Search PubMed⌕ Search

Biomedical subjects

J Novak

Publications and source records attributed to J Novak.

At least 73 records · Page 4Linked to original sources
PubMed1992

Inactivation of p53 gene in human and murine osteosarcoma cells.

We examined structure and expression of the p53 and Rb genes in a C3HOS transplantable mouse model of osteosarcoma. The results were compared to analogous studies conducted with five human osteosarcoma cell lines. The p53 gene was found rearranged in the mouse tumour. The rearrangement mapped to the first intron region of the p53 gene and as a result, no p53 expression could be detected in C3HOS tumours. Using p53 genomic probes, we have detected the same rearrangement in the original radiation-induced tumour and the various clones that were isolated from it. Deletion and rearrangement of the p53 gene were also found in three out of five of the human osteosarcoma cell lines (MG-63, G-292, Saos-2). No p53 expression could be detected in these three cell lines. In the affected human osteosarcoma cell lines, the rearrangement involved the first intron region. In addition, the mouse tumor was analysed for structural and expression changes in the Rb and the c-myc genes. Normal expression of both genes were detected in the murine tumour. Only one (Saos-2) human osteosarcoma cell line exhibited gross structural alteration in the retinoblastoma gene. The results suggest that the inactivation of p53 may be an important step in the development of osteosarcomas, and that a rearrangement affecting the first intron is common in osteosarcomas.

Animals↗
PubMed1992

Renal actions of endothelin during mannitol and saline expansion.

We evaluated the effects of volume expansion with saline (0.5 ml kg-1 min-1, n = 13) and with 10% mannitol in saline (0.5 ml kg-1 min-1, n = 13) on the cardiorenal actions of endothelin-1 (ET) in rats anesthetized with sodium pentobarbital. We also evaluated to what extent the calcium channel antagonist, verapamil (0.02 mg kg-1 min-1), altered the cardiorenal actions of endothelin in volume-expanded rats (n = 10 with saline and n = 10 with mannitol). In five rats from each group, renal blood flow was measured with an electromagnetic flow probe. Sixty minutes after surgery, control clearances were collected, ET (110 ng kg-1 min-1) was then infused for 30 min, and recovery clearances were collected for 60 min. ET caused a similar increase in mean arterial blood pressure and decrease in renal blood flow and the glomerular filtration rate in the saline and mannitol groups. Verapamil significantly attenuated but did not abolish the ET-induced increase in mean arterial blood pressure in both saline- and mannitol-treated rats. By contrast, the calcium channel antagonist had no effect on the ET-induced decrease in either the glomerular filtration rate or renal blood flow in saline-treated rats, but significantly attenuated these responses to ET in mannitol-expanded animals. These data demonstrate that (i) the systemic and renal responses to ET are not affected by expansion with saline or mannitol and (ii) the renal vasoconstriction prompted by endothelin is not affected by verapamil in saline-expanded rats, but is attenuated by the Ca2+ channel antagonist during expansion with mannitol. These data suggest that during volume expansion with mannitol, but not with saline, the ET-induced renal vasoconstriction occurs primarily at intrarenal resistance sites that are dependent upon extracellular Ca2+.

Animals↗
PubMed1991

Gender differences in adults' knowledge about fat and cholesterol.

Cognitive learning theories suggest that an individual's prior knowledge is a major factor for determining what can be learned. The objectives of this study were to compare the organization of knowledge about fat and cholesterol in adult, middle-class men and women and changes in that knowledge after reading an educational bulletin. Forty men and 48 women participated in two semistructured interviews to assess their knowledge; half received a US Department of Agriculture bulletin on fat and cholesterol at the end of the first interview. Concept maps (two-dimensional representations of an individual's cognitive knowledge structure) were made from the interview transcripts to assess knowledge organization. Both genders had limited knowledge, scoring less than 25% of the maximum possible score at interview 1. Overall, known and not known concepts were similar in men and women; however, women had slightly more integrated knowledge and more misconceptions than men. Both groups receiving the bulletin made significant gains in knowledge at interview 2, but knowledge gains were twice as great in men as in women. Our findings indicate that practitioners need not create separate materials about fat and cholesterol for middle-class men and women.

Adult↗
PubMed1991

Tilt test for diagnosis of unexplained syncope in pediatric patients.

Thirty-five teenage patients with a history of presyncope or syncope underwent a passive head-up tilting to reproduce symptoms of syncope. If tilting alone did not induce syncope, isoproterenol infusion was given to increase heart rate to 150 to 160 beats per minute. In 80% of patients with a history of syncope, identical symptoms could be reproduced during tilting: an abrupt fall in blood pressure combined with profound nodal bradycardia, ranging from 32 to 86 beats per minute. These symptoms were quickly reversed by returning the patient to the supine position. For patients with frequent occurrences of syncope, especially when there was a history of trauma sustained during these episodes, a therapeutic regimen of either beta blockers or 9 alpha-fluorocortisol was begun. The mechanisms of this common cause of syncope in childhood is neurocardiogenic in response to venous pooling and catecholamine-induced tachycardia. The tilt test is an excellent and cost-effective test for the workup of unexplained syncope in childhood.

Adolescent↗
PubMed1990

Extracorporeal CO2 removal in a lung lavage induced respiratory distress syndrome.

Ten pigs with experimental respiratory distress syndrome were treated by extracorporeal CO2 removal (ECCO2-R) combined with low frequency positive pressure ventilation (LPPV). After lung damage had been induced by repeated lung lavages a PEEP trial was conducted in order to find the appropriate PEEP for the damaged lungs. This PEEP was then applied during the ECCO2-R/LPPV period. Blood gas values improved significantly on extracorporeal bypass within a short time (pre-bypass paO2: 54.2 +/- 3.7 vs 168.5 +/- 31.6 mmHg after 15 min on bypass, p less than 0.001) and were kept constant during the next 4 hours. Minute ventilation (MV) was reduced from 4.01 +/- 0.31 to 0.74 +/- 0.07 l/min (p less than 0.0001), FiO2 of the ventilator from 1.0 to 0.46 +/- 0.08 (p less than 0.0001) whereas FiO2 of the membrane lung (ML) was not changed significantly (FIO2ML 0.59 +/- 0.07 vs 0.53 +/- 0.06). During controlled mechanical ventilation (CMV), comparable adequate gas exchange was only achieved at a significantly higher mean airway pressure (Paw 14.1 +/- 0.08 vs 21.2 +/- 0.47 cmH20, p less than 0.0001). Hemodynamic variables did not change significantly during bypass time. ECCO2-R/LPPV driven by a simple renal perfusion system allows adequate gas exchange in experimental respiratory failure.

Animals↗
PubMed1989

Effects of phenobarbital and 3-methylcholanthrene on the hepatic cytochrome P-450 metabolism of various alkoxyresorufin ethers in the cotton rat (Sigmodon hispidus).

1. Microsomes isolated from phenobarbital and 3-methylcholanthrene induced cotton rats (Sigmodon hispidus) were tested for o-dealkylase activity with methoxy-, ethoxy-, pentoxy- and benzoxyresorufin ethers. 2. The activity of 3-methylcholanthrene induced microsomes was greater than controls. 3. Activity of phenobarbital induced microsomes was not different from controls. 4. There was a distinct difference between male and female animals. 5. The results obtained from cotton rats are markedly different from results obtained from Sprague-Dawley (S-D) rats.

Animals↗
PubMed1989

Effects of different intensities of fatigue on performing a sport skill requiring explosive muscular effort: a test of the specificity of practice principle.

The purpose of this study was to ascertain the effects of high, moderate, and low physical fatigue on performing the shot put, a sport skill that requires explosive muscular effort. 44 subjects practiced the shot put until mastery was achieved. They then experienced one of four fatigue intensities during a 20-trial practice period (no fatigue, 45, 60 or 75% of their predicted maximum oxygen uptake) to induce light, moderate, or heavy fatigue, respectively, after which subjects then engaged in criterion performance for 5 trials under each of the fatigue intensities, with one week in between. Distance thrown and expert assessment of performance technique were dependent variables. Analysis indicated that criterion performance was optimal for both distance and form after subjects experienced light fatigue during practice and criterion performance. The specificity of practice hypothesis was partially supported for the light fatigue condition, but not for the other intensities.

Adolescent↗
PubMed1988

Gastric bleeding in pseudoxanthoma elasticum.

We report a case of pseudoxanthoma elasticum and gastrointestinal bleeding, and document the degenerative changes of the gastric arterioles occurring over a 26-yr period. In addition to the internal elastic lamellar degeneration and dystrophic calcification, we describe the presence, ultrastructurally, of an abnormal collagen fiber. These degenerative changes in the gastric vascular bed can be a direct cause of gastrointestinal bleeding.

Gastrectomy↗
PubMed1987

In vitro activity of ciprofloxacin against gram-positive bacteria. An overview.

A review of European data published before July 1986 and data from the authors' laboratory showed very similar activity of ciprofloxacin against gram-positive bacteria in all studies. Mean minimal inhibitory concentrations against 50 percent (MIC50) and 90 percent (MIC90) of staphylococcal strains were 0.32 and 0.59 mg/liter, respectively. The drug was equally active against staphylococcal strains resistant and susceptible to methicillin and/or gentamicin. The range of MIC50 and MIC90 values for Streptococcus faecalis and Streptococcus faecium was between 0.25 and 1 mg/liter and 1 to 8 mg/liter, respectively. Ciprofloxacin inhibited group A and group B streptococci at concentrations of 0.5 to 2 mg/liter. Group C and G strains were less susceptible (MICs, 2 to 16 mg/liter). Penicillin-resistant and penicillin-susceptible pneumococci and the Viridans streptococci were inhibited by 0.5 to 4 mg/liter. MIC50 and MIC90 values of ciprofloxacin against Corynebacterium, including group JK, and anaerobic gram-positive cocci were 1 and 8 mg/liter, respectively, and against anaerobic gram-positive rods, were 2 and 16 mg/liter, respectively. Listeria monocytogenes strains were inhibited by 0.12 to 2 mg/liter. Ciprofloxacin showed bactericidal activity against staphylococci and streptococci in minimal bactericidal concentration tests and in killing kinetic studies. The in vitro activity of the drug was influenced neither by the method employed, by the medium used, by the pH of the medium, nor by the size of the inoculum. Resistance to ciprofloxacin developed in staphylococci in a step-wise manner. First-step mutants usually showed a fourfold to eightfold decrease in susceptibility. Contrary to the situation in gram-negative organisms, resistant mutants did not show reduced growth.

Ciprofloxacin↗
PubMed1987

Comparison of unique leucovorin and 5-fluorouracil "escalating" and "maximum" dosage strategies.

In this study (GI 6384), regimens are compared which, in phase II investigations, produced 2-fold increases in the historical rates of objective and minor responses. These regimens were associated with overall survival exceeding 1 year. In arm 1, 5-fluorouracil (FUra) alone, 500 mg/m2 on days 1 through 5 was escalated in 25-mg/m2 increments in monthly courses to produce mild to moderate toxicity. This allows an examination of dose-response relationships and comparisons of therapeutic index. In arm 2, leucovorin (LV), was escalated from 25 to 250 to 500 mg/m2 beginning 1 hour before a bolus FUra (30 mg/kg) every 3 weeks. Arm 3 (not previously tested) employed LV (25 mg/m2) 1 hour before FUra (600 mg/m2) given weekly for 6 weeks. It tested the efficacy of low-dose LV. Arm 4 tested high-dose LV (500 mg/m2) as a 2-hour infusion beginning 1 hour before a bolus FUra (600 mg/m2) weekly for 6 weeks. In a preliminary analysis of this study, findings are statistically consistent with the anticipated high frequencies of objective response. It also finds evidence of biological activity across the wide range of LV dosages and that LV produces an apparent favorable change in FUra side effects from hematological to gastrointestinal toxicities. One or more regimens may favorably change the anticipated prognosis of patients with measurable cancer of the colon and rectum.

Age Factors↗
PubMed1987

The role of glutathione reductase in maintaining human granulocyte function and sensitivity to exogenous H2O2.

Human granulocytes (polymorphonuclear leukocytes, PMN) produce H2O2 and other reactive oxygen species while undergoing phagocytosis. To examine the role of the glutathione cycle in metabolizing H2O2, we incubated PMN with 1,3-bis (2-chloroethyl) nitrosourea (BCNU). Incubation of PMN with BCNU results in a dose-dependent inhibition of PMN glutathione reductase (GRED), with 50% inhibition occurring at approximately 2 micrograms/mL BCNU. PMN hexose monophosphate shunt activity stimulated with an exogenous H2O2-generating system was inhibited only when the GRED activity was reduced to less than 30% of control. BCNU-treated cells contained lower levels of reduced sulfhydryls and reduced glutathione, which decreased even more in the presence of an exogenous H2O2-generating system. The effect of BCNU and exogenous H2O2 on various aspects of phagocytosis were examined. Exposure of BCNU-treated PMN to an H2O2-generating system resulted in an inhibition of chemotactic peptide-induced shape changes and degranulation. The ability of BCNU-treated cells to produce O2- was diminished only when the PMN were incubated with an H2O2-generating system in the presence of cyanide. Ingestion of opsonized bacteria by BCNU-treated PMN was unaffected by incubation in an H2O2-generating system even in the presence of cyanide. We conclude that PMN GRED is inhibited by BCNU, the ability of PMN to metabolize H2O2 is affected only when GRED is reduced more than 70%, this inhibition affects the glutathione content of these cells, and some, but not all of the phagocytic functions of GRED-inhibited PMN are inhibited after exposure to an H2O2-generating system.

Carmustine↗
PubMed1985

Comparative activity of the penem antibiotic Sch 34343 against gram-negative and gram-positive bacteria with special reference to multiresistant strains.

A new penem antibiotic, Sch 34343, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative staphylococci equally well, being five times more active than cefamandole and ten times more active than methicillin. Most methicillin-resistant staphylococci were inhibited by concentrations between 0.25 and 4 mg/l, but a small group of highly resistant strains were observed. Sch 34343 was eight times less active than ampicillin and penicillin G, but as active as piperacillin against enterococci. The drug showed excellent activity against various streptococci. Sch 34343 was as bactericidal as flucloxacillin, ampicillin and penicillin G against staphylococci, enterococci and streptococci, respectively, in killing kinetic tests. Enterobacteriaceae susceptible to third-generation cephalosporins were approximately five times less susceptible to Sch 34343, but MICs were far below the susceptibility breakpoint. Sch 34343 was equally active against Citrobacter and Enterobacter strains that were highly resistant to third-generation cephalosporins and to aztreonam. Together with thienamycin, this drug seems to be a good alternative for the treatment of infections caused by bacteria resistant to third-generation cephalosporins and to aztreonam.

Anti-Bacterial Agents↗
PubMed1984

Periodontal response after tooth movement into intrabony defects.

The present study was undertaken since conflicting evidence exists regarding the effect of such tooth movement on levels of connective tissue attachment. Localized intrabony pockets were produced around isolated incisors in four rhesus monkeys. The root surfaces were planned to the level of the bone at the base of the angular bony defects. An oral hygiene regime was begun and continued for the remainder of the study. The experimental teeth were moved orthodontically into, and through, the original area of the intrabony defect. Two months after cessation of active tooth movement, block specimens were removed for histologic analysis. Control specimens comprised those teeth with induced periodontal defects, but without tooth movement. In specimens not subjected to tooth movement, angular bony defects were present and epithelium lined the root surface to the apical extent of instrumentation. The alveolar bone adjacent to the orthodontically moved teeth no longer had angular defect morphology. On the pressure side, epithelium lined the root surface, was interposed between root surface and bone and terminated at the apical limit of root instrumentation. On the tension side, the crest of the bone was located apical to the level of root planing, and epithelium lined the instrumented portion of the root surface. It was concluded that orthodontic tooth movement into intrabony periodontal defects was without effect upon the levels of connective tissue attachment.

Alveolar Process↗