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Biomedical subjects

D M Matthews

Publications and source records attributed to D M Matthews.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Mechanisms of peptide transport.

This review touches on the development of the concept of transmembrane transport of peptides, which originated more than 100 years ago, and discusses present knowledge of the phenomenon, with special reference to intestinal absorption of peptides. It deals with (1) Peptide transport in animal small intestine and its main features--active transport of di- and tripeptides into the absorptive cells, the question of sodium or proton dependence of peptide transport, the independence of peptide and amino acid transport, competition for transport between peptides, the number of transport systems involved, the influence of molecular structure on peptide transport, transport kinetics and relative rates of absorption of peptides and amino acids, nutritional and therapeutic aspects of peptide transport, mechanisms of absorption of small peptides of dietary origin and mechanisms of absorption of biologically active peptides (2) Peptide transport in other animal cells and tissues (3) Peptide transport in microorganisms (4) Peptide transport in higher plants and (5) Physiological advantages of peptide transport. The concluding remarks stress that though most of the salient features of peptide absorption may have been established by 1975, more investigators might usefully be engaged in studying the many remaining questions concerning peptide transport in the animal body, and point out the unfortunate effects of too narrow an approach to problems in the field.

Amino Acids↗
PubMed1987

The use of captopril and captopril plus frusemide as antihypertensive agents in non-insulin dependent diabetes.

After all previous antihypertensive treatment had been stopped, blood pressure and glucose tolerance were measured in 16 hypertensive non-insulin treated diabetics before and again six weeks after treatment with captopril, an angiotensin-converting enzyme inhibitor. Supine blood pressure fell from 184 +/- 4.1/103 +/- 2.6 to 165 +/- 5.2/88 +/- 2.1 mmHg (P less than 0.001) and erect from 179 +/- 5.2/102 +/- 3.2 to 158 +/- 5.6/87 +/- 2.6 mmHg (P less than 0.005). The area under the oral glucose tolerance curve fell from 2313.6 +/- 154 to 2192.8 +/- 146 mmol/min/l (P less than 0.02). There was no change in plasma insulin, total glycosylated haemoglobin or fructosamine. Four patients who failed to show lowering of supine diastolic pressure below 95 mmHg were additionally given oral frusemide with further improvement in blood pressure and no alteration in carbohydrate intolerance. It was concluded that captopril alone is usually an effective antihypertensive agent in non-insulin dependent diabetes with the addition of frusemide benefiting resistant cases. Glucose intolerance did not worsen with either captopril alone or captopril plus frusemide.

Blood Glucose↗
PubMed1987

Noradrenaline response to edrophonium (Tensilon) and its relation to other autonomic tests in diabetic subjects.

Noradrenaline responses following 10 mg intravenous edrophonium were assessed in 32 insulin-treated diabetic men, allocated to 4 groups according to their responses to 5 cardiovascular autonomic tests. The group with the most severe autonomic involvement had no rise in plasma noradrenaline, in contrast to the other 3 groups, whereas the heart rate fell in all 4 groups. There were significant correlations between individual noradrenaline responses, cardiovascular reflex tests, 24 hour heart rate variation and pupil cycle time, depending on whether predominantly parasympathetic or sympathetic pathways or both were involved. These results indicate that the noradrenaline response to edrophonium cannot be used as a test of early sympathetic dysfunction in diabetics; and that autonomic nervous system involvement occurs simultaneously in different body systems.

Autonomic Nervous System Diseases↗
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↗
PubMed1986

Platelet-density analysis and intraplatelet granule content in young insulin-dependent diabetics.

This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.

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↗
PubMed1985

Analysis of the relationship between T cell subsets and in vitro B cell responses in multiple myeloma.

To determine whether or not recently reported imbalances in putative immunoregulatory subsets of T-cells are related to impaired B-cell function in patients with multiple myeloma, we enumerated the level of T-lymphocyte subsets in and the pokeweed mitogen induced B-cell differentiation responses of blood mononuclear cells obtained from 13 patients. T-cell subsets were enumerated with the monoclonal antibodies OKT3 (peripheral T cells), OKT4 (helper/inducer cells) and OKT8 (suppressor/cytotoxic cells) using the Ortho Spectrum III fluorescence analyzer. B-cell differentiation was assessed with a reverse hemolytic plaque assay to enumerate immunoglobulin secreting cells in pokeweed mitogen stimulated cultures. Compared to controls, patients showed reduced percentages of OKT4 cells, increased percentages of OKT8 cells, and reduced OKT4/OKT8 ratios. Pokeweed mitogen induced responses were heterogeneous, but markedly depressed in 5/13 patients (hyporesponders). The percentages of OKT4 and OKT8 lymphocytes and OKT4/OKT8 ratios were similar in PWM responders and hyporesponders. Furthermore, there was no correlation between the ratio and the magnitude of the PWM response in individual patients. The data suggest that imbalances in putative immunoregulatory subsets of T cells, although common in multiple myeloma, are not likely a primary cause of impaired in vitro polyclonal B cell responses seen in this disease.

Antibodies, Monoclonal↗
PubMed1984

Uptake of a series of neutral dipeptides including L-alanyl-L-alanine, glycylglycine and glycylsarcosine by hamster jejunum in vitro.

This paper is the last of a set reporting an investigation of the kinetics of jejunal uptake and inhibitory ability of a series of neutral dipeptides, glycylglycine, L-ananyl-L-alanine, L-valyl-L-valine and L-leucyl-L-leucine, with progressively longer and more lipophilic side chains. The results suggested that at pH 5, uptake of L-alanyl-L-alanine, like that of L-valyl-L-valine and L-leucyl-L-leucine, was the result of two processes, uptake of intact peptide and uptake of free amino acid released extracellularly. On the other hand, uptake of glycylglycine was entirely in the form of intact peptide. In contrast to uptake of L-valyl-L-valine and L-leucyl-L-leucine, the proportion of intact L-alanyl-L-alanine taken up by mediated transport was greatest at the lowest concentration studied and smallest at the highest concentration. Taking the series of results as a whole, whereas the corresponding series of amino acids, glycine, L-alanine, L-valine and L-leucine, showed a progressive increase in apparent affinity for uptake and a decrease in Vmax, we could find no such regular progression with the peptides. The results of work on inhibition of uptake of one dipeptide by another were unexpectedly complex. Examples were the very powerful inhibitory effect of L-valyl-L-valine on uptake of glycylsarcosine, not suggested by the Kt of the former peptide, and the failure of glycylsarcosine to cause complete inhibition of uptake of L-alanyl-L-alanine and L-leucyl-L-leucine, though it could completely inhibit uptake of L-valyl-L-valine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1984

Infection of human endothelial cells by human T-cell leukemia virus type I.

The effects of the human T-cell leukemia virus type I (HTLV-I) on cultured human endothelial cells were evaluated. Coculture of endothelial monolayers with either irradiated HTLV-producing lymphocytes or cell-free virus resulted in the production of multinucleated syncytia. The development of syncytia was inhibited by sera from patients with adult T-cell leukemia/lymphoma (ATLL). HTLV antigens were present on endothelial syncytia passaged in culture for greater than 3 months as detected by an anti-p19 monoclonal antibody, which detects a core protein of HTLV-I, and by ATLL sera. Moreover, these HTLV-infected endothelial cells were then able to infect and transform normal cord blood T lymphocytes with HTLV. These studies demonstrate that human endothelial cells are susceptible to productive HTLV-I infection in vitro and may have relevance for the spectrum of human disease associated with this family of retroviruses.

Antibodies, Monoclonal↗
PubMed1984

Delayed recovery of left ventricular function after antithyroid treatment. Further evidence for reversible abnormalities of contractility in hyperthyroidism.

Sequential measurements of systolic time intervals, left ventricular dimensions, and the derived indices of contractility were undertaken at rest and during isometric exercise in 15 hyperthyroid patients before, during, and after antithyroid treatment. At rest hyperthyroidism was characterised by a shortened pre-ejection period and increased velocity of circumferential shortening of the left ventricle. During isometric exercise, however, the pre-ejection period increased significantly beyond that predicted for normal subjects, and the velocity of circumferential fibre shortening fell by 30%. In contrast, both the pre-ejection period and the velocity of circumferential fibre shortening were unchanged during exercise after a stable euthyroid state had been achieved for at least three months. Comparison between exercise responses and thyroid status during antithyroid treatment showed that a biochemical euthyroid state may be achieved many weeks before normalisation of contractile response to exercise. These findings support the hypothesis of reversible depression of left ventricular function in hyperthyroidism. Responses at rest principally reflect the peripheral actions of thyroid hormone excess.

Adult↗
PubMed1984

Kinetics of uptake of L-leucine and glycylsarcosine into normal and protein malnourished young rat jejunum.

The impact of malnutrition on peptide and amino acid absorption has been studied in the immediate postweaning period. At this time peptide uptake is quantitatively more important than amino acid uptake and the vulnerability of the infant to malnutrition is great. Everted rings of rat jejunum were used to investigate the uptake of the peptide glycylsarcosine (Gly-Sar) and the amino acid L-leucine. The animals had been weaned on to isocaloric diets containing 18% or 4% protein. The rats deprived of protein at this age showed a marked growth disturbance with considerable reduction in gut length in addition to poor weight gain. Mediated influx of Gly-Sar and leucine per centimeter of jejunum was reduced in the malnourished animals: Vmax, 77 +/- 7.1 (SEM) and 65 +/- 3.6 compared with 85 +/- 10.6 and 77 +/- 4.4 nmol . min-1 . cm-1., respectively. But, when expressed in relation to body weight, the maximal transport capacity showed a marked increase with malnutrition, values being 126 and 111 nmol-1 . cm-1 . 100 g-1 body weight compared with 39 and 35 nmol-1 . cm-1 . 100 g-1 body weight for Gly-Sar and leucine respectively.

Animals↗