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Biomedical subjects

L Morgan

Publications and source records attributed to L Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Soluble IL-6R in plasma cell dyscrasias.

The understanding of the biology of multiple myeloma has advanced significantly in the past few years. The identification of the pivotal role of Interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), and how the ligand receptor complex interacts with the signal transducer gp130 has provided new biological insights into plasma cell disorders. Some studies have suggested that sIL-6R levels may have prognostic significance in MM, however this is not a consistent finding. Here the biology and function of IL-6 and sIL-6R are reviewed and the clinical significance of sIL-6R discussed.

Humans↗
PubMed1997

Protein phosphorylation and the regulation of cell-cell junctions in brain endothelial cells.

Endothelial cells lining the capillaries of the brain have two properties that distinguish them from their peripheral counterparts: (1) tight junctions of extremely low permeability; and (2) low rates of fluid-phase endocytosis. In combination, these features limit the nonspecific flux of ions, proteins, and other substances into the central nervous system environment, creating the blood-brain barrier. This barrier is not immutable. Tight junction permeability can be rapidly increased, which may play a role in the development of a variety of brain pathologies. We have therefore been interested in mechanisms regulating junctional permeability and strategies for interfering with this regulation. What is becoming increasingly apparent is that junctions are not passive mechanical entities; rather, they are targets for a variety of signaling pathways.

Animals↗
PubMed1996

Catalytic and EPR studies of the beta E204Q mutant of the chloroplast F1-ATPase from Chlamydomonas reinhardtii.

The mutation E204Q in the beta subunit of the chloroplast F1-ATPase was made by biolistic transformation of Chlamydomonas reinhardtii. The yield of chloroplast F1-ATPase (CF1) purified from thylakoids was unaltered, suggesting that the mutation did not affect protein assembly. However, photoautotrophic growth of Chlamydomonas strains containing beta E204Q was virtually abolished, and the effect of the mutation on the light-driven ATPsynthase activity catalyzed by purified thylakoids was comparable to the change in the photoautotrophic growth rate. The loss of ATPsynthase activity in the mutant was not the result of uncoupling. Addition of wild-type CF1 to mutant thylakoids depleted of CF1 reconstituted ATPsynthase activity indicating that the mutation did not affect assembly of F0. Furthermore, the mutant CF1F0 was capable of catalyzing ATPase-dependent proton pumping as measured by fluorescence quenching of 9-amino acridine. Although the mutation significantly affected the apparent kcat/K(m) of the Mg(2+)-ATPase activity of the purified CF1-ATPase, no significant effect on the apparent kcat was observed with the mutant compared to wild-type. No significant changes in the ability of Mg2+ or Mn2+ to serve either as a cofactor or as an inhibitor of ATPase activity were observed in the mutants relative to the wild-type CF1-ATPase. EPR spectra were also taken of VO2+ bound at catalytic site 3 in its latent form. In a large fraction of the latent enzyme, a carboxyl group has displaced the nucleotide-phosphate coordination to the metal which results in the free-metal inhibited form (M3). No significant effects on the gII and AII 51V hyperfine parameters were observed between wild-type and mutant. However, the mutation increased the abundance of the M3 form relative to the M3-N3 form (metal-nucleotide-coordinated form). On the basis of these results, beta E204 is not the carboxyl group that displaces the nucleotide phosphate as a ligand to form the free-metal inhibited enzyme form which predominates in site 3 in the latent state. Instead, the data are consistent with a role in which beta E204 is essential to protonate an inorganic phosphate-oxygen to make that oxygen a good leaving group to facilitate ATP synthesis and, via this role in H-bonding, increases the abundance of the functional metal-nucleotide complex bound to the catalytic site.

Animals↗
PubMed1996

Glycated proteins as indices of glycaemic control in diabetic patients with chronic renal failure.

This study investigates the reliability of glycated haemoglobin, measured by electroendosmosis or by affinity chromatography, fructosamine, and albumin adjusted fructosamine, as indices of glycaemic control in Type 1 diabetes complicated by chronic renal failure. Twenty uraemic diabetic patients took part in the study, including 5 patients managed conservatively, 6 on CAPD, 3 on haemodialysis, and 6 renal transplant recipients. Results were compared with those from 15 diabetic subjects with normal renal function. In renal patients, there was significant correlation between glycated haemoglobin measured by electroendosmosis (r = 0.45; p = 0.04) or by affinity chromatography (r = 0.57; p = 0.01) and mean capillary blood glucose concentrations over the previous 6 weeks. The regression equations did not differ significantly between subjects with renal failure and those with normal renal function, suggesting that similar ranges can be used in interpreting glycated haemoglobin results from each group of patients. Patients on haemodialysis may be an exception; there was evidence that glycated haemoglobin may be misleadingly low in such subjects. Fructosamine correlated significantly with mean blood glucose concentrations measured over the previous week in patients with normal renal function (r = 0.75; p = 0.001), but not in patients with chronic renal failure (r = -0.1; p = 0.71). Calculation of an albumin adjusted fructosamine result failed to improve the correlation with blood glucose concentrations. The use of fructosamine cannot be recommended as an index of glycaemic control in uraemic patients.

Blood Glucose↗
PubMed1996

DNA polymorphisms and linkage disequilibrium in the angiotensinogen gene.

A number of recent studies have implicated the angiotensinogen gene in the aetiology of essential hypertension in Caucasian, Japanese and African Caribbean subjects. We have genotyped 153 healthy white Caucasian subjects at a dinucleotide repeat polymorphism and seven diallelic sites in the coding or flanking regions of the angiotensinogen gene, including one polymorphism not previously studied. We have also documented patterns of linkage disequilibrium between polymorphisms. There is evidence of variation in the frequency of several mutations when compared with published results from other Caucasian control populations, possibly due to cryptic ethnic differences between these groups. This should be considered in the design and interpretation of studies of the angiotensinogen gene.

Adult↗
PubMed1996

Angiotensinogen: molecular biology, biochemistry and physiology.

Angiotensinogen is the only known substrate for the enzyme renin. Angiotensin II, the end product of the reaction, is an extremely potent vasoconstrictor and a major determinant of salt and water homeostasis. It is also a growth factor. Angiotensinogen has been identified as a non-inhibitory member of the serine proteinase inhibitor family. Although the most abundant source of plasma angiotensinogen is the liver, the use of Northern blotting and reverse transcriptase PCR techniques has confirmed angiotensinogen mRNA expression in a wide range of tissues, including the kidney, brain, vascular tissue, adrenal gland, placenta and leucocytes. The sequencing of the rat and human angiotensinogen genes has increased our understanding of this protein and its role in physiology and the pathogenesis of human disease. Early observations on the regulation of angiotensinogen are now explicable at the molecular level, with the identification of the core promoter, hormone and acute phase responsive elements and tissue-specific enhancers. The role of angiotensinogen in the aetiology of hypertensive disorders has been tested in transgenic animals, and in case-controlled genetic association and linkage studies. This review examines our current understanding of angiotensinogen, in the light of recent advances.

Angiotensinogen↗
PubMed1996

Serum neural cell adhesion molecule in multiple myeloma and other plasma cell disorders.

Serum embryonic neural cell adhesion molecule (eNCAM) levels were measured at diagnosis in 92 patients with plasma cell disorders. Significantly elevated levels of serum eNCAM were detected in patients with multiple myeloma when compared to both normal controls and patients with monoclonal gammopathy of uncertain significance (MGUS). Very high levels of serum eNCAM were seen in patients with high tumour burdens. There was a significant correlation between serum eNCAM and beta 2-microglobulin (beta 2m) (r = 0.33; P = 0.002), but not between serum eNCAM and C-reactive protein or serum albumen. There was a trend towards longer survival for patients with low serum NCAM. The median survival of the low serum eNCAM group (eNCAM < 20 U/ml) was 36 months compared to 16 months for the high serum eNCAM group (log rank test chi 2 = 2.42, P = 0.1). Serum eNCAM is a new marker of tumour mass in multiple myeloma and correlates with clinical stage and beta 2m. Patients with low serum eNCAM levels may have a survival advantage. Serum eNCAM warrants further evaluation as a tumour marker and prognostic factor in multiple myeloma.

Aged↗
PubMed1996

L-selectin in patients with common variable immunodeficiency (CVID): a comparative study with normal individuals.

L-selectin in one of the key members of the selectin family of adhesion molecules and initiates leucocyte attachment to specialized high endothelial venules. The shed form, which retains functional activity, can be detected in biological fluids and is increased in diseases of many kinds. In the present study, we investigated L-selectin expression on leucocytes and measured the soluble form in the plasma of healthy individuals and patients with CVID. A significant loss of L-selectin expression is found on CVID B cells, which is marked by the presence of a substantial population of L-selectin-negative B cells in the peripheral blood of some CVID patients. On CD4+ T cells, the loss in L-selectin expression affects mostly the CD45RO+ population. Peripheral blood leucocytes other than lymphocytes express L-selectin molecule normally. Moreover, soluble L-selectin was detected in significantly increased levels in CVID plasma compared with healthy controls. Our data suggest that the loss of L-selectin expressed by lymphocytes may be due to increased or aberrant lymphocyte activation in CVID patients who remain immunodeficient, and down-regulation of L-selectin from these lymphocytes may significantly contribute to the elevated levels of soluble L-selectin in the plasma, which may in turn affect further lymphocyte trafficking.

B-Lymphocytes↗
PubMed1996

The entero-insular axis in polycystic ovarian syndrome.

We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7-36 amide) (GLP-1(7-36) amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting (P = 0.05) and integrated (P < 0.01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide (P < 0.05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-1(7-36) amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher (P = 0.05) in patients with PCOS. Women with PCOS had similar fasting but higher (P < 0.05) integrated IRI:C-peptide molar ratios than controls. Fasting and integrated IPI:IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS, GIP and GLP-1(7-36) amide do not contribute to the stimulated hyperinsulinaemia in PCOS.

Adult↗
PubMed1996

Leptospirosis in California sea lions (Zalophus californianus) stranded along the central California coast, 1981-1994.

Prevalence of leptospirosis was determined in California sea lions (Zalophus californianus) stranded live along the central California (USA) coast between January 1981 and December 1994. Clinical signs of renal disease were seen in 764 (33%) of 2338 animals examined; 545 (71%) of these 764 animals died, with similar gross lesions of nephritis. In silver impregnation stains of sections of formalin-fixed kidney, numerous loosely coiled spiral organisms were observed. Leptospira pomona kenniwicki was cultured from four kidney samples in 1991. Epizootics of leptospirosis occurred in 1984, 1988, 1991, and 1994, and were more common in the autumn, typically affecting juvenile males. In 1991 and 1994, 47 animals sampled had antibody titers to L. pomona greater than 1:3200. In 1992, 20 animals sampled were seronegative, and in 1993 three of 20 animals sampled had low titers to L. pomona.

Animals↗
PubMed1995

Mitogen activation of a nuclear alkaline phosphatase in normal activated lymphocytes.

B cell differentiation is punctuated by V(D)J joining in the heavy chain of the pro-B cell, VJ joining in the light chain of the pre-B cell, switch recombination, and somatic hypermutation in the mature B cell. The regulatory signals controlling these events and the developmental program leading to them is poorly understood. We have identified a new phosphatase activity that is expressed in lymphocytes and for which high expression is restricted to mature B cells. This new phosphatase is transiently expressed in nuclear extracts of mitogen-activated splenic B cells. The phosphatase is a monoesterase that is active on both dNMPs and pNPP. The phosphatase has been partially purified by column chromatography and is inhibited by orthovanadate, molybdate, tetramisole, and EDTA and requires Mn2+ for activation. Monoesterase activity requires a pH above the neutral range. The activity profile in the presence of the inhibitors and the requirement for basic pH suggest that this enzyme is an alkaline phosphatase.

Alkaline Phosphatase↗
PubMed1995

Longitudinal change of refractive error in infants during the first year of life.

Using cycloplegia, the change in ametropia of 113 infants was followed at 3 month intervals over the first year of life. Scatterplots of the spherical equivalent power show that the dioptric differences exhibit a significant myopic shift of -0.38 ds between 26 and 36 weeks and -0.38 ds between 36 and 52 weeks. The spread of the dioptric differences (95% CI) does not appear to be related to the magnitude of the ametropia present and decreases with time. By 12 months of age the frequency distribution of the spherical equivalent appears to become leptokurtic as it is in the adult. On average the astigmatism was of low degree (less than 1 dioptre cylinder) and with the rule. Anisometropia was rarely seen. The results of this longitudinal study point to an optimal time for screening and perhaps prescribing for 'abnormal' refractive error between 9 and 12 months of age.

Aging↗
PubMed1995

Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism?

Two cases of Cushing's syndrome are reported in which apparently autonomous adrenal adenomata were associated with the presence of pituitary tumours. In one case the patient was apparently cured by unilateral adrenalectomy, although she was noted to have radiological evidence of an intrasellar tumour; serum cortisol was not suppressed by dexamethasone and ACTH was undetectable. Serum ACTH in the second case was initially 31 ng/l but became undetectable during the course of investigation. Transsphenoidal removal of a corticotroph adenoma did not affect serum cortisol and she proceeded to unilateral adrenalectomy. The pathogenesis of autonomous macronodular hyperplasia is discussed, as well as the options for management.

Adenoma↗