Search PubMed⌕ Search

Biomedical subjects

S Grant

Publications and source records attributed to S Grant.

At least 253 records · Page 14Linked to original sources
PubMed1989

Normal values for human umbilical venous and amniotic fluid pressures and their alteration by fetal disease.

Umbilical venous and amniotic fluid pressures were measured in 68 human pregnancies at the time that cordocentesis was performed. Normal umbilical venous pressure was unrelated to gestational age and remained within a tight range (5.3 +/- 2.3 mm Hg, mean +/- SD). Fetuses with an elevated umbilical venous pressure had disorders consistent with either hepatomegaly or congestive heart failure. Umbilical venous pressure was significantly increased before treatment in two fetuses with immune hydrops; it rapidly declined with treatment. Neither gestational age nor umbilical venous pressure was significantly different in the groups that received and did not receive pancuronium. There was a strong relationship between amniotic fluid pressure and gestational age in normal pregnancy (r = 0.54, p less than 0.0001). Women with hydramnios had amniotic fluid pressures greater than control subjects (p = 0.0007). This investigation documents normal human amniotic fluid and fetal umbilical venous pressures. These measurements are altered by disease and may prove to be of diagnostic and therapeutic value in the future.

Amniotic Fluid↗
PubMed1989

Familial hypoparathyroidism due to an abnormal parathyroid hormone molecule.

The case of a 53-year-old man with familial hypoparathyroidism in the presence of circulating immunoreactive PTH is discussed. The patient responded to exogenous PTH by an increase in urinary cAMP excretion and by several post cyclase parameters including an increase in serum calcium and 1,25-dihydroxyvitamin D, an increase in urinary phosphate excretion and a decrease in urinary calcium. Immunoreactive PTH was detected in this patient's serum by three separate anti-PTH antisera. This immunoreactive PTH behaved aberrantly with these antisera. Nonparallelism to the standard curve was seen in two radioimmunoassays and the material was detected by an antiserum which preferentially binds bovine PTH. No circulating PTH binding activity was detectable. Family studies confirmed the genetic nature of the abnormality. HPLC studies revealed the presence of an abnormally hydrophobic fraction containing immunoreactive PTH. We believe these findings constitute strong evidence for the presence of an abnormal PTH molecule with reduced biological activity resulting in hypoparathyroidism.

Adult↗
PubMed1989

The Scottish first episode schizophrenia study. VII. Two-year follow-up. Scottish Schizophrenia Research Group.

Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms.

Clinical Trials as Topic↗
PubMed1989

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) on 3'-azido-3'-deoxythymidine (AZT)-mediated biochemical and cytotoxic effects on normal human myeloid progenitor cells.

Administration of 3'-azido-3'-deoxythymidine (AZT) to patients with acquired immunodeficiency syndrome (AIDS) causes significant anemia and neutropenia. The bone marrow cytotoxicity of AZT has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined the effect of human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on AZT-mediated biochemical perturbations and in vitro growth inhibition of normal bone marrow myeloid progenitor cells. Exposure of nonadherent, bone marrow mononuclear cells (BMMC) to 100 ng/ml of rGM-CSF for 6 h resulted in approximately twofold increments in the mean intracellular deoxycytidine triphosphate (dCTP) and thymidine triphosphate (dTTP) levels. Administration of 10 microM AZT alone to BMMC for 6 h markedly reduced dCTP and dTTP levels and generated significant levels of AZT triphosphate (AZT-TP). Coadministration of rGM-CSF (100 ng/ml) along with AZT (10 microM) partly restored dCTP and dTTP levels and significantly reduced AZT-TP levels. Furthermore, simultaneous exposure of BMMC for 4 h to 100 ng/ml of rGM-CSF reduced the mean DNA incorporation of [3H]AZT (10 microM) from 27.2 to 19.1 pmol/micrograms of DNA. Additionally, the inhibitory effects of AZT (10 microM) on granulocyte-macrophage colony-forming unit (CFU-GM) colony growth were significantly reduced in the presence of 100 ng/ml of rGM-CSF. These in vitro studies suggest that rGM-CSF partly corrects AZT-mediated biochemical perturbations as well as reduces the cytotoxicity of AZT in normal human bone marrow myeloid progenitor cells.

Cell Division↗
PubMed1988

Role of protein kinase C in phosphorylation of vinculin in adriamycin-resistant HL-60 leukemia cells.

In response to phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA), HL-60 cells differentiate to macrophage-like cells and exhibit the ability to phosphorylate vinculin in vitro. Adriamycin-resistant HL-60 (HL-60/ADR) cells similarly demonstrate this characteristic without prior treatment with TPA. Since protein kinase C (PK-C) is a cellular TPA receptor, we have examined the role of this enzyme in the inherent ability of HL-60/ADR cells to phosphorylate vinculin. DEAE-cellulose chromatography of cell extracts revealed that HL-60/ADR cells contained 2-fold more PK-C than did the parental cell line. All PK-C activity was found in the cytosol of wild type HL-60 cells, whereas 85% of PK-C activity was cytosolic and 15% was membrane-bound in HL-60/ADR cells. After a 2-day treatment with 10 nM TPA, PK-C activity was reduced 80-90% in both cell lines regardless of its intracellular distribution. Immunoblotting of cell extracts from HL-60/ADR cells or HL-60 cells following treatment with TPA revealed increased levels of a 52-kDa species of similar mass to M-kinase. Coincident with these changes after TPA treatment was a reduction in Ca2+ and phospholipid-independent phosphorylation of vinculin in vitro in extracts from HL-60/ADR cells, whereas HL-60 cells exhibited an elevation of this phosphoprotein. The phosphorylation of vinculin in TPA-treated HL-60 cells or untreated HL-60/ADR cells was blocked by antibodies to protein kinase C. These results suggest that it is not the absolute level of protein kinase C but rather the proteolytic activation of PK-C to a Ca2+ and phospholipid-independent form which is associated with the utilization of vinculin as an endogenous substrate.

Cell Differentiation↗
PubMed1988

Cholesterol in the plasma very low density lipoprotein fraction in patients with type III hyperlipoproteinemia: analysis of factors which modulate its concentration.

Anthropometric data, plasma lipoprotein lipid levels, and post-heparin lipoprotein lipase (PHLPL) activity were measured in nine patients with type III hyperlipoproteinemia (HLP) and two hypocholesterolemic subjects with the apo-E2/2 phenotype. Five type III HLP patients were treated with clofibrate. Log PHLPL activity was inversely correlated (r = -0.667, p less than 0.05) and age was positively correlated (r = 0.706, p less than 0.05) with cholesterol levels in the VLDL fraction of plasma from type III HLP patients. The correlation between log PHLPL and VLDL cholesterol levels remained significant when age was held constant in partial correlation analysis. Together age and log PHLPL activity accounted for 77% of individual variation in VLDL cholesterol levels in the type III patients. Clofibrate treatment raised PHLPL activity (+48%, p less than 0.05) and reduced the levels of VLDL cholesterol (-67%, P less than 0.05), VLDL triglycerides (-40%, P less than 0.02), and the ratio cholesterol/triglyceride in VLDL (-50%, P less than 0.05) in five type III HLP patients. Mean PHLPL activity was higher in the hypocholesterolemic subjects with the apo-E2/2 phenotype compared to the type III HLP patients. These results suggest that lipoprotein lipase activity and factors associated with age modulate the levels of abnormal and atherogenic remnant particles (beta-VLDL) in the VLDL plasma fraction of type III HLP patients.

Adult↗
PubMed1988

Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.

Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The cells produce both proinsulin I and II and efficiently process each into mature insulin, in a manner comparable to normal beta cells in isolated islets. Electron microscopy reveals typical beta-cell type secretory granules, in which insulin is stored. Insulin secretion is inducible up to 30-fold by glucose, although with a lower threshold for maximal stimulation than that for normal beta cells. beta TC lines can be repeatedly derived from primary beta-cell tumors that heritably arise in the transgenic mice. Thus, targeted expression of an oncogene with a cell-specific regulatory element can be used both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype.

Adenoma, Islet Cell↗
PubMed1988

Genetic regulation of the quinic acid utilization (QUT) gene cluster in Aspergillus nidulans.

A large number of quinic acid non-utilizing qut mutants of Aspergillus nidulans deficient in the induction of all three quinic acid specific enzymes have been analysed. One class the qutD mutants, are all recessive and are non-inducible at pH 6.5 due to inferred deficiency in a quinate ion permease. Two regulatory genes have been identified. The QUTA gene encodes an activator protein since most qutA mutants are recessive and non-inducible although a few fully dominant mutants have been found. The QUTR gene encodes a repressor protein since recessive mutations are constitutive for all three enzyme activities. Rare dominant non-inducible mutants which revert readily to yield a high proportion of constitutive strains are inferred to be qutR mutants defective in binding the inducer. The gene cluster has been mapped in the right arm of chromosome VIII in the order: centromere - greater than 50 map units - ornB - 12 map units - qutC (dehydratase)-0.8 map units-qutD (permease), qutB (dehydrogenase), qutE (dehydroquinase), qutA (activator)-4.4 map units - qutR (repressor)-20 map units - galG. This organization differs from that of the qa gene cluster in Neurospora crassa, particularly in the displacement of qutC and qutR.

Aspergillus nidulans↗
PubMed1988

Effect of marathon training on the plasma lactate response to submaximal exercise in middle-aged men.

Twenty-one previously sedentary male volunteers (aged 35-50 years) undertook a defined marathon training programme lasting 30 weeks. At weeks 0 (T1), 15 (T2) and 30 (T3) they underwent measurement of maximal oxygen uptake (VO2 max), submaximal VO2 and submaximal plasma lactate concentration during cycle ergometry. No exercise was taken for 24-48 hours prior to testing. During training aerobic power increased significantly (p less than 0.001) from an initial VO2 max at T1 of 33.9 +/- 6 (mean +/- sd) ml.kg-1min-1 to 39 +/- 5.6 ml.kg-1min-1 at T2 but the T3 value of 39.2 +/- 5.2 ml.kg-1min-1 was not significantly different from that at T2. Plasma lactate concentration of 4 mmol.l-1 (OBLAw) occurred at a significantly (P less than 0.05) higher workload (155 +/- 28 w) at T2 compared with T1 (132 +/- 30 w) but the T3 figure was 137 +/- 34 w. OBLA VO2 at T1 was 2.04 +/- 0.42 l.min-1, at T2 was 2.24 +/- 0.04 l.min-1 but at T3 was 2.03 +/- 0.30 l.min-1 (T1:T2 P less than 0.05, T1:T3 NS). OBLA % VO2 max at T1 was 75 +/- 12%, at T2 was 73 +/- 11% but at T3 was 62 +/- 10% (T1:T2 NS, T1:T3 P less than 0.01).

Adult↗
PubMed1988

Atrial natriuretic hormone has biological effects in man at physiological plasma concentrations.

Whether atrial natriuretic hormone (ANH) has biological effects at physiological plasma levels in man is not known. Accordingly, we investigated the effects of a 3-h low dose infusion of human ANF (0.75 pmol/kg.min; i.e. 0.0023 micrograms/kg.min) in six normal men, whose sodium intake was normal while sitting, in a single blind, random order, placebo-controlled study. The ANF infusions induced changes in plasma ANH concentrations entirely within the range for normal subjects. The small increases in plasma ANH values were associated with a significant rise in urinary excretion of sodium, magnesium, calcium, and cGMP. PRA and plasma aldosterone concentrations uniformly decreased to 50% and 64% of placebo values, respectively. Systolic and mean arterial pressures fell significantly from preinfusion values during the ANH infusions. These findings constitute strong evidence that ANH is a hormone of physiological significance in the regulation of body fluid volumes in normal man.

Adult↗
PubMed1988

Association of p93c-fes tyrosine protein kinase with granulocytic/monocytic differentiation and resistance to differentiating agents in HL-60 leukemia cells.

A 93-kDa tyrosine protein kinase (p93) identified previously as the gene product of the c-fes proto-oncogene, is highly expressed in HL-60 leukemia cells induced to differentiate to the granulocyte or monocyte phenotype. We have now studied the relationship of p93 to the differentiation process by using a dimethyl sulfoxide (DMSO)-resistant subline of HL-60 cells (HL-60/DMSO) or the parental cell line treated with peptide or protein substrates of p93. Treatment of HL-60/DMSO cells with DMSO induced neither differentiation nor the expression of p93; however, cotreatment with IFN-alpha and DMSO resulted in partial differentiation and the concomitant induction of p93 activity. Treatment of wild-type HL-60 cells by the coaddition of the p93 substrates poly(Glu,Tyr)1:1, poly(Glu,Tyr)4:1, poly(Glu,Ala,Tyr)6:3:1, angiotensin II or vasoactive intestinal peptide with DMSO or IFN-tau partially blocked differentiation and concurrently diminished the induction of p93 activity. The inhibitory concentrations of the p93 substrates were related to their Km values. These results indicate that there is an obligatory association between the expression of p93 and granulocyte/monocyte differentiation in this cell line.

Cell Differentiation↗
PubMed1988

Characterization of receptors for a T cell derived cytosolic BCGF-60kD.

A 60 kD cytosolic protein derived from human peripheral blood T cells has been shown to mediate proliferation in BCGF responsive long term B cell cultures. In this report, we show cBCGF-60kD can be radioiodinated with no significant loss of biologic activity and bound specifically to B cell surface membrane receptors. The time course of 125I-cBCGF-60kD demonstrated that binding reached saturation within 40 minutes, (T 1/2 of 15 minutes). Scatchard analyses of ligand-receptor binding identified a high affinity receptor (0.6(-3) x 10(3) receptors per cell) having a dissociation constant of 1-8 pM. Partial cross-competition experiments with a secreted, T cell derived BCGF-12kD identified a potential receptor heterogeneity on BCGF responsive B cell line.

B-Lymphocytes↗
PubMed1988

Effect of recombinant GM-CSF on the metabolism of cytosine arabinoside in normal and leukemic human bone marrow cells.

Human recombinant GM-CSF (rGM-CSF) is under investigation as a growth-protective agent for normal hematopoietic elements in phase I trials of myelosuppressive chemotherapy and in bone marrow transplantation. We determined the effect of rGM-CSF on the metabolism of high dose Ara-C in bone marrow mononuclear cells (BMMCs) from healthy volunteers and patients with ANLL. Cells were incubated with rGM-CSF alone, Ara-C alone, or a combination of the two drugs. Treatment with rGM-CSF alone yielded approximately a twofold increment in intracellular dCTP pools in normal BMMCs but not in leukemic blasts. Exposure to rGM-CSF in conjunction with Ara-C corrected Ara-C-mediated declines in dCTP levels and decreased cytosine arabinoside triphosphate (Ara-CTP) accumulation in normal BMMCs but not in their leukemic counterparts. Furthermore, when exposure to Ara-C was preceded by treatment with rGM-CSF for 18 hr, an even greater reduction in the Ara-CTP/dCTP pool ratio was observed in normal versus leukemic elements; however, this did not significantly change Ara-C DNA incorporation in the two cell types. The differential effect of rGM-CSF on the phosphorylation of Ara-C in normal BMMCs versus leukemic blasts has potential implications for the use of a regimen consisting of rGM-CSF and high dose Ara-C in the treatment of ANLL with chemotherapy or autologous bone marrow transplantation.

Bone Marrow↗
PubMed1987

Energy requirements of pregnancy in Scotland.

Measurements of energy intake, basal metabolic rate, body weight and composition, and physical activity were made on 88 women throughout pregnancy. Mean weight gain (from 10 wk to 40 wk gestation) was 11.7 kg, birthweight 3370 g, and placental weight 641 g. Maternal fat gain (from 10 wk) calculated by three methods was 2.1 kg. The total rise in basal metabolism for the whole of pregnancy was calculated to be 126 MJ (1 MJ = 239 kcal). The total increase in energy intake was estimated as 88 MJ. There was little evidence of any changes in either the energy cost of physical activity or the time spent in these activities. The total energy cost of laying down fetal and maternal tissues and the increased metabolism was 281 MJ, which was offset by a possible increase in energy intake of only 88 MJ. The most likely explanation for the deficit of 193 MJ is that many small reductions in energy expenditure occurred which were not detectable by the methods used.

Adipose Tissue↗
PubMed1987

Cardiovascular effects of training for a marathon run in unfit middle aged men.

The effects of a 30 week exercise programme on serum lipid values, blood pressure, and cardiac function were assessed in a group of sedentary men aged 35-50 training for their first marathon. Mean serum cholesterol concentration (n = 33) fell by 12% from 6.54 (SE 0.18) to 5.76 (0.15) mmol/l (mean fall 0.78 mmol/l; 95% confidence interval 0.52 to 1.04 mmol/l), serum triglyceride concentration (n = 33) by 22% from 1.56 (0.17) to 1.21 (0.09) mmol/l (mean fall 0.34 mmol/l; 95% confidence interval 0.12 to 0.56 mmol/l), and mean blood pressure (n = 27) by 10% from 102 (2) to 92 (2) mm Hg (mean fall 10 mm Hg; 95% confidence interval 7 to 13 mm Hg). These changes were not explained by changes in body composition. Peak exercise left ventricular end diastolic volume (n = 16) increased with training; as a result of this and an increased exercise left ventricular ejection fraction peak exercise cardiac output increased from 19.9 (1.2) to 23.1 (3.0) l/min (mean rise 3.2 l/min; 95% confidence interval 1.5 to 5.0 l/min). Maximum oxygen consumption increased from 33.9 (1.6) to 39.0 (1.3) ml/kg/min (mean rise 5.0 ml/kg/min; 95% confidence interval 1.8 to 8.2 ml/kg/min). This study showed favourable effects on coronary risk factors and cardiac function and supports the place of regular exercise in coronary prevention programmes.

Blood Pressure↗