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Biomedical subjects

J Penner

Publications and source records attributed to J Penner.

15 recordsLinked to original sources
PubMed1997

Functional analysis of mouse keratin 8 in polyoma middle T-induced mammary gland tumours.

Keratin 8 and 18 are commonly used as tumorigenic markers for various types of carcinomas. They are known to be involved in cell migration, cell invasiveness, plasminogen activity and drug and radiation resistance. To ascertain a potential function for simple epithelium keratins in mammary adenocarcinoma in vivo, keratin-8-deficient mice (mK8) were mated with transgenic mice carrying the middle T oncogene driven by the MMTV promoter. The resulting mK8 knockout and control progeny carrying the middle T transgene developed mammary gland tumours with the same incidence. However, the onset of palpable mammary gland tumours occurred earlier in mK8 mutant than in control mice. This effect was prominent in males where the onset in control animals is delayed overall, because of the lower hormonal inducibility of the MMTV promoter. Metastatic foci were observed in the lungs of all females and of a few males, independently of the genotype. Histological analysis revealed no morphological differences of the tumorigenic cells in primary tumours nor in metastatic foci. As expected, keratin 8 was absent in the mK8 tumours. Keratin 7 (mK7), keratin 18 (mK18) and keratin 19 (mK19) protein were observed in both primary and metastatic foci. These results constitute the first in vivo analysis of the role of simple epithelium keratins in mammary carcinogenesis. It demonstrates that the latency, but not the incidence nor the morphological features, of PyV middle T-induced mammary gland tumours is affected by keratin 8 deficiency.

Age Factors↗
PubMed1994

Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice.

We report that keratin 8 (mK8) gene disruption causes colorectal hyperplasia in FVB/N mice. The intestinal lesions affect uniformly the cecum, colon, and rectum but not the small intestine. The elongation of the crypts is accompanied by an inflammation of the lamina propria and submucosa. Hepatic, renal, and pancreatic functions tested in clinical assays are within nonpathological range, suggesting that the major defect lies in colonic epithelial cells. Still, small but consistent elevation in the hepatic enzymes alanine (AST) and asparate (ALT) aminotransferase are observed, along with a 70% increase in spleen weight. No homozygous mouse line has been established, because of a markedly reduced fertility of the mK8-/- females. Previously, we reported that the mK8- targeted mutation causes embryonic lethality in (C57B1/6x129Sv) mice. This strong effect of the genetic background on the mK8- mutant phenotype emphasizes the importance of using several inbred mouse strains to reveal the polygenic contribution to mutant phenotypes. Our results demonstrate that genetic modifiers of K8/K18 filament functions, with profound effects on embryogenesis and gut functional integrity, are differentially active in the FVB/N and C57B1/6 genetic backgrounds. More importantly, the increase in mK8-/- gut epithelial cell number, rather than cell disruption, contrasts with the known function of epidermal keratins in providing mechanical strength.

Aging↗
PubMed1992

Omeprazole therapy for Helicobacter pylori infection.

To determine whether omeprazole eradicates Helicobacter pylori infection of the gastric antrum, six adolescents and one adult with H. pylori colonization of the antrum were entered into a clinical, open trial of medical therapy. Histologic evidence of antral gastritis and three complementary methods to document H. pylori colonization of the stomach (silver stain, urease testing, and culture of antrum) were obtained before and after an 8-week course of omeprazole. In vitro susceptibility to omeprazole and restriction endonuclease analysis were performed on H. pylori isolates obtained from patients before and after omeprazole therapy. Each of the seven patients treated with omeprazole had continued active inflammation in the antrum and one or more features indicative of persisting H. pylori colonization. Minimum inhibitory concentrations and DNA fingerprints of H. pylori isolated after therapy were identical to those of the pre-treatment bacterial isolates in each of the four subjects examined. We conclude that omeprazole therapy alone did not eradicate H. pylori infection of the human antrum. Continued bacterial colonization was not related to either acquired bacterial resistance to the drug or reinfection of the stomach with a different H. pylori strain.

Adolescent↗
PubMed1990

Use of molecular typing to study the epidemiology of Serratia marcescens.

Although Serratia marcescens is a well-known nosocomial pathogen, investigation of its hospital ecology has been limited by the lack of available typing techniques. During an investigation of the occurrence of this organism in a neonatal intensive care unit, we evaluated a number of such techniques. Using a selective medium, we conducted prospective surveillance of neonatal rectal colonization and environmental contamination with S. marcescens. In 8 months of surveillance, 5.1% (20 of 394) of the infants admitted to the unit became colonized. Most sink surfaces and drains were also culture positive. Differences between isolates could not be detected in biotypes from a commercial identification system (MicroScan) or by antibiograms, total protein fingerprints, or plasmid profiles. Serogrouping and genomic DNA restriction endonuclease analysis revealed the presence of six strains that colonized infants and a similar number of environmental strains. These two methods were concordant, with the exception that genomic DNA analysis demonstrated lack of relatedness between some strains within the same serogroup. DNA restriction endonuclease analysis was practical and reliable. The differences this method detected between environmental and neonatal strains provided strong evidence that the environment was not an important reservoir for S. marcescens in our neonatal intensive care unit.

Cross Infection↗
PubMed1987

Exchange-transfusion with pyridoxalated polymerized hemoglobin: effects on liver PO2.

To examine the efficacy of modified stroma-free hemoglobin in maintaining liver PO2, rats were exchange-transfused to hematocrit 10% using pyridoxalated polymerized hemoglobin (plp-polyHb, 10-12 g/dl) prepared from crystalline Hb. Following hemodilution, plasma Hb was 7.4 g/dl, and rats were normotensive. Mean liver PO2 was 3.4 vs 23.3 mm Hg in sham-exchanged controls. Other rats, hemodiluted similarly with 6% albumin or hydroxyethylstarch, were hypotensive and died. At 24 hours plasma Hb was 2.0 g/dl, indicating an intravascular half-life of approximately 16 hours. Hepatic PO2 was 12.4 vs 26.8 mm Hg in nonhemodiluted controls. Data provided by clearance of low-dose indocyanine green suggested reduced plasma volume and depressed liver blood flow. Scattered foci of midzonal hypoxic damage were observed in liver lobules. The basis for hypoxic injury is considered to be due in part to the acute restriction of oxygen supply induced by exchange-transfusion with plp-polyHb. The rate of loss of intravascular hemoglobin and diminished plasma volume could have contributed to oxygen insufficiency as well. Endotoxin present in the plp-polyHb was not a factor.

Animals↗
PubMed1984

Platelet interactions with polylysine coated beads: a microscopic and chemical analysis.

Gel filtered human platelets were mixed with polylysine coated polyacrylamide beads. Platelet binding to individual beads within one preparation was variable, yet high and the bound platelets appeared to involve non-activated platelets. Some cells appeared to be in contact with more than one bead. When the attachment process was neutralized with 1 mg/ml of polyanionic dextran sulfate, significantly fewer platelets remained attached to the beads. Platelets which were recovered in the washes also were non-activated. Attached cells were capable of being activated and underwent release reactions when exposed to either ADP or thrombin. Release reactions were monitored by the liberation of either serotonin or beta-thromboglobulin. Platelets which were iodinated prior to attachment gave evidence that the failure to neutralize the bead before vortexing resulted in lower specific activities of bound iodine/protein.

Acrylic Resins↗
PubMed1978

Deep venous thrombosis and postsplenectomy thrombocytosis.

Eighty-six patients undergoing elective splenectomy have been investigated preoperatively and postoperatively by serial platelet counts and leg scanning using iodine 125-labeled fibrinogen. The presence of deep leg vein thromboses detected by labeled fibrinogen was confirmed by dye phlebography. In only five patients (6%) did deep venous thrombosis develop. In none of these five patients did an elevation in platelet count to 600,000/cu mm develop before or at the time of development of the thrombosis. None of 21 other patients who did have a rise in platelet count greater than 1,000,000/cu mm had evidenced of venous thrombosis. These data do not substantiate the need for routine prophylactic antithrombotic therapy in patients in whom postsplenectomy thrombocytosis develops.

Adult↗
PubMed1976

Effects of hypophysectomy and acute growth hormone treatment upon glucose metabolism in adipose tissues and isolated adipocytes of rats.

Glucose oxidation and incorporation into lipid were measured in epididymal adipose tissues and isolated adipose cells of normal and hypophysectomized rats in an effort to determine whether the acute hypoglycemic effect of a systemic growth hormone (GH) injection was related to alterations in the glucose metabolism of adipose tissue. The rats were fed rat chow or a high sucrose diet and received 100 mug GH intraperitoneally 30 minutes or three and one-half hours before sacrifice. Hypophysectomized rats showed a lower plasma glucose as compared with normal rats on both diets. Thirty minutes after a GH injection there was a further decrease of the plasma glucose which, however, was not present in those rats receiving GH three and one-half hours before sacrifice. Adipose tissues from hypophysectomized rats fed the high sucrose diet showed a blunted insulin sensitivity as compared with normal rats on a similar diet. The insulin sensitivity of these tissues was further decreased 30 minutes after a GH injection. Basal glucose metabolism of isolated adipocytes from hypophysectomized rats, as compared with normal rats, was depressed if they were fed rat chow, was at normal levels if they were fed the high sucrose diet and was increased if they were fed the sucrose diet and received triiodothyronine and cortisone supplements. No manipulations of diet or hormonal treatments made the isolated adipocyte from hypophysectomized rats sensitive to insulin either 30 minutes or three and one-half hours after a GH injection. Since basal glucose utilization is not enhanced by GH injection and both the blunted insulin sensitivity of adipose tissue and the absent insulin sensitivity of adipopocytes would be expected to produce hyperglycemia rather than hypoglycemia, it is concluded that immediate systemic effects of a GH injection on carbohydrate metabolism are not related to changes in glucose metabolism of the peripheral adipose tissues.

Adipose Tissue↗
PubMedDate not supplied

In vitro experiments on catheter-related infections due to gram-negative rods.

Although many complications may arise with the use of central venous catheters, catheter-related bacteremia is considered to be the most serious complication. Microflora on the patient's skin (coagulase-negative staphylococci, Staphylococcus aureus) is thought to represent the major source of microorganisms causing catheter-related infections. Gram-negative rods are increasingly observed as causative agents. We therefore performed an in vitro study to elucidate the pathogenesis of polymer-associated infections caused by enterobacteriaceae and nonfermenters and to study the resistance of polymer surface-grown gram-negative rods against antibiotics. Using a modification of the semiquantitative method for culturing vascular cannulas on solid media described by Maki et al., we studied the adherence of various gram-negative rods to 1-cm segments of silastic catheters, a material used for Port-A-Cath-systems. Organisms were obtained from the American Type Culture Collection (Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa, Enterobacter cloacae). All organisms but Klebsiella showed extensive irreversible adherence. Production of an extracellular slime substance was observed only with antimicrobially treated Pseudomonas. After 'infection', the silastic catheter segments were treated with various antimicrobial agents. The following antibiotics were used either individually or in combination: cefotaxime, ciprofloxacin, imipenem, fosfomycin and gentamicin. Despite the fact that the antibiotic concentrations used were many times greater than the respective MICs of the various antibiotics, none of the antibiotics tested succeeded in eliminating the organisms. E. coli was found to be the most susceptible organism. These in vitro data substantiate our clinical impression that it is hardly possible to successfully eliminate the colonization of central venous catheters with gram-negative rods by using the antimicrobial agents employed here.

Anti-Bacterial Agents↗