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Biomedical subjects

N Frank

Publications and source records attributed to N Frank.

At least 19 recordsLinked to original sources
PubMed2001

Ethanol enhances the formation of endogenously and exogenously derived adducts in rat hepatic DNA.

To investigate the role of ethanol in chemically-induced carcinogenesis, we exposed Wistar rats to ethanol, either as an acute dose or for prolonged periods in a liquid diet and looked for effects on endogenously and exogenously derived DNA adducts. Changes in the cytochrome P450 protein (CYP 2E1) and its catalytic demethylase activity were also followed in order to provide a sequence of relatively well understood changes that are associated with free radical production and, therefore, potentially capable of affecting DNA. The exocyclic DNA adducts, ethenodeoxyadenosine (varepsilondA) and ethenodeoxycytidine (varepsilondC), known to arise from oxidative stress and lipid peroxidation (LPO) sources, were detected in the liver DNA of Wistar rats at background concentrations of 4-6 (varepsilondA) and 25-35 (varepsilondC) adducts per 10(9) parent bases. When rats were given either an acute dose of ethanol (5g/kg, i.g.) or exposed for 1 week to ethanol in a liquid diet (5%, w/v), etheno adduct levels were increased approximately 2-fold and this was statistically significant for varepsilondC (P<0.05 and P<0.02, respectively) for the two separate treatments.In N-nitrosodimethylamine (NDMA)-treated rats, acute ethanol treatment significantly increased the level of O(6)-methylguanine (O(6)-MeG) in hepatic DNA and this was paralleled by a decrease in O(6)-alkylguanine DNA alkyltransferase (ATase) activity; immunohistochemistry confirmed this increase of O(6)-MeG in both hepatic and renal nuclei. When rats were given ethanol in the diet and treated with NDMA, O(6)-MeG levels in hepatic DNA increased at 1 week which coincided with the peak of CYP 2E1-dependent NDMA-demethylase activity. Single cell gel electrophoresis of liver cells showed that after 1 week of exposure to ethanol, there was a small but significant increase in the frequency of DNA strand breaks induced by NDMA (P<0.05); after 4 weeks the increase was 1.4-fold (P<0.01). Our results indicate that exposures to ethanol, which resulted in blood ethanol concentrations similar to those seen in chronic alcoholics and increased levels of expression of the CYP 2E1 protein can exacerbate the DNA damaging effects of endogenous and exogenous alkylating agents. These observations provide indications of possible mechanisms for the carcinogenic or co-carcinogenic action of ethanol.

Alkylating Agents↗
PubMed2001

Fistulation of the auditory tube diverticulum (guttural pouch) with a neodymium:yttrium-aluminum-garnet laser for treatment of chronic empyema in two horses.

Two horses with chronic empyema of the auditory tube diverticulum (guttural pouch) were refractory to medical treatment; empyema was bilateral in 1 horse and unilateral in the other. Both horses were treated by fistulation of the cartilage of the pharyngeal orifice by use of a neodymium:yttrium-aluminum-garnet laser in a noncontact manner. To maintain patency of the fistulae, indwelling catheters were placed into the openings created by the laser. For both horses, long-term follow-up did not reveal complications, and both owners were satisfied with results of the procedure. The authors recommend this procedure for horses that are unresponsive to medical treatment for chronic guttural pouch empyema.

Animals↗
PubMed2001

Inhibition of the initial wave of NF-kappaB activity in rat muscle reduces ischemia/reperfusion injury.

Nuclear factor kappaB (NF-kappaB) is thought to play an important role in the expression of genes expressed in response to ischemia/reperfusion (I/R) injury. In this report, the activation of NF-kappaB in rat skeletal muscle during reperfusion following a 4-h ischemic period was studied. NF-kappaB activation displayed a biphasic pattern, showing peak activities from 30 min to 3 h postperfusion and 6 h to 16 h postperfusion, with a decline to baseline binding activity levels between 3 h and 6 h. Inhibition of NF-kappaB activation was investigated using proline dithiocarbamate (Pro-DTC). NF-kappaB binding activity during reperfusion was significantly reduced by intravenous administration of Pro-DTC. Additionally, Pro-DTC resulted in decreased muscle edema and neutrophil activity, with an increased percentage of muscle survival compared with vehicle controls. These results demonstrate that NF-kappaB is activated during reperfusion in a biphasic manner and that the regulation of the initial phase of NF-kappaB activation affords physiological protection against a severe ischemic stress. Selective inhibition of NF-kappaB during early reperfusion may therefore be a therapeutic intervention for I/R injury.

Active Transport, Cell Nucleus↗
PubMed2000

Assessment of dysfunctional working models of self and others in schizophrenic patients: a summary of data collected in nine nations. International Research Group.

OBJECTIVE: To investigate the cross-cultural feasibility of a new scale for assessing dysfunctional working models of self and others, and to evaluate its discriminative power. METHOD: Schizophrenic patients (N=351), non-psychotic patients (N= 86) and non-clinical subjects (N= 511) collected in 10 centres completed the DWM-S. Current psychopathology was assessed by means of the BPRS. RESULTS: Alpha coefficients were high in all samples. Mean scores on the DWM-S appeared to be comparable in all countries, suggesting cross-national generalizability. No significant correlation was found with sex, age, levels of psychopathology and duration of illness. Discriminant analyses showed that more than 70% of the schizophrenic patients are correctly classified. CONCLUSION: The DWM-S is an easily administered self-report instrument which allows to pinpoint internal dysfunctional working models of self and others in various types of patients. It is a useful tool for case conceptualization, especially when psychotherapeutic interventions are part of the treatment programme.

Adult↗
PubMed2000

Academic performance and perceived validity of grades: an additional case for self-enhancement.

The authors investigated the role of academic self-esteem and academic performance in U.S. college students' perceptions of the validity of their grades (overall grade point average [GPA]). A sample of 208 (80 male, 128 female) college students completed a survey that included an academic self-esteem scale and a measure of the perceived validity of grades. The authors assessed academic performance level by the participants' actual overall GPAs. The results of a hierarchical multiple regression analysis supported the weak form of self-enhancement theory (J. S. Shrauger, 1975). Thus, regardless of their self-esteem levels, the students with higher GPAs, compared with those with lower GPAs, tended to see the overall GPA as a more valid indicator of academic ability.

Achievement↗
PubMed2000

A survey of camel (Camelus dromedarius) diseases in Jordan.

Information on incidences of camel (Camelus dromedarius) diseases in Jordan is scarce. In this survey, 369 live and 156 slaughtered camels were examined in four Jordanian geographic regions and the proportion of diseased camels was calculated. Intestinal parasite ova were detected in 98% of camels; one or more species of external parasites were found on the skin of all camels; 33% had nasal myiasis; and hydatid cysts were identified in 44% of the slaughtered animals. Sarcoptic mange (Sarcoptes scabiei var. cameli) and trypanasomiasis, two diseases of economic importance, were also diagnosed in 83% and 33% of the 32 and 257 examined camels, respectively. Rabies virus was detected in eight camels by use of fluorescent antibody examination of brain tissues. Foreign-body accumulation within the first and second stomach compartments was the predominant gastrointestinal disease of slaughtered adult camels (22%). Ten percent of slaughtered camels had bacterial pneumonia, with Pasteurella hemolytica most often isolated (56% of pneumonic lungs). Further investigation into the relationship between parasite burden and health in camels is required to assess the significance of the high prevalence of parasites.

Animals↗
PubMed1999

Inhibition of the transcriptional activator protein nuclear factor kappaB prevents hemodynamic instability associated with the whole-body inflammatory response syndrome.

BACKGROUND: The transcription factor nuclear factor kappaB mediates the expression of a number of inflammatory genes involved in the whole-body inflammatory response to injury. We and others have found that dithiocarbamates specifically inhibit nuclear factor kappaB-mediated transcriptional activation in vitro. OBJECTIVE: We hypothesized that inhibition of nuclear factor kappaB with dithiocarbamate treatment in vivo would attenuate interleukin 1 alpha-mediated hypotension in a rabbit model of systemic inflammation. METHODS: New Zealand White rabbits were anesthetized and cannulated for continuous hemodynamic monitoring during 240 minutes. Rabbits were treated intravenously with either phosphate-buffered saline solution or 15 mg/kg of a dithiocarbamate, either pyrrolidine dithiocarbamate or proline dithiocarbamate, 60 minutes before the intravenous infusion of 5 micrograms/kg interleukin 1 alpha. Nuclear factor kappaB activation was evaluated by electrophoretic gel mobility shift assay of whole-tissue homogenates. RESULTS: Infusion of interleukin 1 alpha resulted in significant decreases in mean arterial pressure and systemic vascular resistance, both of which were prevented by treatment with dithiocarbamate. Pyrrolidine dithiocarbamate induced a significant metabolic acidosis, whereas proline dithiocarbamate did not. Nuclear factor kappaB-binding activity was increased within heart, lung, and liver tissue 4 hours after interleukin 1 alpha infusion. Treatment with dithiocarbamate resulted in decreased nuclear factor kappaB activation in lung and liver tissue with respect to that in control animals. CONCLUSIONS: These results demonstrate that nuclear factor kappaB is systemically activated during whole-body inflammation and that inhibition of nuclear factor kappaB in vivo attenuates interleukin 1 alpha-induced hypotension. Nuclear factor kappaB thus represents a potential therapeutic target in the treatment of hemodynamic instability associated with the whole-body inflammatory response.

Acidosis↗
PubMed1999

Localized oral Fusarium infection in an AIDS patient with malignant lymphoma.

We report here a case of localized oral Fusarium infection in an AIDS patient who developed an ulceration in the soft palate. Fusarium solani was identified by histopathology and culture. We believe this to be the second reported case of oral Fusarium infection in a patient with haematological malignancy and the first reported association of oral Fusarium infection with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1999

Construction and preliminary characterization of a library of "lethal" preterminal protein mutant adenoviruses.

Adenoviruses containing lethal in-frame insertion mutant alleles of the preterminal protein (pTP) gene were constructed with cell lines that express pTP. Thirty in-frame insertion mutant alleles, including 26 alleles previously characterized as lethal and 4 newly constructed mutant alleles, were introduced into the viral chromosome in place of the wild-type pTP gene. The viruses were tested for ability to form plaques at 37 degrees C in HeLa-pTP cells and at 32 degrees C and 39.5 degrees C in HeLa cells. Two of the newly constructed viruses exhibited temperature sensitivity for plaque formation, one virus did not form plaques in the absence of complementation, seven additional mutants exhibited a greater than 10-fold reduction in plaque formation in the absence of complementation, and another eight mutants exhibited stronger phenotypes than did previously characterized in-frame insertion mutants in the plaque assay. These mutant viruses offer promise for analysis of pTP functions.

Adenoviruses, Human↗
PubMed1999

Effect of hypothyroidism on blood lipid concentrations in horses.

OBJECTIVE: To measure and compare concentrations of selected blood lipids before and after thyroidectomy in horses. ANIMALS: 5 healthy adult mares. PROCEDURE: Mares were confirmed to be euthyroid. Thyroidectomy was performed, and hypothyroidism was confirmed. Selected blood lipid variables were measured before hypothyroidism was induced and weekly for 4 weeks after induction. Plasma concentrations of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), serum triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA) were measured. The composition of VLDL and LDL also was examined. RESULTS: Mean plasma concentrations of VLDL and LDL increased significantly after thyroidectomy. By 4 weeks after thyroidectomy, a ninefold increase in mean plasma concentration of VLDL and a threefold increase in LDL, compared with baseline values, were detected. After thyroidectomy, mean percentage of TG in VLDL increased significantly, whereas free cholesterol and cholesterol ester content decreased. Mean percentage of TG in LDL also increased by 3 to 4 weeks after thyroidectomy. Serum concentrations of TG and TC increased, whereas serum NEFA concentration decreased. CONCLUSIONS: Hypothyroidism significantly alters blood lipid concentrations of horses. After thyroidectomy, markedly high VLDL concentration, appearance of TG-rich VLDL, increased serum concentrations of TG and TC, and decreased blood concentration of NEFA were evident. CLINICAL RELEVANCE: Examination of blood lipid concentrations of horses may be useful for detecting naturally acquired hypothyroidism.

Animals↗
PubMed1998

Primary hyperparathyroidism with osteodystrophia fibrosa of the facial bones in a pony.

A 17-year-old pony mare was admitted for evaluation of progressive enlargement of the facial bones during the preceding 9 months. Laboratory testing revealed that the pony had hypercalcemia, hypophosphatemia, high urinary fractional excretion of phosphorus, and high serum concentration of intact parathyroid hormone (185.1 pmol/L; reference range, 0.25 to 2.0 pmol/L). On the basis of these findings, a diagnosis of primary hyperparathyroidism was made by ruling out nutritional secondary hyperparathyroidism, chronic renal disease, and pseudohyperparathyroidism resulting from neoplasia. Although primary hyperparathyroidism is best treated by surgical removal of the affected parathyroid gland, the owners declined surgical exploration of the neck in this pony. Because of the poor prognosis, the pony was euthanatized. A functional lesion of the parathyroid tissue was not located on necropsy or histologic examination. Difficulty localizing and grossly identifying parathyroid tissue in horses complicates definitive diagnosis and treatment of primary hyperparathyroidism.

Animals↗
PubMed1998

Induction of apoptosis by thiuramdisulfides, the reactive metabolites of dithiocarbamates, through coordinative modulation of NFkappaB, c-fos/c-jun, and p53 proteins.

Prolinedithiocarbamate (PDTC) and diethyldithiocarbamate (DDTC) are cancer chemopreventive agents and can be biotransformed to prolinethiuramdisulfide (PTDS) and tetraethylthiuramdisulfide (disulfiram; DTDS), respectively. We found that the reactive metabolites PTDS and DTDS induced apoptosis after G1/S arrest. Phosphorylation of cyclin E, inhibition of cyclin-dependent kinase 2 activity, and degradation of cyclin E were found in human hepatoma Hep G2 cells during apoptosis. Moreover, PTDS and DTDS decreased the level of bcl-2 but increased the level of p53. In contrast, PDTC, DDTC, and ammonium dithiocarbamate (ADTC) did not induce apoptosis; rather they led to the induction of p53 and p21 followed by G1/S arrest. PDTC, DDTC, and ADTC also arrested cells in G1 phase. We then examined the effects of PTDS and DTDS on the signal transduction mechanisms leading to apoptosis. Although the transcription factors NFkappaB and AP-1 cooperatively decreased their DNA-binding activities to kappaB and 12-O-tetradecanoylphorbol-13-acetate-responsive elements, respectively, and p53 increased DNA-binding activity in the early stage but decreased it in the latter stage after treatment with PTDS, when the human Hep G2 cells were undergoing apoptosis. In summary, our results indicated that (i) PTDS and DTDS induced apoptosis and G1/S arrest mediated by p53, whereas PDTC, DDTC, and ADTC induced p53-dependent p21 expression leading to G1/S arrest; (ii) PDTC, DDTC, and ADTC induced p21/KIP1/CIP1 expression in a p53-dependent pathway leading to G1/S arrest; and (iii) NFkappaB, AP-1, and bcl-2 were downregulated during PTDS- and DTDS-induced apoptosis. These results suggested that PTDS and DTDS induced p53-dependent apoptosis, whereas PDTC, DDTC, and ADTC induced G1/S arrest. Apoptosis is regulated by the modulation of intracellular effectors such as NFkappaB, AP-1, and bcl-2 and activation of p53 in early stages.

Alcohol Deterrents↗
PubMed1998

Listeria monocytogenes and Escherichia coli septicemia and meningoencephalitis in a 7-day-old llama.

Listeria monocytogenes and Escherichia coli were isolated from blood collected on presentation and tissues samples taken postmortem. Listeria monocytogenes was isolated from cerebrospinal fluid collected antemortem. The importance of passive transfer of immunity, the subtlety of neurologic signs in early meningitis, and considering blood-CSF penetration in antimicrobial selection are discussed.

Animals↗
PubMed1997

Child temperament, parenting discipline style, and daytime behavior in childhood sleep disorders.

Fifty-two children without significant sleep disturbance seen at a primary care clinic for well-child care were compared on measures of temperament, parenting style, daytime behavior, and overall sleep disturbance to three diagnostic subgroups identified in a pediatric sleep clinic: children with obstructive sleep apnea (n = 33), parasomnias (night terrors, sleepwalking, etc.) (n = 16), and behavioral sleep disorders (limit-setting disorder, etc.) (n = 31). The mean age of the entire sample was 5.7 years. Temperamental emotionality in the behavioral sleep disorders group was associated with a higher level of sleep disturbance (p < .001); parenting laxness was associated with sleep disturbance in the general pediatric population (p < .01); and intense and negative temperament characteristics seemed to be associated with clinically significant behavioral sleep disturbances. Ineffective parenting styles and daytime disruptive behaviors were more likely to be associated with the milder sleep disturbances found in children in a primary care setting.

Analysis of Variance↗
PubMed1997

Recombinant plasmid mobilization between E. coli strains in seven sterile microcosms.

Transfer by mobilization of a pBR derivative recombinant plasmid lacking transfer functions (oriT+, tra-, mob-) from one E. coli K12 strain to another was investigated in seven sterile microcosms corresponding to different environments. These microcosms were chosen as representative of environments that genetically engineered microorganisms (GEMOs) encounter after accidental release, namely attached biomass in aquatic environments (biofilm), soil, seawater, freshwater, wastewater, mouse gut, and mussel gut, GEMOs survived in the same way as the host strains in all microcosms. Recombinant DNA mobilization occurred in the mouse gut, in sterile soil, and in biofilm. The plasmid transfer rates principally reflected the environmental conditions encountered in each microcosm.

Animals↗