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Biomedical subjects

M J Thomas

Publications and source records attributed to M J Thomas.

At least 163 records · Page 9Linked to original sources

Effects of phthalic acid esters (PAEs) on the neonate and aspects of teratogenic actions.

A review of the literature reveals that several different phthalic acid esters (PAEs) are capable of causing testicular damage. Phthalate-induced zinc deficiency is consistent with germinal epithelial damage. Among experimental animals, mice perhaps show the greatest sensitivity to phthalate-induced terata, but high doses/exposure are required. Little toxicologic information is available with regard to phthalate-induced effects upon the neonate.

Animals↗

Divergent effects of bacterial lipopolysaccharide on immunity to orally administered protein and particulate antigens in mice.

We have investigated whether bacterial lipopolysaccharide (LPS) influences immune responses to dietary protein antigens in experimental animals. Simultaneous intravenous administration of LPS to normal mice fed ovalbumin (OVA) prevented the induction of tolerance for serum IgG antibody responses but did not alter the tolerance of systemic delayed-type hypersensitivity (DTH). In addition, exogenous LPS did not enhance the ability of spleen accessory cells to present OVA to primed T cells. LPS-unresponsive C3H/HeJ mice developed full tolerance of both humoral and cell-mediated immunity after feeding a range of doses of OVA that was equal in degree and persistence to that seen in normal, congenic C3H/HeOla mice and also had normal antigen-presenting cell (APC) activity for OVA. In contrast, C3H/HeJ mice were primed by feeding SRBC instead of developing the systemic tolerance found in normal C3H mice. Our results indicate the complexity of mechanisms that may regulate systemic immunity to orally administered antigens of different forms. Nevertheless, LPS does not modulate DTH responses to fed OVA and does not enhance APC activity, and we conclude that bacterial LPS may be unable to influence hypersensitivity to dietary proteins in man.

Animals↗

Faster assay of H2 in breath by dedicated instruments compared with conventional gas chromatography.

Recently available instruments dedicated to the clinical assay of hydrogen in breath were tested and the results compared with those from a conventional thermal conductivity gas chromatograph. We found the Quintron Model 12 Microlyzer and the GMI Exhaled Hydrogen Monitor to give much faster and more sensitive results than the Gow-Mac 550 conventional gas chromatograph, and their readout is digital rather than graphical. Linearity of response, accuracy, and precision were similar for all those instruments. Maintenance requirements and performance characteristics of the three instruments are compared in detail and practical advice is given on daily operation.

Breath Tests↗

Desorption chemical ionization mass spectrometry of 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholines and analogues.

Ammonia desorption chemical ionization of ether-linked phospholipids of the type 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (platelet-activating factors) and a series of analogues revealed a systematic fragmentation pattern that is characteristic for these compounds. The predominant ions included the protonated molecular ion and a series of fragments derived from the molecular ion having the following nominal mass losses: MH-14, MH-42, MH-59, and MH-183. Deuterated ammonia was used to elucidate the nature of several fragments. In addition, desorption chemical ionization was used to quantitate 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine at the nanogram/sample level.

Ammonia↗

Effect of 15-lipoxygenase-derived arachidonate metabolites on human neutrophil degranulation.

Products of the 15-lipoxygenase pathway of arachidonate metabolism, prepared by techniques that effectively free them from contaminants, were examined for their ability to influence human neutrophil degranulation. 15(S)-Hydroxyicosatetraenoate [15(S)-HETE], 8(S),15(S)-dihydroxyicosatetraenoate, and 5(S),15(S)-dihydroxyicosatetraenoate did not directly stimulate this response, but 5(S),15(S)-dihydroxyicosatetraenoate (158-5000 nM) enhanced degranulation responses elicited by platelet-activating factor and its structural analogues. It had no such effect on the degranulation responses elicited by a tripeptide chemotactic factor, phorbol myristate acetate, leukotriene B4, or ionophore A23187. In many of these respects, the potentiating actions of 5,15-dihydroxyicosatetraenoate paralleled the actions of 5(S)-hydroxyicosatetraenoate. Indeed, these two metabolites had potentiating actions on platelet-activating factor that were non-additive and, under specific conditions, cross-desensitized each other. Based on the structural specificity demonstrated by these and other mono- and dihydroxyeicosatetraenoates in potentiating platelet-activating factor as well as their mutual cross-desensitizing actions, we suggest that 5-hydroxylated arachidonate metabolites act by a structurally specific receptor to potentiate human neutrophil responses to certain stimuli.

Exocytosis↗

Facile synthesis of platelet-activating factor and racemic analogues containing unsaturation in the sn-1-alkyl chain.

Platelet-activating factor, 1 (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), and octadecyl-PAF were synthesized chemically as the racemates. The sn-1-O-alkyl isomers were isolated after treatment of the racemates with phospholipase A2 and subsequent reacetylation of the 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholines released. Analogues of PAF containing unsaturated alkyl moieties at the sn-1 position (2, 4, 5) were synthesized by utilizing the methoxyethoxymethyl protecting group as a novel method for preparing unsaturated alkyl lipids. This procedure provides a facile means for preparing unsaturated either phospholipids of defined structure that may be tritiated to high radiospecific activity for metabolic studies. Unsaturation in the alkyl chain had minimal effect on the bioactivities examined in this study.

Animals↗

A prospective trial of young red cells in 48 patients with transfusion-dependent thalassaemia.

Young red cells (YRBC) prepared on a cell washer were compared to whole blood in a randomized prospective trial in 48 transfusion dependent patients with thalassaemia major. A minor but statistically significant decrease in blood consumption was observed in the group receiving YRBC. However, no difference was seen in transfusion interval, mean haemoglobin and rate of haemoglobin fall between the two groups. Filtered blood was shown to be as effective as frozen blood in eliminating non-haemolytic febrile transfusion reactions in all the trial patients. We conclude that any reduction in the rate of iron loading brought about by the use of YRBC is clinically insignificant and does not justify the expense, time and work required to produce young red cells for use in a large transfusion dependent thalassaemic population.

Adolescent↗

Young red cell preparation--a comparison of available methods.

Four possible methods of preparing young red cells (YRBC) which exploit the relationship between red cell ageing and density are compared. Of these, two cell separators and the IBM cell washer are shown to be capable of producing YRBC suitable for clinical use. YRBC prepared from the IBM 2991 cell washer are recommended for clinical trials because of lower cost, greater convenience and lower white cell contamination compared to cell separator-derived YRBC.

Cell Separation↗

Gallbladder filling and response to cholecystokinin are not affected by vagotomy.

We studied the effects of vagotomy on gallbladder (GB) motility in prairie dogs and humans with infusion cholescintigraphy. Twelve male prairie dogs were anesthetized and given an intravenous infusion of 120 microCi of diethyl-HIDA for 150 minutes. Images were acquired every 10 minutes. Then cholecystokinin (CCK)-8, 1.5 micrograms/kg, was given as a bolus, and images were acquired for another 30 minutes. We repeated the studies giving 300 micrograms/kg of atropine 20 minutes before administration of CCK-8. All animals underwent truncal vagotomy, and the studies were repeated 1 and 3 months later. The GB filled in a stepwise fashion; partitioning of bile varied from one 10-minute period to the next and averaged 20% +/- 2%/80% +/- 3% during the 150-minute period. Episodic partial GB emptying (ejection fraction 19% +/- 2%; intervals of 70 +/- 5 minutes) occurred during this phase. GB filling and partitioning of bile were unchanged after vagotomy. GB ejection fraction in response to CCK-8 was 69% +/- 6% in controls, 74% +/- 5% after atropine, 78% +/- 8% 4 weeks after vagotomy, and 66% +/- 6% 3 months after vagotomy. Sixteen human subjects were studied after parietal cell vagotomy (six patients) or truncal vagotomy and drainage (10 patients). GB filling average 2.5% +/- 2% per minute in patients who underwent truncal vagotomy and 3% +/- 1% per minute in patients who underwent parietal cell vagotomy. GB emptying in response to CCK-33 (0.02 U/kg/min) was 74% +/- 7% in patients who underwent truncal vagotomy and 82% +/- 4% in patients who underwent parietal cell vagotomy. Thus neither GB filling nor GB emptying in response to CCK was altered by cholinergic blockade or vagotomy.

Animals↗

Recurrent biliary stricture. Patterns of recurrence and outcome of surgical therapy.

We analyzed the course of 50 consecutive patients with recurrent biliary stricture (at least one previous repair) to determine the pattern of recurrence and the outcome of additional treatment. The presenting manifestations included cholangitis in 40 percent of the patients, jaundice in 30 percent, and pain in 17 percent. Sixty-seven percent had become symptomatic within 2 years of their previous repair and 90 percent within 7 years. Ten (20 percent) patients were treated by end-to-end anastomosis of the bile duct, and 40 (80 percent) patients by bilioenteric anastomosis (hepaticojejunostomy in 32 patients and hepaticoduodenostomy in 8). Two patients (4 percent) died postoperatively. After repair of recurrent stricture, 38 (76 percent) patients had no further symptoms. In 11 (22 percent), another recurrence developed: 6 (55 percent) of the 11 did well after another operation and in 4 (36 percent), a third recurrence developed which was successfully treated by a fourth operation in 3 of the patients. Thus, two thirds of recurrent strictures were evident by 2 years and 90 percent by 7 years. The chance of another recurrence was about 25 percent after treatment of a first recurrence. There was no evidence that prolonged stenting contributed to a good result. Treatment of recurrent stricture should consist of anastomosis between the duct and the intestine, usually a hepaticojejunostomy.

Biliary Tract Diseases↗

Studies of the reactivity of HO2/O2- with unsaturated hydroperoxides in ethanolic solutions.

A study of the reactivity of HO2/O2- with unsaturated hydroperoxides/peroxides was carried out in a stopped-flow spectrophotometer equipped with an O2--generating plasma lamp. The results show that, in 80% aqueous ethanol solution containing either 0.05 M H2SO4 (for HO2 studies) or 0.005 M KOH (for O2- studies), these oxy-radicals do not react with oleic acid hydroperoxide, linoleic acid hydroperoxide, 1-hydroperoxy-2-cyclooctene, and tert-butyl allyl peroxide. These findings are discussed in the light of conflicting evidence concerning the reaction of HO2/O2- with organic hydroperoxides/peroxides.

Chemical Phenomena↗

Mineral oil (follicular) lipidosis: II. Histologic studies of spleen, liver, lymph nodes, and bone marrow.

Tissues obtained from 600 routine autopsies were studied. Mineral oil lipidosis was present in the spleen (76 per cent), liver (45 per cent), bone marrow (26 per cent), and lymph nodes; more than 50 per cent of the lymph nodes from the mesentery, porta hepatis, and mediastinum were affected. Mineral oil and its metabolic products produce a nonfibrogenic reaction in these tissues. The differential diagnosis of mineral oil lipidosis in lymph nodes with reaction to radiopaque oils and Whipple's disease is discussed. The presence of mineral oil in para-aortic (42 per cent) and internal iliac (15 per cent) lymph nodes could result in false-positive readings after lymphangiography.

Bone Marrow↗

Biological effects of di-(2-ethylhexyl) phthalate and other phthalic acid esters.

Esters of o-phthalic acid are widely distributed in the ecosystem. The phthalate acid esters (PAE's) are used as plasticizers in the manufacture of polyvinylchlorides. They are also used as solvents in certain industrial processes and as vehicles for pesticides. The PAE's are used in enormous quantities for a variety of industrial uses in the formulation of plastics. While there are a number of important PAE's, di-ethylhexyl phthalate has perhaps been used the most extensively in the formulation of plastics used in medical devices and blood bag assemblies. The metabolism, biodistribution and excretion varies to some extent among the various PAE's. There are species differences with respect to the metabolism of the PAE's. The route of administration, and the level and length of exposure, are known to affect the toxicological profile of the various PAE's. There is little evidence of bioaccumulation of the various PAE's, and only at very large doses have there been reports of overt toxicity. Evidence for the carcinogenicity of certain PAE's apparently is related to prolonged exposure to high levels.

Animals↗