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Biomedical subjects

D S Gill

Publications and source records attributed to D S Gill.

At least 73 records · Page 4Linked to original sources
PubMed1988

Observations on the intracellular accumulation of methotrexate and 5-methyltetrahydrofolate in uninduced, dimethylsulphoxide-induced and 1,25-dihydroxyvitamin D3-induced HL60 cells, and blood-monocyte-derived human macrophages.

The 90-min-uptake (37 degrees C) of 3H-methotrexate (3H-MTX) by uninduced HL60 cells was inhibited by 2,4-dinitrophenol, iodoacetate, ouabain, p-chloromercuriphenylsulphate and p-chloromercuribenzoate indicating its dependence on intracellular ATP, the Na+ and K+-activated ATPase of the cell membrane and sulphydryl groups on the cell surface. There was a marked reduction in the 90-min-uptake (37 degrees C) of 3H-MTX and 14C-methyltetrahydrofolate (14C-mTHF) when HL60 cells were induced to differentiate into neutrophil myelocytes and metamyelocytes by incubation with DMSO; a smaller reduction was seen when HL60 cells were induced to differentiate into mononuclear phagocytes by incubation with 1 alpha,25-dihydroxyvitamin D3 ([OH]2D3). Although it has been reported that the transport system mediating folate uptake has a higher Km value for mTHF and MTX in normal than in malignant cells, the Km values for these substrates were lower in blood-monocyte-derived macrophages than in uninduced HL60 cells or [OH]2D3-induced-macrophages. Values for the 90-min-uptake (37 degrees C) of 3H-MTX and 14C-mTHF in human blood-monocyte-derived macrophages were higher than the corresponding values in uninduced HL60 cells and [OH]2D3-induced macrophages.

Biological Transport, Active↗
PubMed1988

Increased histamine content in leukocytes and platelets of patients with peripheral vascular disease.

Since histamine has recently been shown to play an important role in the pathogenesis of atherosclerosis in experimental nonketotic diabetes, and since leukocytes and platelets contain most of the histamine in blood, we have determined the levels of histamine in these cells from patients with peripheral vascular disease (PVD), insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The leukocyte and platelet histamine concentration in PVDs was significantly greater than that in controls, IDDMs and NIDDMs. Histamine content of leukocytes and platelets from IDDMs and NIDDMs did not differ from that in control subjects. The higher histamine content of leukocytes and platelets in PVD may lead to a greater release of this amine at sites of vascular endothelial damage. Increased histamine release may increase endothelial permeability and contribute to further vascular injury as observed in experimental models of diabetes and hypercholesterolemia.

Adult↗
PubMed1988

Sodium fluoride stimulates osteocalcin in normal subjects.

To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.

Adult↗
PubMed1988

Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease.

Intraplatelet serotonin (5-HT) content was determined in 23 patients with type I (insulin-dependent) diabetes mellitus (IDDM), 23 patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM), 29 patients with peripheral vascular disease (PVD) and 34 age-matched normal subjects. Intraplatelet 5-HT content in normal subjects showed an age-related decline (r = -0.45; P less than 0.008), as has been previously demonstrated. The median 5-HT content in platelets of the young normal subjects was 4.36 (range: 3.62-6.79) nmol 10(-9) platelets, while that in the elderly normal subjects was 3.87 (range: 2.8-6.0) nmol 10(-9) platelets and that in young + elderly subjects was 4.05 (range: 2.8-6.8) nmol 10(-9) platelets. The median intraplatelet 5-HT content was significantly lower (P less than 0.002) in IDDM patients: 3.0 (range 1.3-6.3), NIDDM patients: 2.5 (range 1.7-5.8), PVD patients: 2.42 (range 0.94-4.98) nmol 10(-9) platelets than that in all young + elderly healthy subjects. The presence of hypertension in DM patients caused a small but significant (P less than 0.05) decrease in intraplatelet 5-HT content, whilst its presence had no effect in PVD patients. In a smaller study, it was established that NIDDM and PVD patients have significantly (P less than 0.002) greater plasma 5-HT concentrations than controls. Insulin-dependent diabetes mellitus patients had greater plasma 5-HT concentrations but this did not achieve statistical significance despite a 66% increment in its value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Mapping of antigenic domains of Sendai virus nucleocapsid protein expressed in Escherichia coli.

Several nonoverlapping epitopes were mapped on the primary sequence of the Sendai virus NP protein. After a complete cDNA clone of the Sendai virus NP gene was expressed in Escherichia coli, deletion constructs were used to generate a series of overlapping NP fragments deleted at their C termini. Immunoblot analyses with 11 monoclonal antibodies identified four antigenic sites. All of these sites resided in the C-terminal half of NP and were also the only sites detected with a polyclonal serum. These findings confirm and extend the evidence that the C terminus of the NP protein represents the domain exposed on the surface of the nucleocapsid. One of the monoclonal antibodies reacted with a site, comprising only 6 amino acids, lying with a hinge between an alpha-helix and a beta-strand in the predicted secondary structure of NP. Since this antibody is a potent inhibitor of in vitro viral RNA synthesis (K. L. Deshpande and A. Portner, Virology 139:32-42, 1984), the epitope may be critical to the flexibility of the NP molecule that makes the RNA template accessible during RNA synthesis.

Antibodies, Monoclonal↗
PubMed1988

Patient tolerance to intravenous potassium chloride with and without lidocaine.

Hypokalemia is a common electrolyte abnormality. Intravenous repletion therapy with potassium chloride (KCl) in concentrations greater than 80-100 mEq/L is not recommended due to patient intolerance. Since this guideline at times may be clinically impractical, this study was designed to examine use of peripheral vein infusions of high concentration KCl therapy. Tolerance to KCl 20 mEq/65 ml iv with and without lidocaine 50 mg was evaluated in 18 hypokalemic subjects in a randomized, placebo-controlled, double-blind study. Subjective and objective assessments of adverse effects were determined throughout the infusion period. Pain was assessed by both verbal descriptor and visual analog scales and correlated significantly following infusion of KCl with or without lidocaine. Multivariant analysis demonstrated differences in pain perception between solutions, with significantly less pain following KCl with lidocaine versus KCl infusions. Transient adverse effects occurred in both groups, but the incidence was not statistically different. Use of concentrated iv KCl infusions may benefit hypokalemic patients with hypervolemia and/or severe potassium deficits. Addition of lidocaine clearly improves patient tolerance to intravenous KCl replacement.

Adolescent↗
PubMed1988

Follicular fluid histamine concentrations in infertile women with pelvic adhesions.

Dense pelvic adhesions can arise as a result of pelvic infection, endometriosis, peritonitis, or pelvic surgery. The burnt-out disease is associated with evidence of a chronic inflammatory response. One of the chemical mediators of inflammation is histamine; and human and animal studies have indicated a role for histamine in the ovulatory process. In women with dense pelvic adhesions we have found significantly elevated concentrations of histamine in the follicular fluid when compared with the follicular fluid obtained from women without adhesions. This may lead to premature ovulation during a normal cycle, resulting in the release of an immature oocyte. It is possible that this may contribute to the lower fertility in women who have pelvic endometriosis but patent fallopian tubes, and in those patients where tubal patency has been restored following tubal surgery.

Female↗
PubMed1988

Secretion of atrial natriuretic peptide and digoxin-like immunoreactive substance during pregnancy.

We investigated the secretion of atrial natriuretic peptide (ANP) and digoxin-like immunoreactive substance (DLIS) during pregnancy, labor, and the puerperium, as measured in maternal and umbilical cord plasma. There were no significant changes in maternal concentrations of ANP during all three periods, and the concentrations were similar to those found in nonpregnant controls and in umbilical cord plasma. Maternal concentrations of DLIS increased significantly in the second half of pregnancy, peaked during labor, then decreased abruptly within 24 h of expulsion of the infant and placenta to values approaching the nonpregnant range. DLIS concentrations in umbilical cord plasma, however, were significantly higher than in maternal plasma during labor. The abrupt fall in DLIS in maternal plasma and the absence of a significant difference in DLIS concentrations between arterial and venous cord plasma suggest that, during pregnancy, the fetus, not the placenta, is the source of DLIS in maternal plasma.

Atrial Natriuretic Factor↗
PubMed1988

Increased histamine in plasma and tissues in diabetic rats.

In view of the previous observation that the histamine content of the aorta in rats with streptozotocin-induced diabetes mellitus is increased significantly over that in controls, we have investigated the effect of experimental diabetes on the histamine content of the plasma, the aorta, the kidney, the heart, the lung and the brain. Our data show that the histamine content of the plasma, the aorta, the heart, the kidney, the lung and the brain is significantly greater in diabetic rats than that found in controls. This increase in plasma and tissue histamine content may contribute to the increase in capillary and endothelial permeability known to occur in diabetes, and may have a role to play in the pathogenesis of diabetic micro- and macroangiopathy.

Animals↗
PubMed1987

Histamine uptake by human platelets.

We have investigated the uptake of histamine by human platelets. Incubations were carried out in platelet rich plasma prepared by using sodium citrate as an anticoagulant at histamine concentrations of 2.5 nmol X 1(-1), with and without stirring, in a platelet aggregometer cuvette at 37 degrees C. Stirring increased platelet histamine uptake significantly. Conventional platelet aggregating agents (e.g. adrenaline) significantly increased platelet histamine uptake at sub-aggregatory concentrations. Histamine uptake by platelets may be a useful index of platelet behaviour when studying the effect of subaggregatory concentrations of platelet agonists in conditions where platelet aggregation is altered, e.g. peripheral vascular disease and diabetes mellitus.

Adult↗
PubMed1987

Intergenic sequences of the vesicular stomatitis virus genome (New Jersey serotype): evidence for two transcription initiation sites within the L gene.

The intergenic sequences of vesicular stomatitis virus of the New Jersey serotype [VSV (NJ): Ogden strain] have been determined by dideoxy sequencing across the gene junctions of the viral RNA genome using deoxyoligonucleotide primers. The N-NS, NS-M, and M-G intergenic sequences of VSV (NJ) are identical to the consensus intergenic sequence for VSV of the Indiana serotype [VSV (IND)]: 3'-AUACU7GAUUGUCNNNAG-5' (genome sense; N denotes any nucleotide), where 3'-AUACU7-5' encodes the 3' terminus and the start of the polyadenylate tract of the preceding mRNA, 3'-UUGUCNNNAG-5' encodes the 5' terminus of the succeeding mRNA, and 3'-GA-5' is a nontranscribed dinucleotide. Notably, the NS-M junction of VSV (NJ) does not contain the anomalous dinucleotide 3'-CA-5' which is found at the NS-M junction of VSV (IND). In striking contrast to VSV (IND), the G-L intergenic sequence of VSV (NJ) contains a 19-base insertion between the nontranscribed dinucleotide and the consensus mRNA start sequence. During in vitro transcription, the L mRNA of VSV (NJ) may initiate at two distinct sites: the first start site (3'-CCUUAUCUUC-5') is that flanking the nontranscribed dinucleotide, and the second start site is a consensus mRNA start sequence located 20 bases downstream from the nontranscribed dinucleotide. However, the L mRNA isolated form VSV (NJ)-infected cells appears to initiate only at the consensus start sequence. The possible role of these start sites in L mRNA synthesis is discussed.

Amino Acid Sequence↗
PubMed1987

Impaired carboxylation of osteocalcin in warfarin-treated patients.

The total circulating osteocalcin and ratio of inactive (noncarboxylated; GLU) to active (carboxylated; GLA) form of circulating osteocalcin were measured in patients receiving long term warfarin treatment (n = 20), age-matched control patients not receiving warfarin treatment (n = 10), and normal subjects before and after the administration of 30 mg warfarin (n = 7). There was no significant difference in the total osteocalcin concentrations between the control patients and the patients receiving long term warfarin treatment, and it did not significantly change after warfarin ingestion in the normal subjects. The GLU/GLA ratio was significantly increased (P less than 0.002) in the patients receiving long term warfarin treatment compared with that in the control patients. There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects. This study demonstrates that osteocalcin carboxylation in humans is a vitamin K-dependent process and that circulating osteocalcin is structurally altered by warfarin administration. This finding has pathophysiological implications for the fetal warfarin embryopathy syndrome, bone disease associated with chronic liver diseases, and possibly for osteoporosis, in which vitamin K deficiency has been implicated.

1-Carboxyglutamic Acid↗
PubMed1987

Hyperparathyroidism and low serum osteocalcin despite vitamin D replacement in primary biliary cirrhosis.

Thirty-six patients with primary biliary cirrhosis (PBC) receiving calcium and calciferol supplements (100,000 IU monthly by im injection) were investigated for their calcium, vitamin D, PTH, and osteocalcin status. The corrected plasma calcium concentrations in PBC patients were significantly greater than those in normal subjects. While the mean serum 25-hydroxycholecalciferol and 1,25-dihydroxyvitamin D concentrations in these patients were similar to those in normal subjects, the mean serum PTH concentration was significantly greater, and it was supranormal in 11 patients. Three patients had elevated corrected calcium concentrations; 1 of them had a concomitant increase in ionized calcium and a supranormal PTH level, and another had a high normal PTH. Ionized calcium concentrations were normal in the rest. Serum osteocalcin concentrations were significantly lower in the patients compared with those in normal subjects. These results indicate that PTH concentrations are frequently elevated in PBC patients despite adequate vitamin D supplementation and normal or even supranormal plasma calcium concentrations. Nonsuppression of PTH concentrations and autonomy of PTH secretion suggest that vitamin D deficiency and secondary hyperparathyroidism in such patients probably occur much earlier in the natural history of this disease than is currently realized. Persistent nonsuppressible hypersecretion of PTH probably contributes to the bone disease of primary biliary cirrhosis. The low osteocalcin concentrations probably reflect diminished osteoblastic activity, which may also contribute to osteopenia in these patients.

Adult↗
PubMed1986

Complete nucleotide sequence of the matrix protein mRNA of vesicular stomatitis virus (New Jersey serotype).

The complete nucleotide sequence of the mRNA of the matrix (M) protein of vesicular stomatitis virus [New Jersey serotype, VSV(NJ)] was derived from a cDNA clone and mRNA. The mRNA is 758 nucleotides long (excluding polyadenylic acid) and encodes a protein of 229 amino acids. The predicted amino acid sequence was compared with that of the corresponding protein of Indiana serotype [VSV(IND)] and a fish rhabdovirus, spring viremia of carp virus (SVCV). An amino acid identity of 62% was found between the M proteins of VSV(NJ) and VSV(IND) while only 24% was present between VSV(NJ) and SVCV. A highly basic NH2-terminal domain followed by a proline-proline-X-tyrosine sequence was present in all the three M polypeptides. Except for the L gene sequence, the complete nucleotide sequence of the four genes of VSV(NJ) are now known. The comparison of the amino acid sequences between the Indiana and New Jersey serotypes demonstrates a high degree of homology between these genes except for the phosphoprotein gene, NS.

Amino Acid Sequence↗
PubMed1986

Identification of a domain within the phosphoprotein of vesicular stomatitis virus that is essential for transcription in vitro.

A full-length cDNA copy of the phosphoprotein (NS) mRNA of vesicular stomatitis virus (New Jersey serotype) was inserted into pGEM4 vector downstream of the promoter for bacteriophage SP6 RNA polymerase. Transcription of the cDNA in vitro resulted in the synthesis of NS mRNA, which was subsequently translated into NS protein in a cell-free rabbit reticulocyte system. The biological activity of the expressed NS protein was demonstrated by in vitro synthesis of mRNA by transcription-reconstitution with purified viral L protein and N-RNA template. Deletion mapping of the NS gene defined a specific domain between amino acid residues 213 and 247, which was essential for in vitro transcription. Removal of the COOH-terminal 21 amino acids, on the other hand, did not have a significant effect on transcription. This domain appears to be involved in efficient binding of NS protein to the N protein-RNA template.

Chromosome Deletion↗