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Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 271 records · Page 15Linked to original sources
PubMed1977

Formation of oxalate in pyridoxine or thiamin deficient rats during intravenous xylitol infusions.

Glucose, fructose, sorbitol and xylitol were assessed as precursors of oxalate in normal rats and rats deficient in thiamin or vitamin B-6. Urinary excretions of oxalate, glyoxylate and glycine were increased significantly in vitamin B-6 deficient rats infused with xylitol when compared with all other groups. Using [U-14C]xylitol, oxalate was shown to be derived directly from this polyalcohol in vitamin B-6 deficient rats. These results suggest that vitamin B-6 deficiency may be a factor contributing to oxalate crystal deposition seen in some patients infused with xylitol.

Animals↗
PubMed1977

Calcium, phosphorus and magnesium turnover.

The body content of calcium, phosphorus and magnesium is important, not only from the structural or supporting aspect, but also from the aspect of cellular function. Membrane integrity, nervous tissue conduction, neuromuscular excitability, muscle contraction, hormone secretion, intermediary metabolism and synthesis, to mention but a few activities, are all influenced by these elements. The normal body content and turnover of calcium, phosphorus and magnesium are outlined, together with a brief description of their physiological roles, emphasizing intracellular functions rather than their predominance within the skeleton. Regulatory mechanisms, particularly for calcium, involving vitamin D and its metabolites, parathormone, and possibly calcitonin, are discussed within the context of maintaining normal body content and turnover. Homeostatic mechanisms maintaining plasma concentrations in health and disease, as far as they have been identified, are also outlined. Lastly, disorders of calcium, phosphorus and magnesium turnover are considered from the aspect of altered plasma concentrations of these substances. Throughout emphasis is given to common problems and their practical management. Metabolic bone disease and uncommon disorders of bone and bone mineral are not discussed specifically.

Calcitonin↗
PubMed1977

Metabolic disposition of chlorambucil in rats.

1. The metabolic dispositionof chlorambucil, 4-p-(di-2-chloroethyl)aminophenylbutyric acid, was studied in the rat. 2. After oral administration of [14C]chlorambucil to rats, plasma, liver, and kidney showed the highest concentration of 14C. After intravenous administration, plasma and kidney were heavily labelled. Although plasma contained as much as 10% of the administered dose in the first few hours after administration, the level decreased to 1% by 24 h. Elimination of radioactivity was mainly through the kidney. 3. Ten metabolites were isolated and characterized by mass spectrometry. Most metabolites had undergone oxidation on the butyric acid side-chain to form phenylacetic acid and benzoic acid derivatives. Spontaneous degradation products of [14C]chlorambucil were analysed and compared with the metabolites.

Administration, Oral↗
PubMed1977

The role of the macrophage as the stimulator cell in contact sensitivity.

In this study we examined the requirement for the type of stimulator cell for thymus-derived (T) lymphocyte activation to simple chemical haptens. T cells from picryl chloride-immune guinea pigs were challenged in vitro with various trinitrophenyl (TNP)-conjugated syngeneic stimulator cells and the extent of activation was determined by an increase in DNA synthesis. Hapten-specific T cell activation occurred with TNP-conjugated peritoneal exudate cells (PEC) and purified macrophages but not with TNP-conjugated erythrocytes, thymocytes, or nonadherent lymph node cells or PEC. In addition, T cell activation also occurred with TNP-conjugated guinea pig leukemia cells, but only in the presence of macrophages. Furthermore, it was shown that macrophages were required to process and/or present TNP-conjugated leukemia cell antigens rather than simply providing a growth-promoting function. These results suggest that a macrophage-like stimulator cell is required for hapten-specific T cell activation and that this particular stimulator cell may be important in contact sensitivity.

Animals↗
PubMed1977

Nature of the antigenic complex recognized by T lymphocytes. IV. Inhibition of antigen-specific T cell proliferation by antibodies to stimulator macrophage Ia antigens.

We have previously demonstrated that nonimmune guinea pig T lymphocytes could be specifically sensitized with TNP-modified allogeneic macrophages after eliminating the alloreactive T cells with bromodeoxyuridine (BUdR) and light treatment. This procedure allowed the unique opportunity to use anti-Ia sera directed against the Ia antigens of only the stimulator macrophages or responder T cells to determine against which cell type anti-Ia would block TNP-specific stimulation. It was found that the TNP-specific DNA synthetic response of BUdR and light-treated T cells stimulated with TNP-modified allogeneic macrophages was totally eliminated by anti-Ia sera directed solely against the allogeneic stimulator macrophage. In contrast, anti-Ia sera directed only against the responder T cells had no effect on their response to TNP-modified allogeneic macrophages. These findings indicate that macrophage Ia antigens are required for efficient T cell-macrophage interactions and raise the possibility that T cell Ia antigens may not be required for collaboration with macrophages. This latter possibility was substantiated by experiments in which we show that treating T cells with anti-Ia sera and complement to remove the Ia-positive cells either before or after priming, or both, had no effect on their ability to be primed and restimulated with TNP-modified macrophages.

Animals↗
PubMed1976

Nature of the antigenic complex recognized by T lymphocytes. I. Analysis with an in vitro primary response to soluble protein antigens.

In order to analyze the genetic factors involved in the regulation of macrophage-T-cells interaction we have developed an in vitro primary response to soluble protein antigens in which nonimmune guinea pig T cells can be sensitized and subsequently challenged in tissue culture with antigen-pulsed macrophages. Antigen-specific T-cell activation, as measured by increased DNA synthesis, occurred when syngeneic antigen-pulsed macrophages were used for both initial sensitization and secondary challenge. No T-cell activation occurred when allogeneic antigen-pulsed macrophages were used for secondary challenge of cells primed when syngeneic macrophages. When allogeneic antigen-pulsed macrophages were used in both primary and secondary cultures it was difficult to assess antigen-specific stimulation due to the substantial mixed leukocyte reaction. However, when T cells from F1 animals were primed with parental antigen-pulsed macrophages they responded only to the parental macrophages used for initial sensitization but not to those of the other parent. These results are discussed with respect to T-cell recognition of a complex antigenic determinant which may include I-region gene products.

Animals↗
PubMed1976

Phenformin and lactic acidosis.

Thirty-eight patients who presented with diabetes and a changed state of consciousness satisfied the criteria for lactic acidosis. Sixteen patients were non-ketotic, and 15 of these were receiving phenformin on admission. In all but one of these 15 patients, however, additional renal or cardiovascular abnormalities, or both, could be identified, which supported a multifactorial aetiology for lactic acidosis. Advanced age and cardiovascular and renal disease are absolute contraindications to the use of phenformin in diabetics.

Adolescent↗
PubMed1976

Diabetes and associated variables in the South Australian Aboriginal.

Diabetes of a predominant maturity-onset type has been identified as being up to ten times more prevalent in South Australian Aborigines than in Caucasians. On the evidence provided, nutritional status and obesity are thought to be dominant in the aetiology of the hyperglycaemia, although relative hyperinsulinaemia in full blood Aborigines suggests a significant racial genetic effect. It is suggested on these and other grounds that the diabetic genotype may represent a factor of previous survival advantage to the Aboriginal, now rendered deleterious by urbanization. The degree of hyperglycaemia, and its association with hyperlipidaemia, obesity, retinal arteriovenous changes and abnormal electrocardiographic findings, accentuates the significance of the diabetes, and underlines the serious need for ongoing nutritional education in these communities.

Adult↗
PubMed1976

Blood pressures and electrocardiographic findings in the South Australian Aborigines.

Blood pressure measurements were recorded in 522 adults and 141 10-19 year-old full and part blood Aborigines in five communities. The means for systolic and diastolic blood pressures at 40 years were close to those reported for Europeans, although below this age, values tended to be lower, and above 40 years tended to be higher than those reported in the Tecumseh study. Hypertension, as defined by the Princeton criteria, was present in 29%, more often in the men (1-6 to 1-0), and eight subjects satisfied the criteria for hypertensive heart disease (HHD). 522 electrocardiograms were recorded on adult subjects at five Aboriginal communities and classified according to categories of the Minnesota code. Of the 210 abnormalities observed, minor T wave inversions and minor S-T segment depression were the most commonly encountered, and were more frequent in female subjects. Q wave changes typical of myocardial infarction was found in 5% of the tracings and occurred mainly in older men. If hypertension and certain ECG codes are assumed to be "risk factors" for the development of clinical ischaemic heart disease (IHD), the urbanized Aboriginal had a higher prevalence compared with Caucasian subjects of the Busselton study. "Probable" and "suspect" ECG changes of IHD, although mainly in the older subjects, were found to be associated with hyperglycaemia, as recognised in Western society. It is postulated that urbanized Aborigines are prone to cardiovascular degenerative disease to a similar or possibly larger extent than Caucasians.

Adolescent↗
PubMed1976

Visual acuity and retinal changes in South Australian Aborigines.

Eye examinations were carried out a four Aboriginal reserves. Of 361 Aboriginal adults tested, 64 had a visual defect (visual acuity of 6/9 or worse) in each eye, a prevalence of 18%, with an additional 79 (22%) with a similar loss of acuity in one eye only; these were more frequently seen at the urbanized reserve of Koonibba. Only one full blood Aboriginal child within the less urbanized communities had a reduced visual acuity, whereas seven (10%) part blood children at a more urbanized reserve had reduced vision in both eyes, with a further nine (13%) in one eye only, not unlike figures quoted for South Australian school children. Vascular changes in the fundus oculi were observed and occurred more often when hypertension and/or hyperglycaemia were present. They consisted of arteriovenous crossing changes (26%), swelling of the retinal veins (3%) and altered light reflex (41%) and were not infrequently seen in the younger adult (20% of adults under 30 years had AV crossing changes and 46% had widened light streak). Analysis suggests that, although hypertension and hyperglycaemia are related to retinal vascular changes, other factors, as yet unidentified, are present in the Aboriginal population under consideration.

Adult↗
PubMed1976

Oxalate excretion during carbohydrate infusions.

Oxalate metabolism was assessed in normal rats and rats deficient in vitamins B-1 and B-6 during intravenous infusions of solutions containing glucose, fructose, sorbitol or xylitol. Urinary excretions of oxalate, glyoxylate and glycine were considerably increased in vitamin B-6 deficient rats infused with xylitol. Significant amounts of 14C-oxalate were excreted only in vitamin B-6 deficient rats infused with U 14C-xylitol. Correction of vitamin B-6 deficiency resulted in a return to normal of urinary oxalate excretion and percentage of U 14C-xylitol excreted as 14C-oxalate. The results suggest that xylitol metabolism produces an increased activity in pathways leading to oxalate formation in vitamin B-6 deficient rats.

Animals↗
PubMed1975

Effect of infection with gonococci on myeloperoxidase activity of leucocytes.

Lyosomal myeloperoxidase activity in human phagocytic leucocytes was stimulated by incubation with virulent (T1) and avirulent (T4) forms of Neisseria gonorrhoeae. The amount of activity, assayed by bacterial iodination (125-iodine) after 30 min. exposure to the pagocytes in the absence of serum, was about fifty times greater in cells infected with T4 strains. In the presence of heated human serum, or its IgG component, myeloperoxidase activity increased, but T1-Stimulated activity was significantly less than that of T4 and was not proportional to multiplicity of infection. From these results and from those of a previous study we conclude that T1 can stimulate leucocyte myeloperoxidase activity from an extracellular location, that for this activity a serum fraction is required, and that this may be a mechanism responsible for some of the killing of the membrane associated T1.

Humans↗