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Biomedical subjects

A M MacLeod

Publications and source records attributed to A M MacLeod.

At least 73 records · Page 4Linked to original sources
PubMed1994

Non-S-layer glycoproteins in eubacteria.

Glycoproteins are proving to be quite common in prokaryotes. Those in S-layers are the best understood in terms of structure. Numerous eubacteria produce non-S-layer glycoproteins about which relatively little is known. The glycans on such proteins and the nature and sites of their linkages to proteins are novel in those glycoproteins which have been examined in any detail. The possible functions of the glycans are mostly not understood. Eubacterial non-S-layer glycoproteins and the glycosylation systems producing them deserve more attention.

Amino Acid Sequence↗
PubMed1994

Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK1 receptor.

As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.

Acylation↗
PubMed1994

Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism?

It is believed that human proximal tubular cells may possess immunological function and play an important role in a variety of renal disease states such as interstitial nephritis, allograft rejection and drug induced nephrotoxicity. The role of cytokines and nitric oxide in the human forms of these disease states is not clear. In this study we examined the effect of stimulation with the cytokines IL-1 beta. TNF-alpha and IFN-gamma, individually and in combination, upon primary cultures of human proximal tubular cells. Nitric oxide production increased significantly within 24 hours following cytokine stimulation. This response was inhibited, in a dose dependent manner, by L-NMMA. PCR amplification of mRNA extracted from control and cytokine stimulated human proximal tubular cells revealed a NOS product with a > 97% homology with human hepatocyte inducible nitric oxide synthase. The results of this study clearly show that human proximal tubular cells, in primary culture, are capable of producing nitric oxide in response to an immune challenge secondary to the induction of nitric oxide synthase.

Amino Acid Oxidoreductases↗
PubMed1994

Use of 2H2O to study labeling in plasma glucose and hepatic glycogen during a hyperglycemic clamp.

In this study, we demonstrate the use of 2H2O, in a manner analogous to 3H2O, to study gluconeogenic flux (deuterium labeling at the carbon-6 position of glucose) relative to overall flux through glucose 6-phosphate (deuterium labeling at the carbon-2 position of glucose) into glucose output and glycogen synthesis during hyperglycemia. Before the study (4 days), jugular and carotid catheters were placed. Rats were fasted for 17 h before the study. 2H2O was infused for 2 h at 3 ml/h, with a subsequent 1-h equilibration period. A hyperglycemic clamp at 180 mg/dl (10 mM) was then performed for 90 min (plasma samples obtained at 10-min intervals). At the end of the experiment, anesthesia was induced and the liver removed. Gas chromatography-mass spectroscopy isotopomer analysis of four different mass clusters from glucose was used to determine deuterium enrichment on the carbon-2 (E2D) and carbon-6 (E6D) positions of plasma glucose and glycogen-glucose. The results show that the labeling pattern in glycogen and plasma glucose was virtually identical. In addition, the E6D-to-E2D ratio in plasma glucose did not change during hyperglycemia. Additional studies were performed to show that the E6D-to-E2D ratio was decreased in the fed state and that the fed animal, compared with the fasted rat, had a marked increase in the ratio when given an epinephrine infusion. Thus it was concluded that this was a robust new technique for analyzing glucose and glycogen metabolism in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Membranous nephropathy and granulomatous interstitial nephritis in sarcoidosis.

A 56-year-old woman developed nephrotic syndrome in association with pulmonary sarcoidosis. Renal biopsy revealed both granulomatous interstitial nephritis and membranous nephropathy. Treatment with steroids resulted in a decrease in proteinuria and there was no deterioration in renal function over a subsequent period of 10 months. This case provides further evidence that secondary membranous nephropathy associated with sarcoidosis should be treated with steroids.

Female↗
PubMed1994

Chronic renal failure: factors influencing nephrology referral.

Factors influencing referral of all 304 patients who developed persistent renal failure during one year were studied in the stable Grampian population. The annual incidence of chronic renal failure (CRF) (creatinine > or = 300 mumol/l) was 450/million of the population and of persistent advanced CRF (creatinine > or = 500 mumol/l), 132/million. After excluding those aged > 80 years and those with advanced malignancy, the corresponding incidence figures were 240/million/year and 81/million/year. Only 109 patients (35.8%) were referred to a nephrologist. Patients were divided according to age and coexisting disease into low, medium and high risk groups; 69% of CRF patients in the low, 58% in the medium, and 21% in the high risk group were referred (100%, 88% and 37%, respectively, of the patients with advanced CRF). Two-year patient survival in the low, medium and high risk groups was 100%, 63% and 27%, respectively, in referred patients, and 100%, 48% and 14%, respectively, in non-referred patients. This method of risk stratification identifies patients (particularly those with advanced CRF) likely to have a poor outcome irrespective of referral to a nephrologist. Earlier referral for interventions to delay the progress of the patients' renal and comorbid illnesses has considerable implications for future planning and funding of renal services.

Adolescent↗
PubMed1993

Induction of nitric oxide synthase in human mesangial cells.

Synthesis of nitric oxide (NO) has been implicated in the development of glomerulonephritis in animal models of the disease. Rat mesangial cells can be stimulated to express an inducible form of NO synthase (NOS) in vitro. Little is known however, about the pathway of induction in human mesangial cells. Here, we report that human mesangial cells require multiple cytokines, unlike rat mesangial cells which require only single stimulants, to produce NO. Our experiments suggest that both interleukin-1 beta (IL-1 beta) and interferon gamma (IFN-gamma) must be present together to elicit a response whilst tumour necrosis factor alpha (TNF-alpha) augments this. The production of nitrite, a stable end product of NO metabolism, was inhibited by NG-monomethyl-L-arginine (L-NMMA), L-nitro-arginine-methyl-ester (L-NAME), cycloheximide and the glucocorticoid dexamethasone.

Amino Acid Oxidoreductases↗
PubMed1993

Influence of coexisting disease on survival on renal-replacement therapy.

Survival of patients on renal-replacement therapy (RRT) is no longer improving. Increasingly, such patients are older and have co-morbid conditions affecting organs other than the kidney. In a retrospective study, we calculated actuarial survival of 375 patients starting RRT during a 6 1/2 year period at renal units in Aberdeen and Dundee, UK, after stratification of patients into three risk groups (low, medium, and high) based predominantly on co-morbidity and to a lesser extent on age. 2-year survival differed significantly between low, medium, and high risk groups both before (86%, 60%, and 35%, respectively; p < 0.002 for all comparisons) and after (90%, 70%, 46%; p < 0.004 for all comparisons) excluding early deaths (within 90 days of starting RRT). Overall survival was 61% in Aberdeen and 68% in Dundee (p = 0.04), but 73% and 74%, respectively, when deaths in the first 90 days were excluded (p = 0.73). We conclude that RRT is a highly successful treatment (86% 2-year survival) for patients aged under 70 with no co-morbid conditions (low-risk group); that coexisting non-renal disease has an important influence on survival of patients on RRT; and that risk stratification and analysis of data including and excluding early deaths should allow more valid comparison of data from different centres.

Adolescent↗
PubMed1993

Measurement of regional cerebral blood flow with positron emission tomography: a comparison of [15O]water to [11C]butanol with distributed-parameter and compartmental models.

To further our understanding of the best way to measure regional CBF with positron emission tomography (PET), we directly compared two candidate tracers ([15O]water and [11C]butanol, administered intravenously) and two popular implementations of the one-compartment (1C) model: the autoradiographic implementation representing a single PET measurement of tissue radioactivity over 1 min and a dynamic implementation representing a sequence of measurements of tissue radioactivity over 200 s. We also examined the feasibility of implementing a more realistic, and thus more complex, distributed-parameter (DP) model by assigning fixed values for all of its parameters other than CBF and tracer volume of distribution (Vd), a requirement imposed by the low temporal resolution and statistical quality of PET data. The studies were performed in three normal adult human subjects during paired rest and visual stimulation. In each subject seven regions of interest (ROIs) were selected, one of which was the primary visual cortex. The corresponding ROI were anatomically equivalent in the three subjects. Regional CBF, Vd, tracer arrival delay, and dispersion were estimated for the dynamic data curves. A total of 252 parameter sets were estimated. With [11C]butanol both implementations of the 1C model provided similar results (r = 0.97). Flows estimated using the 1C models were lower (p < 0.01) with [15O]water than with [11C]butanol. In comparison with the 1C model, the constrained version of the DP used in these studies performed inadequately, overestimating high flow and underestimating low flow with both tracers, possibly as the result of the necessity of assigning fixed values for all of its parameters other than CBF and Vd.

Adult↗
PubMed1993

Secondary polycythaemia associated with idiopathic membranous nephropathy.

A 44-year-old man developed idiopathic membranous nephropathy and true secondary polycythaemia. With advancing azotemia, polycythaemia gradually resolved and venesection was no longer required. Only 2 cases of polycythaemia associated with membranous nephropathy have been reported previously. Secondary polycythaemia is a rarely reported association of membranous nephropathy and may increase the risk of thromboembolism, which might be prevented with venesection.

Adult↗
PubMed1993

Social deprivation indices of patients on renal replacement therapy (RRT) in Grampian.

The social deprivation scores of 169 patients who resided in Grampian region and commenced renal replacement therapy (RRT) in Aberdeen during the period 1 January 1985-30 June 1991 were measured when their serum creatinine concentrations were first > = 300 mumol/l, using the Jarman Underprivileged Area (UPA) and Carstairs indices. The numbers in the population of Grampian for each score were obtained from the Information Services team of Grampian Health Board based on the 1981 census. Comparison of the numbers of patients in each category of both Jarman and Carstairs indices showed no differences between the observed numbers of patients and the numbers in the general population. Thus in this study social deprivation occurred no more frequently in those commencing RRT than in the general population.

Health Care Rationing↗
PubMed1993

An immunohistological study of epidermal growth factor receptor and neu receptor and neu receptor expression in proliferative glomerulonephritis.

Many forms of glomerulonephritis including IgA nephropathy are characterized by mesangial cellular proliferation. Since epidermal growth factor is a potent mitogen for cultured human mesangial cells, we have attempted to localize and quantify the expression of its receptor in normal and abnormal renal biopsies using immunohistochemistry. Using a particular antibody (Amersham, clone EGFR1), the epidermal growth factor receptor (EGF-R) was shown to be predominantly localized in the mesangium of the glomerulus. Visual estimates of intensity of staining suggested that expression of this receptor may be increased in some IgA disease patients with mesangial proliferative glomerular lesions. The neu receptor which has a 50% homology with EGF-R was, however, absent from the glomerulus and cultured mesangial cells did not express detectable levels. Expression of EGF-R by cultured mesangial cells, as assessed by immunostaining, was weak and it was not possible to induce detectable upregulation using different cytokines. The factors leading to increased expression of EGF-R in glomerulonephritis, therefore, remain unknown. Our findings suggest that signalling via EGF-R may play a role in the pathogenesis of proliferative glomerulonephritis. Despite its homology with EGF-R, the neu receptor is unlikely to have similar importance.

Cells, Cultured↗
PubMed1992

Streptomyces lividans glycosylates an exoglucanase (Cex) from Cellulomonas fimi.

Exoglucanase Cex from Cellulomonas fimi is a glycoprotein [Langsford et al., J. Gen. Microbiol. 130 (1984) 1367-1376]. Cex produced by Streptomyces lividans from the cloned cex gene is also glycosylated. The extent and nature of glycosylation are similar for Cex from both organisms. The glycosylation affords protection against proteolysis for the enzymes from both organisms when they are bound to cellulose, but not in solution. The ability to glycosylate cloned gene products enhances the utility of Streptomyces as a host for the production of heterologous polypeptides.

Actinomycetales↗
PubMed1992

Submandibular gland transfer in the correction of dry eye.

Following rabbit experiments which showed that microvascular submandibular gland transfer could ameliorate the deleterious effects of lacrimal gland ablation, a clinical transfer of the submandibular salivary gland to the temple region was performed. The beneficial results from this initial operation have led to the procedure being used in a total of eight patients with 12 transfers. The procedure has led to increased moisture in the eye and decreased symptoms but the assessment of change in corneal function and pathology is difficult.

Adolescent↗