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Biomedical subjects

D S Gill

Publications and source records attributed to D S Gill.

At least 55 records · Page 3Linked to original sources

Antidepressant response to sleep deprivation as a function of time into depressive episode in rapidly cycling bipolar patients.

Three patients with treatment-resistant rapidly cycling bipolar disorder were studied with multiple sleep deprivations (SD) during several depressive episodes to assess the effect of phase or duration of a depressive episode on SD response. There was little response to SD early in a depressive episode, but responses were often robust late in an episode, sometimes triggering its termination. In 2 subjects, the duration of antidepressant response to SD increased linearly as time into episode increased. Neither the number of SD given in an episode nor the medication status of the patients appeared to account for the observed increases in antidepressant response. These results suggest that the neurobiological substrates underlying depression may change over the course of an episode, resulting in an increased responsivity to sleep deprivation later compared with earlier in the course of an episode in rapidly cycling patients. The generalizability of these findings to unipolar patients remains to be explored.

Adult↗

Brain regions involved in recognizing facial emotion or identity: an oxygen-15 PET study.

The functional neuroanatomy of emotion recognition is inadequately understood despite well-documented clinical situations where emotion recognition is impaired (aprosodia). Oxygen-15 water positron-emission tomography (PET) was used to study 9 healthy women volunteers during three match-to-sample conditions, each repeated twice: a study task matching facial emotions and control tasks matching spatial positions or facial identity. Results suggest that the higher order functional neural network for recognizing emotion in visual input likely involves the right anterior cingulate and the bilateral inferior frontal gyri.

Adult↗

Rickets in Nigerian children: a consequence of calcium malnutrition.

Eleven Nigerian children with clinically and radiologically proven rickets were assessed biochemically. The children had low or low normal concentrations of total and corrected calcium, and elevated plasma alkaline phosphatase (ALP) activity, but normal plasma phosphate concentrations. Their serum 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations were not significantly different from those in controls, but the ratio of 1,25-(OH)2D to 25-OHD was significantly greater than that in controls. Parathyroid hormone (PTH) concentrations were greater in rachitic children, and there was a significant correlation between 1,25-(OH)2D and PTH concentrations. Osteocalcin concentrations in rachitic children were not significantly different from those in controls, but they were markedly elevated in the three patients with the highest 1,25-(OH)2D and PTH concentrations. One child, from whom a sample of bone (from a corrective osteotomy) was available for histological examination, showed markedly thickened osteoid seams, characteristic of rickets. All the rachitic children had a calcium intake of less than 150 mg daily. Treatment of these rachitic children with calcium gluconate (1 g/d) led to clinical, radiological, and biochemical healing of rickets. We conclude that rickets in Nigerian children is not due to vitamin D deficiency, but to a lack of calcium. This observation has implications regarding the pathogenesis, treatment, and prevention of rickets/osteomalacia in Nigeria and possibly other African and tropical countries.

Alkaline Phosphatase↗

Intraplatelet serotonin, beta-thromboglobulin, and histamine concentrations and thromboxane A2 synthesis in renal disease.

Intraplatelet serotonin (5-HT), beta-thromboglobulin (beta-TG), and histamine content as well as platelet total thromboxane A2 (TXA2) synthesizing capacity were measured in 53 patients with chronic renal disease: nephrotic syndrome (n = 18); end-stage renal failure (ESRF; n = 13); continuous ambulatory peritoneal dialysis (CAPD; n = 9); hemodialysis (HD; n = 13). These indices of platelet function were correlated with plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations. When compared with controls, intraplatelet 5-HT was significantly reduced in all patient groups studied and beta-TG was diminished in all patient groups except CAPD. Total platelet TXA2 synthesizing capacity was increased in ESRF and HD groups. Intraplatelet histamine content was not altered in any of the patient groups studied. There was a significant inverse correlation between intraplatelet 5-HT content on the one hand and plasma TC, LDL-C, and TG on the other. The depletion of intraplatelet 5-HT and beta-TG and the increase in total TXA2 synthesizing capacity are consistent with platelet activation in chronic renal disease. The correlation between these indices of platelet activation and TC, LDL-C, HDL-C, and TG suggests that changes in the concentrations of these lipids may contribute to the activation of platelets in these conditions.

Adolescent↗

The nucleoproteins of human parainfluenza virus type 1 and Sendai virus share amino acid sequences and antigenic and structural determinants.

The complete nucleotide sequence of the nucleoprotein (NP) gene of human parainfluenza virus type 1 (hPIV-1) was determined from a cDNA clone of mRNA. The mRNA is 1683 nucleotides long (excluding polyadenylic acid) and encodes a protein of 524 amino acids with a predicted Mr of 57,548. An amino acid identity of 83% was predicted between the NPs of the human pathogen hPIV-1 and the murine paramyxovirus, Sendai virus, compared to 72% similarity at the level of the nucleotide sequence. In contrast, the amino acid sequence identity between the NPs of hPIV-1 and hPIV-3 was 59%, suggesting a more distant evolutionary relationship. The NP amino acid sequences of hPIV-1 and Sendai virus were highly conserved in the amino-terminal half of the molecule, in which 395 of the first 420 amino acids were identical. Of 11 monoclonal antibodies (MAbs) targeted against the Sendai virus NP, five cross-reacted with the hPIV-1 NP. The MAbs that cross-reacted recognize epitopes within regions of high amino acid similarity between the NPs of the two viruses. Also, five of the eight MAbs raised against hPIV-1 NP cross-reacted with Sendai virus NP. Taken together, our observations suggest that the essential amino acid sequence determinants of the NP structures of hPIV-1 and Sendai virus are conserved despite changes in their nucleotide sequences during evolution. This implies that there was a selective pressure to maintain the important functional domains of the protein.

Amino Acid Sequence↗

Plasma histamine in patients with chronic renal failure and nephrotic syndrome.

Plasma histamine concentrations were measured using a commercially available monoclonal antibody radioimmunoassay in 38 patients with nephrotic syndrome, end stage renal failure, those receiving haemodialysis, and those receiving continuous ambulatory peritoneal dialysis to determine whether histamine may mediate damage to glomerular capillaries and arterial endothelium. Plasma histamine concentrations were significantly increased in all four patient groups when compared with those of controls and were the highest in two patients with pruritus. Raised plasma histamine concentrations in such patients are consistent with the hypothesis that histamine may contribute to the damage to glomerular capillaries and to arterial endothelium. These effects may be relevant to the pathogenesis of glomerular disease and atherosclerosis. Histamine may also contribute to the pathogenesis of pruritus in patients with chronic renal failure.

Adolescent↗

Histamine synthesis and catabolism in various tissues in diabetic rats.

In view of the observations that (1) plasma histamine concentrations are significantly higher in diabetic patients and diabetic rats than those in controls, and (2) tissue concentrations of histamine are elevated in rats with experimental diabetes, we have investigated histamine synthesis, as reflected by histidine decarboxylase (HDC) activity, and histamine catabolism, as reflected by histaminase activity, in various tissues of the diabetic rat. Rats with streptozotocin-induced diabetes mellitus (DM) showed an increase in histamine synthesis in various tissues; this was most marked in the aorta and to a lesser, but significant, extent in the kidneys, lungs, and heart, but not in the brain, stomach, or skin. Tissue content of histamine was significantly increased in all tissues except the stomach and skin. We conclude that tissue histamine synthesis is significantly increased in diabetic animals and that this increase is most marked in the aorta. The elevation in HDC activity in these tissues probably accounts for the increase in tissue and plasma concentrations of histamine in diabetic animals, since there is no change in histamine catabolism. This increase in histamine synthesis and release may contribute to the pathogenesis of endothelial damage in diabetic microangiopathy and macroangiopathy.

Animals↗

The hemagglutinin-neuraminidase glycoproteins of human parainfluenza virus type 1 and Sendai virus have high structure-function similarity with limited antigenic cross-reactivity.

Human parainfluenza virus type 1 (hPIV-1) is closely related to Sendai virus on the basis of cross-reactivity of antisera. We examined this association further by using monoclonal antibodies to the Sendai virus hemagglutinin-neuraminidase (HN) glycoprotein to determine the relationship between overall protein structure and the hemagglutination and neuraminidase functions. Of 10 monoclonal antibodies representing four nonoverlapping antigenic sites on the HN of Sendai virus, only 4 from two sites cross-reacted with hPIV-1, indicating a limited conservation of epitopes. One of these four inhibited the hemagglutinating activity of hPIV-1 comparably to Sendai virus, but none appreciably inhibited the neuraminidase activity of hPIV-1. The ability of some of these monoclonal antibodies to inhibit only hemagglutinating or neuraminidase activity of either virus provided evidence for two separate active sites on the HN molecule. To determine the overall structural relationship of the HNs of hPIV-1 and Sendai virus, we cloned and sequenced the HN gene of hPIV-1. The HN clone was made from genomic RNA and was identified by hybrid-arrested in vitro translation of mRNA. The predicted HN protein sequence of hPIV-1 was identical in length to that of Sendai virus and had a shared identity of 72%. There was a marked conservation of structural elements (cysteines, prolines, and glycines), which would predict a similar molecular conformation. However, there were 10 potential glycosylation sites on the HN of hPIV-1, compared with 5 on Sendai virus. Some of these sites may be responsible for the inability of the Sendai virus monoclonal antibodies to cross-react. The results of our study support a close structure-function relationship between hPIV-1 and Sendai virus but suggest limited antigenic cross-reactivity.

Amino Acid Sequence↗

Effects of phenytoin sodium on doubling time, deoxyuridine suppression, 3H-methotrexate uptake and 57Co-cyanocobalamin uptake in HL60 cells.

Phenytoin sodium (5-50 micrograms/ml) caused a dose-dependent prolongation of the doubling time of the human promyelocytic leukaemia cell line, HL60. This effect was unassociated with any alteration in cell viability. HL60 cells which were pre-incubated with 15 micrograms/ml phenytoin sodium for 1 or 48 h and then incubated with the same concentration of the drug plus either 3H-methotrexate (3H-MTX) or 57Co-cyanocobalamin for 90 min, showed an altered accumulation of both radioactive compounds when compared with control cells. Control cells were not pre-incubated with the drug and were subsequently studied in the absence of the drug. Pre-incubation with the drug for 1 h resulted in a 34% increase, and pre-incubation for 48 h in a 19% reduction in the accumulation of 3H-MTX. Pre-incubation for 1 or 48 h caused a 29% reduction in the accumulation of 57Co-cyanocobalamin. Cells cultured in the presence of 15 micrograms/ml phenytoin sodium for 48 h also gave a slightly increased deoxyuridine-suppressed value; this abnormality was partially corrected by the addition of 50 micrograms/ml folinic acid to the test system but was unaffected by the addition of 1 microgram/ml cyanocobalamin. The data indicate that the effects of phenytoin sodium on the proliferation of HL60 cells may have been slightly mediated via a reduced uptake of folate and possibly also of vitamin B12. They also suggest that one of the mechanisms underlying some of the undesirable effects of long-term therapy with phenytoin may be a drug-related impairment of both folate and vitamin B12 uptake by certain cells, including haemopoietic and neural cells.

Cell Division↗

Pregnancy-associated thrombocytopenia: definition, incidence and natural history.

We have sought to clarify the definition and importance of newly diagnosed thrombocytopenia in pregnant women by establishing an appropriate reference interval for the platelet count, and by observing the outcome in a cohort of thrombocytopenic pregnant women. The mean platelet count was lower in 2,155 healthy pregnant than non-pregnant women, and varied with race, but did not fall with increasing gestation, except in Black women. 101 of approximately 2,800 women became newly thrombocytopenic during pregnancy by conventional criteria (platelets less than 150 x 10(9)/l), without an apparent cause. Using the reference intervals established during the study, however, 24 of these women would not have been regarded as thrombocytopenic. No bleeding tendency was observed in the mothers or their infants. Maternal platelet counts became normal in the postnatal period. Thrombocytopenia occurring for the first time during pregnancy may be a different condition from auto-immune thrombocytopenia, and we suggest the term 'pregnancy-associated thrombocytopenia' (PAT). PAT does not appear to be epidemic; it does not threaten the fetus, but it cannot be distinguished from auto-immune thrombocytopenia in individual cases.

Blood Platelets↗

Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease.

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.

Adult↗

Normal ionized calcium, parathyroid hypersecretion, and elevated osteocalcin in a family with fluorosis.

Sera from five patients with skeletal fluorosis were investigated for total calcium, ionized calcium, phosphate, alkaline phosphatase, 25 hydroxyvitamin D (25 OHD), 1,25 dihydroxyvitamin D (1,25[OH]2D), parathyroid hormone, and osteocalcin concentrations. Total and ionized calcium concentrations were normal in four and subnormal in one, but PTH concentration was elevated in all five. The patient with a subnormal calcium concentration also had subnormal 25 OHD and 1,25(OH)2D concentrations and a supranormal PTH concentration. The remaining four had supranormal PTH concentrations despite normal total and ionized calcium concentration, and normal 25 OHD and 1,25(OH)2D levels. Osteocalcin concentration was markedly elevated in all patients, as was alkaline phosphatase activity. These observations show for the first time that patients with fluorosis have markedly elevated osteocalcin, a marker of osteoblastic activity, and that they may have significantly elevated PTH concentrations in the presence of normal total and ionized calcium concentrations.

1-Carboxyglutamic Acid↗

Effect of starvation and sampling time on plasma alkaline phosphatase activity and calcium homeostasis in the rat.

The effect of starvation and sampling time on plasma alkaline phosphatase activity, total plasma calcium concentration and whole blood ionized calcium concentration was determined in the rat. Starvation caused a significant fall in total and ionized calcium concentrations as well as in alkaline phosphatase activity. These changes were accompanied by a fall in whole blood pH and an increase in the anion gap and a decrease in urinary excretion of calcium. These indices were restored to normal following refeeding. There was no change in serum 25-OH vitamin D concentrations following starvation for 3 days. Alkaline phosphatase activity showed a pattern compatible with the presence of a circadian rhythm when sampling took place between 0800 and 1800 h. Total and ionized calcium concentrations did not show such a rhythm when animals were fed the present diet.

25-Hydroxyvitamin D 2↗

Pseudomonas pseudomallei pneumonia with septicemia--case report.

A case of Pseudomonas pseudomallei pneumonia with septicemia is described. The onset was insidious with paucity of systemic symptoms except fever. Diabetes mellitus and alcoholism were associated problems. Initially blood cultures were negative but subsequently P. pseudomallei was isolated. The outcome was fatal. Unless diagnosed early and treated appropriately, patients often succumb to septicemic shock.

Alcoholism↗

Evaluation of creatinine clearance estimation in an elderly male population.

Thirty-one medically stable, elderly males (age 75 +/- 8.3 yrs) participated in a prospective study evaluating the accuracy of 16 methods of estimating creatinine clearance. Serum creatinine values were determined on the mornings of days 1, 4, and 5 to assure stable renal function. On the morning of day 3, a 24-hour urine collection was initiated. A statistically significant correlation existed between the measured and estimated clearance values for all 16 formulas. The correlation (r less than 0.65) was lower than that in previously published studies, however. Five of the formulas (1A, 5A, 5B, 7A, 7B) demonstrated no statistical difference between mean measured and estimated values. In this population, formula 2B was the least biased and formula 9B the most accurate. For all 16 methods, the bias was minimal and the relative accuracy of the estimated methods was comparable. The results support using methods to estimate creatinine clearance only as a rough bedside prediction of renal function in elderly males.

Aged↗