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K Williams

Publications and source records attributed to K Williams.

At least 379 records · Page 21Linked to original sources
PubMed1990

Characterization of polyamines having agonist, antagonist, and inverse agonist effects at the polyamine recognition site of the NMDA receptor.

The endogenous polyamines spermine and spermidine increase the binding of [3H]MK-801 to NMDA receptors. This effect is antagonized by diethylenetriamine (DET). We report here that spermine increases the rates of both association and dissociation of binding of [3H]MK-801, suggesting that it increases the accessibility of the binding site for MK-801 within the ion channel of the receptor complex. 1,10-Diaminodecane (DA10) inhibited the binding of [3H]MK-801. This effect was due to a decrease in the rate of association with no change in the rate of dissociation of [3H]MK-801. The effect of DA10 was not mediated by an action of DA10 at the binding sites for glutamate, glycine, Mg2+, or Zn2+, and was attenuated by DET. This suggests that DA10 acts at the polyamine recognition site. In hippocampal neurons the NMDA-elicited current was decreased by DA10, an effect opposite to that of spermine. The effects of spermine and DA10 were selectively blocked by DET. It is concluded that DA10 acts as a negative allosteric modulator or inverse agonist at the polyamine recognition site of the NMDA receptor.

Animals↗
PubMed1990

Bioassay-directed fractionation of 1-nitropyrene metabolites: generation of mutagrams by coupling reverse-phase HPLC with microsuspension mutagenicity assays.

We have performed bioassay-directed fractionation of a model complex mixture (rabbit lung S9-generated metabolites of 14C-radiolabeled 1-nitropyrene) by assaying reverse-phase HPLC fractions using two microsuspension mutagenicity assays. A forward-mutation assay measuring mutation at the gpt locus (8-azaguanine resistance) in Salmonella typhimurium TM677 was performed in a total volume of 100 microliters, and a reverse-mutation assay measuring mutation at the hisD3052 allele in S. typhimurium TA98 was performed in a total volume of 200 microliters. HPLC fractions were collected every 30 s for 45 min, resulting in 90 fractions per run. The HPLC chromatogram (absorbance at 280 nm) and the 14C profile were compared to the mutagenicity profiles (mutagrams) and to the mutagenic potencies of pure metabolites studied separately. The results indicate that a fine dissection of the mutagenic fractions can be obtained by coupling HPLC to microsuspension mutagenicity assays. Differences observed between the mutagrams generated by the two bacterial strains were most likely due to metabolic (nitroreductase) differences between the two strains. This method should be generally applicable to the bioassay-directed chemical analysis of complex mixtures.

Animals↗
PubMed1990

Temperament characteristics and clinical outcomes in young children with diabetes mellitus.

Thirty-four children with diabetes and their mothers were studied to investigate the relationship between individual differences, as measured via the temperament construct, and disease-related indices. Analysis of variance revealed that child characteristics such as age, sex, duration of disease, higher activity level, and shorter attention-span were related to behavioral compliance. Multivariate discriminant analyses revealed that combinations of certain child and maternal characteristics were highly efficient in distinguishing between children in adequate vs poor glycemic control and behavioral compliance. The optimum model for classification of regimen adherence used a combination of child characteristics. The optimum model for glycemic control used both child and parent temperament characteristics.

Blood Glucose↗
PubMed1990

Description of a medium for isolating Anaerobiospirillum spp., a possible cause of zoonotic disease, from diarrheal feces and blood of humans and use of the medium in a survey of human, canine, and feline feces.

Anaerobiospirillum spp., motile, spiral anaerobic bacteria, have been implicated as a cause of diarrhea and bacteremia in humans. Anaerobiospirillumlike organisms and Anaerobiospirillum succiniciproducens were reported from 17 cases of diarrhea. Sixteen of the patients did not have any underlying disorders and recovered from the infection; the other one, who had a heart defect, did not. The formulation of a selective medium for Anaerobiospirillum spp. has enabled a survey of human, cat, and dog feces as possible sources for these anaerobic bacteria. Anaerobiospirillum spp. were not isolated from 527 "normal" human feces but were found in both cat and dog feces. We also describe biochemical tests and API ZYM results of A. succiniciproducens and anaerobiospirillumlike organisms.

Adult↗
PubMed1990

A randomised comparison of ceftazidime and piperacillin, both in combination with flucloxacillin for treatment of febrile episodes in neutropenic children. Finnish Three-Centre Study.

111 febrile episodes in 98 neutropenic children were randomly treated with either ceftazidime (CAZ) 150 mg/kg/day or with piperacillin (PIP) 200 mg/kg/day, both combined with flucloxacillin (FLUC) 50 mg/kg/day. A total of 37/47 (79%) eligible episodes in the CAZ group and 41/53 (77%) in the PIP group were cured without needing to stop the initial therapy. The success without modification of the treatment in the verified septicaemias in the CAZ group was 8/18 (44%) and in the PIP group 5/18 (28%). Of the bacteriologically documented infections, 13/24 (54%) in the CAZ group and 11/24 (46%) in the PIP group were cured without modification of the therapy. Similarly, 17/31 (55%) of all the isolated bacteria in the CAZ group and 14/33 (42%) in the PIP group were eradicated with the initial therapy. Overall there were 13 deaths of which 4 in the CAZ group and 5 in the PIP group occurred during the infection. An increasing granulocyte count exceeding 0.25 x 10(9)/l at the end of the therapy was a good prognostic sign for the outcome of the infection. This study indicates that CAZ is as effective as PIP in the treatment of infections in neutropenic children.

Adolescent↗
PubMed1990

Electron dense artefactual deposits in tissue sections: the role of ethanol, uranyl acetate and phosphate buffer.

The occurrence of electron dense deposits in sections of aldehyde-fixed tissue prepared for transmission electron microscopy has been attributed to a number of conflicting factors. In an attempt to clarify this, the precipitating effect of different combinations of phosphate or cacodylate buffer, glutaraldehyde, ethanol and uranyl acetate was investigated in test tubes. As a preliminary investigation the combination of phosphate buffer, ethanol and uranyl acetate was investigated in heart and kidney tissue fixed in glutaraldehyde with or without postosmication. The essential factors in the formation of electron dense deposits in these tissues appear to be phosphate buffer, ethanol, and uranyl acetate, although glutaraldehyde may contribute in some way. The nature and intensity of the deposits seem to vary with the sequence of combination of these factors. Osmium did not appear to be an essential factor in the reaction since deposits were observed in both osmicated and unosmicated tissue. To avoid such deposits, a postosmication distilled water wash for 20 to 30 min followed by en bloc staining with aqueous uranyl acetate is advised if phosphate buffer is used as a fixative vehicle or buffer wash after the primary fixative.

Animals↗
PubMed1990

Phenytoin hypersensitivity.

Phenytoin hypersensitivity is a potentially fatal reaction to the chemical diphenylhydantoin. It is important to inform patients of possible complications and early sentinel signs of adverse drug reactions.

Acute Kidney Injury↗
PubMed1989

A new class of orally active glycol renin inhibitors containing phenyllactic acid at P3.

We prepared a new series of renin inhibitors based on dipeptide glycols, replacing the P4-P3 subsites with an O-(N-morpholinocarbonyl)-3-L-phenyllactic acid residue. This modification proved bioisosteric with Boc-L-phenylalanine, giving rise to highly potent human renin inhibitors (1-5 nM), e.g., SC-46944 (IC50 = 5 nM). Moreover, this change produced compounds that are orally efficacious in reducing plasma renin activity in salt-depleted marmosets.

Animals↗
PubMed1989

South Birmingham Coronary Prevention Project: a district approach to the prevention of heart disease.

The South Birmingham Coronary Prevention Project is described, in which health checks by practice nurses in GPs' surgeries are combined with direct patient access to a secondary referral system. Where appropriate, health check attenders are offered the choice of either (a) counselling by the practice nurse, (b) direct referral to their GP, or (c) direct referral to secondary intervention, including specialist dietary advice for patients with high (greater than 6.5 mmol/l) serum cholesterol, stress management training for mild hypertension (diastolic blood pressure greater than 90 less than 105 mmHg), and smoking cessation groups. Significant reductions in blood pressure (p less than 0.005) and serum cholesterol levels (p less than 0.001) have been achieved. Further, substantial numbers of smokers have ceased since attending smoking cessation groups. This multidisciplinary approach to the identification and modification of risk factors for coronary heart disease may provide a powerful adjunct to wider ranging population interventions.

Coronary Disease↗
PubMed1989

Precise excision of telomere-bearing transposons during Oxytricha fallax macronuclear development.

In ciliated protozoa, development of the macronucleus from a copy of the germ line micronucleus involves elimination of a large number of sequences by DNA splicing akin to precise excision of transposons. The known examples of such internal eliminated sequences (IESs) are not repetitive. The telomere-bearing elements (TBE1s) of Oxytricha fallax are a family of transposons. We show that two particular TBE1s are also IESs. TBE1-1 and TBE1-2 disrupt a micronuclear region that codes for macronuclear DNA. A variety of tests indicates that each TBE1 and one copy of the flanking target repeat is absent from most, if not all, molecules of the macronuclear DNA, as if the TBE1s were precisely excised during macronuclear development. Three alternative explanations for the absence of TBE1-1 and TBE1-2 from the macronuclear DNA were tested. First, because two other highly homologous versions of that DNA are also found in the macronucleus, recombination between versions during or after macronuclear development could have bypassed the elements. Recombination in the regions flanking the elements was not detected. Second, micronuclear DNA blots show no evidence of a micronuclear counterpart of the macronuclear region that lacks TBE1-1. Third, TBE1-2 was demonstrated in two sexually independent cell lines. This shows that it pre-existed in the germ line, as opposed to having transposed into the micronuclear DNA subsequent to the generation of the macronucleus of the vegetative line that is usually studied. We conclude that TBE1-1 and TBE1-2, and possibly many of the other approximately 1900 micronucleus-limited TBE1s are excised as IESs during macronuclear development. These transposons appear to enjoy the luxury of relaxed constraints on family expansion, because they are removed from the genome before it is expressed. We discuss the possibility that all IESs are transposon-derived, that all are excised by transposition machinery, and that linear excision products are early intermediates in transposition.

Animals↗
PubMed1989

A case of interstitial deletion of 10q25.2----q26.1.

A de novo interstitial deletion of chromosome 10, del(10)(pter----q25.2::q26.1----qter), was detected in a newborn female with facial anomalies, failure to thrive, and subsequent developmental delay. This case is compared with 10 previous reports of monosomy 10q within the q25----qter region.

Chromosome Deletion↗
PubMed1989

Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site.

A heat-stable factor of low molecular weight that increases the binding of [3H]MK-801 to rat brain membranes in the presence of maximally effective concentrations of L-glutamate and glycine was purified from bovine brain by reverse phase and ion-exchange high pressure liquid chromatography. The stimulatory activity was due to the presence of spermidine in the active fractions. Polyamines including spermine and spermidine are found in high concentrations in mammalian tissue. These compounds increase the affinity of N-methyl-D-aspartate (NMDA) receptors for [3H]MK-801 when assays are carried out in the presence of 100 microM L-glutamate and 100 microM glycine. At concentrations of 1 to 300 microM, a number of di- and triamines, including NH2(CH2)3NH2, NH2(CH2)3NH(CH2)2NH2, and NH2(CH2)3NH(CH2)3NH2, have partial or full agonist-like activity similar to that of spermidine. Other polyamines, including putrescine, cadaverine, NH2(CH2)2NH(CH2)2NH2, and CH3NH(CH2)3NHCH3, at concentrations of 1 to 100 microM, inhibited the binding of [3H]MK-801 in the presence of spermine, L-glutamate, and glycine but not in the presence of only L-glutamate and glycine. It is concluded that these compounds are selective antagonists of the effects of spermine at the NMDA receptor. These results suggest that there may be a polyamine recognition site on the NMDA receptor complex.

Animals↗
PubMed1988

Survey of the long term incidence of osteonecrosis of the hip and adverse medical events in rheumatoid arthritis after high dose intravenous methylprednisolone.

A prospective, randomised, double blind, matched cohort survey using retrospective data was undertaken to assess the long term incidence of osteonecrosis of the hip and adverse medical effects occurring after intravenous pulsed methylprednisolone used in the treatment of rheumatoid arthritis over the period 1977-86. One hundred and forty three patients were matched for age, sex, duration and severity of the disease, erosive and serological status. Information was obtained by direct questioning and from hip x rays, the latter being read independently by two 'blind' radiologists. Two definite cases of osteonecrosis were identified, one in both the treated and control groups and three possible cases (radiological disagreement) in the treated group. Adverse medical events, when analysed by systems, were similar in both groups. This study did not provide evidence of increased osteonecrosis of the hip or adverse medical events in the treated group compared with the control group.

Adult↗