PubMed Health⌕ Search

Biomedical subjects

S Whiting

Publications and source records attributed to S Whiting.

14 recordsLinked to original sources
PubMed1996

Occurrence of rheumatoid arthritis is not increased in the first degree relatives of a population based inception cohort of inflammatory polyarthritis.

OBJECTIVE: To determine the risk of rheumatoid arthritis (RA) in first degree relatives of a true population based sample of probands with inflammatory polyarthritis. METHODS: In a case-control study, a two stage screening procedure was used to ascertain the prevalence of RA in 518 first degree relatives of 207 Norfolk Arthritis Register cases registered in 1990 and 414 first degree relatives of 180 local controls. An initial joint symptom and medical history questionnaire was followed by a physical examination, and serological and radiological evaluation of those with symptoms. RESULTS: The prevalence of RA in the first degree relatives of all the Norfolk Arthritis Register cases was 7.7/1000, compared with 4.8/1000 in the first degree relatives of the controls, with a risk ratio of 1.6 (95% confidence interval 0.3 to 8.7). This very modest increase was also seen when the analysis was restricted to the first degree relatives of Norfolk Arthritis Register cases who satisfied the American Rheumatism Association criteria for RA: prevalence rate 7.2/1000. CONCLUSION: There was no evidence of an important increased familial risk of RA in this community based sample. These data are compatible with others from immunogenetic studies showing only weak HLA associations with community ascertained RA.

Adolescent↗
PubMed1993

Portal endotoxin and cytokine responses during abdominal aortic surgery.

Interleukin-6 (IL-6) is a major marker of tissue injury. Surgery induces a systemic IL-6 response related to the magnitude of the operation. An exaggerated IL-6 response is associated with the development of major complications after aortic aneurysm repair. Endotoxemia is a potent stimulus for cytokine release and may occur during aortic surgery. This study attempted to examine whether the observed IL-6 response during abdominal aortic surgery is related to the development of portal endotoxemia. Serial samples of inferior mesenteric and systemic venous blood were obtained before, during, and after aortic cross-clamping in eight patients undergoing elective aortic aneurysm surgery. Portal endotoxemia was detected in only five of the eight patients during the surgery, and there was no correlation with the IL-6 response. Both portal and systemic IL-6 levels rose during the course of surgery, but, by the time of abdominal wound closure, the mean portal IL-6 levels were eight times higher than the systemic IL-6 levels. These results suggest that the portal circulation draining the colon is a major source of the previously observed systemic IL-6 response to aortic surgery. The IL-6 response is not clearly related to portal endotoxemia but may reflect occult cellular injury in the colon occurring during surgery.

Aged↗
PubMed1992

Retroviral envelope protein fusions to secreted and membrane markers.

We have analyzed a series of Moloney murine leukemia (M-MuLV) envelope (env) protein fusions to the marker proteins invertase and placental alkaline phosphatase (PLAP), expressed in Psi2 retrovirus packaging cells. The yeast invertase protein, fused at its third amino acid residue to the amino-terminal signal sequence and 17 residues of the mature M-MuLV env protein, retained its enzymatic activity and was secreted from mammalian cells. However, env protein fusions to the C-terminal portion of invertase were inactive. In contrast, some, but not all, env protein fusions at the C-terminal region of PLAP were enzymatically active: PLAP fusions containing long C-terminal portions of env localized to the rough endoplasmic reticulum (RER) and possessed low enzyme activity levels, while fusion constructs containing relatively short portions of the M-MuLV env gene localized to the Golgi and had higher activity levels. Those proteins that localized to the Golgi also were processed, in part, to forms of 67 to 68 kDa, the size of the mature PLAP protein. Since PLAP ordinarily is transferred to a phosphatidyl-inositol glycan tail (PIG-tail) in the Golgi and then transported to the plasma membrane, it appears that Golgi-localized PLAP-env fusions are processed imperfectly. PLAP itself, when expressed in Psi2 cells, accumulated at the plasma membrane and, unlike the PIG-tailed Thy-1 protein, was not incorporated into virus particles. Thus, the reported incorporation of the Thy-1 protein into M-MuLV virions does not appear to be a consequence of its glycoprotein tail.

Alkaline Phosphatase↗
PubMed1990

Clobazam as an add-on drug in the treatment of refractory epilepsy of childhood.

We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur.

Adolescent↗
PubMed1990

Transport and assembly of gag proteins into Moloney murine leukemia virus.

We have studied the process of Moloney murine leukemia virus (M-MuLV) assembly by characterization of core (gag) protein mutants and analysis of wild-type (wt) gag proteins produced by cells in the presence of the ionophore monensin. Our genetic studies involved examination of linker insertion mutants of a Gag-beta-galactosidase (Gag-beta-gal) fusion protein, GBG2051, which is incorporated into virus particles when expressed in the presence of wt viral proteins. Analysis indicated that the amino-terminal two-thirds of the gag matrix domain is essential for targeting of proteins to the plasma membrane; mutant proteins localized to the cytoplasm or were trapped on intracellular membranes. Mutations through most of the coding region of the gag capsid domain generated proteins which were released from cells in membrane vesicles but not in virions. In contrast, linker insertions into p12gag or carboxy-terminal portions of the matrix or capsid coding regions did not affect assembly of fusion proteins into virus particles. Monensin, which blocks vesicular transport, inhibited gag protein intracellular transport and release from cells. Our results suggest that a significant proportion of M-MuLV myristylated gag proteins travel via vesicles to the cell surface. Specific matrix protein polypeptide regions and myristic acid modification are both necessary for appropriate gag protein transport, while capsid protein interactions appear to mediate the final phase of virion formation.

Acylation↗
PubMed1989

Flunarizine as a supplementary medication in refractory childhood epilepsy: a double-blind crossover study.

We report a double blinded cross-over study involving Flunarizine versus placebo in the treatment of refractory childhood epilepsy. The patients studied were between the ages of 2 and 18; and were having more than 4 seizures per month not responsive to regular anticonvulsant medications. Of the 34 patients treated, 8 had a 50% decrease in their seizures during the placebo phase, 5 had a 50% decrease during the Flunarizine phase, and 1 patient had a 50% increase in seizures while taking Flunarizine. The remaining 25 patients showed no change in seizure activity in either phase. Patients having partial seizures with secondary generalization tended to do better on Flunarizine than those with other seizure types. Monitoring serum Flunarizine levels showed no significant difference between patients having improved seizure control and those who were unimproved. No significant side effects were noted with this medication, nor were any significant drug interactions noted.

Adolescent↗
PubMed1985

Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus.

We describe neurochemical abnormalities found in the brains of 2 patients with autopsy-confirmed Hallervorden-Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. gamma-Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden-Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden-Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.

Adult↗
PubMed1985

Permanent cortical visual impairment in children.

Fifty patients with permanent cortical visual impairment were evaluated. They had a characteristic behaviour profile, usually with residual sight but poor visual attention. 30 of the 50 also had damage to the anterior visual pathway. Visual evoked potential mapping was shown to have a clear advantage over visual evoked responses, and using that in conjunction with CT and clinical data enabled several subgroups of cortical visual impairment to be identified. The diagnosis probably is more common than previously recognised, and should be suspected when there is greater delay in visual development in other areas and the degree of visual loss is unexplained by ocular findings. Using traditional criteria for cortical blindness may mean that many children are not diagnosed, which has serious implications for their rehabilitation.

Adolescent↗
PubMed1981

Different distributions of kinetically apparent molecular varieties of alpha 2-macroglobulin in health and in patients with cryptogenic fibrosing alveolitis.

1. Proteinase inhibitors have been studied in whole serum by using a kinetic method that avoids potentially damaging protein separation procedures. 2. The alpha 2-macroglobulin of an individual can be allocated unambiguously into one of seven categories according to the binding of trypsin to inhibitor in two kinetically apparent binding modes (beta- and alpha-modes). 3. The distribution of alpha 2-macroglobulin beta:alpha ratios in a healthy adult population is defined, and shown to be independent of sex and age. 4. The distribution of beta:alpha ratios in a group of patients with cryptogenic fibrosing alveolitis was found to be significantly different (P less than 0.005) from the normal distribution. 5. Changes in the beta:alpha ratio were noted in five of six patients with cryptogenic fibrosing alveolitis after treatment, but on no occasion when two healthy subjects were assessed a total of nine times. 6. The molecular interpretation and the possible importance of altered proteinase inhibition in inflammation and fibrosis are discussed.

Adult↗
PubMed1981

The problem of depression in adolescence.

The subjects for this study were tested using MMPI Scales 2 and 4 and the Beck Depression Inventory. There were four different groups studied, adolescent male patients, adolescent female patients, mothers, and fathers. The first null hypothesis stated that there will be no significant incidence of depression among adolescents hospitalized in a specific hospital facility. It is obvious that the null hypothesis was rejected for adolescents, both male and female, in the sample on the basis of the MMPI results. The second null hypothesis stated that there will be no significant incidence of depression among parents of adolescents admitted to a specific hospital for psychiatric treatment. There is not sufficient evidence to suggest that parents are depressed to a significant degree; therefore, the second null hypothesis is not rejected based on the results of the tests used in this study. However, there were a significant number of fathers who fell within the range of mild depression. Mothers did not appear depressed. The third null hypothesis stated that there will be no significant relationship between the presence of depression in hospitalized adolescents and the presence of depression in one or both parents. There was not evidence to permit rejection of this hypothesis; thus, there is not proof on the basis of this study that there is a correlation between family members.

Adolescent↗
PubMed1979

Cinnarizine in the treatment of chronic asthma.

1 Cinnarizine, an inhibitor of calcium ion transport across smooth muscle cell membrane, has been shown to exert an anti-asthmatic effect in patients with chronic asthma. 2 It is postulated that antagonism to calcium ion transport across the mast cell membrane may cause the compound to have a pharmacological effect similar to sodium cromoglycate. 3 Cinnarizine is orally active and its therapeutic effect is demonstrated in a double-blind, cross-over, placebo controlled study. 4 Patient benefit was shown by a significant improvement in peak flow rate. A non-significant trend towards a reduction in symptomatic bronchodilator usage and a decrease in asthma symptom score was also shown. 5 It is concluded that cinnarizine could well prove to be the first of a new family of anti-asthmatic drugs offering a protective effect when taken systemically.

Adult↗