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Biomedical subjects

M Cahill

Publications and source records attributed to M Cahill.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of age, sex and the oral contraceptive on the platelet membrane fibrinogen binding site (glycoprotein IIb/IIIa).

1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 males. 3. For both agonists there was no significant difference in Bmax or Kd between the sexes. A trend towards increasing affinity (reduced Kd) with age was noted in the female group following ADP stimulation. This was not considered to be physiologically relevant. In the group as a whole no significant relationship of Bmax and Kd with age was demonstrated. 4. A further group of eight women taking low dose oestrogen combined oral contraceptive pill were studied on days 7, 14, 21 and 28 of the treatment cycle and compared with eight women with regular ovulatory cycles. No significant variations in Bmax or Kd were detected within or between cycles in these two groups.

Adenosine Diphosphate↗
PubMed1992

Food in low-income families.

This descriptive study used both quantitative and qualitative research methods to examine the food and nutrient intake, food purchasing patterns and budgeting strategies of 29 sole-parent low-income families with dependent children living in Corio Shire, Victoria, in 1989-90. Expenditure on food and nonalcoholic beverages when compared with the average for all Australian households showed that the study families allocated a greater proportion, but similar amounts of money to cereals, dairy products, fruit and vegetables and miscellaneous foods, and less to meat, nonalcoholic beverages and food eaten away from home. Despite large differences in the amount of money spent in the first and second weeks of a social security payment period, the nutrient density of the parents' diets was maintained at a similar level in both weeks. The only exception was vitamin C, for which the median intake was significantly lower in the second week, consistent with reduced purchases of fruit and vegetables in the same period. In interviews with 13 of the parents a variety of purchasing and budgeting strategies were described, indicating common concerns with making the most of their limited resources. The data from this study support the notion that low-income families give priority to food purchases above other expenses such as recreation. They also support the view that low-income families are concerned about health and nutrition and manage to consume nutritionally sound diets under difficult circumstances. Nutrition education programs could support them in this endeavour.

Adult↗
PubMed1991

125I-fibrinogen binding to platelets in myeloproliferative disease.

Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain.

Blood Platelets↗
PubMed1991

Specific gangliosides increase rapidly in rat liver following partial hepatectomy.

Rat liver gangliosides (sialic acid containing glycosphingolipids) were analyzed by HPTLC and HPLC following either partial hepatectomy or sham operation. Analysis of whole liver gangliosides by HPTLC demonstrated that within 6 h after partial (68%) hepatectomy, there was a significant increase in GM1 compared to both sham and control animals. By 48 h, GM1 was further increased and the polysialylgangliosides GD1a, GD1b and GT1b had also risen significantly, whereas changes in GM3 were negligible. Gangliosides associated with the plasma membrane were increased up to 3.5-fold in regenerating liver compared to sham-hepatectomized controls as assessed by HPLC. Although elevations in membrane gangliosides were associated with hepatocyte proliferation, they did not closely follow the growth curve. The time course of changes in ganglioside biosynthesis suggests differential upregulation of GM3 synthase and GD3 synthase in regenerating livers.

Animals↗
PubMed1988

Differential coupling of smooth muscle and liver vasopressin (V1) receptors to guanine nucleotide binding proteins.

We report the reconstitution of the smooth muscle vasopressin V1 receptor functionally coupled to a pertussis toxin-insensitive guanine nucleotide-binding protein. This V1 receptor was spontaneously coupled to this guanine nucleotide-binding protein upon solubilization in the absence of agonist, in contrast to our earlier report on the liver V1 receptor, which required agonist for coupling. The smooth muscle V1 receptor was reconstituted as a high affinity receptor (Kd = 5 nM), with a slow rate of agonist dissociation. Upon the addition of guanosine 5'-thiotriphosphate, there was a decrease in receptor affinity (Kd = 30 nM) concomitant with an increase in the rate of ligand dissociation. The ability of the smooth muscle V1 receptor to spontaneously couple to a guanine nucleotide-binding protein(s) suggests that in the absence of agonist it exists as a high affinity receptor. The smooth muscle V1 receptor may, therefore, be more sensitive to plasma concentrations of vasopressin than its liver homologue.

Animals↗
PubMed1988

Effect of des arginine9-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture.

Bradykinin (BK) fragments, des arg1-BK, des arg1,pro2-BK, des phe8,arg9-BK and des pro7,phe8,arg9-BK were synthesized and along with des arginine9-BK (daBK), tested for their ability to induce prostacyclin synthesis in homogeneous cultures of cells from the calf pulmonary artery. Of the fragments daBK was the only peptide, in addition to bradykinin (BK), to activate the synthesis of prostacyclin (PGI2) and platelet activating factor (PAF) in endothelial cells and PGI2 in fibroblasts and smooth muscle cells. Half-maximal activation of PGI2 synthesis differed with the cell type. The other fragments tested did not directly affect PGI2 synthesis. These fragments also did not inhibit daBK or BK activation of PG synthesis. BK bound to endothelial cells with a dissociation constant (Kd) of 2.1 nM and a Bmax of 47.9 fmoles/10(6) cells. The Kd for the binding of BK to smooth muscle cells and fibroblasts was somewhat higher, 4.9 nM and 7.9 nM, respectively. None of the fragments tested, including daBK, altered the binding of BK. Des arg9[leu8]-BK, reported to be a competitive antagonist of the bradykinin B1 receptor, inhibited daBK induced PG of PAF synthesis in endothelial cells but had little effect of BK binding or BK induced PG synthesis. Finally, the BK antagonist [thi5,8, d-phe7]-BK blocked both BK binding and the ability of either BK or daBK to induce PG synthesis, thus substantiating that the binding of these kinins is a step in the activation of PG synthesis.

Bradykinin↗
PubMed1987

Time-course studies of the distribution of [1-14C]acrylonitrile in rats after intravenous administration.

Intravenous injection of acrylonitrile (ACN) causes adrenal hemorrhagic necrosis. ACN and its metabolites react with glutathione and bind covalently with macromolecules. Hence the purpose of this investigation was to measure the distribution and covalent binding of radiolabel derived from [1-14C]ACN in order to determine whether binding of ACN or its metabolites may be implicated in the pathogenesis of ACN-induced adrenal injury. Following intravenous injections of ACN, concentrations of total radiolabel were highest in the blood, liver, duodenum, kidneys, and adrenals. Except for blood, there was a time-dependent decrease in total radiolabel in these tissues. Compared with other major organ systems, the levels of covalently bound radiolabel were lower in the adrenal glands. These results do not support a role of covalent binding of ACN or its metabolites in the adrenal toxicity of ACN, but suggest that the initial high concentrations of total radiolabelled compounds derived from ACN could play a role in the action of ACN on the adrenal glands.

Acrylonitrile↗
PubMed1983

The influence of gamma radiation on arachidonic acid release and prostacyclin synthesis.

Cultured pulmonary artery endothelial cells produce PGI2 as their primary prostaglandin. Conditions which inhibit cell division have been shown to accelerate the synthesis of this compound. Exposure of endothelial cells to gamma radiation results in an irreversible cessation of growth and enhanced production of PGI2. The level of PGI2 measured after radiation exposure exceeds that observed in cultures rendered quiescent by serum reduction. This indicates a role for gamma radiation in the elevation of PGI2 levels which is distinct from its effect on cell division. Results presented indicate that exposure to gamma radiation does not, in and of itself, elevate PG levels but capacitates cells for enhanced production when presented with appropriate stimuli. Increased PGI2 synthesis appears to be a result of an observed increase in arachidonic acid release and an activation of cyclooxygenase.

Animals↗
PubMedDate not supplied

Autologous stem cell transplantation in myeloma: the St James's Hospital experience, 1997-2003.

BACKGROUND: High-dose treatment with autologous stem cell transplantation (ASCT) has become the standard of care for patients with myeloma below the age of 65 years. AIMS: We report an audit of 60 patients (median age: 52.5 years) who underwent ASCT in the National Bone Marrow Transplant centre in St James's Hospital in Dublin between 1997 and 2003 inclusive. METHODS: Clinical and laboratory data were retrieved from patient medical records and hospital information management systems. RESULTS: Thirty-six patients had IgG, 11 IgA, 1 IgD, 9 light chain and 3 non-secretory MM. Fifty-seven (95%) patients received anthracycline-corticosteroid combination chemotherapy prior to autografting. There was no transplant-related mortality (TRM). Complete (CR) and Partial Responses (PR) were seen in 16 (29.6%) and 29 (53.7%) of those evaluable (n = 54 (90%)). The actuarial Progression-Free (PFS) and Overall Survival (OS) rates at five years are 13% and 55% respectively. CONCLUSION: Centre outcome is comparable to published international series and supports the use of ASCT in the treatment of this malignancy.

Aged↗
PubMedDate not supplied

Insulin-like growth factor-1 and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration.

Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.

Animals↗
PubMedDate not supplied

Research involving persons with cognitive impairments: results of a survey of Alzheimer disease research centers in the United States.

Research involving persons with cognitive impairments presents ethical and practical challenges, including how to obtain valid informed consent. We asked the directors of the 29 U.S. research centers funded by the National Institute on Aging as "Alzheimer Disease Centers" to provide us with policies or guidelines used in their centers or associated institutions with regard to research involving cognitively impaired subjects. Twenty-four of the 29 centers (83%) responded. Five institutions (21%) had authored their own institutional policies, seven (29%) used guidelines issued by the Department of Health and Human Service's Office for Protection from Research Risks, and 12 (50%) had no policy or guidelines. The five institutional policies addressed a variety of issues, including obtaining consent from cognitively impaired subjects or their authorized representatives, subjects' assent to research participation, and guidance concerning determination of subjects' intellectual capacity. A well-written policy on the protection of cognitively impaired research subjects is one way a research institution demonstrates that it gives serious attention to the rights and welfare of these vulnerable persons. We recommend that all institutions conducting such research author written policies articulating appropriate safeguards for these vulnerable subjects. To promote the protection of cognitively impaired subjects, federal agencies and other funding groups may want to consider requiring written institutional policies as one condition of receiving funds to conduct such research.

Aged↗
PubMedDate not supplied

Eyelid hypertrichosis associated with latanoprost is reversible.

A 56-year-old woman with primary open-angle glaucoma in an only eye presented with hypertrichosis after using Latanoprost to lower IOP. After trabeculectomy with adjunctive Mitomycin C, IOP was well controlled and antiglaucoma medications could be discontinued. At eight-month follow-up the abnormal eyelashes had disappeared.

Antihypertensive Agents↗