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D Weir

Publications and source records attributed to D Weir.

At least 37 records · Page 2Linked to original sources
PubMed1994

Folate/vitamin B12 inter-relationships.

Folate deficiency causes anaemia owing to impaired purine and pyrimidine biosynthesis. Vitamin B12 deficiency causes an identical anaemia owing to metabolic trapping of intracellular folate. Vitamin B12 also causes nerve damage. Unlike the anaemia, the nerve damage is probably owing to inhibition of methyltransferase involved in nerve cell biosynthesis. This decreased activity is owing to a reduction in the availability of SAM, the methyl donor, together with product inhibition by its demethylated form, SAH.

Animals↗
PubMed1993

Reversed-phase high-performance liquid chromatographic method for the quantitation of endogenous folate catabolites in rat urine.

We describe a reversed-phase high-performance liquid chromatographic procedure for the analysis of rat urine for p-aminobenzoylglutamate (pABGlu) and its acetamido derivative (p-acetamidobenzoylglutamate, apABGlu). These two catabolites arise following the in vivo cleavage of the folate molecule at the C-9-N-10 bond. Known quantities of high-specific-activity tritiated forms of the catabolites are added as internal standards to aliquots of rat urine. Following preliminary sample clean-up on C18 Sep-Pak cartridges, including derivatisation in the case of pABGlu, the urinary extracts are quantitated by HPLC. The present assay makes possible for the first time the determination of endogenous folate breakdown in the rat.

4-Aminobenzoic Acid↗
PubMed1993

Flow cytometric analysis of surface major histocompatibility complex class II expression on human epithelial cells prepared from small intestinal biopsies.

A technique for preparing viable, single cell suspensions of the epithelial layer of small intestinal tissue obtained endoscopically is described. Constant agitation of four biopsies for 60 min in the presence of chelating and reducing agents gave yields of 1.2-6.7 x 10(6) cells, of which 11-30% were intraepithelial lymphocytes (IEL). Passage through a nylon wool column removed dead cells. This preparation was suitable for flow cytometric analysis. Using this technique, surface MHC class II molecule expression was studied in 14 patients with normal small intestinal mucosa. Fluorescence labelling of these cells showed strong HLA-DR expression by epithelial cells (EC), DP was expressed less strongly, while little DQ expression could be detected. This technique demonstrates that small intestinal biopsies taken during routine endoscopy can yield adequate numbers of viable epithelial cells to perform flow cytometric analysis.

Adolescent↗
PubMed1992

The quantitative analysis of endogenous folate catabolites in human urine.

In man folates are catabolized and excreted as inactive cleaved degradation products, a mixture of pteridines and p-aminobenzoylglutamate (pABGlu) or its acetamido derivative (apABGlu). The daily rate of excretion represents the inescapable use of the vitamin in metabolic activity and thus has implications for determining the recommended dietary allowance for the vitamin. Furthermore, the rate of catabolism has been suggested to rise during pregnancy and in certain disease states. A method is described for the quantitative extraction and assay of the folate catabolites pABGlu and apABGlu in human urine. Aliquots of 24-h urine collections are acidified and applied to columns of Dowex 50W cation-exchange resin. The catabolites are selectively batch-eluted with increasing concentrations of HCl. The fraction containing pABGlu is diazotized and then applied to a C18 Sep Pak column for further purification and concentration. The fraction containing apABGlu was deacetylated and reapplied to the Dowex column and then treated identically to the pABGlu fraction. The methanolic concentrates of both extracts were evaporated to dryness and reconstituted with water and pABGlu was regenerated by reductive cleavage of the diazotized material with Zn/HCl. The extracts of the two catabolites were separated by reverse-phase HPLC using a Radial Pak C18 column. Recovery of isolated material was monitored by the addition of high specific activity tritiated labels of both compounds added as internal standards to all urine aliquots prior to purification and analysis.

4-Aminobenzoic Acid↗
PubMed1991

The effect of Mycoplasma arthritidis infection on the phagocytic activity of macrophages in rats and mice.

The phagocytic activity of mononuclear phagocytes of A/J mice and Wistar rats was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. In mice, the overall phagocytic activity was significantly increased at the end of the first week (P less than 0.0001), but the increase was marginal by the third and fourth weeks after injection. A significant increase in the relative weight of liver and spleen was observed even when phagocytic activity had returned to levels similar to those of controls (P less than 0.001). In rats, the overall phagocytic activity was significantly increased until the fourth week (P less than 0.00001). There was not, however, an increase in the relative weight of liver and spleen as observed for the mice. The results are discussed in the context of factors contributing to the pathogenic mechanisms responsible for differences in the patterns of arthritis due to mycoplasma observed in mice and rats.

Animals↗
PubMed1990

Severity of cirrhosis and the relationship of alpha 1-acid glycoprotein concentration to plasma protein binding of lidocaine.

The concentration of alpha 1-acid glycoprotein, the major determinant of the plasma protein binding of basic drugs, and the extent of lidocaine protein binding was related to the severity of liver disease in 30 cirrhotic patients. In comparison with matched control subjects, alpha 1-acid glycoprotein concentration (77 +/- 7 versus 37 +/- 3 mg/dl; mean +/- SEM; p less than 0.01) and lidocaine binding (69% +/- 2% versus 35% +/- 2%; p less than 0.01) was markedly reduced. There was a significant negative correlation (r = 0.78; p less than 0.01) between free lidocaine and alpha 1-acid glycoprotein concentration. Furthermore, both were significantly related to the severity of liver disease, as assessed by use of the Child Turcotte classification.

Adult↗
PubMed1990

HLA-DP and coeliac disease: family and population studies.

We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001). Furthermore, nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb fragment. However, disease frequency was still increased in the DP alpha 3.5 positive/DP beta 4.9 negative group. In seven families, each with at least two affected members, while the DP alpha 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype--for example, those associated with DR3 or DR7--and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DR/DQ regions.

Celiac Disease↗
PubMed1989

Source of methyl groups in brain and nerve tissue in the rat.

Previous studies that demonstrated that mouse brain accumulated significantly more radioactivity from subcutaneously administered 5-methyltetrahydrofolate labelled in the methyl group compared to the label in the folate moiety are open to two interpretations. The methyl group could have been transferred to another compound (probably methionine) prior to its transport into the brain. Alternatively, if plasma 5-methyltetrahydrofolate per se is significantly involved in the provision of methyl groups to brain and nerve tissue it would be expected that the folate moiety would be returned to the plasma to complete the cycle and thus would appear not to have been taken up. In this article, using competition experiments that exploit the differences in the mechanism of transport of methionine and 5-methyltetrahydrofolate into brain and nerve, evidence is presented that in the rat the methyl group of 5-methyltetrahydrofolate is transported after its conversion to methionine.

Animals↗
PubMed1988

The taper of clinical preparations for fixed prosthodontics.

Convergence angles of full-coverage preparations were measured in a clinical environment and compared with each other and the ideal taper of 4 to 10 degrees. Despite educational emphasis, the practical application of preparation design routinely exceeds the ideal taper and casts a different light on retention and resistance characteristics described in both laboratory and theoretical work. Comparison of preparations done by residents and by prosthodontists in this study showed that ideal preparation taper is seldom achieved. Given the complex interrelationships of clinical, theoretical, and mechanical factors that determine the retention and resistance characteristics of a preparation in vivo, it is advisable to design preparations that blend retentive characteristics with functional demands. Because it is difficult to assess preparation taper intraorally, efforts should be directed to using other retentive devices, especially on posterior preparations where ideal taper is difficult to achieve.

Dental Cavity Preparation↗
PubMed1988

Birth weights in term infants. A 50-year perspective.

An improvement in prenatal care over several generations could enhance the birth weights of term infants. We reviewed data on live-born, singleton infants born at our university medical center between 1935 and 1985. Our review of 42,185 such pregnancies revealed that the mean birth weight (3,279 g) of a term infant has not changed significantly during the past 50 years. The frequency of term infants' weighing less than 2,500 g has not changed, but there has been a significant increase in the percentage of macrosomic infants (greater than 4,000 g), from 3 to 14, in the last 15 years. White infants have been consistently heavier than black infants, by an average of 179 g (6.3 oz). Differences in mean birth weights have been consistently greater for male than female infants (123 g, 4.6 oz) and for multiparous than primiparous deliveries (79 g, 2.8 oz), regardless of race. Impressions from these data, spanning three generations, should be helpful for prenatal counseling.

Birth Weight↗
PubMed1984

A comparison of the effect of oral controlled release morphine and intramuscular morphine on gastric emptying.

The effect on gastric emptying of the administration of oral controlled-release morphine 20 mg and intramuscular morphine 10 mg is compared. Gastric emptying was estimated by the measurement of paracetamol absorption. Statistically significant differences exist between the two treatments. There is slight inhibition of gastric emptying with the oral preparation and almost complete inhibition with intramuscular morphine.

Acetaminophen↗
PubMed1984

Pharmacokinetics of the major metabolites of D-penicillamine in patients with rheumatoid arthritis.

The pharmacokinetic disposition of D-penicillamine and its major metabolites, penicillamine cysteine disulfide ( PSSC ) and penicillamine disulfide ( PSSP ) has been studied in eight patients with rheumatoid arthritis. Plasma concentrations of D-penicillamine, PSSP and PSSC displayed similar characteristics in terms of times to maximum concentrations and biphasic elimination from plasma. Initial t1/2 (alpha) phase ranged from 0.86 to 4.41 h for parent drug and 0.81 to 4.41 h for metabolites. Final t1/2 (beta phase) ranged from 3.4 to 9.45 h for D-penicillamine and 5.62 to 21.7 h for the metabolites. Total drug and metabolites detected in urine accounted for 12.0 to 48.7% of oral drug.

Adult↗
PubMed1983

Conversion in vitro of urinary (+)-penicillamine to its major metabolites, PSSP and PSSC.

To investigate the discrepancy between the apparent pharmacokinetic disposition of (+)-penicillamine in plasma and urine, the spontaneous degradation of (+)-penicillamine was studied in acidified and non-acidified urine. Degradation was prevented by acidification. The oxidized metabolites were converted to reduced (+)-penicillamine by electrolysis.

Biotransformation↗
PubMed1981

Effect of acute and chronic alcohol ingestion on the rate of folate catabolism and hepatic enzyme induction in mice.

1. Folate deficiency is commonly found in alcoholic subjects although the causative mechanism is uncertain. It has been suggested that microsomal enzyme induction resulting from chronic alcohol ingestion might accelerate the rate of folate catabolism thus causing deficiency. 2. By using an experimental animal model to determine the rate of catabolism of [3H]pteroylglutamate (folic acid) by the quantitative estimation of the two urinary catabolites p-[3H]aminobenzoylglutamate and [3H]acetamidobenzoylglumate, we have measured both the rate of folate catabolism and the extent of microsomal-enzyme induction in mice after acute and chronic alcohol ingestion. 3. Despite significant evidence of enzyme induction in the chronic alcohol group, there was no difference in the rate of folate catabolism after acute or chronic alcohol ingestion when compared with that of the controls.

4-Aminobenzoic Acid↗