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Biomedical subjects

J W Olson

Publications and source records attributed to J W Olson.

At least 91 records · Page 5Linked to original sources

alpha-Difluoromethylornithine, an inhibitor of polyamine synthesis, attenuates monocrotaline-induced pulmonary vascular hyperresponsiveness in isolated perfused rat lungs.

Monocrotaline-induced pulmonary hypertension in rats is preceded by an early and prolonged activation of lung ornithine decarboxylase (ODC) and a resultant increase in lung polyamine levels. These changes coincide in time with a transient period of pulmonary vascular hyperresponsiveness to angiotensin II. We therefore tested the hypothesis that enhanced lung ODC activity is necessary for the occurrence of monocrotaline-induced pulmonary vascular hyperresponsiveness. Adult male rats were given a subcutaneous injection of either 105 mg/kg monocrotaline or its vehicle and were treated concurrently with either alpha-difluoromethylornithine (DFMO), a specific, irreversible inhibitor of ODC, or saline. One week post monocrotaline treatment, animals were sacrificed and vascular responsiveness to angiotensin II and KCl was assessed in isolated, buffer perfused lungs. Relative to control preparations, lungs from monocrotaline-treated animals exhibited significantly larger vasoconstrictor responses upon challenge with 0.1 or 0.5 microgram angiotensin II. In contrast, angiotensin II-induced responses in lungs from rats treated with monocrotaline plus DFMO were not different from control. DFMO treatment alone had no impact on angiotensin responses. Vasoconstrictor responses evoked by 30 and 45 mg KCl were not different in lungs from monocrotaline-treated animals relative to control nor were they influenced by concurrent treatment with DFMO. Neither the polyamines (putrescine, spermidine, or spermine) nor DFMO influenced angiotensin II-induced vasoconstriction in normal lungs when added acutely to the perfusate reservoir. These observations suggest that the polyamines, although not serving as regulators of vascular reactivity in the normal pulmonary circulation, are causally related to the evolution of pulmonary vascular hyperresponsiveness observed in lungs from monocrotaline-treated rats.

Angiotensin II↗

Prolonged activation of rat lung ornithine decarboxylase in monocrotaline-induced pulmonary hypertension.

Polyamines are believed to have an essential role in cellular growth and differentiation. Activation of ornithine decarboxylase, the initial rate-limiting enzyme in polyamine biosynthesis, is an early event characteristic of cell growth processes. Monocrotaline-induced pneumotoxicity is associated with cellular hypertrophy and proliferation, most notably pronounced medial thickening of pulmonary arterioles and hypertrophy of right ventricular myocardial cells. We reasoned that polyamines may be causally related to these events and, therefore, elevations in lung and right ventricular ornithine decarboxylase activities might precede development of pulmonary hypertension and right ventricular hypertrophy. To test this hypothesis adult male rats were given monocrotaline (105 mg/kg, s.c.); lung and right and left ventricular ornithine decarboxylase activities, pulmonary artery pressure, and right ventricular hypertrophy were assessed at 1, 4, 7, 10, 14, 16 and 21 days post treatment. Lung ornithine decarboxylase activity was increased approximately 8-fold on day 1 and remained elevated through day 7. Right ventricular ornithine decarboxylase activity was not elevated above control values at any time. Elevated pulmonary artery pressure and right ventricular hypertrophy were not apparent until day 16 and day 14 respectively. Thus, sustained activation of lung ornithine decarboxylase occurred at least 1 week prior to the development of pulmonary hypertension, suggesting that polyamines may play an important role in the pulmonary vascular remodeling that accompanies monocrotaline-induced pneumotoxicity.

Animals↗

Polyamines and the development of monocrotaline-induced pulmonary hypertension.

Previous work in our laboratory has shown that the development of monocrotaline-induced pulmonary vascular disease in rats is preceded by a prolonged activation of lung ornithine decarboxylase (ODC). We now report that significant increases in rat lung adenosylmethionine decarboxylase activity and levels of the diamine putrescine and the polyamines, spermidine and spermine, are produced by a single dose of monocrotaline (MCT). Lung putrescine levels were increased from days 7 through 21, and both spermidine and spermine were first elevated at day 10 following MCT administration. This sustained elevation of lung polyamine levels substantially preceded the development of right ventricular hypertrophy and pulmonary hypertension, which were first evident at days 14 and 16, respectively. Continuous treatment with alpha-difluoromethylornithine, a highly specific enzyme-activated, irreversible inhibitor of ODC activity, prevented the development of MCT-induced pulmonary toxicity. It thus appears that ODC and the polyamines may be important mediators of hypertensive pulmonary vascular disease that develops in response to monocrotaline administration.

Adenosylmethionine Decarboxylase↗

Hereditary hemorrhagic telangiectasia: prosthetic management and considerations.

The dentist should be aware of the signs, symptoms, and significance of hereditary hemorrhagic telangiectasia. A patient who had unusual involvement of the masticatory mucosa and for whom construction and function of complete dentures did not result in discomfort or oral bleeding is described. Dentures may have a positive effect on the size and number of telangiectasias. A gradual decrease in the size of a nodular lesion of the mandibular edentulous ridge is documented over a 3-year period.

Dental Care for Persons with Disabilities↗

Material adherent to probes during a periodontal examination. Light and electron microscopic observations.

The material adherent to a periodontal probe during the examination of deep periodontal pockets was studied with light and electron microscopy. Most of the specimens contained bacteria with a morphology which has been associated with a pathogenic flora. The findings suggest that periodontal probes may have the potential of transmitting pathogenic bacteria from involved sites to other sites in the mouth, although it remains to be demonstrated that this will result in actual implantation of the organisms at the new sites.

Adult↗

Histiocytosis X: a clinical presentation.

A 56-year-old male complained of chronic oral ulcers. Initial workup revealed diffuse alveolar bone destruction and other systemic disturbances including diabetes insipidus. Biopsy suggested histiocytosis X and further tests verified the diagnosis. A clinical differential diagnosis is developed, follow-up is presented and the entities comprising histiocytosis X are discussed.

Carcinoma, Squamous Cell↗

Prolonged ornithine decarboxylase induction in regenerating carcinogen-treated liver.

A cascade of events leading to hypertrophy has been proposed and implicated in growth regulation in a variety of normal and neoplastic cells and tissues. There is a tightly coupled temporal sequence: (a) cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAPK) activation; (b) ornithine decarboxylase (ODC) induction; and (c) the accumulation of the organic cation, spermidine, resulting in an increased spermidine/spermine ratio characteristic of both normal and neoplastic growth. The specific activation of type I cAPK has been implicated to ODC induction, and the amounts of type I and type II cAPK alter as a function of growth and transformation. Therefore, we wished to study the alterations in these biochemical parameters as well as that of a putative marker of preneoplastic hepatocytes, gamma-glutamyltranspeptidase, in a rapid multistep hepatocarcinogenesis system. We found a marked and prolonged increase in the cAPK ratio followed by a similar pattern of ODC induction after a single carcinogenic dose of diethylnitrosamine and again in response to partial hepatectomy. Liver foci were detectable within four days of partial hepatectomy in animals that received the entire carcinogen regimen, and the foci contained significant and increasing amounts of gamma-glutamyltranspeptidase activity. The increase in ODC activity was followed closely by an increased spermidine/spermine ratio. Total type I activity in the cytosol decreased most dramatically at the time of foci formation, suggestive of selective activation and turnover. These data suggest that the prolonged activation of cAPK and elevation of ODC may be necessary for hepatocarcinogenesis.

Animals↗

The relationship of the cyclic nucleotide system to inhibition of hepatic drug metabolism in Walker 256 carcinoma-bearing rats.

The hepatic cyclic nucleotide system and hepatic monooxygenase activity were examined in male rats following intramuscular or subcutaneous Walker 256 carcinosarcoma transplantation. Twelve days of continuous s.c. tumor growth significantly increased hepatic cyclic AMP levels, while levels of cyclic GMP, cytochrome P-450, cytochrome b-5, and p-chloro-N-methylaniline metabolism were significantly decreased. Whole blood from 6 day i.m. tumor-bearing rats incubated with liver slices obtained from non-tumor-bearing rats produced significantly elevated hepatic cyclic AMP levels concurrent with significantly depressed hepatic p-chloro-N-methylaniline metabolism. The chronological monitoring of tumor growth demonstrated a close temporal relationship between decreased cyclic AMP-dependent protein kinase activity, microsomal metabolism of p-chloro-N-methylaniline, and the mixed-function oxidase system. Significant changes in these hepatic enzyme systems occurred as early as 17 hours following tumor transplantation. At this same time, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed the appearance of a 184,000 molecular weight protein in hepatic tissue from all tumor-bearing rats. These studies are compatible with the proposal that the hepatic cyclic AMP system may modulate toxohormone effects on hepatic drug biotransformation.

Animals↗

Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3':5'-monophosphate-dependent protein kinase activation after a single administration of diethylnitrosamine.

After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.

Animals↗

Compartive behavioral effects of dibutyryl cyclic AMP and prostaglandin E1 in mice.

Three behavioral tests, spontaneous locomotor activity (SLMA), exploratory behavior (EB) and rotarod performance (RP), a measure of neuromuscular coordination, were used to stuey the interaction of PGE1 (1 mg/kg i.p., 10 min. pretreatment) with DBcAMP (25 mg/kg i.p., 25 min. pretreatment) in mice. A dose-response relationship of PGE1 (0.01-5.0 mg/kg) to SLMA was determined, with a significant decrease in SLMA produced by a dose of 0.1 mg/kg. decreases in SLMA were produced by PGE1 (79%), DBcAMP (41%) and DBcAMP-PGE1 combination (71%). Similar decreases in EB were observed. Although no significant difference between controls and DBcAMP was observed in RP, 52% of mice tested were RP failures following PGE1 and a 100% failure rate was induced by the combination. Mice were treated with a second injection of DBcAMP or PGE1 or the combination 24 hr following the first injection. Behavioral activity of these mice was observed 25 min (DBcAMP) or 10 min (PGE1) after the second dose was administered. A second injection of DBcAMP failed to decrease SLMA and EB from controls; moreover, SLMA began to return towards control levels as early as 2 hr between injections. The second injection of PGE1 or DBcAMP+PGE1 produced the same behavior as that produced by the first injection. On the basis of these results, the relationship of cyclic nucleotides and PGs to behavioral activity is discussed.

Animals↗

Resident participation in residency programs.

Residents need to participate more fully in decisions involving their educational process and their learning/work setting. In the Department of Family Medicine at the University of Miami School of Medicine, residents are involved in designing their curriculum, monitoring their work/learning settings, selecting their peers, and evaluating their peers and faculty. This style of residency program has significant implications not only for patient care but also for future physicians, medical departments, and medical associations.

Curriculum↗

Primary care in a penal institution. A study of health care problems encountered.

The kinds of health care problems encountered in a 600-man panel institution were studied. Five hundred twenty-eight problems were identified in 333 inmates seen on sick call. The large number of psychosocial problems (194 out of 528) and the wide diversity of problems (125 in 333 inmates) were documented. The questionable suitability of the medical model for health care in this type of setting is discussed. The implications for primary health care delivery and education are considered.

Adult↗

Cross-power spectral density analysis of pursuit tracking. Evaluation of central and peripheral pathology.

Twenty-one normal subjects were evaluated for pursuit tracking performance at frequencies of .2, .4, .8, 1.2 and 1.6 Hz. Measures of phase (lead or lag of target), gain (amplitude of response) and spectral purity (distortion of smooth tracking) were obtained by a cross-power spectrum analysis of the stimulus input and the eye movement output. It was determined that normal subjects could quite adequately track a target moving at .4 Hz. After establishing this parameter for normals, 43 patients with central and peripheral pathology related to the vestibulo-oculomotor system were tested at this frequency. Data revealed that not only central lesions but also peripheral labyrinthine impairment could cause a marked decrement in pursuit tracking ability. Also, marked changes in tracking were evident following both central and peripheral surgical procedures.

Adolescent↗

Vestibular responses to bithermal caloric and harmonic acceleration.

Vestibulo-oculomotor responses from 33 patients with either peripheral labyrinthine or central pathology were compared using the standardized Fitzgerald-Hallpike bithermal caloric and harmonic accelerations. In numerous cases (40%), patients with normal caloric responses reflected abnormalities in either their phase relationships or labyrinthine preponderance to sinusoidal acceleration. Results clearly indicate that harmonic acceleration provides additional information to the clinician in the evaluation of vestibulo-oculomotor pathology that is not reflected in the responses to standard caloric tests.

Adult↗

Dental endosseous implant assessments in a type 2 diabetic population: a prospective study.

Diabetes mellitus, a prevalent disorder worldwide, is associated with systemic adverse sequelae, such as wound healing alterations, which may affect osseointegration of dental implants. This prospective multicenter study assessed the success of 2-stage endosseous root-form implants (3 different implant systems) placed in the mandibular symphysis of 89 male type 2 diabetic subjects. The implants were uncovered approximately 4 months after placement, restored with an implant-supported, Hader bar clip-retained overdenture, and maintained at scheduled follow-up data collection examinations for 60 months after loading. Sixteen (9.0%) of the 178 implants failed. Life table methods calculated implant survival at approximately 88%, from prosthesis placement through the 60-month follow-up, and at approximately 90% from implant placement through the observation period. No implants failed between surgical placement and uncovering, 5 failed at uncovering, 7 failed after uncovering before prosthesis placement, and 4 failed after prosthesis placement. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) values were determined before implant placement (baseline) and approximately 4 months later at surgical uncovering (follow-up). The 5-year implant outcomes (successes versus failures) were analyzed against the following predictor variables: (1) baseline and follow-up FPG values, (2) baseline and follow-up HbA1c values, (3) subject age, (4) duration of diabetes (years), (5) baseline diabetic therapy, (6) smoking history, and (7) implant length. Regression analysis found only duration of diabetes (P < .025) and implant length (P < .001) to be statistically significant predictors of implant failure. There was no statistically significant difference in failure rates between the 3 different implant systems used. This study supports the use of dental implants in type 2 diabetic patients.

Adult↗