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Biomedical subjects

G M Murphy

Publications and source records attributed to G M Murphy.

At least 217 records · Page 12Linked to original sources

Induction of pancreatic tumours by longterm duodenogastric reflux.

The incidence of pancreatic cancer is increased in patients who have undergone gastric surgery. An animal model is described in which pancreatic hyperplasia and adenoma formation developed within 56 weeks. The effects of a simple gastrojejunostomy were compared with those after a split gastrojejunostomy, in which the jejunum was transected and the two limbs implanted separately into the greater curvature of the glandular stomach 1 cm apart. After 56 weeks no animals in the simple gastrojejunostomy group had pancreatic hyperplasia whereas all 10 animals in the split gastrojejunostomy group had generalised pancreatic hyperplasia with macroscopic nodules. Microscopy of the nodules showed that in nine animals hyperplastic nodules had developed, and four of these also had adenomatous nodules. The remaining animal had enlarged lymph nodes. Pancreatic hyperplasia was associated with jejunal hyperplasia. Jejunal morphometry showed that the villus height was doubled and the villus height:crypt depth ratio was higher in the split gastrojejunostomy group compared with those animals with a simple gastrojejunostomy. This finding represents a new model for the investigation of pancreatic neoplastic change.

Adenoma↗

Effect of simulated sunlight on Langerhans' cells in malignant melanoma patients.

The effect of artificial sunlight on the number and HLA class II expression of Langerhans' cells was studied in 10 patients with malignant melanoma and 10 control volunteers. The total number of Langerhans' cell decreased in both groups but at 96 h there was a greater and significant decrease (p less than 0.01) in the number of Langerhans' cells in the melanoma group, compared with controls. This decrease persisted and was still greater in the melanoma group (p less than 0.02) at one week post-irradiation. There was a rise in Langerhans' cell count over the following 3 weeks in both groups. Unexpectedly, during this period in the melanoma group-but not controls-there was a significant median peak rise above pre-irradiation levels (p less than 0.001). Alteration in the response of Langerhans' cells to sunlight may play a part in the aetiology of malignant melanoma.

Adult↗

Local increase in interleukin-1-like activity following UVB irradiation of human skin in vivo.

Using an in vivo skin chamber method, we demonstrated increased release of interleukin-1 (IL-1)-like activity at the site of irradiation with 3 times the minimal erythema dose of ultraviolet B (UVB). IL-1-like activity was estimated using the mouse thymocyte amplification assay. UVB-augmented release of IL-1-like activity peaked 1 h after irradiation and levels returned to baseline by 2 h. Release of IL-1-like activity from human skin after exposure to UV radiation may account for some of the local and systemic features of the sunburn response.

Adult↗

Is the ex vivo rat gastric chamber model suitable for studying the gastrotoxicity of refluxed duodenal contents? Initial results using deoxycholic acid.

Duodenogastric reflux has been implicated in the pathogenesis of gastric mucosal disease but the relative toxicities of its constituents are not known. The suitability of the ex vivo rat gastric chamber model for systematic studies of bile acid gastrotoxicity was assessed using deoxycholic acid (DCA 0.2-5.0 mmol/l). Acute challenge with 5.0 mmol/l DCA produced significant loss of gastric transmucosal potential difference (delta PD = 25.9 +/- 3.3 mV: mean +/- SEM; p less than 0.01) compared with saline challenge (1.5 +/- 0.5 mV). Significant delta PD values were produced by DCA concentrations down to 0.5 mmol/l (16.0 +/- 2.8 mV). Challenge with 5.0 mmol/l DCA also caused significant increases in chamber fluid concentrations of nucleic acid (2.8 +/- 0.3 micrograms/ml; p less than 0.05) and acid phosphatase (130 +/- 23.4 microU/ml; p less than 0.01). This study demonstrates DCA gastrotoxicity at concentrations comparable to human intragastric total bile acid concentrations and the suitability of this model for studying the toxic components of refluxed duodenal contents.

Animals↗

Tentative identification of a digoxin-like immunoreactive substance.

Three independent immunoassays gave significantly different results when digoxin concentrations were measured in plasma samples from a 68-year-old male patient with renal and liver impairment. These differences were used to provide a means of isolating a digoxin-like immunoreactive substance (DLIS) by high-pressure liquid chromatography. Examination of this fraction by fast atom bombardment-mass spectrometry provided data to support the hypothesis that excess bile acids might be the source of the DLIS in our patient which may also explain the DLIS observed in neonates.

Aged↗

The presence of neutrophils in human cutaneous ultraviolet-B inflammation.

We report the first observation of neutrophils in the dermal inflammatory infiltrate in human skin soon after moderate ultraviolet-B (UVB) irradiation. Thus human UVB-induced cutaneous inflammation, in this as in other respects, appears to resemble other human acute inflammatory responses to injury.

Adult↗

Inhibition of UV radiation-induced DNA damage by a 5-methoxypsoralen tan in human skin.

Previously untanned buttock skin of 4 volunteers (skin type II; tan with difficulty as they sunburn easily) was treated with various sunscreen preparations and solar--simulated radiation (SSR) or SSR alone for 2 weeks. One week later, the treatment sites were challenged with a DNA-damaging dose of SSR--twice the minimal erythema dose (2 MED). Skin biopsy samples were assayed for the levels of unscheduled DNA synthesis (a measure of DNA damage), melanin distribution, and skin thickening. 5-Methoxypsoralen-containing sunscreen preparations plus SSR or SSR alone induced melanogenesis and increased the stratum corneum thickness, but only the former regimen afforded a high degree of protection against subsequent SSR-induced DNA damage. 5-Methoxypsoralen-free sunscreen preparations plus SSR induced negligible tanning, skin thickening, and photoprotection. These findings are relevant to the risk-benefit analysis of sunscreen preparations, especially in skin type II, as they provide evidence that a 5-methoxypsoralen-induced tan is protective against the DNA-damaging effects of solar UV radiation, and thus has the potential to reduce the carcinogenic risk of exposure to such radiation.

5-Methoxypsoralen↗

Streptococcus sanguis surface antigens and their interactions with saliva.

Saliva-binding molecules of Streptococcus sanguis and their receptors were investigated. Streptococcal cell surfaces were extracted with a barbital buffer and examined immunochemically. Strains G9B and Blackburn, which adhere specifically to saliva-coated hydroxyapatite via immunologically related adhesins, possess 80-, 62-, and 52-kilodalton (kDa), and 52-, 42-, and 29-kDa polypeptides, respectively, which correlate with adhesion to saliva-coated hydroxyapatite. Nonadherent strains Adh- and M-5 lack these antigens. In an immunoblot overlay, the putative adhesins bound to a 73-kDa receptor present in submandibular saliva but not in parotid saliva. G9B also contains a 160-kDa surface protein which bound to an unidentified receptor in both submandibular and parotid saliva samples. Blackburn barbital-extracted components bound to 78- and 70-kDa receptors in parotid saliva. These bacterial-salivary interactions may be important in the regulation of oral ecology.

Antigens, Bacterial↗

Cholinergic urticaria, passive transfer experiments from human to monkey.

Passive transfer experiments in cholinergic urticaria were carried out from 16 patients to a Macaca cymnologous monkey. Intravenous Evans blue dye was used to demonstrate vascular permeability. The animal was challenged after 24 h first by heating the serum-injected dorsal skin to 45 degrees C and secondly by superinjection of acetylcholine into serum-injected sites, and a control site. Local heat proved insufficient to evoke a response. Seven of 16 serum-injected sites showed positive reaction to acetylcholine, control injection of acetylcholine did not. These experiments suggest the presence of a serum factor in cholinergic urticaria which, with acetylcholine, causes increased vascular permeability.

Acetylcholine↗

A histological study of the evolution of solar urticaria.

The histological evolution of solar simulator-induced lesions of solar urticaria was investigated in four severely affected white patients. A series of two to 32 minimal whealing doses of radiation, each much lower than the 24-hour minimal erythema dose, was administered to separate buttock sites. Biopsy specimens were obtained from the exposed areas at five minutes and two and 24 hours later, as well as from adjacent nonexposed skin. Lesions showed a statistically significant dose-dependent increase, predominantly perivascular, in upper dermal neutrophil and eosinophil numbers at five minutes and two hours, but not at 24 hours, and at higher radiation doses in mononuclear cell numbers by 24 hours. Nonirradiated patient skin and irradiated control subject skin was not similarly affected. These changes may be associated with the pathogenesis of solar urticaria.

Adult↗

Lucilia cuprina induced hyperammonaemia and alkalosis associated with pathology in sheep.

Gross and microscopical examinations were done in 12 sheep infested with Lucilia cuprina larvae. All the sheep became hyperammonaemic and alkalotic. Six sheep died and 6 survived, one being moribund before euthanasia. Necropsy revealed severe acute dermatitis and congestion of the liver, heart, kidney, spleen and lungs. Ecchymotic haemorrhages were present in the heart, kidneys and adrenal glands of severely infested sheep. Microscopical examination showed mild to severe vacuolation of the central nervous system in all sheep. In severely infested sheep, skin, lung, heart, kidney, and liver tissues were infiltrated by mononuclear cells, neutrophiles or lymphocytes. Fibrin thrombi were present in vessels. Elevated concentrations of lipid soluble ammonia in blood were positively correlated with tissue abnormality and early death.

Alkalosis↗

Symptomatic dermographism (factitious urticaria)--passive transfer experiments from human to monkey.

Passive transfer experiments were carried out on three species of monkey, Macaca mulatta, Macaca nemestrina and Macaca fascicularis, using human serum from patients affected with severe symptomatic dermographism (factitious urticaria), cholinergic urticaria, chronic idiopathic urticaria and normal subjects. The monkeys were tested for dermographism by means of a calibrated dermographometer 24 h after intradermal injection of the serum, using Evans blue as a marker. Positive responses were seen initially in the M. nemestrina. Four sites injected with serum from patients with severe symptomatic dermographism gave positive responses, one site injected with serum from a normal subject produced a faint response. One of the four responses was reproduced one month later in M. fascicularis. These results indicate that passive transfer of dermographism is possible from human to monkey.

Animals↗

A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis.

A patient with primary biliary cirrhosis is reported in whom UV phototherapy alone was repeatedly effective in controlling severe pruritus. Symptomatic relief was sustained by introducing cholestyramine at a low dosage, despite previous failure of the drug alone to produce any therapeutic benefit, even in large doses. Bile acid concentrations were measured in sera, urine and suction blister fluid from skin exposed to ultraviolet light before, during and following treatment. The findings suggest that phototherapy reduces cutaneous bile acid levels which can subsequently be maintained by low dose cholestyramine. Routine liver function tests remained unaltered. This combination of phototherapy and cholestyramine may be useful in controlling severe pruritus in primary biliary cirrhosis when the drug alone is not tolerated or is ineffective.

Adult↗