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Biomedical subjects

J Novak

Publications and source records attributed to J Novak.

At least 19 recordsLinked to original sources
PubMed1997

Role of nitric oxide in modulating the long-term renal and hypertensive actions of norepinephrine.

We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-induced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-term control of renal hemodynamics and arterial pressure. To achieve this goal, we examined the effects of an intrarenal infusion of norepinephrine (NE) (0.1 microgram.kg-1.min-1) for 7 days in conscious, chronically instrumented control dogs and in dogs pretreated with a synthesis inhibitor, L-NAME (3 micrograms.kg-1.min-1 intrarenally). Both groups of dogs also received captopril (15 micrograms.kg-1.min-1) plus angiotensin I] intravenously to clamp the renin-angiotensin system throughout the protocol. In control dogs (n = 6), intrarenal infusion of NE decreased renal plasma flow by 9% (134 +/- 10 to 122 +/- 14 mL/min) and glomerular filtration rate by 16% (49 +/- 4 to 41 +/- 5 mL/min) while having no effect on mean arterial pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pretreated with intrarenal L-NAME (n = 9), NE decreased renal plasma flow by 37% (129 +/- 8 to 81 +/- 16 mL/min) and glomerular filtration rate by 32% (47 +/- 3 to 32 +/- 5 mL/min) while increasing mean arterial pressure from 104 +/- 5 to 113 +/- 6 mm Hg. The results of this study demonstrate that NO plays an important role in modulating the long-term actions of NE on renal function and arterial pressure.

Adrenergic alpha-Agonists↗
PubMed1996

Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation.

Ocular retardation (or) is a murine eye mutation causing microphthalmia, a thin hypocellular retina and optic nerve aplasia. Here we show that mice carrying the OrJ allele have a premature stop codon in the homeobox of the Chx10 gene, a gene expressed at high levels in uncommitted retinal progenitor cells and mature bipolar cells. No CHX10 protein was detectable in the retinal neuroepithelium of orJ homozygotes. The loss of CHX10 leads both to reduced proliferation of retinal progenitors and to a specific absence of differentiated bipolar cells. Other major retinal cell types were present and correctly positioned in the mutant retina, although rod outer segments were short and retinal lamination was incomplete. These results indicate that Chx10 is an essential component in the network of genes required for the development of the mammalian eye, with profound effects on retinal progenitor proliferation and bipolar cell specification or differentiation. off

Alleles↗
PubMed1996

Characterization of PepB, a group B streptococcal oligopeptidase.

Group B streptococci were recently reported to possess a cell-associated collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly purified enzyme nor crude group B streptococcal cell lysate solubilized a film of reconstituted rat tail collagen, an activity regarded as obligatory for a true collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced amino acid sequence showed 66.4% identity to the PepF oligopeptidase from Lactococcus lactis, a member of the M3 or thimet family of zinc metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase activity and degraded a variety of small bioactive peptides, including bradykinin, neurotensin, and peptide fragments of substance P and adrenocorticotropin.

Amino Acid Sequence↗
PubMed1996

Role of renal nerves in mediating the hypertensive effects of nitric oxide synthesis inhibition.

Recent studies suggest that enhanced renal sympathetic nervous activity plays an important role in mediating the renal hemodynamic and electrolyte excretion changes associated with acute inhibition of NO synthesis. The purpose of this study was to determine the importance of renal nerves in mediating the long-term hypertensive and renal actions of NO synthesis blockade. To achieve this goal, we infused N(G)-nitro-L-arginine methyl ester (L-NAME) at a rate of 25 microg/kg per minute for 2 weeks in control dogs and in bilaterally renal-denervated dogs. NO synthesis blockade in control dogs increased arterial pressure by 18%, from 94 +/- 3 to 111 +/- 4 mm Hg, and decreased heart rate from 74 +/- 4 to 57 +/- 4 beats per minute (bpm). L-NAME also decreased renal plasma flow from 195 +/- 18 to 166 +/- 18 mL/min while having no effect on glomerular filtration rate (67 +/- 7 versus 63 +/- 6 mL/min). In the renal-denervated dogs, inhibition of NO synthesis increased arterial pressure by 14%, from 92 +/- 4 to 105 +/- 5 mm Hg, and decreased heart rate from 80 +/- 4 to 65 +/- 5 bpm. Renal plasma flow in this group decreased from 195 +/- 20 to 165 +/- 20 mL/min, whereas glomerular filtration rate remained unchanged (66+/- 6 versus 64 +/- 6 mL/min). In addition, renal excretion of sodium and water in response to L-NAME was similar in each group. The results of this study indicate that the long-term hypertensive and renal effects of NO synthesis inhibition in the dog are not dependent on activation of the renal sympathetic nervous system.

Animals↗
PubMed1996

Predictive value of proliferation-related markers, p53, and DNA ploidy for survival in patients with soft tissue spindle-cell sarcomas.

In a retrospective study of 60 spindle-cell sarcomas of peripheral soft tissues, we evaluated the extent of immunostaining with antibodies against Ki-67, proliferating cell nuclear antigen, and p53 protein and flow-cytometric DNA ploidy, their relation to tumor location, depth, histologic type, size, mitotic rate, and extent of tumor necrosis, as well as their influence on survival. Although Ki-67-labeled nuclei were detected in only 41 tumors (68%) and their number varied from 1 to 50%, proliferating cell nuclear antigen immunoreactive nuclei were found in each tumor, with their number ranging from 20 to 99%. p53 Protein was found in 26 cases (43%), and its labeling ranged from 1 to 80%. Although Ki-67 labeling significantly correlated with mitotic rate, no correlation could be found between proliferating cell nuclear antigen or p53 labeling and any other variables studied. Thirty-eight percent of the tumors were diploid, and 64% were aneuploid. Factors that significantly reduced survival in univariate analysis were increasing size and depth of the tumor, the presence of necrosis, the National Cancer Institute grade, and a tetraploid/hypertetraploid DNA pattern. In multivariate analysis of 49 cases with complete information, only DNA ploidy pattern, tumor size, and tumor necrosis retained their independent prognostic significance.

Biomarkers, Tumor↗
PubMed1995

Lead and nickel alter the cardiorenal actions of endothelin in the rat.

In the current study, we have determined to what extent lead and nickel alter the cardiorenal actions of endothelin in pentobarbital anesthetized female rats. One hour following surgery, 3 x 15-min renal clearances were collected and endothelin (ET)-1 was infused iv at 110 ng/kg/min for 30 min during which time an additional two clearances were collected. Lead (infused as lead acetate throughout the experiment) at 4.8 nmoles/min and 24 nmoles/min significantly attenuated the ET-induced increase in mean arterial pressure (MAP); lead infused at 0.48 nmoles/min had no effect. An ET-induced decrease in the glomerular filtration rate (GFR) in control rats was completely blocked by the higher doses of Pb2+. By contrast, Pb2+ had no effect on angiotensin II or norepinephrine induced increases in MAP. In additional experiments, calcium chloride was infused at 500 nmoles/min for 105 min, then Ca2+ + Pb2+ (4.8 nmoles/min) were infused for another 105 min; in these experiments, there was no Pb(2+)-induced inhibition of the MAP response to endothelin; the GFR response to the peptide remained blocked. NiCl2 reduced the ET-induced increase in MAP only at 24 nmoles/min; at 4.8 and 24 nmoles/min, nickel attenuated the decrease in GFR induced by ET. Finally, Ca2+ infusion had no effect on the inhibition by Ni2+ of the GFR response to ET. These data illustrate that (i) lead inhibits the cardiorenal actions of endothelin; (ii) a Ca(2+)-related process is involved the systemic but not the renal component of this inhibition; (iii) since the heavy metal does not affect angiotensin II or norepinephrine-induced increases in MAP, the inhibition by lead of the systemic response is relatively specific for endothelin; and (iv) nickel also inhibits the renal response to the peptide but higher doses are required to inhibit the systemic response.

Angiotensin II↗
PubMed1995

Effect of race on survival following in-hospital cardiopulmonary resuscitation.

BACKGROUND: Race has been shown to be a significant predictive factor in a number of treatment decisions and outcomes, including survival following out-of-hospital cardiopulmonary resuscitation (CPR). The goal of this study was to determine whether race is associated with the rate of survival to discharge following in-hospital CPR. METHODS: Consecutive adult patients undergoing attempted CPR at three teaching hospitals were identified. Demographic, clinical, and laboratory data from the time of admission, information about the resuscitation attempt, and the outcome of CPR were recorded for each patient. The characteristics of black and non-black patients were compared. Logistic regression was used to determine whether race was a significant independent predictor of CPR outcome. RESULTS: A total of 656 patients were identified. Black patients had a higher mean severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) III score, were more likely to have an initial rhythm of electromechanical dissociation or asystole, were less likely to have an admitting diagnosis of myocardial infarction or a history of coronary artery disease, and had a higher serum creatinine level, lower serum albumin value, and lower 24-hour urine output for the first 24 hours. There was no difference between black and nonblack patients regarding the rate of survival of the resuscitative effort itself. However, black patients were significantly less likely than nonblack patients to survive to discharge following resuscitation (Mantel-Haenszel odds ratio, 0.31; 95% confidence interval, 0.15 to 0.68). This relationship persisted after adjusting for potential confounders such as age, sex, initial cardiac rhythm, diagnosis of pneumonia, serum creatinine level, hospital, and APACHE III score. CONCLUSIONS: Black race is significantly associated with a lower rate of survival to discharge following in-hospital CPR. Further work is needed to explore this association in other settings; to examine the effect of other possible confounding variables, such as tobacco use, socioeconomic status, and marital status; and to further study the determinants of physician decision-making about resuscitation.

Adult↗
PubMed1994

Mineralization and pH relationships in healing skeletal defects grafted with demineralized bone matrix.

Early studies had indicated that tissue repair is initially associated with a lower than normal serum pH that later becomes more alkaline. To determine how tissue pH may affect skeletal healing and mineralization, we used a rat skeletal repair model consisting of a long bone segmental defect grafted with acid-demineralized bone matrix (DBM), a biomaterial possessing both osteoinductive and osteoconductive repair properties. In this study, femoral and tibial diaphyses from young adult Sprague Dawley rats were cut into cylinders approximately 0.5 cm in length, demineralized in acid, perforated to accommodate a needle-type combination pH microelectrode, and grafted around a 0.3-cm-long diaphyseal fibula defect. The pH of repair tissues was recorded at various time intervals up to 28 days postgrafting. Healing and mineralization were monitored histologically and by the ash and calcium content of repair tissues. During the early healing phase, tissue pH was lower than normal serum pH, presumably because of an accumulation of acidic metabolites in tissue fluids. Subsequent pH increases to more alkaline values were accompanied by a rapid mineral deposition phase and a later phase characterized by a slow, gradual increase in tissue calcium content. The results of this study support previous observations suggesting that the pH of repair tissue fluids may play a regulatory role in the healing and mineralization of bone.

Animals↗
PubMed1994

Enzyme-linked immunosorbent assay using a recombinant baculovirus-expressed Bacillus anthracis protective antigen (PA): measurement of human anti-PA antibodies.

We developed an antigen capture enzyme-linked immunosorbent assay (ELISA) which does not require purified protective antigen (PA) for detection of human antibodies to Bacillus anthracis PA. Lysates of Spodoptera frugiperda (Sf-9) cells infected with recombinant baculovirus containing the PA gene were used as the source of PA to develop the ELISA. Recombinant PA from crude Sf-9 cell lysates or PA purified from B. anthracis Sterne strain was captured by an anti-PA monoclonal antibody coated onto microtiter plates. We demonstrated that human serum antibody titers to PA were identical in the ELISA whether we used crude Sf-9 cell lysates containing recombinant baculovirus-expressed PA or purified Sterne PA. Finally, false-positive results observed in a direct ELISA were eliminated with this antigen capture ELISA. Thus, the antigen capture ELISA with crude preparations of baculovirus-expressed PA is reliable, safe, and inexpensive for determining anti-PA antibody levels in human sera.

Animals↗
PubMed1994

Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model.

Osteomyelitis with Staphylococcus aureus was established in the tibiae of twenty-six adult mongrel dogs. After confirmation of infection at four weeks, all animals had operative débridement and were then divided into three treatment groups. Group 1 (eight animals [sixteen tibiae]) was treated with parenteral administration of gentamicin (three milligrams per kilogram of body weight per day) every eight hours for four weeks. Group 2 (nine animals [nine tibiae]) was treated with a polymethylmethacrylate implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. Group 3 (nine animals [nine tibiae]) was treated with a polylactide/polyglycolide implant containing 100 milligrams of gentamicin that was placed in the tibia for six weeks. All animals were killed at the end of treatment. At that time, specimens of tissue were obtained for quantitative culture as well as for antibiotic immunoassay. In the groups that had been treated with an implant, serum was obtained for the measurement of serum drug levels after débridement; after the implantation; four, seven, and twenty-one days postoperatively; and immediately before the animals were killed. The infection was eradicated in ten of the sixteen tibiae in Group 1, in eight of the nine tibiae in Group 2, and in all nine tibiae in Group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Adenocarcinoma in a sigmoid neovagina 22 years after Wertheim-Meigs operation. Case report.

The development of carcinoma in the neovagina has rarely been reported. Depending on the type of tissue that has been used for the transplant, the tumor appears either as a squamous cell carcinoma or adenocarcinoma. It is important to draw a distinction not only between the patients with squamous cell carcinoma and adenocarcinoma, but also between those with neovagina performed due to congenital absence of the vagina and others in whom the procedure was performed because of an advanced cancer in the true pelvis. In the latter group of patients, it is generally difficult to distinguish a residual disease from a second primary of the same histology. There is no dilemma, however, when the histology differs as in the case presented. The patient reported here underwent surgery for squamous cell carcinoma of the cervix, stage Ib, in 1967. The intervention comprised a Wertheim-Meigs resection and sigmoid vaginoplasty. Considering the favourable histological findings, postoperative irradiation was not indicated. Following the procedure, the patient had been well and free of any major complaint for 22 years after surgery when she presented with a moderately differentiated adenocarcinoma of the neovagina. She was successfully operated upon and had no evidence of disease at the last follow-up examination, two and a half year after surgery.

Adenocarcinoma↗
PubMed1993

Dependence of induction of osteocalcin gene expression on the presence of wild-type p53 in a murine osteosarcoma cell line.

The p53 gene undergoes rearrangement in a high percentage of osteosarcomas, resulting in loss of its expression. A p53-null murine osteosarcoma cell line F6 was transfected with either a wild-type or a mutant p53 gene. Stably transfected cell lines were obtained, and their differentiation capabilities were compared in vitro with the parental cell line. Alkaline phosphatase and osteocalcin expression were measured as early and late differentiation markers, respectively. Induction of alkaline phosphatase expression was not affected by the presence of either p53 gene, whereas osteocalcin expression was seen in cells containing the wild-type p53 gene but not in the parental p53-null or mutant-expressing cell lines. That the induction of osteocalcin was intrinsically dependent on the presence of wild-type p53 was also indicated by the use of a temperature-sensitive Val 135 p53 mutant at 32 degrees C; predominant expression of p53 in the wild-type conformation resulted in osteocalcin expression. While the wild-type p53 gene could suppress tumor formation in vivo, the tumors expressing the mutant p53 gene grew two to three times as large as the tumors that did not express p53. Therefore, the absence of end-point differentiation in bone due to p53 rearrangements may contribute to the maintenance of the tumorigenic phenotype in osteosarcomas.

Alkaline Phosphatase↗
PubMed1992

Hemicellulose bioconversion to polyanionic heteropolysaccharides.

Anionic polysaccharides, traditionally obtained from plant or algal sources, have a variety of commercial uses. Such gums from microorganisms have received increased recent interest. We have initiated a program to investigate the bioconversion of pentosans to rheologically useful anionic extracellular polysaccharides (AEPS). A number of earlier-described species, including Cryptococcus laurentii, Klebsiella pneumoniae, Arthrobacter viscosus, and Pseudomonas ATCC 31260, appear to have potential in this regard. These organisms can individually convert either xylose, enzymatic oligomeric hemicellulose digests, dilute mineral acid hemicellulose ("TVA") hydrolysates, or a five-monosaccharide mixture simulating sulfite process liquors to AEPS. The formation parameters, compositions, mol-wt distributions, and the intrinsic viscosities of these purified AEPS are exemplified. Substitution of pentose as the major substrate for glucose can result in changes in mol-wt distribution or in the percentage of noncarbohydrate substituents in some AEPS. Pursuit of these observations may lead to interesting structure-property relationships and toward rheological applications for pentosan-derived AEPS.

Arthrobacter↗
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↗