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Biomedical subjects

C A Jennings

Publications and source records attributed to C A Jennings.

At least 19 recordsLinked to original sources
PubMed2005

The effects of ziprasidone on regional c-Fos expression in the rat forebrain.

RATIONALE: Typical and atypical antipsychotic drugs produce characteristic patterns of immediate early gene expression in rat forebrain that are considered to reflect their effects in schizophrenia subjects. OBJECTIVE: To use c-Fos immunohistochemistry to investigate the functional neuroanatomical profile of the newly introduced atypical agent ziprasidone. MATERIALS AND METHODS: c-Fos immunohistochemistry was performed on paraformaldehyde-fixed cryosections of rat brains obtained, initially, from animals 2, 4, or 6 h after oral administration of 10 mg/kg ziprasidone or vehicle and, subsequently, from animals 2 h after oral administration of 1, 3, or 10 mg/kg ziprasidone or vehicle. The density of immunoreactive nuclei was assessed in pre-determined forebrain regions. RESULTS: Ziprasidone induced a time-dependent increase in the density of c-Fos-positive nuclei that was maximal at 2 h. At the 2 h time-point, c-Fos expression was significantly (p<0.05) elevated in the shell and core of the nucleus accumbens, lateral and medial caudate putamen, and lateral septum. At 4 h post-dose, c-Fos expression was also significantly increased in the cingulate gyrus. Ziprasidone-induced c-Fos expression was dose-dependent with significant (p<0.05) c-Fos expression observed in the nucleus accumbens (shell and core) and caudate putamen (lateral and medial) at 3 and 10 mg/kg and in the lateral septum at 10 mg/kg. CONCLUSIONS: Increased c-Fos expression in the nucleus accumbens and lateral septum is considered to be predictive of activity against positive symptoms, in the caudate putamen of motor side effect liability, and in the cingulate gyrus of efficacy against negative symptoms. Thus, the observed pattern of c-Fos expression induced in rat brain by ziprasidone is consistent with its reported clinical effects, namely, efficacy against positive symptoms with a therapeutic window over motor side effects and with some activity against negative symptoms.

Animals↗
PubMed2003

The distribution of the orphan bombesin receptor subtype-3 in the rat CNS.

Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor that shares between 47 and 51% homology with other known bombesin receptors. The natural ligand for BRS-3 is currently unknown and little is known about the mechanisms regulating BRS-3 gene expression. Unlike other mammalian bombesin receptors that have been shown to be predominantly expressed in the CNS and gastrointestinal tract, expression of the BRS-3 receptor in the rat brain has previously not been observed. To gain further understanding of the biology of BRS-3, we have studied the distribution of BRS-3 mRNA and protein in the rat CNS. The mRNA expression pattern was studied using reverse transcription followed by quantitative polymerase chain reaction. Using immunohistological techniques, the distribution of BRS-3 protein in the rat brain was investigated using a rabbit affinity-purified polyclonal antiserum raised against an N-terminal peptide. The BRS-3 receptor was found to be widely expressed in the rat brain at both mRNA and protein levels. Particularly strong immunosignals were observed in the cerebral cortex, hippocampal formation, hypothalamus and thalamus. Other regions of the brain such as the basal ganglia, midbrain and reticular formation were also immunopositive for BRS-3. In conclusion, our neuroanatomical data provide evidence that BRS-3 is as widely expressed in the rat brain as other bombesin-like peptide receptors and suggest that this receptor may also have important roles in the CNS, mediating the functions of a so far unidentified ligand.

Animals↗
PubMed2001

Compressive neuropathy of the brachial plexus and long thoracic nerve: a rare complication of heparin anticoagulation.

We present a case of a 69-year-old woman who developed brachial plexopathy and long thoracic nerve palsy secondary to compression from a hematoma while receiving heparin therapy for the treatment of a stroke. The patient was treated conservatively with discontinuation of heparin and had complete resolution of her compressive neuropathy. This is the first report of a patient with long thoracic nerve palsy with a brachial plexopathy complicating anticoagulation. We review the literature on hematoma-induced compressive neuropathies and treatment options. Our review concludes by emphasizing the importance of clinical judgment in determining the best therapeutic modality.

Aged↗
PubMed2000

Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma.

Normal bronchial epithelial cells (NBECs) are at risk for damage from inhaled and endogenous oxidative species and from epoxide metabolites of inhaled polycyclic aromatic hydrocarbons. Epidemiological and in vitro data suggest that interindividual variation in this risk may result from variation in NBEC expression of enzymes that inactivate reactive species by conjugating them to glutathione. Quantitative competitive reverse transcription-PCR was used to measure mRNA levels of glutathione transferases (GSTs) and glutathione peroxidases (GSHPxs) in primary NBECs from subjects with or without bronchogenic carcinoma. Mean expression levels (mRNA/10(3) beta-actin mRNA) in NBECs from 23 subjects without bronchogenic carcinoma compared to those from 11 subjects with bronchogenic carcinoma respectively (in parentheses) were: mGST (26.0, 6.11), GSTM3 (0.29, 0.09), combined GSTM1,2,4,5 (0.98, 0.60), GSTT1 (0.84, 0.76), GSTP1 (287, 110), GSHPx (140, 62.1), and GSHPxA (0.43, 0.34). Levels of GSTP1, GSTM3, and GSHPx were significantly (P < 0.05) lower in NBECs from subjects with bronchogenic carcinoma. Further, the gene expression index formed by multiplying the values for mGST x GSTM3 x GSHPx x GSHPxA x GSTP1 had a sensitivity (90%) and specificity (76%) for detecting NBECs from bronchogenic carcinoma subjects that was better than any individual gene. In cultured NBECs derived from eight individuals without bronchogenic carcinoma and incubated under identical conditions such that environmental effects were minimized, the mean level of expression and degree of interindividual variation for each gene evaluated was less than that observed in primary NBECs. Data from these studies support the hypotheses that (a) interindividual variation in risk for bronchogenic carcinoma results in part from interindividual variation in NBEC expression of antioxidant genes; (b) gene expression indices will better identify individuals at risk for bronchogenic carcinoma than individual gene expression values; and (c) both hereditary and environmental exposures contribute to the level of and interindividual variation in gene expression observed in primary NBECs. Many epidemiological studies have been designed to evaluate risk associated with polymorphisms or gene expression levels of putative susceptibility genes based on measurements in surrogate tissues, such as peripheral blood lymphocytes. Based on data presented here, it will be important to include the assessment of NBECs in future studies. Measurement of antioxidant gene expression in NBECs may identify the 5-10% of individuals at risk for bronchogenic carcinoma. Bronchoscopic sampling of NBECs from smokers and ex-smokers then will allow susceptible individuals to be entered into surveillance and/or chemoprevention studies.

Adolescent↗
PubMed1997

Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease.

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proinflammatory and anti-inflammatory actions, respectively, and thus an imbalance in the expression of these cytokines may contribute to the pathogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alpha mRNA levels in alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with IPF and BOOP and in normal healthy volunteers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subjects. However, macrophages from patients with IPF and BOOP expressed increased levels of IL-10 mRNA compared with healthy controls. In addition, stimulation of alveolar macrophages with lipopolysaccharide in the presence of a neutralizing anti-IL-10 antibody augmented the production of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macrophages may act to control the expression of TNF-alpha. Paradoxically, measurement of IL-10 protein in cell-free BAL fluid revealed lower amounts of the protein in patients with IPF and BOOP compared with healthy controls.

Adult↗
PubMed1997

Diffuse alveolar hemorrhage with underlying isolated, pauciimmune pulmonary capillaritis.

Diffuse alveolar hemorrhage (DAH) resulting from pulmonary capillaritis typically accompanies the systemic vasculitides and collagen vascular diseases. Isolated pulmonary capillaritis and DAH without systemic disease occurs in patients with antineutrophil cytoplasmic antibodies. However, isolated pulmonary capillaritis and DAH is not described for patients without clinical or serologic evidence for an underlying systemic disease. To describe such patients, we undertook a retrospective chart review of 29 patients with DAH and biopsy-proven pulmonary capillaritis from seven Denver hospitals. Eight (28%) were diagnosed with isolated pulmonary capillaritis without clinical, serologic, or histologic evidence of an associated illness. Their median age was 30 yr. No association with occupational or drug exposures was identified. All had lower respiratory tract symptoms; seven had upper respiratory tract symptoms. None demonstrated systemic disease or evidence of glomerulonephritis. All were antineutrophil cytoplasmic antibody negative. Other serologies were not significant where measured. Direct immunofluorescence studies of lung tissue were negative in five. Six presented with acute respiratory failure, four requiring mechanical ventilation. One died during initial hospitalization; seven survived. Median follow-up is 43 mo (7 to 73 mo). Five remain in remission. Two experienced multiple recurrences of DAH but without development of systemic disease while on therapy. Herein we characterize DAH and isolated pulmonary capillaritis in the absence of clinical, serologic, or histologic evidence indicating an accompanying systemic illness. The prognosis for this group appears favorable.

Adult↗
PubMed1996

Pulmonary barotrauma as the cause of pneumoretropharynx in pulmonary lymphangioleiomyomatosis.

A 55-year-old white woman with pulmonary lymphangioleiomyomatosis (LAM) presented to the emergency department with odynophagia and subplatysmal emphysema after a paroxysm of coughing. Lateral neck films showed subcutaneous emphysema and a retropharyngeal air stripe. Chest radiographs showed neither pneumothorax nor pneumomediastinum. Patients with LAM frequently develop pulmonary barotrauma and pneumothoracies. This patient, however, had undergone prior bilateral talc pleuradesis as treatment for recurrent pneumothoracies and, thus, could not manifest this complication of barotrauma. This case illustrates the uncommon occurrence of superior dissection of air after pulmonary barotrauma.

Barotrauma↗
PubMed1996

Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology.

Pulmonary histiocytosis X (PHX) is a diffuse, smoking-related lung disease characterized pathologically by bronchocentric inflammation, cyst formation, and widespread vascular abnormalities and physiologically by exercise limitation. The major mechanism underlying exercise impairment in this disease has not been previously defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on 23 patients with PHX. Two subgroups were identified on the basis of elastic recoil: 12 subjects had an elevated coefficient of elastic recoil with 11 demonstrating a predominant pattern of restriction, and 10 subjects had normal elastic recoil and relatively normal lung function. Exercise performance was severely limited in both subgroups (workload 53 +/- 3%). Abnormalities of ventilatory function and gas exchange were present but did not appear to be exercise-limiting in the majority of subjects. Indices reflecting pulmonary vascular function (DLCO, baseline VD/VT, exercise VD/VT) were abnormal. Strong correlations between overall exercise performance (% predicted VO2max) and indices of vascular involvement were present: DLCO (r = 0.68, p = 0.0004), baseline VD/VT (-0.65, 0.001), exercise VD/VT (-0.67, 0.0004). Similar correlations were found when exercise performance was measured by maximal workload achieved. We conclude that (1) subjects with PHX present with either normal or predominantly restrictive pulmonary physiology and that (2) exercise impairment is common and appears to reflect pulmonary vascular dysfunction.

Adult↗
PubMed1996

Lymphangioleiomyomatosis: the pathophysiology of diminished exercise capacity.

Dyspnea with exertion is nearly always present in patients with pulmonary lymphangioleiomyomatosis, but the mechanisms underlying exercise impairment have not been well defined. Spirometry, lung volumes, lung mechanics, and exercise physiology were performed on a cohort of 16 patients. We determined the relative contribution of airflow limitation, gas exchange abnormalities, and pulmonary vascular abnormalities to the exercise performance achieved. The patients had normal TLC and Vtg, but RV was elevated in 88% of the subjects. A moderate to severe obstructive pattern was present in 69% of the subjects, and the DLCO was reduced, often markedly, in 81% of the subjects. Exercise performance was limited (work load, 68% +/- 6) with abnormalities of ventilatory function and gas exchange present. Strong correlations between overall exercise performance (percent predicted VO2max and maximal work load achieved) and indices of airflow and vascular involvement were present. Poor exercise performance was due primarily to ventilatory limitation. The etiology of this ventilatory limitation appears twofold. First, subjects had a reduced ventilatory ceiling because of airflow limitation. Second, subjects demonstrated an excessive ventilatory response as a result of increased dead-space ventilation thought to be due to disease-associated cystic changes and associated pulmonary vascular dysfunction or destruction.

Adult↗
PubMed1995

Acute epiglottitis in the adult caused by Neisseria meningitidis.

Acute epiglottitis is being increasingly encountered in the adult population. While it has many similarities to its pediatric counterpart, the presentation and associated pathogens are distinct. In addition, although the recent literature has suggested that acute epiglottitis in the adult follows a benign course this is not always the case. Here we describe a case of acute, fulminant epiglottitis in an immunocompetent host, caused by Neisseria meningitidis.

Acute Disease↗
PubMed1995

Pulmonary capillaritis and alveolar hemorrhage associated with the antiphospholipid antibody syndrome.

Pulmonary hemorrhage due to small vessel vasculitis is a well recognized complication of many autoimmune and collagen vascular disorders. The antiphospholipid antibody syndrome (APS) is a disorder associated with hypercoagulability, thrombocytopenia, and thromboembolic phenomena. Pulmonary manifestations include pulmonary embolism, pulmonary hypertension, and respiratory failure associated with diffuse pulmonary infiltrates. We describe a patient with the APS syndrome, without systemic lupus erythematosus, who developed pulmonary hemorrhage due to pulmonary capillaritis with evidence of perivascular immune complex deposition.

Antigen-Antibody Complex↗
PubMed1993

Keeping hostility in perspective: coronary heart disease and the Hostility Scale on the Minnesota Multiphasic Personality Inventory.

Three prospective studies from the early 1980s found that high scores on the Hostility (Ho) Scale of the Minnesota Multiphasic Personality Inventory (MMPI) were associated with an increased incidence of coronary heart disease (CHD) and mortality from CHD and other causes. In the current study, the association between the Ho score and subsequent health status was examined in a 20-year follow-up of 620 general medical patients who completed the MMPI between 1962 and 1965. Univariately, the Ho score from the MMPI was a significant factor for predicting the development of CHD, CHD-related mortality, and total mortality. When two simple risk factors for CHD--age and sex--were also considered, however, the MMPI Ho score was no longer a significant predictive factor.

Adult↗
PubMed1991

Eosinophilic pneumonia associated with reaction to radiographic contrast medium.

We have described what we believe to be the first published case of a reaction to radiographic contrast medium followed by a diffuse eosinophilic pneumonia. This association seems to confirm what is know about the immunologic mechanisms of such reactions, and though further verification of causation is needed, we found it to be the most plausible explanation.

Adult↗
PubMed1990

Modification of an automated vascular diagnostic system for hyperbaric use.

Modifications of an automated, noninvasive vascular diagnostic system (VASCULAB, MedaSonics, Inc.) for measuring blood pressure and plethysmographic blood flow responses to normobaric and hyperbaric oxygenation are described. The system consisted of a pump for inflating and deflating blood pressure cuffs and a microprocessor program controller (VSC21) with ultrasound Doppler, strain-gauge plethysmograph, and chart recorder. Inclusion of the VSC21 controller in the chamber was required for performance of procedures that could not be controlled from outside the chamber. All other components were outside the chamber. For fire prevention the VSC21 controller was nitrogen-purged in an acrylic case mounted on a mobile cart. Pressure-cuff tubes were attached via adapted fittings and connectors in the cart to connector ports in the controller's front panel. Electrical power cables and instrument signal wires were routed through chamber penetrations to an electrical power source and other VASCULAB components, respectively, outside the chamber. Initially, compression of the chamber to pressures in excess of 1.68 bar disabled the VSC21, requiring removal of its front membrane panel and ventilation of its pressure-sensitive keypad switches. This allowed automated assessment of blood pressure and calf blood flow at test pressures of 1.97 and 2.96 bar.

Blood Pressure Determination↗
PubMed1989

Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects.

The ability of four central cholinomimetics to reverse a scopolamine-induced spatial memory impairment or to improve visual recognition memory in primates was examined. Physostigmine (0.04-0.08 mg/kg IM) fully reversed the effects of scopolamine (0.03 mg/kg). Coadministration of pilocarpine (3.0-5.0 mg/kg) caused partial reversal of the scopolamine impairment after intermediate or long retention intervals (10 or 20 s). Treatment with arecoline (0.1-1.8 mg/kg) or nicotine (1.0-2.0 mg/kg) generally did not reverse the effects of scopolamine. A task in which memory could be taxed by increasing the number of visual stimuli presented appeared more sensitive to the effects of cholinomimetics on cognition than the scopolamine reversal model. In this paradigm treatment with physostigmine (0.001, 0.01 or 0.03 mg/kg) increased choice accuracy from about 55 to 70% correct. Arecoline improved performance at one dose only (0.1 mg/kg) which also induced marked adverse side-effects (salivation and tremor). Pilocarpine improved performance in the dose range 0.125-0.35 mg/kg, but not at higher doses which also induced marked salivation. Treatment with nicotine (0.001-2.0 mg/kg tended to improve performance but this did not reach statistical significance. The relevance of these findings for studies in man and for animal models of dementia is discussed.

Animals↗
PubMed1989

Antiparkinsonian efficacy of a novel transdermal delivery system for (+)-PHNO in MPTP-treated squirrel monkeys.

We examined the ability of the antiparkinsonian agent (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) to enter the systemic circulation in therapeutic concentrations after continuous transdermal absorption in squirrel monkeys rendered parkinsonian by MPTP. Direct subcutaneous administration of (+)-PHNO in the dose range of 2.5 to 20 micrograms/kg restored locomotor activity to levels seen in normal monkeys for approximately 1 hour. Application of transdermal patches capable of delivering, into an infinite sink, an estimated 2.6 micrograms/cm2/h of (+)-PHNO over a skin surface area of 4.78 to 19.12 cm2 also restored locomotor activity to the normal range during a 24-hour period. We suggest the use of transdermal application of PHNO as a novel drug delivery system for the improved management of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗