0, 12.2, and 61.0 kDa. When the deduced amino acid sequences of the P. mirabilis urease subunits were compared with the amino acid sequence of the jack bean urease, significant amino acid similarity was observed (58% exact matches; 73% exact plus conservative replacements). The 11.0-kDa polypeptide aligned with the N-terminal residues of the plant enzyme, the 12.2-kDa polypeptide lined up with internal residues, and the 61.0-kDa polypeptide matched with the C-terminal residues, suggesting an evolutionary relationship of the urease genes of jack bean and P. mirabilis.

Amino Acid Sequence↗
PubMed1989

Thrombosis: the major Hickman catheter complication in patients with solid tumor.

Major complications of Hickman catheter placement (thrombosis and infection) were determined in 168 patients with solid tumor (lung, 79; head and neck, 56; esophagus, 24; and miscellaneous, 9). Catheter-related thrombosis was clinically detected in 22 individuals and was detected at autopsy in six (total 17 percent). The 17 percent figure underestimates the true incidence of thrombosis since only 25 percent of study patients had autopsies. Patients with adenocarcinoma of the lung constituted a high risk group. Nine of 20 (45 percent) of these patients had thrombosis compared to 25, 9, and 16 percent of patients with squamous cell cancers of lung, head and neck and esophagus, respectively (p less than 0.002). Three patients with thrombosis had pulmonary emboli and two died. Thrombosis occurred despite daily heparin catheter flushing. INfections occurred in 11 patients. One had suspected endocarditis, one had a subcutaneous tunnel infection, and nine had exit site infections. All responded to local or systemic antibiotics. Better methods to prevent thrombosis are needed.

Adenocarcinoma↗
PubMed1988

Partial trisomy chromosome 5 cosegregating with schizophrenia.

Schizophrenia was associated with a distinct autosomal abnormality in two related mildly dysmorphic individuals. The finding of cosegregation of schizophrenia and a partial trisomy of chromosome 5 in the family suggests a potential location of a gene or genes linked to schizophrenia.

Adult↗