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S Thomas

Publications and source records attributed to S Thomas.

At least 505 records · Page 28Linked to original sources
PubMed1993

A computer program for the algebraic determination of control coefficients in Metabolic Control Analysis.

A computer program (MetaCon) is described for the evaluation of flux control, concentration control and branch-point distribution control coefficients of a metabolic pathway. Requiring only the reaction scheme as input, the program produces algebraic expressions for the control coefficients in terms of elasticity coefficients, metabolite concentrations and pathway fluxes. Any of these variables can be substituted by numeric or simple algebraic expressions; the expressions will then be automatically rearranged in terms of the remaining unknown variables. When all variables have been substituted, numeric values will be obtained for the control coefficients. The program is a computerized implementation of the matrix method for the determination of control coefficients. The features of MetaCon are compared with those of other programs available to workers in Metabolic Control Analysis. Potential benefits of, and methods of using, MetaCon are discussed. The mathematical background and validity of the matrix method rules are discussed, and the algorithm used by MetaCon is described. The matrix method is shown to be a specific case of a previously described general formalism for calculating control coefficients.

Metabolism↗
PubMed1993

PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis.

Scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep and goats. An abnormal protease-resistant form of the host-encoded prion protein (PrP) accumulates in the brains of affected animals. As Sip, a gene controlling the incubation period of experimental and natural scrapie, is linked to the single-copy sheep PrP gene, we sought PrP coding sequence polymorphisms in flocks from the Romanov and Ile-de-France breeds endemically affected with natural scrapie. DNA samples from 153 sheep, including 29 natural scrapie cases, were screened by using polymerase chain reactions and denaturing gradient gel electrophoresis. Four predicted amino acid substitutions were found in the center of the PrP coding region: 112 Met-->Thr, 136 Ala-->Val, 154 Arg-->His, and 171 Gln-->Arg. These substitutions appeared mutually exclusive, defining five coding alleles. The 136Val allele, substituting a highly conserved Ala residue, in a homozygous or heterozygous state correlated with susceptibility to natural scrapie (chi 2 = 64.33, P < 0.001). This correlation indicates that the 136 Val allele may modulate development of the disease, implying a pivotal role for PrP molecules in natural scrapie, as has been observed for experimental scrapie and human prion diseases.

Amino Acid Sequence↗
PubMed1993

A unique c-myc-targeted triplex-forming oligonucleotide inhibits the growth of ovarian and cervical carcinomas in vitro.

A 27-base pair triplex forming oligonucleotide (G27-oligonucleotide) targeted to the "puf" regulatory protein-binding domain of the human c-myc oncogene has been conjugated with the DNA-binding molecule acridine (G27-conjugate) in order to obtain a drug with high binding affinity as well as high sequence specificity. Both the triplex-forming oligonucleotide and its acridine conjugate are shown to form triple-stranded DNA at the site of the target sequence by DNase 1 footprinting. When the cervical carcinoma cell line HeLa was exposed to 4 microM concentrations of the G27-oligonucleotide the viable cell count fell to 89, 56, and 49% of control at 25, 50, and 72 hr. After exposure to 1 microM G27-conjugate the viable cell count fell to 87, 50, and 33% of control. Nonspecific reductions in cell number were found for the control oligonucleotides to 79 and 82% of control. When SKOV-3 cells were exposed to the same concentrations of oligonucleotides, viable cell count in relation to control fell to 43, 50, and 67% with the G27-oligonucleotide and 57, 52, and 53% with the G27-conjugate at 24, 48, and 72 hr. The control oligonucleotides again caused a small nonspecific drop in the viable cell number.

Acridines↗
PubMed1993

Pharmacokinetics of ampicillin and sulbactam in pregnancy.

OBJECTIVE: This study evaluated the effects pregnancy had on pharmacokinetic parameters of ampicillin and sulbactam. STUDY DESIGN: Twenty-two women undergoing cesarean section for obstetric indications were randomly assigned to receive a single intraoperative dose of either 1 gm of ampicillin intravenously or 1 gm of ampicillin plus 0.5 gm of sulbactam intravenously after umbilical cord clamping. Blood was drawn from an indwelling intravenous catheter at 15, 30, 45, 60, 120, 240, and 360 minutes after infusion of the antibiotic for determination of serum ampicillin and/or sulbactam levels. Pharmacokinetic parameters were determined by fitting data (serum concentrations versus time) to a single-compartment model that provided elimination rate constants, beta-intercept (calculated concentration at 0 minutes), area under the time-versus-concentration curve, half-life of the drug, total body clearance, and volume of distribution. After the examination 6 weeks post partum, each subject was given an additional dose of the drug she had received during cesarean section, and a second pharmacokinetic study was performed and compared with the previous results. RESULTS: Pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased the total body clearance in comparison with these parameters in the nonpregnant state for ampicillin. Sulbactam kinetics were similarly affected, although these changes failed to attain statistical significance. CONCLUSION: Because pregnancy is associated with more rapid elimination of beta-lactam drugs, physicians treating infections in pregnant or newly parturient women should consider using shorter intervals between antibiotic doses when a range of dosage intervals is under consideration.

Ampicillin↗
PubMed1993

Effect of addition of antimicrobial drugs to human collagen membrane.

Antimicrobial agents included in graft material for use in guided tissue regeneration of periodontally diseased tissue may be of value in combating infection, but may also alter the properties of the membrane material and exert an effect upon the host immune response. Metronidazole, niridazole and tinidazole were added to a cross-linked freeze-dried human type I collagen membrane in various doses and the following measured: (i) daily drug release into an aqueous solution, (ii) minimum inhibitory concentration (MIC) of the drugs against periodontopathogens, (iii) the effect of the drugs on mechanical properties of the membrane, and (iv) degradation by bacterial collagenase. In addition, the effects of the drugs on in-vitro cellular response was assessed by measuring blastogenesis of mononuclear cells obtained from patients suffering from periodontal disease and age/sex matched controls following incubation with the periodontopathogen Actinobacillus actinomycetemcomitans (AaY4). It was found that the collagen membranes released high levels of the drugs, at concentrations well above the MIC values. The mechanical properties of the membranes were not affected by the addition of the drugs, although resistance to the collagenases were. The cellular immune response was likewise suppressed in both patient and controls at drug doses comparable with the in-vitro drug release patterns. It is concluded that incorporation of antimicrobial drugs in a collagen barrier membrane may be of value when used in guided tissue regeneration.

Aggregatibacter actinomycetemcomitans↗
PubMed1993

A quantitative evaluation of the aetiological role of betel quid in oral carcinogenesis.

Computer aided search and review of bibliographies of published papers and monographs revealed 17 case control studies of oral cancer and betel quid chewing from 1933 to 1990. Studies were assessed and site specific risk of oral cancer associated with chewing betel quid with and without tobacco in the quid among smokers and non-smokers was computed. Tobacco smoking and chewing betel quid containing tobacco arose as important risk factors for oral cancer, betel quid without tobacco significantly increased risk in only one study. Heterogeneity in estimates of risk among studies was reduced by restricting analysis to those with more exact definition of exposure and site of the cancer. Variation in risk among studies reflects bias in selection and inadequate definition of exposure and tumour site and an inability to control effectively for confounding. Further studies, addressing these issues are advised, to clarify the role of betel quid without tobacco as a carcinogen, alone and in combination with tobacco smoke.

Areca↗
PubMed1993

Suppression of anchorage-independent growth after gene transfection.

A novel procedure for isolating anchorage-dependent cells has been developed. It involves negative selection of cells growing in suspension followed by clonal replica screening for anchorage-dependent growth. Cells which have regained anchorage-dependent growth have been isolated from a library of the Chinese hamster ovary cell line, CHO-K1, transfected with pSV2neo and human genomic DNA. One anchorage-dependent clone, 1042AC, has been studied in detail. Anchorage-dependent growth of 1042AC is stable when cultured as adherent monolayers, but revertants appear rapidly when cultured in suspension. Suppression is unlikely to be due to loss or mutation of hamster genes conferring anchorage-independent growth as hybrids between 1042AC and CHO-K1 have the suppressed phenotype of 1042AC. Furthermore, a population of cells obtained from the hybrid by selecting for revertants to anchorage-independent growth showed selective loss of the transgenome derived from 1042AC. The growth suppression was not due to transfection of the human Krev-1 gene, which has previously been shown to restore anchorage-dependent growth, nor was there any evidence of alteration in the endogenous hamster Krev-1 gene. However, evidence for a human gene being responsible for the suppressed phenotype has not been obtained yet.

Animals↗
PubMed1993

Prognostic markers in cancers of the head and neck region.

Increasing research initiatives in head and neck cancer over the past 5 years have resulted in the identification of several 'new' biologic parameters which may be of prognostic importance. This review discusses the limitations of traditional parameters and outlines several promising developments in the study of proliferation markers, molecular biology, immunobiology and flow cytometry as they relate to head and neck cancer.

Biomarkers, Tumor↗
PubMed1993

Hydatidemesis: a bizarre presentation of abdominal hydatidosis.

A 31 year old male presented with high grade fever and abdominal pain of 20 days duration. At the age of 9 he had been operated on for a solitary retroperitoneal hydatid cyst and had been asymptomatic until the age of 21 when he sustained a blunt injury to the abdomen. An exploratory laparotomy for splenic rupture revealed multiple intra-abdominal hydatid cysts, which were removed. The patient remained well until the present episode. An ultrasound examination revealed multiple intra-abdominal hydatid cysts. Seven days after admission, the patient developed hydatidemesis (hydatid cysts and membranes in the vomitus) and hydatidenteria (passage of hydatid membranes in the stools), and his pain and fever subsided. A Gastrografin study and a computerized tomography (CT) scan revealed hydatid cysts communicating with the stomach and duodenum. In view of his disseminated recurrent abdominal hydatidosis, he was treated with high dose, long-term albendazole along with regular follow up. This is the first documented case of disseminated abdominal hydatidosis presenting with a cystogastric fistula and hydatidemesis.

Adult↗
PubMed1993

Communication and level of AIDS knowledge among homeless African-American mothers and their children.

One hundred and thirty residents and their children from eight transitional living shelters in the midwest participated in a study designed to assess their level of knowledge about HIV/AIDS, concerns about susceptibility to the virus, patterns of general communication, and level of comfort in discussing sexual and HIV/AIDS related matters within the family unit. Overall, parents and children demonstrated significant misinformation about HIV/AIDS and did not perceive themselves as being at risk for contracting the virus. Parents who possessed more formal education were more knowledgeable about HIV/AIDS, sexuality, and reported greater levels of parent-child communication. Parents who possessed higher levels of self-esteem indicated that they discussed sexual topics with their children more than parents with lower levels of self-esteem and that when sexual matters were discussed the mother was the agent of communication.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Large solitary luteinized follicle cyst of pregnancy and puerperium.

A case of large solitary luteinized follicle cyst of pregnancy and the puerperium, arising in a 22 year old primipara, three months post partum, is presented with clinical and pathological details. This is a rare type of follicle cyst and has to be differentiated from a cystic neoplasm.

Adult↗
PubMed1993

Support that prolongs life. Ventilation in motor neurone disease.

In several countries, including the US, active management of MND is practised using ventilatory support to manage respiratory insufficiency. Respiratory failure should be anticipated, so that rational and informed choices for survival can be made by patient, family and healthcare team. The choice to withdraw from life support should be available. Some productivity and quality of life can be maintained in the most disabled patients.

Cost of Illness↗
PubMed1993

Zinc deficiency and childhood-onset anorexia nervosa.

BACKGROUND: We studied the association of zinc deficiency and childhood-onset anorexia nervosa because the relationship is controversial. METHOD: Anorexia nervosa was diagnosed on the basis of determined food avoidance, weight loss, preoccupation with body weight and energy intake, distorted body image, fear of fatness, self-induced vomiting, excessive exercising, and laxative abuse. Twenty-six such children, admitted to a specialized eating disorders program within a children's hospital, formed the basis of the study. Zinc status was determined by measuring fasting plasma zinc levels and 24-hour urinary zinc excretion using atomic absorption spectrophotometry. Nutritional status was determined by using weight-for-height ratios. A trial of zinc supplementation was attempted using a 12-week double-blind crossover design, with 6 weeks of placebo and 6 weeks of treatment with 50 mg daily of oral zinc sulphate. RESULTS: Zinc deficiency was found to be common, with a significant correlation between fasting plasma zinc levels and malnutrition (Pearson r = .586, p = .004). Introduction of a normal diet rapidly returned zinc levels and weight-for-height ratios to the normal range. Children entering the study with relatively normal zinc levels gained weight no faster than those with low plasma zinc levels. Of seven trials of zinc supplementation, only three were completed, as inadequate oral intake threatened the health of the remaining four. CONCLUSION: Low zinc levels are common in childhood-onset anorexia nervosa, appear to be secondary to self-starvation, and are rapidly reversible without zinc supplementation.

Administration, Oral↗
PubMed1993

Motor neurone disease: a progressive disease requiring a coordinated approach.

1. Such a variety of causes are implicated for MND that it is unlikely a single cause exists. 2. There is no actual treatment for the disease other than alleviating symptoms and improving function by the use of aids and appliances. 3. Care of people with MND is highly specialised, requiring multidisciplinary cooperation to ensure effective patient care. 4. Nurses owe it to their patients to acquaint themselves with the disease and support networks available.

Female↗