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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 397 records · Page 22Linked to original sources

In vitro effect of transforming growth factor-beta on progression of HIV-1 infection in primary mononuclear phagocytes.

In vitro-differentiated monocytes can be infected with the monocytotropic isolate of HIV-1/ADA. The infection is characterized by formation of giant cells and production of virus that can be found in cell supernatants or cell-associated. In this study, we demonstrate that the above described parameters of infection can be enhanced by a factor present in acidified M phi supernatants, suggesting that it might be transforming growth factor beta-1 (TGF-beta 1). When recombinant or purified TGF-beta were examined, similar activities were detected. This effect apparently is not because of changes in the cellular phenotype that could favor infection. The effect of TGF-beta is exerted on cells once infection is established or on cells with active virus production. The activity can be also demonstrated using U-937 cells.

Cells, Cultured↗

Risk factors for stroke in middle aged British men.

OBJECTIVE: To determine the risk factors for stroke in a cohort representative of middle aged British men. DESIGN: Prospective study of a cohort of men followed up for eight years. SETTING: General practices in 24 towns in England, Wales, and Scotland (the British regional heart study). SUBJECTS: 7735 men aged 40-59 at screening, selected at random from one general practice in each town. MAIN OUTCOME MEASURE: Fatal and non-fatal strokes. RESULTS: 110 of the men had at least one stroke; there were four times as many non-fatal as fatal strokes. The relative risk of stroke was 12.1 in men who had high blood pressure (systolic blood pressure greater than or equal to 160 mm Hg) and were current smokers compared with normotensive, non-smoking men. Diastolic blood pressure yielded no additional information, and former cigarette smokers had the same risk as men who had never smoked. Heavy alcohol intake was associated with a relative risk of stroke of 3.8 in men without previously diagnosed cardiovascular disease. Men with pre-existing ischaemic heart disease had an increased risk of stroke, but only when left ventricular hypertrophy on electrocardiography was also present. CONCLUSIONS: Systolic blood pressure, cigarette smoking, and left ventricular hypertrophy on electrocardiography in men with pre-existing ischaemic heart disease were found to be the major risk factors for stroke in middle aged British men. Heavy alcohol intake seemed to increase the risk of stroke in men without previously diagnosed cardiovascular disease. A large proportion of strokes should be preventable by controlling blood pressure and stopping smoking.

Alcohol Drinking↗

The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome.

Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 degrees C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 degrees C followed by rewarming to 40 degrees C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

(-)-Deprenyl can induce soluble superoxide dismutase in rat striata.

(-)-Deprenyl (0.25 or 2 mg/kg) or saline was injected daily into male Wistar rats for 3 weeks. The striata were dissected out and soluble and particulate superoxide dismutase activity measured. (-)-Deprenyl at 2 mg/kg induced a significant increase in the soluble but not the particulate form of the enzyme. The possibility that this action contributes to the ability of (-)-deprenyl to retard nigral degeneration in man and prolong life in rats is discussed.

Animals↗

A comparative study of the structure of egg-white riboflavin binding protein from the domestic fowl and Japanese quail.

1. The riboflavin binding proteins from domestic fowl and Japanese quail have been isolated and their structures compared by circular dichroism, fluorescence and peptide mapping. 2. The two proteins have similar secondary structures, but differ in their tertiary structures as reflected in the environments of aromatic amino acid side chains. 3. Differences in amino acid sequence between the proteins are indicated by the digestion patterns obtained with thermolysin, chymotrypsin and V8 proteinase from Staphylococcus aureus. Both proteins are resistant to digestion by trypsin.

Animals↗

The use of FT-IR for the determination of stratum corneum hydration in vitro and in vivo.

Measurement of the water content of stratum corneum plays an important role in physiological and therapeutic inquiries in dermatology. There are many techniques available for non-invasive determination of skin hydration such as measurement of electrical, mechanical, thermal and spectroscopic properties of the skin. Most techniques, however, suffer from the fact that they do not employ a direct measurement of water content rather a property caused by skin hydration. Recently, Potts et al., (Arch. Derm. Res. 277, 489-495, 1985) developed an FT-IR method for the determination of water content of the skin both in vitro and in vivo. The method employed attenuated total reflectance infrared (ATR-IR) to measure a weak O-H stretch formed by the presence of water at 2100 cm-1. This absorbance is distant from interferences due to skin and most topically applied substances and therefore may be used in the quantitation of skin water content (hydration). This report describes the use of this technique in an investigation into the effect of occlusion on the water content of the skin. Method development and validation employing an in vitro system is also discussed.

Body Water↗

EGF and TGF-alpha stimulate retinal neuroepithelial cell proliferation in vitro.

Peptide growth factors have been shown to have diverse effects on cells of the CNS, such as promoting neuronal survival, neurite outgrowth, and several other aspects of neuronal differentiation. In addition, some of these factors have been shown to be mitogenic for particular classes of glial cells within the brain and optic nerve, and recently two peptide growth factors, fibroblast growth factor and nerve growth factor, have been shown to have mitogenic activity on the CNS neuronal progenitors. We now report that two members of another peptide growth factor, epidermal growth factor and transforming growth factor-alpha, are mitogenic for retinal neuroepithelial cells in primary cultures and provide evidence for the presence of both of these factors in normal developing rat retina.

Animals↗

Role of plasma non-esterified fatty acids during and after exercise.

1. The importance of circulating non-esterified fatty acids as a substrate during and after low-grade exercise has been examined by using a nicotinic acid analogue to inhibit lipolysis. Seven healthy men received acipimox or placebo on separate occasions. After 90 min, bicycle exercise was performed for 45 min (40% of pre-determined maximum oxygen uptake), followed by a 60 min recovery period. 2. The plasma concentration of non-esterified fatty acids increased during exercise after placebo (320 +/- 80 to 630 +/- 110 mumol/l) and remained elevated in the post-exercise period. Basal concentrations were lower after acipimox (100 +/- 10 mumol/l; P less than 0.05); they declined to 60 +/- 10 mumol/l during exercise and remained at this level for the rest of the study. 3. Lipid oxidation increased from 0.8 +/- 0.1 to 4.2 +/- 0.5 mg min-1 kg-1 during exercise after placebo (P less than 0.001) and remained elevated in the post-exercise period (1.2 +/- 0.1 mg min-1 kg-1). It was lower after acipimox, but still increased from 0.3 +/- 0.1 to 2.3 +/- 0.2 mg min-1 kg-1 with exercise. Carbohydrate oxidation was increased after acipimox compared with after placebo, but only reached significance during the post-exercise period (P less than 0.05). 4. Although acipimox abolished the rise in the plasma concentration of non-esterified fatty acids during exercise, there was only a 50% decrease in the rate of lipid oxidation. This suggests that an alternative source of non-esterified fatty acids makes an important contribution to the supply of lipid for oxidation during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The independent effect of ketone bodies on forearm glucose metabolism in normal man.

Ketone bodies and non-esterified fatty acids (NEFA) inhibit insulin stimulated glucose uptake in muscle in-vitro. In man the infusion of ketone bodies lowers plasma NEFA levels thus confounding the interpretation of individual effects. The aim of this study was to examine the effect of ketone bodies on insulin mediated forearm glucose metabolism independent of the changes in the plasma NEFA levels. Seven healthy men received sodium 3-hydroxybutyrate (15 mumol kg-1 min-1) or sodium bicarbonate (control) for 240 min. Heparin (0.2 U kg-1 min-1) and insulin (0.01 U kg-1 h-1) were infused for 90 min (pre-clamp), followed by insulin alone (0.025 U kg-1 h-1) and euglycaemia was maintained (clamp). Plasma NEFA levels and rates of forearm NEFA uptake (+23 +/- 14 and +49 +/- 21 [mean +/- SEM] nmol 100 ml forearm [FA]-1 min-1) were comparable during the pre-clamp periods, and were suppressed equally during hyperinsulinaemia. Sodium 3-hydroxybutyrate infusion raised the blood ketone body levels from 70 +/- 4 mumol/l to a plateau of 450 +/- 30 mumol/l, while control levels declined from baseline (ketone body vs control; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans.

The purpose of this study was to examine the effect of physiological plasma nonesterified fatty acid (NEFA) levels on insulin-stimulated forearm and whole body glucose uptake and substrate oxidation during euglycemia and hyperglycemia. Seven healthy men received Intralipid and heparin for 210 min in two studies, with saline as control in two further studies. Insulin (0.05 U.kg-1.h-1) was infused from 60 min, and euglycemia was maintained during lipid (EL) and control (EC) studies, and hyperglycemia was maintained in the other studies (HL and HC). Forearm NEFA uptake was comparable in the lipid studies (+61 +/- 10 and +52 +/- 8 nmol.100 ml forearm-1.min-1, EL and HL) and was suppressed in the controls. With Intralipid, forearm glucose uptake decreased during euglycemia but not during hyperglycemia (+3.85 +/- 0.34 vs. +3.34 +/- 0.25 mumol.100 ml forearm-1.min-1, EC vs. EL, P less than 0.02), with comparable changes in whole body glucose uptake. Glucose oxidation and forearm alanine release decreased with Intralipid at both blood glucose levels, with no significant change in the rates of nonoxidative glucose disposal. These observations support the operation of the glucose-fatty acid cycle at physiological plasma NEFA levels at both blood glucose concentrations, but this was associated with a decrease in peripheral insulin sensitivity only during euglycemia.

Adult↗

Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis.

To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography.

Abscess↗

A comparison of measurements of lean body mass derived by bioelectrical impedance, skinfold thickness and total body potassium. A study in obese and non-obese normal subjects.

The measurement of body composition is an important part of metabolic and epidemiological research, but most currently available methods are complex and expensive. We have, therefore, compared measurements of fat mass (FM) and lean body mass (LBM), obtained using a commercially available bioelectrical impedance monitor (The Holtain Body Composition Monitor) (IMP), and by measuring skinfold thickness (SFT), with values obtained by measuring total body potassium (TBK). Twenty subjects, 10 with a body mass index (BMI) less than 30 (kg m-2), (non-obese) and 10 with BMI greater than or equal to 30 (obese) took part in the study. There was a strongly significant linear relationship between LBM calculated from TBK and that calculated from impedance (IMP), in both non-obese and obese groups analysed separately (non-obese: r = 0.92; p less than 0.001 and obese: r = 0.92; p less than 0.001) and together (all: r = 0.89; p less than 0.001). LBM calculated from TBK was strongly linearly correlated with values derived from SFT for non-obese (r = 0.91; p less than 0.001) but not for obese subjects. Mean values of LBM of non-obese subjects derived by each method were not significantly different (TBK: 51.3 +/- 10.40 kg; IMP: 53.18 +/- 10.37 kg; SFT: 48.87 +/- 9.48 kg), but significant differences existed when the subjects were obese (TBK: 51.86 +/- 9.65 kg; IMP: 58.69 +/- 8.55 kg; SFT: 67.61 +/- 8.14 kg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗