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Biomedical subjects

M E Thomas

Publications and source records attributed to M E Thomas.

At least 37 records · Page 2Linked to original sources

Postnatal development of uncoupling protein, uncoupling protein mRNA, and GLUT4 in adipose tissues of goats.

Adipose tissues have been characterized in newborn goats on the basis of the presence of the 32,000-M(r) mitochondrial uncoupling protein (UCP) diagnostic of brown fat, and early postnatal developmental changes have been determined. Both internal (perirenal, pericardial, and omental) and subcutaneous (hindlimb and neck regions) adipose tissues in newborn goats contained UCP and are therefore brown fat. The insulin-sensitive glucose transporter, GLUT4, was also present in adipose tissues of newborn goats, implying a potential for insulin-stimulated glucose uptake at birth. UCP was still evident in the perirenal fat of goats at 3 wk of age, but the mitochondrial concentration was only 4%, and the amount per cell a mere 0.2%, of that in the newborn. UCP was not detectable, however, in either the omental or subcutaneous adipose tissue at 3 wk of age and had disappeared from the subcutaneous fat before 2 wk. In contrast to UCP, GLUT4 remained throughout the initial 3 wk of postnatal life. The mRNA for UCP was detected in perirenal adipose tissue of newborn goats, indicating that the gene coding for the protein is being expressed at around birth. UCP mRNA was not, however, detectable in the other fat depots; nor was it evident in the perirenal adipose tissue at > or = 2.5 days of age. It is concluded that the adipose tissues of newborn goats (both internal and subcutaneous) represent brown fat and that there is a rapid transition toward white fat over the first weeks of life. This transition occurs at different rates in different depots but is not markedly faster in goats than in other ruminants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Contribution of proteinuria to progressive renal injury: consequences of tubular uptake of fatty acid bearing albumin.

Proteinuria is a marker of a poor prognosis in the glomerulonephritides and progressive renal disease. Recent animal studies have directly implicated proteinuria in inflammatory tubulointerstitial injury. The proximal tubule takes up significant amounts of lipid in the human nephrotic syndrome. We propose that proximal tubular uptake and metabolism of lipids, notably fatty acid bearing albumin, contributes to the chronic tubulointerstitial infiltration and injury associated with heavy proteinuria. Work in our laboratory has shown that a novel nonpolar lipid released by proximal tubules endocytosing fatty acid-bearing albumin is a potent macrophage chemoattractant. We have also studied the metabolic destiny of fatty acids liberated upon proximal tubular catabolism of albumin. Palmitate was preferentially metabolized to phosphatidylcholines, phosphatidylinositols and diglycerides. Oleate and linoleate were metabolized to triglycerides. Palmitate was profoundly inhibitory to OK cell growth, whilst oleate was stimulatory. In nephrosis, faced with an unregulated influx of fatty acids on albumin, the proximal tubule metabolizes them to a variety of lipids, some of which have pathological effects. Thus, the metabolism of albumin-bound fatty acids by the proximal tubule during heavy proteinuria may directly underlie subsequent tubulointerstitial inflammation and altered response to injury.

Albumins↗

Lipoprotein(a) in patients with proteinuria.

Lipoprotein(a) (Lp(a)) has recently been recognized to be a risk factor for coronary heart disease. Lp(a) median values in the absence of renal disease are around 10 mg/dl. Higher levels (greater than or equal to 30 mg/dl) correlate with the occurrence of coronary heart disease, particularly in the presence of elevated cholesterol. We have studied Lp(a) in 76 adults with proteinuria. Fifty had glomerular diseases and 26 non-glomerular diseases, with renal function varying from normal to advanced chronic renal failure. Lp(a) values were shifted to the right, with a median of 21.0 mg/dl, and 25% of patients had values of 30 mg/dl or more. Lp(a) did not correlate with cholesterol, age, lipoprotein subclasses, apoproteins A-I or B-100, albumin, creatinine, or creatinine clearance. Median Lp(a) values did not differ significantly comparing men versus women, or glomerular versus non-glomerular disease. Lp(a) may inhibit fibrinolysis, and is deposited in atherosclerotic lesions. Although the cause of these elevated Lp(a) levels is uncertain, we propose that they contribute to the increased risk of coronary heart disease in the nephrotic syndrome, and may play a role in progressive renal disease.

Adolescent↗

Some properties of the human platelet vasopressin receptor.

Aggregation of human platelets by vasopressin is potently inhibited by 1-[beta mercapto-(beta, beta'-cyclopentamethylene propionic acid)]-L-arginine vasopressin, a selective vasopressor (V1) antagonist. 1-Desamino-8-D-arginine-vasopressin, a selective anti-diuretic (V2) agonist failed to induce aggregation and acted as a weak antagonist. Vasopressin analogues which lacked the N-terminal amino group or which contained an uncharged amino acid residue at position 8 acted as partial agonists for the human platelet. The response to such partial agonists could be enhanced by increasing the cytosolic Ca2+ concentration but not by altering the level of cyclic-3', 5'-AMP. These observations provide further evidence indicating that the platelet vasopressin receptor is of the V1 sub-type.

Adenosine Diphosphate↗

Anaerobiospirillum species isolated from humans with diarrhoea.

Flagellated anaerobic motile spiral bacteria were isolated from the faeces of two patients with diarrhoea. They were recovered by the microaerophilic culture method used to detect campylobacters but demanded anaerobic conditions for subculture. Electron microscopy and other investigations showed them to be closely related to Anaerobiospirillum succiniproducens first described in beagle dogs and subsequently in three humans with bacteraemia.

Adult↗

Monitoring infectious diseases using routine microbiology data. I. Study of gastroenteritis in an urban area.

Sources of information for monitoring infectious disease are routine data, special surveys and ad hoc investigations. In practice much use is necessarily made of routine notifications and laboratory records although this reporting is often incomplete and may therefore be biased. In a retrospective study of a 16-year series (up to 1968) of routine records concerning the diagnosis of gastroenteritis at one Public Health Laboratory we found it possible to identify biases. During school outbreaks of dysentery, laboratory investigation of diarrhoea increased appreciably and such response to publicity affects the use of routine data in surveillance. Although the patients examined were probably representative diagnostically, their selection may not have reflected the age incidence of disease. Valid geographical comparisons within the urban area were not feasible because medical practitioners differed in their use of laboratory facilities and in their habits of notification. Nevertheless, as far as can be established retrospectively, these data did reflect time trends in disease incidence and so had value for monitoring purposes. Several of the biases defined are likely to apply to other sets of routine data. A further communication will describe a statistical method of correcting for quantifiable bias.

Adolescent↗

Virus diarrhoea associated with pale fatty faeces.

Steatorrhoea was a significant feature in an outbreak of rotavirus gastroenteritis which affected adults and infants in hospital. Fat globules or fatty acid crystals were obvious by light microscopy (LM) in faeces from 14 of 25 patients examined. Ten of the fatty stools and two of the remainder were very pale. By electron microscopy (EM) a rotavirus was seen in 11 of the 14 fatty faeces and in only two of 11 specimens without visible fat. In a further study of pale or fatty faeces 20 such specimens sent for laboratory examination from patients not involved in the hospital outbreak were compared microbiologically with a similar number which were neither pale nor fatty. Viruses were found by EM in 11 (55%) of the pale or fatty stools; eight rotaviruses, two astroviruses and an uncultivable adenovirus were seen; one further patient had acute jaundice. In contrast, no viruses were seen by EM in the twenty specimens which were normally pigmented and without evident fat. Steatorrhoea was significantly associated with rotavirus infection of the alimentary tract which usually presented as a fatty enteritis. We conclude that rotaviruses certainly, and other viruses possibly, can impede both the digestion of fat and the pigmentation of the faeces. Inspection and LM of faeces are easy. In acute enteritis a fatty or pale stool is an indication for virological examination.

Adult↗

Suppressor cell activity in a proliferative disorder of T lymphocytes.

We report details of the immunological profile of a patient with the candidiasis endocrinopathy syndrome who has developed T-type chronic lymphocytic leukaemia. The patient is anergic to a panel of delayed hypersensitivity skin tests, and has poor in vitro mitogenic responses, but B cell function in vivo is not impaired. Subsequent functional studies have revealed that cells from the patient have a significant suppressive effect in coculture (P less than 0.05) on the responses of healthy donor lymphocytes (NR) to the mitogen phytohaemagglutinin (PHA). A degree of selectivity for the suppressive effect is suggested by the lack of similar effects on coculture responses to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Mitomycin C treatment of the patient's cells reduced their suppressive activity but significant suppression was still observed in the majority of PHA cocultures. The suppressor activity required the presence of the patient's cells in cocultures, as no suppression was observed when the patient's serum or cell culture supernatant were included instead of the patient's cells in NR cultures.

Adult↗

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. IV. A monoclonal antibody reacting specifically with a subpopulation of human B lymphocytes.

The technique of somatic cell hybridization has been used to produce a monoclonal antibody (designated FMC7) against the human B lymphoblastoid cell line HRIK. By indirect immunofluorescence FMC7 reacted with a total of 3 out of 10 B cell lines, but failed to bind T and Null cell lines. On normal peripheral blood, FMC7 bound between 3 and 6% of mononuclear cells. When normal peripheral blood mononuclear cells were fractionated, FMC7 reacted with only the B-enriched fraction, staining some but not all cells expressing SMIg. Double marker analysis indicated that the antigen detected by FMC7 is not identical with any of the conventional B cell markers, including surface membrane IgM, C3 receptors, Fc receptors, and the binding site for mouse erythrocytes. Another monoclonal antibody, FMC1, which reacts specifically with B lymphocytes, binds a separate antigenic determinant. Thus, FMC7 appears to recognize a previously undetected marker present specifically on a subpopulation of human B lymphocytes. FMC7 reacts with some but not all B cell leukemias and may have diagnostic applications in leukemia.

Animals↗

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. III. A marker defining a subpopulation of lymphocytes which cuts across the normal T-B-null classification.

A somatic cell hybrid line which secreted antibody reacting selectively with a proportion of the white cells in human blood was prepared. The hybridoma appeared to be monoclonal, and the antibody secreted stained 67% of the lymphocyte population in blood. It reacted less well with granulocytes and monocytes. The lymphocytes stained comprised 80% of the T cells and 50% of the B cells. The antibody showed no recognizable pattern in its reactivity with cell lines and leukaemic cells, although B cells tended to react less well than T cells, null cells, or myeloid leukaemic cells. The expression of the antigenic determinant is discussed in relation to the classification of leucocytes. This determinant and certain other markers exhibited differential expression on closely related cells, and yet were shared by more distantly related cells.

Antibodies↗

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. I. A hybridoma secreting antibody against a marker specific for human B lymphocytes.

A hybridoma has been isolated from the products of fusion of a myeloma cell line with spleen cells from mice immunized with a human B cell line. After cloning, the hybridoma secretes antibody with the following properties: (i) Human B-lymphoblastoid cell lines react with the antibody while T and null cell lines do not. (ii) The antibody reacts with the majority of leucocytes in the blood of patients with CLL, but with a minority of cells in the blood of patients with AML or ALL of the null or T type. (iii) The antibody reacts with 9-21% of mononuclear cells in normal peripheral blood. The reacting cells are not T cells and overlap extensively with cells identified as B cells by other markers. The antigen identified by this antibody appears to be distinct from known B cell markers, and is put forward as a new B cell marker with diagnostic potential.

Animals↗