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Biomedical subjects

R H Williams

Publications and source records attributed to R H Williams.

At least 55 records · Page 3Linked to original sources

Nucleotide sequence of cucumber mosaic virus RNA. 1. Presence of a sequence complementary to part of the viral satellite RNA and homologies with other viral RNAs.

The nucleotide sequence of the 3389 residues of RNA 1 (Mr 1.15 X 10(6) of the Q strain of cucumber mosaic virus (CMV) was determined, completing the primary structure of the CMV genome (8617 nucleotides). CMV RNA 1 was sequenced by the dideoxy-chain-termination method using M13 clones carrying RNA 1 sequences as well as synthetic oligonucleotide primers on RNA 1 as a template. At the 5' end of the RNA there are 97 noncoding residues between the cap structure and the first AUG (98-100), which is the start of a single long open-reading frame. This reading frame encodes a translation product of 991 amino acid residues (Mr 110791) and stops 319 nucleotide residues from the 3' end of RNA 1. In addition to the conserved 3' region present in all CMV RNAs (307 residues in RNA 1), RNAs 1 and 2 have highly homologous 5' leader sequences, a 12-nucleotide segment of which is also conserved in the corresponding RNAs of brome mosaic virus (BMV). CMV satellite RNA can form stable base pairs with a region of CMV RNAs 1 and 2 including this 12-nucleotide sequence, implying a regulatory function. This conserved sequence is part of a hairpin structure in RNAs 1 and 2 of CMV and BMV and in CMV satellite RNA. The entire translation products of RNA 1 of CMV and BMV could be aligned with significant homology. Less prominent homologies were found with alfalfa mosaic virus RNA 1 translation product and with tobacco mosaic virus Mr-126000 protein.

Amino Acid Sequence↗

Tryptamine-induced vasoconstrictor responses in rat caudal arteries are mediated predominantly via 5-hydroxytryptamine receptors.

It has been suggested that tryptamine can stimulate specific receptors distinct from those for 5-hydroxytryptamine (5-HT). We have examined this possibility in the rat isolated caudal artery, paying particular attention to the involvement of monoamine oxidase metabolism and alpha-adrenoceptors, two factors that can complicate the quantification of antagonist potencies at 5-HT receptors. 5-HT and tryptamine were agonists over the concentration-ranges 3.0 X 10(-8) - 3.0 X 10(-5) mol l-1 and 1.0 X 10(-6) - 3.0 X 10(-4) mol l-1 respectively. The sensitivity of the caudal artery to tryptamine was increased by about 44 fold in the presence of iproniazid (5.0 X 10(-5) mol l-1) and about 17 fold in the presence of pargyline (1.0 X 10(-5) mol l-1), while responses to 5-HT and methoxamine were unaffected. In the absence of iproniazid, ketanserin and methysergide were potent antagonists of responses to 5-HT with pA2 values of 9.08 and 9.11 and slopes of the Schild regressions of 1.15 and 1.00 respectively. However, against tryptamine the antagonists were weaker such that pA2 values were similar to those against 5-HT but the slopes of the Schild regressions were 0.47 and 0.47. In the presence of iproniazid (or pargyline), the 5-HT antagonists were more potent against tryptamine such that the pA2 values and the slopes of the Schild regressions were not significantly different from those against 5-HT. Phentolamine was a weak antagonist of responses to both 5-HT and tryptamine in the presence of iproniazid. 5 The findings in this study suggest that the contractile action of tryptamine in rat caudal artery is mediated predominantly by the same receptor as 5-HT and that the differential inactivation of tryptamine by monoamine oxidase enzymes largely accounts for the different susceptibilities of 5-HT and tryptamine to the antagonists examined.

Animals↗

Nucleotide sequence of cucumber-mosaic-virus RNA 2 reveals a translation product significantly homologous to corresponding proteins of other viruses.

The nucleotide sequence of the 3035 residues of RNA 2 (Mr 1.03 X 10(6) ) of the Q strain of cucumber mosaic virus (CMV) was determined by sequencing M13 clones of the RNA 2 cDNA and by dideoxy sequencing using primers prepared either from M13 clones or by chemical synthesis. A single long open reading frame starts at the second AUG from the 5' end of RNA 2 and encodes 839 amino acids (Mr 94333). This frame has flanking regions of 92 nucleotides at the 5' terminus and 423 nucleotides at the 3' terminus. Computer analysis of the nucleotide sequence showed that CMV RNA 2 has a significant homology with RNA 2 of brome mosaic virus (BMV) and alfalfa mosaic virus (AMV) and also with a region for tobacco mosaic virus (TMV) RNA encoding the read-through part of the 183-kDa protein. About 400 amino acids in the central region of the CMV RNA 2 translation product have a striking homology with the corresponding proteins encoded by BMV and AMV and with the read-through part of the TMV 183-kDa protein. Hydrophobicity plots of CMV and BMV RNA translation products also had apparent similarities. It is concluded that CMV is related to BMV, AMV and TMV in order of increasing evolutionary divergence.

Amino Acid Sequence↗

Reye's syndrome associated with long-term aspirin therapy.

Reye's syndrome has been infrequently described in children receiving long-term salicylate therapy. We report the clinical and laboratory findings of two children in whom Reye's syndrome developed while taking salicylates for systemic inflammatory disorders. Monitoring of hepatocellular function should be considered in children who are receiving long-term salicylate therapy.

Adolescent↗

Abrogation of calcium exclusion by erythrocytes under hypotonic stress.

Normal human erythrocytes in isotonic suspension maintain a high gradient of calcium ion concentration across the membrane, with the cytosol [Ca2+] several orders of magnitude below plasma concentration. Despite the high degree of exclusion maintained against the entry of Ca2+, the osmotic resistance of red cells in hypotonic saline is significantly augmented by the presence in the medium of Ca2+ in concentrations greater than 0.07 mmol/l. Resistive particle spectroscopy showed this to occur without alteration of the mean critical haemolytic volume; furthermore, in the presence of Ca2+ there was a reduction in cell volume at prolytic osmolalities when compared with cells in calcium-free sodium chloride solutions. This is shown to be due to augmentation of the prolytic loss of K+ in the presence of Ca2+ through calcium-sensitive channels, and indicates that the pathway for passive K+ efflux uncovered in the prolytic state is indistinguishable from that of normal passive K+ diffusion. It is also demonstrated that the prolytic red cell membrane is permeable to Ca2+ and admits the divalent cation to the inner aspect of the plasma membrane. These changes are comparable to those of cells prior to haemolysis in vivo, as in the irreversibly sickled cell, and are therefore not specific to the latter condition.

Calcium↗

Effect of volume expansion and plasma chloride on function of the loop segment.

To determine the effect of acute volume expansion and changes in plasma chloride on fluid and chloride uptake in superficial loop segments of rats, this segment was microperfused in vivo at 22 nl/min with a fluid containing Na 145, Cl and 36Cl 130, and HCO3 15 meq/liter during hydropenia and after acute volume expansion with 0.15 M NaCl, 0.15 M NaHCO3, or an isotonic bicarbonate Ringer (Cl 106 meq/liter) solution. Fractional fluid, chloride, and 36Cl reabsorption and early distal chloride concentration did not change during maintained hydropenia (time control) or during volume expansion with NaCl (plasma chloride 120 meq/liter) or bicarbonate Ringer solution (plasma chloride 104 meq/liter). Absolute and fractional reabsorption of chloride and 36Cl increased, without change in fluid reabsorption, and early distal chloride diminished after infusion of NaHCO3 (plasma chloride 90 meq/liter). It is concluded that acute volume expansion, per se, has no effect on either net fluid or net chloride absorption in the superficial loop segment at the load studied. Hypochloremia is associated with increased net reabsorption of chloride and an increased unidirectional efflux of chloride from the loop segment during acute volume expansion, most likely due to a gradient effect on the thick ascending limb of the loop of Henle.

Animals↗

A comparison of the in vitro and in vivo activities of conjugates of anti-mouse lymphocyte globulin and abrin.

Anti-mouse lymphocyte globulin and normal immunoglobulin have been conjugated to abrin using two procedures, one involving linkage through an amide bond and a piperazine ring and the other the introduction of two amide bonds flanking a disulphide bridge. The four conjugates produced were equipotent as inhibitors of protein synthesis in rabbit reticulocyte lysates. Each antibody-containing conjugate was a more effective inhibitor of protein synthesis in cultured cells than the equivalent normal immunoglobulin-containing conjugate. In addition the conjugates with disulphide linkage groups were ten times more potent than their counterparts. The disulphide conjugates were also twice as toxic to mice in an acute toxicity test but when used to suppress their immune responses to sheep red blood cells it was the non-disulphide-linked conjugates that were superior. In all instances antibody-containing conjugates were more powerful immunosuppressants than those containing normal IgG. The results are taken to indicate a relative lack of stability of the disulphide conjugates in the tissues.

Abrin↗

Reduced Coxsackie antibody titres in type 1 (insulin-dependent) diabetic patients presenting during an outbreak of Coxsackie B3 and B4 infection.

The potential role of antecedent viral infection in the pathogenesis of Type 1 (insulin-dependent) diabetes was investigated by measuring antibody titres to several viruses in serum obtained at the time of diagnosis of diabetes. An outbreak of Coxsackie B4 infection followed by a wave of Coxsackie B3 and B5 infections occurred in Seattle during the time viral serology was obtained in the diabetic patients. Antibody titres to Cocksackie B5 and Influenza A and B viruses were comparable in diabetics and matched control subjects, but antibody titres to Cocksackie B3 and B4 were lower in the diabetics and a low antibody titre to Coxsackie B3/B4 was associated with a significantly increased relative risk of diabetes.

Antibodies, Viral↗

Lipid composition of the superficial stratum corneum cells of pig epidermis.

Stratum corneum was removed from the surface of pig skin using a wet brushing technique. The material so obtained was fractionated into cell clumps, discrete cells and fine material by differential filtration through nylon gauzes. Ceramide, cholesterol and free fatty acid accounted for about 95% of the lipid present in each fraction: phospholipid and glycolipid were not detected. Material removed by successive brushings showed no detectable differences in lipid composition.

Animals↗

Determinants of gastric inhibitory polypeptide and insulin secretion.

The plasma concentrations of gastric inhibitory polypeptide (IR-GIP), insulin, and glucose were measured in 5 dogs after administration of various constituents of food. IR-GIP responses produced by galactose and fructose were minimal compared to those of glucose. Corn starch caused a significant early increase in insulin and glucose concentrations, although the rise in IR-GIP was delayed. The responses after starch were delayed, possibly due to the necessity for hydrolytic cleavage. Neither individual fatty acids (palmitic, oleic, and linoleic), monoolein, nor glycerol produced increases in IR-GIP comparable to those observed with lesser amounts (on a molar basis) of corn oil alone. None of four amino acids tested orally (arginine, leucine, alanine, and phenylalanine) caused increases in IR-GIP concentrations, but they increased insulin concentrations. Although glucose-induced IR-GIP responses were not inhibited by the amino acids (1 g/kg) tested, increasing concentrations (up to 1 g/kg) of either alanine or arginine caused progressive inhibition of corn-oil-stimulated IR-GIP responses, in spite of the expected amino-acid-induced rises in insulin concentrations. These results confirm the specificity of the IR-GIP secretory response for glucose and triglyceride, and suggest that certain food constituents (such as amino acids) may modify the GIP secretory response to a meal.

Administration, Oral↗

Hemodynamic and single nephron function during the maintenance phase of ischemic acute renal failure in the dog.

We studied ischemic acute renal failure in 28 dogs by micropuncture, microsphere, morphologic, and whole kidney hemodynamic techniques, 18 to 24 hours after the renal artery was clamped (clamping time, 60 to 90 min). Before the artery was clamped, renal blood flow (RBF) averaged 3.49 +/- (SEM) 0.23 ml/min x g and was not significantly different (3.70 +/- 0.34 ml/min x g) 18 hours after the ischemic episode. RBF autoregulatory capability was, however, significantly reduced. Fractional outer cortical blood flow decreased slightly from 41 +/- 2 to 36 +/- 3% (P less than 0.05) postischemia. Single nephron glomerular filtration rate (SNGFR) was highly variable from one animal to the next and ranged from 0 to 87 nl/min (mean, 36 +/- [SEM] 7 nl/min) in a manner similar to whole kidney inulin clearance, which ranged from 0 to 0.56 ml/min x g (mean, 0.30 +/- 0.05 ml+min x g). The correlation coefficient between SNGFR and inulin clearance was highly significant, indicating an association between SNGFR and whole kidney GFR. Proximal tubule pressure (PTP) averaged 20 +/- (SEM) 1 mm Hg. In 6 dogs, the glomerular filtration coefficient (Kf) was determined by measurements of stop-flow pressure, colloid osmotic pressure, SNGFR, PTP, and single nephron filtration fraction, Kf was below that obtained for control animals. Scanning electron microscopy (SEM) studies indicated that the endothelial fenestrations were reduced in number and size. These studies suggest that one major characteristic of ischemic nephropathy in the dog is a derangement in the filtration process. The maintenance of RBF in the postischemic phase may occur by utilization of the autoregulatory reserve of the renal vasculature.

Acute Kidney Injury↗