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Biomedical subjects

M Cassidy

Publications and source records attributed to M Cassidy.

At least 55 records · Page 3Linked to original sources
PubMed1993

Heterogeneity studies of hamster calcitonin following acute exposure to cigarette smoke: evidence for monomeric secretion.

Various acute stimuli, including cigarette smoke, induce hypercalcitonemia in man and hamsters. We have shown that this occurs also in thyroidectomized subjects. In the present study we have further explored this phenomenon of secretion from the lungs by studying, simultaneously, the HPLC characteristics of pulmonary tissue and serum in control hamsters and in animals immediately following short-term exposure to cigarette smoke. In addition, we have studied the immunoheterogeneity of lung calcitonin 24 hours following the acute exposure. Control lungs contained monomeric immunoreactive calcitonin (M-iCT), high molecular mass iCT (H-iCT), and CT fragments. Immediately following smoke exposure, there was an acute decrease of lung iCT by radioimmunoassay (RIA) which consisted primarily of a decrease in M-iCT by HPLC. Simultaneously, the iCT increase in the serum by RIA was shown by HPLC to involve M-iCT. Twenty-four hours after smoke inhalation, the lung iCT by RIA and M-iCT by HPLC had returned towards control levels. These findings document the molecular characteristics of lung iCT following acute cigarette smoke stimulation, and suggest that under certain circumstances M-iCT may be actively secreted by the lung. It remains to be determined whether this type of secretion reflects hemocrine or paracrine release and what the physiological role for such a secretion may be.

Animals↗
PubMed1993

N-acetylaspartylglutamate catabolism is achieved by an enzyme on the cell surface of neurons and glia.

N-Acetylaspartylglutamate (NAAG) is a nervous system-specific, acidic dipeptide which is released from neurons in a manner consistent with a function in synaptic neurotransmission. The hydrolysis of NAAG to produce glutamate and N-acetylaspartate was analyzed in cell cultures prepared from murine brain cells. Peptidase activity against NAAG was found in cultures which contained both neurons and glia, as well as in cultures of glia alone. Several lines of evidence were obtained in support of the hypothesis that this peptidase activity is predominantly bound to the extracellular face of the plasma membranes of these cells. Glutamate released from NAAG accumulated in the extracellular medium. Extracellular application of peptidase inhibitors effectively reduced NAAG hydrolysis. Peptidase activity was not secreted into the cell culture medium by intact cells, and lysed cells did not release detectable peptidase activity beyond that obtained with intact cells. Replacement of extracellular sodium with choline inhibited peptide uptake while stimulating apparent extracellular NAAG hydrolysis by intact cells in culture. Finally, the steady rise in extracellular glutamate as a consequence of NAAG hydrolysis by these brain cells, including glia, supports the conclusion that glutamate uptake is not tightly coupled to peptidase activity and thus that NAAG serves as a significant source of glutamate in the synaptic space following depolarization-induced peptide release.

Animals↗
PubMed1993

Localization and transport of N-acetylaspartylglutamate in cells of whole murine brain in primary culture.

N-Acetylaspartylglutamate (NAAG) is the most abundant neuropeptide in the mammalian nervous system. Considerable data support the hypothesis that NAAG is synaptically released in a manner consistent with neurotransmission. Primary murine brain cultures containing neurons and glia expressed 1.2-3.5 nmol of NAAG/mg of protein. In contrast to conclusions drawn from immunohistochemistry, pure glial cultures also expressed high levels of NAAG (0.6-2.11 nmol/mg of protein). These data suggest that although a subpopulation of neurons contains very high NAAG levels, micromolar concentrations of the peptide also are present in glia. Both culture types demonstrated robust extracellular peptidase activity when incubated with NAAG, as well as peptide transport. Uptake of [3H]NAAG was both temperature and sodium dependent, yet relatively insensitive to the presence of extracellular glutamate. These results indicate that synaptically released NAAG, as well as that which may be released from glia, is removed from the extracellular space by direct uptake as well as the robust enzymatic degradation of the peptide. A kinetic analysis of this NAAG transport (estimated Km = 1.8 microM) suggests a high-affinity NAAG transport system. The balance of the two processes of direct peptide uptake and peptide hydrolysis would markedly influence the sequence of receptor-mediated events that follow NAAG release.

Animals↗
PubMed1993

A pilot scheme for improving the accuracy of serum cholesterol measurement in Scotland and Northern Ireland.

The measurement of plasma cholesterol is subject to particularly stringent requirements of bias and imprecision because clinically important action limits lie within the bulk of the population distribution. A pilot scheme was conducted with the aim of improving the accuracy of the assay of cholesterol in 26 laboratories in Scotland and Northern Ireland. This involved the distribution of three sets of authentic human sera with varying cholesterol concentrations assigned by the reference Abell-Kendall method which was established and validated in a central laboratory. The precision (coefficient of variation) of cholesterol testing was 1.71% across all laboratories at the first distribution and this did not alter subsequently. Mean bias was initially 4.07% (median 4.14%) relative to the Abell-Kendall assigned values and this figure had fallen to 1.12% (median 0.92%) by the third distribution. We conclude that through a standardization scheme it is possible in a relatively short time to improve bias significantly and meet the criterion of < 2-3% bias required for optimum cholesterol measurement.

Bias↗
PubMed1993

Prevalence and severity of Doppler-detected valvular regurgitation and estimation of right-sided cardiac pressures in patients with normal two-dimensional echocardiograms.

To assess the prevalence and severity of Doppler-detected valvular regurgitation, as assessed by multiple Doppler modalities, in patients with structurally normal hearts, we analyzed Doppler echocardiograms in a consecutive sample of 206 referred patients who were found to have completely normal M-mode and two-dimensional echocardiograms. Valvular regurgitation was detected by Doppler in 94 percent, and 56 percent had regurgitation in at least two valves (mitral, tricuspid, and/or aortic). Mitral, tricuspid, and aortic regurgitation was detected in 73 percent, 68 percent, and 12 percent, respectively, with moderate regurgitation occurring in 6 percent, 5 percent, and 2 percent, respectively. The presence of mitral and tricuspid regurgitation was not related to age, although the prevalence of moderate regurgitation was three times more prevalent (p < 0.05) in those > 50 years old compared with those < or = 50 years. Aortic regurgitation was two to three times more prevalent (p < 0.01) in patients > 50 years compared with younger subjects, and moderate aortic regurgitation was three times more prevalent in older patients. Of those with measurable right-sided cardiac pressures, estimated right atrial pressure was < 10 mm Hg in 93 percent of patients, and estimated pulmonary artery systolic pressure was < or = 30 mm Hg in 57 percent of patients. Estimated right atrial pressure was > 10 mm Hg in only 7 percent, and only 13 percent had estimated pulmonary artery systolic pressure > or = 40 mm Hg. These data indicate a very high prevalence of trivial and mild mitral and tricuspid regurgitation in patients with otherwise "normal" hearts, suggesting that these findings are physiologically normal. These data should be considered when addressing management in patients with Doppler-detected valvular regurgitation in order to prevent "iatrogenic heart disease."

Adolescent↗
PubMed1992

Resin-bonded bridges: 2. Treatment planning, clinical gases and failures.

This is the second paper in the two-part series which considers the developments and clinical techniques of resin-bonded bridges with the emphasis on methods for increasing success from a functional and aesthetic view point. Part 1 focused on the development and types of resin-bonded bridge and tooth preparation. This article describes the clinical application of this type of bridge and discusses failures.

Adolescent↗
PubMed1991

GenBank.

The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 56,000,000 nucleotides in 45,000 entries. The input stream of data coming into the database has largely been shifted to direct submissions from the scientific community on electronic media. The data have been installed in a relational database management system and are made available in this form through on-line access, and through various network and off-line computer-readable media. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service.

Base Sequence↗
PubMed1991

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.

Animals↗
PubMed1990

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.

Animals↗
PubMed1989

Selective distribution of N-acetylaspartylglutamate immunoreactivity in the extrapyramidal system of the rat.

N-Acetylaspartylglutamate (NAAG), a neuron-specific dipeptide, was found by immunocytochemistry to be localized in specific compartments of the extrapyramidal system of the rat. Cellular and neuropil NAAG-like immunoreactivity (NAAG-IR) was evident throughout the pallidum, entopeduncular nucleus, subthalamic nucleus, and all subdivisions of the substantia nigra. By contrast, only a minority of cells of the caudate-putamen and those of the accumbens nucleus stained positively for NAAG. In general, neuronal NAAG-IR was widespread in all ventroposterior output zones of the extrapyramidal system, while cellular immunostaining was greatly reduced in the corticostriate receptive zones. These data suggest that NAAG may serve some neuronal communication function in the extrapyramidal processing circuits and output projections to the thalamus and midbrain. Additionally, neuronal NAAG immunolabeling differentiates corticostriate receptive zones from pallidal and nigral subdivisions of the extrapyramidal system in the rat.

Animals↗
PubMed1989

Malignant melanoma lately diagnosed.

To assess the clinical impression that patients in Dublin were presenting with late, deep, poor prognosis lesions, a 10 year retrospective review of patients with malignant melanoma was performed. The pathological data on 186 patients was examined and clinical follow-up obtained on 151 of these (80%). The mean period of follow-up was 35 months. Females predominated in a ratio of 3:1. Incidence figures for the two five year periods (1976-80) and (1981-85) indicated a rise in the latter period of over 100%. There was a marked delay in presentation after the onset of symptoms i.e. new pigmented lesions or changes in pre-existing lesions (mean = 21 months). Only 45% of lesions were less than 1.5mm in depth. Females presented with a higher percentage of good prognosis lesions reflected in a superior five year survival figure of 70% compared with 43% for males. The results of this study suggest an increase in incidence and mortality from malignant melanoma in this country. Patients appear to be unaware of the significance of pigmented lesions, presenting late with deep poor prognosis tumours.

Adolescent↗
PubMed1989

Effect of aerobic training on left ventricular diastolic filling.

The effects of aerobic training on left ventricular diastolic filling were determined and related to the effects on maximal oxygen uptake, left ventricular systolic function, and left ventricular mass. Nine untrained healthy males with a mean age of 32 years underwent a ten-week program of bicycle training. Echocardiographic left ventricular mass, maximal oxygen uptake, radionuclide-derived left ventricular ejection fraction, and average left ventricular filling rate were obtained before and after training. Training resulted in significant increases in maximal oxygen uptake (from 30 +/- 6 (mean +/- S.D.) to 40 +/- 7 ml/kg/min, p less than 0.001) and average left ventricular filling rate (from 2.04 +/- 0.36 to 2.22 +/- 0.31 end-diastolic volumes/sec, p less than 0.05), but no changes in heart rate, systolic blood pressure, left ventricular ejection fraction, or left ventricular mass. These data indicate that short-term high-intensity aerobic training enhances average left ventricular diastolic filling independent of any change in left ventricular geometry, systolic function, heart rate, or blood pressure.

Adult↗
PubMed1987

Cellular localization of N-acetylaspartylglutamate in amphibian retina and spinal sensory ganglia.

Antisera were produced against N-acetylaspartylglutamate (NAAG) and were used to localize the molecule within the retina and spinal sensory ganglia of Rana pipiens. NAAG immunoreactivity (IR) in the retina was confined to a subpopulation of amacrine and bipolar cells. The dipeptide was present in the perikarya of these cells and their neurites which terminated in two discrete bands of the inner plexiform layer. Some NAAG-IR was also present in the outer plexiform layer and the inner segment layer. In spinal ganglia, a subpopulation of relatively large sensory neuron cell bodies expressed NAAG-IR. These data are consistent with the hypothesis that this dipeptide has a function which is specific to discrete subclasses of neurons. In the amphibian retina, the NAAG distribution can be related to the reported involvement of the N-methyl-D-aspartate receptor in neurotransmission at the level of amacrine and ganglion cells.

Animals↗
PubMed1987

Aluminium loading during therapeutic plasma exchange.

Graphite furnace atomic absorption spectroscopy was used to demonstrate a fivefold increase in the median plasma aluminium levels of four patients undergoing therapeutic plasmapheresis. This plasma aluminium loading resulted from contamination of albumin incorporated in the replacement fluids and took place during its preparation, with albumin aluminium levels of 646, 669, and 715 micrograms/liter present in three representative samples. Aluminium overload may result in the development of encephalopathy and osteomalacia in patients with renal impairment, indicating the need to monitor aluminium levels in the albumin-containing replacement fluids to avoid this potential hazard.

Aluminum↗