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Biomedical subjects

D M Matthews

Publications and source records attributed to D M Matthews.

At least 19 recordsLinked to original sources
PubMed1991

Post-traumatic hypothalamic-pituitary dysfunction presenting with biochemical features of primary hypothyroidism.

Two cases of post-traumatic hypothalamic-pituitary dysfunction are described where the primary pathology was shown to be understimulation of the pituitary by hypothalamic hormones. In each case, the biochemical presentation was a low serum thyroxine and elevated TSH concentration mimicking primary hypothyroidism. Treatment with thyroxine before cortisol replacement was not beneficial. In both cases, hydrocortisone therapy alone resulted in a rise in serum thyroxine and fall in serum TSH. Chronic cortisol deficiency may directly impair the thyroid response to TSH, whilst thyroxine appears to exert its feedback primarily at pituitary rather than hypothalamic level.

Adult↗
PubMed1990

Kinetics of influx of peptides and amino acids into hamster jejunum in vitro: physiological and theoretical implications.

1. This paper reports a comparison of the kinetics of influx into hamster jejunum of a series of dipeptides of neutral, basic and acidic amino acids, and a tripeptide of neutral amino acids, with those of corresponding free amino acids. 2. Kt, the substrate concentration at which the transport rate is half the maximal transport rate, and Vmax, the maximal transport rate, were more similar from one peptide to another than among amino acids, with the result that, over a wide range of concentrations, rates of influx of individual peptides varied much less than those of amino acids. 3. It is suggested that this may account for the rates of absorption of amino acids being closely related to the amino acid composition of the protein fed, instead of being widely dissimilar as with corresponding mixtures of free amino acids. 4. With neutral amino acids, both Kt and Vmax. fell with increasing length of the side-chain, as observed on many previous occasions. This did not occur with the corresponding homologous dipeptides, which shows that the hypothesis that the apparent affinity for transport is related to the lipophilic properties of the side-chain cannot be applied to peptides.

Amino Acids↗
PubMed1989

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗
PubMed1989

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗
PubMed1988

Photodynamic therapy: response of normal canine urethra using a cylindrical fiber.

Normal urethral response to photodynamic therapy (PDT) utilizing a cylindrical fiber was assessed in ten study and two control NIH fox-hounds. The canine urethras were treated 48 hours after intravenous injection of 3 mg/kg dihematoporphyrin ether (Photofrin II). A 1-mm fused silica optical fiber, with the distal 2-3 cm modified for cylindrical light distribution (660-microns diameter), was placed in the pendulous urethra. An argon-pumped dye laser delivered 100 mW of 630-nm light for 7 minutes (42 J) to the treatment area. Urethroscopy using either a 2.5-mm or a 2.8-mm flexible pediatric bronchoscope with video recording capability was performed immediately after PDT (12 animals) and 6 weeks later (nine animals); intravenous urography was performed 3 days and 6 weeks after PDT. There was no evidence of either urethral damage or stricture formation in any animal. Histopathology of the first three study specimens, obtained at 6 weeks, confirmed the absence of any pathology. Flexible instrumentation facilitates post-treatment assessment. This study demonstrates for the first time that, when a cylindrical fiber is used, photodynamic therapy may be applied to the urethra without damage to the normal urethral mucosa. This result has implications for potential treatment of initial or recurrent carcinoma in situ of the urethra using PDT.

Animals↗
PubMed1988

The importance of the time interval between insulin injection and breakfast in determining postprandial glycaemic control--a comparison between human and porcine insulin.

This study assessed the effect of the time interval between insulin injection and breakfast in determining subsequent postprandial glycaemic control and also whether this differed between highly purified porcine insulin and human insulin (crb) in six diabetic patients (age range 24-36 years, duration of diabetes greater than 10 years) usually treated with twice daily Actrapid MC and Monotard MC and with stable insulin requirements and diabetic control. On separate mornings each patient was given, after an overnight fast, their usual dose of either Actrapid MC and Monotard MC or Humulin S and Humulin Zn injected 5, 20, or 40 min before a standard breakfast. The postprandial glycaemic profile was not significantly different at any of the three time intervals with Actrapid MC and Monotard MC. However, with the human insulin the profile was significantly better at the 40 min interval than at the 5 min interval (p less than 0.05) and this was also better than any of the profiles with the porcine insulin, there being a significant difference between the two types of insulin (p less than 0.05). These findings suggest that the time interval between insulin injection and breakfast may be more important with human insulin than with porcine insulin.

Adult↗
PubMed1987

Consequences of fluid loss in patients treated with ACE inhibitors.

Three patients are described in whom haemodynamic collapse and acute renal failure occurred following intercurrent gastrointestinal fluid loss during treatment with an angiotensin converting-enzyme inhibitor. The possible consequences of blockade of the formation of angiotensin II during fluid loss are discussed.

Acute Kidney Injury↗
PubMed1987

Changes in some aspects of platelet function with improvement of glycaemic control over 6 months.

Numerous platelet abnormalities, particularly hyperaggregation, have been described in diabetic patients, and it has been suggested that these may contribute towards the pathogenesis of microvascular complications. In the present study, the changes that occur in ADP-induced aggregation, sensitivity to a stable prostacyclin analogue (Iloprost), aggregation-induced thromboxane B2 production and platelet cyclic AMP levels were investigated in 9 young insulin-dependent diabetics, in which the glycaemic control significantly improved in one group (n = 5; HbA1 from 11.9-9.0%) over a 6 month period. With improvement of glycaemic control there was no significant change in the concentration of ADP required to produce 50 percent of the maximum aggregation wave response. However, there was a significant increase in the responsiveness of platelets to Iloprost and increased platelet thromboxane B2 production. There was no significant difference between the basal platelet cAMP levels before or after exposure to Iloprost. This study suggests that with improved short-term glycaemic control, although there are changes in platelet function, there may be no alteration in the homeostatic balance.

Adenosine Diphosphate↗
PubMed1986

Transient modulation and internalization of T4 antigen induced by phorbol esters.

Phorbol esters are known to alter the expression of surface antigens and receptors on a variety of mammalian cell types. On T lymphoblastoid cell lines and peripheral blood T cells, phorbol esters have been shown to selectively reduce the expression of the T4 antigen. To more fully characterize this process, we have examined the metabolic requirements for this phorbol ester effect, and have evaluated the relationship between phorbol ester-induced T4 loss and the expression of receptors for phorbol-12,13-dibutyrate (PDB) on purified peripheral blood T4 cells. We observed that the loss of T4 on peripheral blood lymphocytes (PBL) occurred at PDB concentrations at which 10 to 15% of phorbol ester binding sites were occupied. The loss of T4 was inhibited at 4 degrees C, and by azide, methylamine, and sodium fluoride, but not by inhibitors of DNA synthesis. When cells were exposed to phorbol esters for greater than 2 days, the T4 antigen was again expressed on the cell surface despite the continued presence of phorbol esters. Cells which had recovered T4 were resistant to the effects of freshly added PDB on this antigen, and this resistance correlated with a 55% reduction in phorbol ester binding sites. Studies on fixed PBL T4 cells and MOLT-4 cells by immunofluorescence microscopy demonstrated that the decreased expression of T4 from the cell surface correlated with a bright clustering of T4 within the cytoplasm, indicating that PDB had induced an internalization of this antigen. These observations demonstrate that the binding of phorbol esters to specific receptors on lymphocytes initiates metabolically dependent events which result in the internalization of the T4 antigen. These findings may be relevant to mechanisms by which T4 functions as a signal-transducing molecule in vivo.

Adult↗
PubMed1985

Absence of the OKT4 epitope on blood T cells and thymus cells in a patient with thymoma, hypogammaglobulinemia, and red blood cell aplasia.

Human helper/inducer T-lymphocytes that express the T4 antigen are important in the regulation of B and T cell functions. Several epitopes of the T4 molecule have now been recognized; however, the precise role of these molecules in the function of helper/inducer T cells is unclear. We studied a patient with thymoma, hypogammaglobulinemia, and red blood cell aplasia whose blood lymphocytes and thymus cells did not express the epitope recognized by OKT4 monoclonal antibody but did display the T4 epitopes recognized by OKT4A and Leu3A monoclonal antibodies. The absence of the OKT4 epitope on the patient's thymus cells suggested that the abnormality occurred during early T cell differentiation. The patient had intact delayed hypersensitivity to 4/4 antigens, and his blood lymphocytes proliferated normally to phytohemagglutinin, concanavalin A, pokeweed mitogen, tetanus toxoid, and allogeneic cells. The patient's T cells demonstrated augmented suppressor activity that was localized to the OKT8+ population rather than to the unusual T4 subset. Irradiation abrogated suppressor activity and rendered his T cells capable of providing help for polyclonal B cell differentiation. The data emphasize the limitations of OKT4 as the sole reagent for characterizing the subset of human helper/inducer cells and demonstrate that the expression of the T4 epitope recognized by OKT4 monoclonal antibody is not required for certain helper/inducer T cell functions in vitro and in vivo.

Adult↗
PubMed1979

Interference by methylcobalamin analogues with synthesis of cobalamin coenzymes in human lymphocytes in vitro.

1. 72 h uptake of cyano[57Co]cobalamin and formation of 57Co-labelled methylcobalamin, adenosylcobalamin and hydroxocobalamin has been estimated with and without the addition of methylcobalamin analogues in phytohaemagglutinin-stimulated lymphocytes from healthy human subjects. 2. Difluorochloromethylcobalamin reduced cell uptake of cyanocobalamin and caused a disproportionate reduction in synthesis of adenosylcobalamin. 3. Methylcobalamin-palladium trichloride reduced cell uptake of cyanobalamin more effectively than did difluorochloromethylcobalamin and reduced the formation of methylcobalamin, adenosylcobalamin and hydroxocobalamin in proportion. 4. The results suggest that in addition to inhibiting uptake of cyanocobalamin, one or both compounds may have interfered directly with the mechanism of synthesis of the cobalamin coenzymes.

Cobamides↗
PubMed1979

Intestinal handling of two tetrapeptides by rodent small intestine in vitro.

Uptake of free Leu and Ala and uptake of these amino acids from the tetrapeptides Leu-Gly-Gly-Gly and Ala-Gly-Gly-Gly has been studied in rings of everted rodent jejunum in vitro. When mediated uptake of free Leu was virtually saturated addition of Leu-Gly-Gly-Gly gave no significant increase in uptake of Leu. Uptake of Leu and of Ala from the tetrapeptides was strongly inhibited by Met, as was uptake of these amino acids from free solution. The results did not suggest that either tetrapeptide was taken up intact by the jejunum.

Alanine↗
PubMed1979

Effects of low cobalamin diet and chronic cyanide toxicity on cobalamin distribution in baboons.

This paper reports the bodily distribution of total cobalamin and individual cobalamins at the termination of an experiment on the effects of a low cobalamin diet and chronic cyanide or thiocyanate administration in baboons. The results show that the distribution of cobalamins in the tissues of the baboon can be altered by a low cobalamin diet and also by chronic intoxication with cyanide, whether or not the animals are on a low cobalamin diet. All animals on the low cobalamin diet showed a reduction in total and individual cobalamins. In blood plasma and erythrocytes, kidney, spleen, testis and brain, the proportion of methylcobalamin tended to be disproportionately reduced in cobalamin-depleted animals. This reduction was lessened or prevented by the administration of cyanide. Neither cyanide not thiocyanate produced a significant increase in the proportion of cyanocobalamin in plasma, though thiocyanate produced a large increase in cyanocobalamin in erythrocytes. In liver, cyanocobalamin was more than doubled by the administration of cyanide to cobalamin-depleted animals.

Animals↗