Search PubMed⌕ Search

Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 163 records · Page 9Linked to original sources
PubMed1992

Calcium and carbonate ion concentrations in gallbladder and hepatic bile.

Calcium carbonate is a major component of gallstones, but there are few data on calcium and carbonate (CO3(2-)) concentrations in human bile. Therefore, in patients undergoing cholecystectomy for gallstones, total [CaTOT] and free ionized [Ca2+] calcium concentrations, pH, PCO2, and total [CO2] were measured and [CO3(2-)] was derived in gallbladder and hepatic bile (aspirated anaerobically at surgery or from T tubes). Gallbladder bile had lower pH (6.96 vs. 7.30) and total [CO2] (14.1 vs. 21.6 mmol/L), higher PCO2 (53.8 vs. 40.2 mm Hg), lower [CO3(2-)] (2.52 vs. 6.11 x 10(5) mol/L) and lower [Ca2+] x [CO3(2-)] ion product (1.88 vs. 4.74 x 10(-8) mol/L) than did hepatic bile. Gallbladder bile pH correlated positively with total [CO2], [CO3(2-)], and [Ca2+] x [CO3(2-)] but negatively with PCO2. Patients with surface gallstone calcification had similar gallbladder bile [CaTOT] and [Ca2+] but higher gallbladder bile pH (7.30 vs. 6.90), lower PCO2 (42.9 vs. 57.2 mm Hg), higher [CO3(2-)] (7.29 vs. 1.84 x 10(-5) mol/L), and higher [Ca2+] x [CO3(2-)] ion product [4.73 vs. 1.45 x 10(-8) (mol/L)2] than those with radiolucent gallstones. There were no differences in these parameters between patients with cholesterol stones and those with pigment stones. These data suggest that the human gallbladder acidifies bile by secreting hydrogen ion and that impairment of this secretion is one cause of calcified gallstone formation in humans.

Adult↗
PubMed1992

Gallstones during octreotide therapy.

Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide, but the reported prevalence of cholecystolithiasis in patients treated with octreotide is variable and little is known about gallstone incidence, composition, pathogenetic mechanisms, dissolvability, and primary prevention. Octreotide treatment apart, in industrialised societies most GBS are mixed in composition, cholesterol-rich (arbitrarily greater than 70% cholesterol by weight), radiolucent (70%), and, given a patent cystic duct (70%), dissolvable in bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) +/- chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes supersaturated with cholesterol (as the molar ratio of cholesterol to phospholipids in biliary vesicles approaches 1:1, the vesicles become unstable); (2) there is an imbalance between pro- and anti-nucleating factors, which favors cholesterol crystal precipitation; and (3) there is stasis within the GB as a result of altered motor function and/or excess mucus that traps the crystals. These changes may be associated with altered (4) biliary bile acid composition (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid composition (arachidonyl-rich lecithin acting as a substrate for mucosal prostaglandin synthesis which, in turn, may influence both gallbladder motility, and mucus glycoprotein synthesis and secretion). During octreotide treatment, meal-stimulated cholecystokinin (CCK) release is impaired leading to GB hypomotility, but little is known about the effects of octreotide on biliary cholesterol saturation, crystal nucleation time, mucus glycoprotein concentration, bile acid or phospholipid fatty acid composition. Most, but not all, reports suggest that the prevalence of GBS in octreotide-treated patients is considerably greater than that in age-, sex-, and weight-matched controls, but proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent before, but developed during, therapy is not always available. Furthermore, there are few data on analysis of GBS composition in patients developing stones during treatment, although initial reports suggest that octreotide-associated GBS are also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment. Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized computerized tomography scanning of the GB, predict stone composition and dissolvability: GBS with scores of less than 100 HU are cholesterol-rich and dissolve well with oral bile acid treatment. However, preliminary results in 11 acromegalic patients treated with 200 to 600 micrograms octreotide/d for 29 to 68 months show that the HU scores range from 23 to 490 (mean +/- SEM, 116 +/- 41), suggesting that at least four of these 11 patients have non-cholesterol stones.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1992

Studies on the pathogenesis of bovine ephemeral fever in experimental cattle. III. Virological and biochemical data.

In an attempt to define the nature of the response of cattle to ephemeral fever infection, a number of indicators of inflammation were monitored during clinical disease. The total Ca, Zn, Fe, Cu, glucose and phosphate in plasma, together with blood ammonia, were assayed relative to changes in the rectal temperature. CaT levels fluctuated markedly and hypocalcaemia occurred in 4 of 8 cattle. Plasma Zn and Fe values fell while plasma Cu levels rose markedly in all cattle. Mean levels of serum NH3 of 20-30 mumol l-1 rose to a peak value of 56 mumoll-1. Plasma glucose levels rose to a peak of 4.6 +/- 0.5 mMl-1 and the plasma phosphate levels fell from 2.4 +/- 0.1 mMl-1 to 1.17 +/- 0.2 mMl-1 during fever. Values of pCO2 fell from a mean of 46.9 +/- 3.6 mmHg to 36.4 +/- 3.1 mmHg and coincided with a rise in pH. Virus was isolated 73 h (+/- 23) after inoculation and persisted until 130 h (+/- 21). The common role of these parameters in generalised inflammation and ephemeral fever is discussed.

Ammonia↗
PubMed1992

Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy.

In a five year study, 55 patients with radiolucent gall stones were treated with the combination of 7.5 mg chenodeoxycholic acid (CDCA) and 5.0 mg ursodeoxycholic acid (UDCA)/kg/day--that is, half the monotherapeutic doses. Side effects were few but four patients could not tolerate the prescribed bile acids because of diarrhoea or nausea. Analysis of fasting duodenal bile confirmed that CDCA+UDCA converted supersaturated into unsaturated bile but the saturation indices did not predict the dissolution response. By actuarial analysis, the confirmed (by ultrasound x2) complete gall stone dissolution rates in all 55 patients were mean (SEM) 29 (7)% at 12 and 44 (8)% at 24 months. The advent of routine computed tomography before treatment enabled comparison of dissolution efficacy in those screened by computed tomography (n = 24), whose maximum gall stone attenuation was less than 100 Hounsfield units, with that in those not screened (n = 29). Although stone size and number were comparable, patients screened by computed tomography had significantly better dissolution rates (p less than 0.025) than those not screened in this way. At 12 months, partial or complete gall stone dissolution rates were 93 (7)% in the screened and 55 (11)% in the non-screened patients. At 18 months, complete dissolution rates were 64 (12%) and 20 (9)% respectively. Computed tomography before treatment is cost effective in selecting those patients likely to achieve gall stone dissolution on treatment with UDCA+CDCA.

Adult↗
PubMed1992

Alzheimer's disease. Beta-amyloid precursor protein expression in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM) was examined using immunocytochemistry for beta-amyloid precursor protein (beta APP) expression in Alzheimer's disease (AD). In mild AD cases, light labeling of the cell body and proximal processes was observed, and small intracellular structures were labeled rarely. In the more severe cases, intense cytoplasmic beta APP labeling was seen, often along with small beta APP-positive structures. Double-labeling experiments demonstrated that in the more severe cases these small structures were also decorated by a neurofibrillary tangle (NFT) antiserum. Other neurons in the severe cases showed incorporation of beta APP into large inclusions, which were also labeled with the NFT antiserum. However, some large inclusions in the severe cases were labeled by the NFT antiserum but contained no beta APP. Extraneuronal NFTs did not show beta APP labeling and did not react with an antibody to the beta-amyloid peptide. These results suggest that increased expression of beta APP coincides with intracellular NFT formation in the nbM, but that the formation of extraneuronal NFTs results in a loss of beta APP immunoreactivity.

Adult↗
PubMed1991

Alzheimer's disease: beta-amyloid precursor protein mRNA expression in mononuclear blood cells.

beta-Amyloid precursor protein (beta APP) mRNA was examined in peripheral mononuclear blood cells (PMBCs) in Alzheimer's disease, Down's syndrome and control subjects. Total RNA from PMBCs was reverse transcribed and then amplified using the polymerase chain reaction (PCR). The 3 major beta APP transcripts were expressed in PMBCs from all subjects. These results suggest that PMBCs could be a circulating source for abnormal amyloid deposition in the brain and in peripheral tissues.

Adult↗
PubMed1991

Isocratic high-performance liquid chromatographic measurement of optimal 5 alpha-steroid reductase activity in Hep-G2 cells.

Measurement of 5 alpha-reductase activity usually involves quantitation of the radiolabelled products of [3H]testosterone. Recently, however, it has been claimed that the activity of 5 alpha-reductase is masked by the activities of 17 beta-hydroxysteroid dehydrogenase and 3-ketosteroid reductase. Therefore in determining 5 alpha-reductase activity in Hep-G2 cells, we have monitored the concentration of androstenedione to ensure that the conditions for measurement of optimum enzyme activity are maintained. Using a polar (cyano) bonded-phase column and hexane-isopropanol (9:1, v/v) as eluent, the ratio of relative retention times (methyl lithocholate used as the reference standard) of the closest peaks, dihydrotestosterone and estradiol, was 1.2, whilst the highest inter-assay coefficient of variation was 2.7%. Therefore this technique appears suitable for the evaluation of 5 alpha-reductase in cell and tissue samples.

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

Alzheimer's disease: beta-amyloid precursor protein expression in plaques varies among cytoarchitectonic areas of the medial temporal lobe.

The anatomic distributions of beta-amyloid peptide (beta AP) and beta-amyloid precursor protein (beta APP) in the medial temporal lobe were examined with immunocytochemistry in Alzheimer's disease. beta AP-containing plaques were found most frequently in the cortical and basal regions of the amygdala, and in the hippocampal CA1, subiculum, and dentate molecular layer. beta APP expression in plaques was found in a similar distribution, with some, but not all beta AP plaques also showing beta APP. In the cortical and basal amygdala, some cases showed beta APP in the centers of plaques, whereas in the hippocampus, all cases displayed beta APP mainly in plaque neurites. The lateral regions of the amygdala contained mainly diffuse beta AP plaques which had little beta APP. These findings suggest that although beta APP expression and beta AP deposition generally colocalize, processing of beta APP may vary among closely interconnected anatomic regions.

Adult↗
PubMed1991

Limbic/mesolimbic connections and the pathogenesis of schizophrenia.

The development of models of the pathogenesis of neuropsychiatric diseases that build on recent advances in chemical neuroanatomy will help to guide future research. The interconnections among limbic, basal ganglia, and cortical structures are used to form the basis of a hypothesis of the pathogenesis of schizophrenia. The adaptive capacity of subcortical dopamine systems is advanced as an explanation of the many states of the disease.

Humans↗
PubMed1991

The amygdala in Down's syndrome and familial Alzheimer's disease: four clinicopathological case reports.

Senile plaques and neurofibrillary tangles were quantified in 14 subnuclei of the amygdala in the brains of 3 patients with Down's syndrome (DS), aged 19, 56, and 64 years, and in 1 patient with familial Alzheimer's disease (AD), aged 54 years. The amygdala of the 19-year-old Down's case contained numerous senile plaques (SPs) but no neurofibrillary tangles (NFTs). The distribution of neuropathological change in the amygdala was similar among the Down's and the Alzheimer's cases. Medical and ventral regions contained more SPs and NFTs than did lateral regions, and the SPs in ventromedial subnuclei generally were the "mature" type with a prominent amyloid core. In general, the numbers of SPs and NFTs were parallel in a given subnucleus with the striking exceptions of the deep medial basal, deep cortical, and lateral central nuclei that contained far more SPs than NFTs, and the medial and lateral superficial cortical nuclei that contained numerous NFTs but few SPs. Several subnuclei strongly interconnected with hippocampus and entorhinal cortex were more heavily involved than subnuclei related to the nucleus basalis of Meynert. The patterns of SP and NFT deposition are consistent with amygdaloid abnormalities found by others in sporadic AD. These findings demonstrate the similarity in amygdaloid pathology among Down's syndrome, familial Alzheimer's disease, and sporadic AD. The presence of senile plaques in the amygdala of the 19-year-old patient with DS suggests that the amygdala is a focus of early pathological change in DS and possibly AD.

Adult↗
PubMed1991

Effect of alpha-difluoromethylornithine on the polyamine levels and proliferation in two transplantable tumours.

The effect of inhibition of polyamine biosynthesis by alpha-difluoromethylornithine (DFMO) on the growth of two murine transplantable tumours was studied. Female CBA mice were implanted with either the sarcoma F (SaF) or an anaplastic mammary carcinoma (CaNT), and 3% DFMO in the drinking water was provided once the tumours were established. Over a 10-day period control SaF tumours increased exponentially from 20 mm3 to over 800 mm3, whereas DFMO-treated SaF reached only 300 mm3. CaNT grew more slowly, requiring 22 days to achieve a similar volume increase, and DFMO was as effective in retarding growth as it had been in SaF. DFMO depleted tumour tissues of putrescine and spermidine, but did not reduce spermine levels. Metaphase arrest experiments with vincristine demonstrated that DFMO could substantially reduce the rates of tumour cell production, but there was no indication the DFMO accelerated the rate of cell loss from the tumours. Despite reduced rates of cell production, labelling studies with bromodeoxyuridine failed to detect differences between control and treated tumours: an increase in transit time through the S-phase was suspected. The number of nuclear organizer regions, detected by the argyrophilia of their associated proteins, was less in DFMO-treated tumours, and within a tumour the degree of silver deposition unequivocally reflected the proliferative heterogeneity. Ultrastructural studies revealed no differences between DFMO-treated and untreated tumours.

Animals↗
PubMed1991

Photoprotection and 5-MOP photochemoprotection from UVR-induced DNA damage in humans: the role of skin type.

Sites on previously unexposed buttock skin in 18 subjects (skin types I-V) were treated daily for 2 weeks with suberythemogenic doses of solar-simulated radiation (SSR) alone, SSR plus a UVB sunscreen, and SSR plus the same sunscreen with 5-methoxypsoralen at 30 ppm. The three sites of treatment (designated SSR, SSR/S, and SSR/S/5-MOP), and a control site that received no SSR or topical treatment, were challenged with 2MED SSR 1 week after the treatment had ceased. Biopsy samples, taken within 15 min after the challenge dose, were assessed for unscheduled DNA synthesis (UDS, interpreted as a measure of DNA damage), melanin deposition, and stratum corneum thickening. Within a given skin type, when compared with controls, the significant increase in either pigmentation or stratum corneum thickening was similar for SSR and SSR/S/5-MOP. SSR/S inhibited these endpoints. Compared with controls, UDS was significantly reduced in skin types III-V by SSR and in all skin types by SSR/S/5-MOP. SSR/S elicited no effect apart from minimal reductions in skin types IV and V. Thus, the increases in pigmentation and stratum corneum thickening seen in all skin types with SSR and SSR/S/5-MOP were accompanied by reduced UDS in all skin types with SSR/S/5-MOP but only in skin types III-V with SSR. These findings suggest that, although induced pigmentation and stratum corneum thickening may account in part for the reduction of UDS, qualitative differences in induced pigmentation may exist in skin types I-II between SSR and SSR/S/5-MOP treatments. The findings can also be interpreted to indicate that SSR/S/5-MOP treatment can afford protection against DNA damage from subsequent exposure to solar ultraviolet radiation. Risk-benefit considerations on the use of sunscreens with and without 5-MOP are discussed and the conclusion is drawn that the judicious use of 5-MOP sunscreens, particularly in skin types I-II, affords an alternative option to those seeking a suntan.

DNA↗