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Biomedical subjects

A S Williams

Publications and source records attributed to A S Williams.

At least 19 recordsLinked to original sources
PubMed1995

The sequence of the stem and flanking sequences at the 3' end of histone mRNA are critical determinants for the binding of the stem-loop binding protein.

Complexes of different electrophoretic mobility containing the stem-loop binding protein, a 45 kDa protein, bound to the stem-loop at the 3' end of histone mRNA, are present in both nuclear and cytoplasmic extracts from mammalian cells. We have determined the effect of changes in the loop, in the stem and in the flanking sequences on the affinity of the SLBP for the 3' end of histone mRNA. The sequence of the stem is particularly critical for SLBP binding. Specific sequences both 5' and 3' of the stem-loop are also required for high-affinity binding. Expanding the four base loop by one or two uridines reduced but did not abolish SLBP binding. RNA footprinting experiments show that the flanking sequences on both sides of the stem-loop are critical for efficient binding, but that cleavages in the loop do not abolish binding. Thus all three regions of the RNA sequence contribute to SLBP binding, suggesting that the 26 nt at the 3' end of histone mRNA forms a defined tertiary structure recognized by the SLBP.

Animals↗
PubMed1995

Methods for assessing splenic macrophage depletion by liposome encapsulated clodronate.

Small unilamellar vesicles containing clodronate (SUVc) injected intravenously will deplete splenic macrophages and the degree of histological depletion can be assessed by determining the clearance and uptake of monoclonal antibody coated erythrocytes. Splenic Fc dependent clearance, assessed in decomplemented animals, provides a more sensitive index of the effects of large multilamellar liposome encapsulated clodronate (MLVc) and SUVc than does the clearance of complement coated erythrocytes on macrophage depletion in the spleen. MLVc were more efficient than SUVc in inducing a reduction in the number of red pulp macrophages within the spleen. Receptor specific red cell uptake in the spleen could be used as an alternative to histology when assessing splenic macrophage depletion. Encapsulation of clodronate is crucial to its depleting effect since the free drug in saline does not change splenic macrophage number or function.

Animals↗
PubMed1995

The effect of liposomally conjugated methotrexate upon mediator release from human peripheral blood monocytes.

The ability of methotrexate (MTX) and a liposomal preparation containing a lipophilic conjugate of methotrexate (MTX-LIPO) to modulate pro-inflammatory mediator release from lipopolysaccharide-stimulated human peripheral blood monocytes was investigated. At non-toxic concentrations MTX-LIPO (10 micrograms MTX per 250 micrograms lipid) was a potent inhibitor of both IL-1 beta and TNF release resulting in 70.07 +/- 2.3% and 59.19 +/- 2.36% (mean +/- S.E.M.) inhibition, respectively, whereas empty liposomes (E-LIPO; 250 micrograms lipid/well) of the same lipid composition and free MTX (up to 100 micrograms/well) had no effect on either mediator.

Cell Survival↗
PubMed1995

Identification and gene expression of anaerobically induced enolase in Echinochloa phyllopogon and Echinochloa crus-pavonis.

Enolase (2-phospho-D-glycerate hydrolase, EC 4.2.1.11) has been identified as an anaerobic stress protein in Echinochloa oryzoides based on the homology of its internal amino acid sequence with those of enolases from other organisms, by immunological reactivity, and induction of catalytic activity during anaerobic stress. Enolase activity was induced 5-fold in anoxically treated seedlings of three flood-tolerant species (E. oryzoides, Echinochloa phyllopogon, and rice [Oryza sativa L.]) but not in the flood-intolerant species (Echinochloa crus-pavonis). A 540-bp fragment of the enolase gene was amplified by polymerase chain reaction from cDNAs of E. phyllopogon and maize (Zea mays L.) and used to estimate the number of enolase genes and to study the expression of enolase transcripts in E. phyllopogon, E. crus-pavonis, and maize. Southern blot analysis indicated that only one enolase gene is present in either E. phyllopogon or E. crus-pavonis. Three patterns of enolase gene expression were observed in the three species studied. In E. phyllopogon, enolase induction at both the mRNA and enzyme activity levels was sustained at all times with a further induction after 48 h of anoxia. In contrast, enolase was induced in hypoxically treated maize root tips only at the mRNA level. In E. crus-pavonis, enolase mRNA and enzyme activity were induced during hypoxia, but activity was only transiently elevated. These results suggest that enolase expression in maize and E. crus-pavonis during anoxia are similarly regulated at the transcriptional level but differ in posttranslational regulation, whereas enolase is fully induced in E. phyllopogon during anaerobiosis.

Amino Acid Sequence↗
PubMed1995

The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat.

Clodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlation between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced > or = 90% inhibition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptor-mediated uptake of these erythrocytes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronate in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.

Animals↗
PubMed1995

Evaluation of antenatal and postnatal support to overcome postnatal depression: a randomized, controlled trial.

This randomized, controlled trial tested the hypothesis that women identified as more vulnerable to developing postnatal depression who attended two specific antenatal groups and one postnatal group have a reduced frequency of postnatal depression from 37 to 15 percent at 6 weeks, 12 weeks, and 6 months postpartum. A modified antenatal screening questionnaire was completed, and women identified as more vulnerable to postnatal depression were stratified by parity and randomly allocated to receive extra support groups or to a control group. The Edinburgh Postnatal Depression Scale (EPDS) was used to detect postnatal depression. Attendance at the support groups was low, 31 percent overall. At six weeks, in the intervention group, 8 (13%) of 64 women scored high (> 12) on the EPDS, compared with 11 (17%) controls. Similarly, at 12 weeks 7 (11%) of 63 versus 10 (15%) of 65 women scored higher than 12, and at 6 months, 9 (15%) of 60 versus 6 (10%) of 64 women scored higher than 12, indicating that the intervention did not reduce postnatal depression. It is possible that the method of applying the intervention, using groups separate from the standard antenatal classes, may have affected attendance. More research is required into ways of reaching and supporting women who may become depressed.

Adult↗
PubMed1994

Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate.

The effect of a novel liposomal preparation containing a phospholipid conjugate of methotrexate (MTX-LIPO) upon macrophage mediator release was investigated in normal and arthritic rats ex vivo. Peritoneal macrophages isolated from MTX-LIPO-treated arthritic rats and stimulated with lipopolysaccharide produced significantly less tumor necrosis factor (TNF) and prostaglandin (PGE2) than did macrophages isolated from saline-treated controls. In the same experimental system, free methotrexate only inhibited prostaglandin release, but it was more potent than MTX-LIPO in this respect. Additional studies are presently underway to investigate the effect of MTX-LIPO and MTX treatment upon the lipopolysaccharide-induced rise in plasma levels of various proinflammatory mediators in vivo. Haematopoietic toxicity was demonstrated in blood isolated from rats treated with free MTX, and this was as characterized by a significant reduction in reticulocyte count compared with MTX-LIPO and saline-treated rats.

Animals↗
PubMed1992

Histologic study of healing after ab interno laser sclerostomy.

We examined the histologic characteristics of healing after ab interno laser sclerostomy in a human eye. A KTP 532 green laser coupled to a 300-microns quartz fiberoptic probe was used to create an ab interno sclerostomy in a terminally ill patient with pigmentary glaucoma. The intraocular pressure increased five days postoperatively and did not respond to medical treatment. The patient died six weeks postoperatively of metastatic lung cancer. Histopathologic analysis showed a patent 150-microns scleral lumen from the anterior chamber to the episclera, surrounded by a 300-microns zone of acellular thermal damage. There was no healing of the lumen. The subconjunctival end of the lumen was capped with a thick episcleral scar, which caused the failure of the operation.

Cicatrix↗
PubMed1989

Acute comitant esotropia in children with brain tumors.

If acute onset of esotropia is comitant, its cause is generally believed to be benign. Although this is, by and large, true, it is now clear that acute comitant esotropia may be associated infrequently with central nervous system illness. We describe six children who presented with acute onset of comitant esotropia, and who were found to have tumors of the brain stem or cerebellum. Four of the patients underwent strabismus surgery after appropriate neurologic and neurosurgical treatment was completed. In none of these patients was ocular motor fusion reestablished.

Acute Disease↗
PubMed1988

The cdc30 mutation in Saccharomyces cerevisiae affects phosphoglucose isomerase, the cell cycle and sporulation.

Spontaneous revertants of the cdc30 mutation in Saccharomyces cerevisiae simultaneously regained the ability to grow and divide at 36.5 degrees C on glucose-containing media along with a more thermostable phosphoglucose isomerase (PGI). An independently isolated allele of cdc30 gave a similar phenotype to that previously described including temperature-sensitivity of PGI. Isoelectric focussing allowed the separation of two isoenzymes of PGI. These results all support the idea that two genes--PGI1 and CDC30--are responsible for PGI activity in yeast. Diploid strains homozygous for the cdc30 mutation sporulated poorly in potassium acetate irrespective of whether the cells had previously been cultured at a temperature that was permissive or restrictive for cell cycle progression. This was not surprising because a strain defective in PGI would not be expected to be able to complete the gluconeogenic events of sporulation.

Alleles↗
PubMed1987

The cdc30 mutation in Saccharomyces cerevisiae results in a temperature-sensitive isoenzyme of phosphoglucose isomerase.

The cdc30 mutation in the yeast Saccharomyces cerevisiae causes cell cycle arrest late in nuclear division when cells are shifted from the permissive temperature of 25 degrees C to the restrictive temperature of 36.5 degrees C. Cell cycle arrest at 36.5 degrees C is dependent upon the carbon source used: a shift-up in glucose containing media results in cell cycle blockade, whereas a shift-up in ethanol, fructose, glycerol, glycerol plus ethanol, or mannose does not. Metabolite analyses showed accumulation of glucose 6-phosphate in a cdc30-bearing strain after a temperature shift-up in glucose-containing medium. Thermal denaturation studies and kinetic measurements indicate the existence of two isoenzymes of phosphoglucose isomerase (EC 5.3.1.9); one of which is apparently altered in the temperature-sensitive cell cycle mutant. We propose that the gene products of both the CDC30 and PG11 genes are required for cell cycle progression in glucose media and that the PGI1 gene product has a regulatory function over the CDC30 gene product.

Cell Division↗
PubMed1986

Fat--again.

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Body Image↗
PubMed1986

A genetic and biochemical analysis of the role of gluconeogenesis in sporulation of Saccharomyces cerevisiae.

The requirement for gluconeogenesis and the pentose phosphate pathway in sporulation of Saccharomyces cerevisiae was investigated using homozygous diploids with mutations in selected portions of the respective metabolic pathways. Mutations affecting the genes FBA1 (fructose-1,6-bisphosphate aldolase), GPM1 (phosphoglycerate mutase) and ZWF1 (glucose-6-phosphate dehydrogenase) were used. Homozygous diploids bearing either fba1-11 or gpm1 mutations were asporogenous, indicating an absolute requirement for gluconeogenesis in sporulation. A strain homozygous for the zwf1 mutation sporulated, but at a reduced level compared to the wild-type. Homozygous spd1-1 mutations restored the ability to sporulate in fba1-11 homozygous diploids; this is believed to occur as a consequence of reduced NH+4 levels in spd1-1-bearing strains, the reduced intracellular NH+4 content serving to promote gluconeogenesis via the residual low levels of enzyme activity present in such mutants.

Fructose-Bisphosphate Aldolase↗
PubMed1981

Myofibrillar protein degradation in the chicken. 3-Methylhistidine release in vivo and in vitro in normal and genetically muscular-dystrophic chickens.

Myofibrillar protein degradation was measured in 4-week-old normal (line 412) and genetically muscular-dystrophic (line 413) New Hampshire chickens by monitoring the rates of 3-methylhistidine excretion in vivo and in vitro. A method of perfusing breast and wing muscles was developed and the rate of 3-methylhistidine release in vitro was measured between 30 and 90min of perfusion. During this perfusion period, 3-methylhistidine release from the muscle preparation was linear, indicating that changes in 3-methylhistidine concentration of the perfusate were the result of myofibrillar protein degradation. Furthermore, the viability of the perfused muscle was maintained during this interval. After 60min of perfusion, ATP, ADP and creatine phosphate concentrations in pectoral muscle were similar to muscle freeze-clamped in vivo. Rates of glucose uptake and lactate production were constant during the perfusion. In dystrophic-muscle preparations, the rate of 3-methylhistidine release in vitro (nmol/h per g of dried muscle) was elevated 2-fold when compared with that in normal muscle. From these data the fractional degradation rates of myofibrillar protein in normal and dystrophic pectoral muscle were calculated to be 12 and 24% respectively. Daily 3-methylhistidine excretion (nmol/day per g body wt.) in vivo was elevated 1.35-fold in dystrophic chickens. Additional studies revealed that the anti-dystrophic drugs diphenylhydantoin and methylsergide, which improve righting ability of dystrophic chickens, did not alter 3-methylhistidine release in vitro. This result implies that changes in myofibrillar protein turnover are not the primary lesion in avian muscular dystrophy. From tissue amino acid analysis, the myofibrillar 3-methylhistidine content per g dry weight of muscle was similar in normal and dystrophic pectoral muscle. More than 96% of the 3-methylhistidine present in pectoral muscle was associated with the myofibrillar fraction. Dystrophic myofibrillar protein contained significantly less 3-methylhistidine (nmol/g of myofibrillar protein) than protein from normal muscle. This observation supports the hypothesis that there may be a block in the biochemical maturation and development of dystrophic muscle after hatching. Free 3-methylhistidine (nmol/g wet wt.) was elevated in dystrophic muscle, whereas blood 3-methylhistidine concentrations were similar in both lines. In summary, the increased myofibrillar protein catabolism demonstrated in dystrophic pectoral muscle correlates with the increased lysosomal cathepsin activity in this tissue as reported by others.

Animals↗