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Biomedical subjects

D O'Shaughnessy

Publications and source records attributed to D O'Shaughnessy.

31 records · Page 2Linked to original sources

Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia.

Cholecystokinin-like immunoreactivity (CCK) and somatostatin-like immunoreactivity (SRIF) were determined in fourteen brains from patients dying with a diagnosis of schizophrenia and in twelve brains from control cases. The schizophrenics had been rated during life and were divided into two groups on the basis of the presence or absence of negative symptoms (affective flattening and poverty of speech). CCK was reduced in temporal cortex of the schizophrenics and in hippocampus and amygdala of those patients with negative symptoms. SRIF was reduced in the hippocampus in samples from the latter group. The selectivity of these changes to limbic lobe may reflect the presence of a degenerative process in that area. The association of changes in hippocampus and amygdala with negative symptoms of schizophrenia suggests a separate mechanism underlying these symptoms.

Aged↗

Neuropeptides in Alzheimer type dementia.

Five neuropeptides (cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), neurotensin (NT) and substance P (SP)) were measured in 14 brain areas (4 cortical areas, hippocampus, amygdala, 3 striatal areas, 2 thalamic areas and 3 subcortical areas-- septum, substantia innominata and hypothalamus) in 12 brains with neuropathologically confirmed Alzheimer type change and in 13 control brains. Choline acetyltransferase (CAT) activity was assessed in 6 of these areas. Levels of SRIF, but not those of the other peptides, were reduced in several cortical areas in Alzheimer-type dementia (ATD). The distribution and magnitude of the reduction in SRIF were less than that of CAT activity and the temporal cortex was the only region in which there was a significant relationship between CAT and SRIF deficits. Peptide levels were unchanged in hippocampus, amygdala, thalamus, hypothalamus and striatum (except for an increase in SP in the putamen). SRIF levels were increased in substantia innominata in ATD. NT and SRIF were significantly, and VIP and SP non-significantly, reduced in the septum in ATD. Thus, apart from these alterations in the septum, SRIF was the only neuropeptide for which major changes were identified and these did not follow either the pattern of neuropathological change (e.g. in amygdala and hippocampus) or of CAT deficits (e.g. in substantia innominata).

Aged↗

Linguistic modality effects on fundamental frequency in speech.

This paper examines the effects on fundamental frequency (F0) patterns of modality operators, such as sentential adverbs, modals, negatives, and quantifiers. These words form inherently contrastive classes which have varying tendencies to produce emphasis deviations in F0 contours. Three speakers read a set of 186 sentences and three paragraphs to provide data for F0 analysis. The important words in each sentence were marked intonationally with rises or sharp falls in F0, compared to gradually falling F0 in unemphasized words. These emphasis deviations were measured in terms of F0 variations from the norm; they were larger toward the beginning of sentences, in longer sentences, on syllables surrounded by unemphasized syllables, and in contrastive contexts. Other results showed that embedded clauses tended to have lower F0, and negative contractions were emphasized on their first syllables. Individual speakers differed in overall F0 levels, while using roughly similar emphasis strategies. F0 levels changed in paragraphs, with emphasis going to contextually new information.

Humans↗

The site of incorporation of sialic acid residues into glycoproteins and the subsequent fates of these molecules in various rat and mouse cell types as shown by radioautography after injection of [3H]N-acetylmannosamine. I. Observations in hepatocytes.

To study the site of incorporation of sialic acid residues into glycoproteins in hepatocytes, we gave 40-g rats and 15-g Swiss albino mice a single intravenous injection of [3H]N-acetylmannosamine (8 mCi) and then sacrificed them after 2 and 10 min. To trace the subsequent migration of the labeled glycoproteins, we injected 40-g rats with 4 mCi of [3H]N-acetylmannosamine and sacrificed them after 20 and 30 min, 1, 4, and 24 h, and 3 and 9 d. Concurrent biochemical experiments were carried out to test the specificity of injected [3H]N-acetylmannosamine as a precursor for sialic acid residues of glycoproteins. In radioautographs from rats and mice sacrificed 10 min after injection, grain counts showed that over 69% of the silver grains occurred over the Golgi region. The majority of these grains were localized over the trans face of the Golgi stack, as well as over associated secretory vesicles and possibly GERL. In rats, the proportion of grains over the Golgi region decreased with time to 37% at 1 h, 11% at 4 h, and 6% at 24 h. Meanwhile, the proportion of grains over the plasma membrane increased from 4% at 10 min to 29% at 1 h and over 55% at 4 and 24 h; two-thirds of these grains lay over the sinusoidal membrane, and the remainder were equally divided over the lateral and bile canalicular membranes. Many silver grains also appeared over lysosomes at the 4- and 24-h time intervals, accounting for 15-17% of the total. At 3 and 9 d after injection, light microscope radioautographs revealed a grain distribution similar to that seen at 24 h, with a progressive decrease in the intensity of labeling such that by 9 d only a very light reaction remained. Because our biochemical findings indicated that [3H]N-acetylmannosamine is a fairly specific precursor for the sialic acid residues of glycoproteins (and perhaps glycolipids), the interpretation of these results is that sialic acid is incorporated into these molecules in the Golgi apparatus and that the latter then migrate to secretion products, to the plasma membrane, and to lysosomes in a process of continuous renewal. It is possible that some of the label seen in lysosomes at later time intervals may have been derived from the plasma membrane or from material arising outside the cells.

Animals↗

The site of incorporation of sialic acid residues into glycoproteins and the subsequent fates of these molecules in various rat and mouse cell types as shown by radioautography after injection of [3H]N-acetylmannosamine. II. Observations in tissues other than liver.

Biochemical evidence from the preceding paper indicated that [3H]N-acetylmannosamine may be used as a fairly specific precursor for the sialic acid residues of glycoproteins (and perhaps glycolipids) in radioautographs of rat liver and duodenum. In order to study the site of incorporation of this label in cell types of various tissues, we gave 40-g rats and 15-g Swiss albino mice a single intravenous injection of 8 mCi of [3H]N-acetylmannosamine and sacrificed them after 2 and 10 min. To trace the subsequent migration of the labeled glycoproteins, we injected 40-g rats with 4 mCi of [3H]N-acetylmannosamine and sacrificed them after 20 and 30 min, 1, 4, and 24 h, and 3 and 9 d. Light microscope radioautographic analysis revealed that in a great variety of cell types the label was initially localized to the Golgi region. Electron microscope radioautographic analysis of duodenal villous columnar and goblet cells, pancreatic acinar cells and Paneth cells, from rats and mice sacrificed 10 min after injection, showed that the silver grains were localized over Golgi saccules (and adjacent secretion granules). In kidney proximal and distal tubule cells reaction was initially localized to the Golgi apparatus in some areas of the kidney cortex whereas in other areas it was more diffuse. In all cells, the proportion of silver grains over the Golgi apparatus decreased with time after injection while an increasing number of grains appeared over secretion products in secretory cells or over the plasma membrane in other cell types. Lysosomes also became increasingly labeled at later time intervals. The above results suggest that in most cell types sialic acid residues are incorporated into glycoproteins (and perhaps glycolipids), primarily in the Golgi apparatus. With time, these newly synthesized molecules migrate to secretion products, to the plasma membrane, or to the lysosomes.

Animals↗

Bombesin, somatostatin and neurotensin-like immunoreactivity in bronchial carcinoma.

Bombesin, a regulatory peptide found in adult lung and in higher concentration during development in the foetal lung, has potent biological actions which include the ability to stimulate the release of a number of hormones. Radioimmunoassay of extracts of tumour, lung and plasma from patients with bronchial carcinoma revealed very high tissue bombesin concentrations in two oat cell carcinomas, with lower levels in two out of six adenocarcinomas exceeding the concentrations found in normal lung. The oat cell carcinomas also contained significant amounts of somatostatin and in one case neurotensin. Neurotensin was further detected in two out of seven squamous tumours and three adenocarcinomas. Secretion of regulatory peptides by bronchial carcinomas may account for some of their ill-understood non-metastatic clinical manifestations.

Adenocarcinoma↗

Nicotine replacement combined with a novel compound (ProBAN) for smoking cessation: a pilot study.

BACKGROUND: Smoking cessation rates with available pharmacological therapies remain suboptimal. Anecdotal observations with a combination of sublingual pralidoxime and ipratropium (ProBAN) suggested that these agents in combination with nicotine gum improved quit rates. OBJECTIVE: To determine whether ProBAN together with nicotine replacement improves quit rates compared with nicotine replacement alone. DESIGN: A 12-week, prospective, double-blind, randomized, placebo controlled pilot study. SETTING: University-affiliated outpatient clinic. POPULATION STUDIED: Healthy adult smokers were recruited via advertisements. Of 107 subjects seen at the screening visit, 27 were excluded because of comorbid illness or concomitant medication use. INTERVENTIONS: Of 80 eligible subjects, 40 were randomly assigned to receive treatment with ProBAN sub- lingual tablets and nicotine gum (treatment group), and 40 to receive placebo tablets and nicotine gum (control group) for 12 weeks. The primary outcome was complete continuous abstinence of smoking from one through 12 weeks after the quit date. MAIN RESULTS: There were no adverse effects in the treatment group. At one week after the quit date, 35% of ProBAN-treated subjects had quit compared with 18% of control subjects (odds ratio [OR] 2.5, 95% CI 0.9 to 7.2). Corresponding quit rates at four weeks were 28% and 15% (OR 2.1, 95% CI 0.7 to 6.5), at eight weeks were 25% and 13% (OR 2.3, 95% CI 0.7 to 7.6), and at 12 weeks were 23% and 13% (OR 2.0, 95% CI 0.6 to 6.7), respectively. CONCLUSIONS: This pilot study indicated that ProBAN combined with nicotine replacement doubled the continuous sustained quit rate compared with nicotine replacement alone, with no adverse effects. Although not statistically significant due to the size of the study, this result suggests that it may be an effective therapy for smoking cessation, and larger studies are warranted.

Administration, Sublingual↗

Treatment of acute focal ischemia with continuous CSF drainage and mannitol.

A simple implanted device was used to occlude acutely the left middle cerebral artery (MCA) of 32 conscious cats. Groups of 18 cats each were treated with continuous cerebrospinal fluid (CSF) drainage, mannitol (1 gm/kg i.v.), or a combination of continuous CSF drainage and mannitol (1 gm/kg i.v.). Eight cats served as a control group. The neurological status of cats treated with mannitol improved transiently. Perfusion with a mixture of colloidal carbon and buffered paraformaldehyde was carried out 12 hours following MCA occlusion. Gross swelling of cerebral tissue, distribution of colloidal carbon, and breakdown of the blood-brain barrier to fluorescein were similar in the 4 groups. Reduction of mean capillary luminal diameter to 4.5 +/- 1.0 micron (control 6.5 +/- 1.0 micron) in the left Sylvian cortex was unaltered by treatment. A significant difference in the distribution of severe neuronal alterations was not demonstrated.

Animals↗

ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.

In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40-80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of -2.02 mmHg (P < 0.01). A significantly greater proportion of patients achieved a seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05), also measured with the same ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.

Adult↗

Strategic planning for a Nursing Information System (NIS) in the hospital setting. Development of a Nursing System Model.

As nursing departments become more involved in automation, strategic planning for computer applications gains importance. Making the switch from manual to automated systems requires an understanding and analysis of the present system. This knowledge allows participants to examine the current information processing routines in relation to how well they support departmental goals. Priorities for projects can be established and alternatives for more efficient and effective information management schemes can be considered. The development of a Nursing System Model to serve this purpose is described. The model provides an overview for planning and identifies data classes created or used in nursing, organized according to the processes which act upon the data during the accomplishment of work activities.

Computer Systems↗

Comparison of the behavioral effects of neurotoxic and systemically toxic agents: how discriminatory are behavioral tests of neurotoxicity?

The behavioral effects of carbon tetrachloride-produced impairment of liver function, insulin-produced reduction of plasma glucose levels, and the reduction of food and water intake have been evaluated. Considerable similarity was found among the behavioral effects of systemically toxic agents, three neurotoxicants (triethyltin, acrylamide, and 2,5-hexanedione), and the neuroleptic drug haloperidol. Measure of motor strength differentiated neurotoxic from non-neurotoxic compounds, while measures of motor activity were equally sensitive to neurotoxic, systemically toxic, and non-neurotoxic agents. These findings demonstrate the importance of assessing systemic toxicity before drawing conclusions about the neurotoxicity of a behaviorally active compound.

Animals↗

Triethyltin-produced decrease and recovery of wheel running and food-reinforced lever pressing in rats.

Behavioral effects of triethyltin were studied in rats living in Wahmann activity cages. Wheel running activity and food-reinforced lever pressing were recorded 23 hr/day from 4 rats. Triethyltin injections (4 mg/kg IP) produced large transient decreases in running, lever pressing, and daily water consumption, without affecting body weight. These measures recovered to pre-treatment levels within 1-2 days. After 4 weekly injections, wheel running was reduced in 2 rats, and increased in 1 rat, while lever pressing remained at baseline levels. Good correlation was noted between the extent of reductions in wheel running and lever pressing, and the extent of characteristic triethyltin-induced morphological lesions in the central and peripheral nervous system. Over the course of repeated treatments, several critical behaviors known to be sensitive to neurotoxicants can be continually monitored using automated testing apparatus. While further validation with more compounds is required, these results suggest that monitoring wheel running, food-reinforced lever pressing, and water consumption may be an inexpensive way to test for behavioral neurotoxicity using small numbers of animals.

Animals↗