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Biomedical subjects

E Stewart

Publications and source records attributed to E Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1997

rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest.

In eukaryotic cells, S phase can be reversibly arrested by drugs that inhibit DNA synthesis or DNA damage. Here we show that recovery from such treatments is under genetic control and is defective in fission yeast rqh1 mutants. rqh1+, previously known as hus2+, encodes a putative DNA helicase related to the Escherichia coli RecQ helicase, with particular homology to the gene products of the human BLM and WRN genes and the Saccharomyces cerevisiae SGS1 gene. BLM and WRN are mutated in patients with Bloom's syndrome and Werner's syndrome respectively. Both syndromes are associated with genomic instability and cancer susceptibility. We show that, like BLM and SGS1, rqh1+ is required to prevent recombination and that in fission yeast suppression of inappropriate recombination is essential for reversible S phase arrest.

Adenosine Triphosphatases↗
PubMed1997

Volunteer participation in context: motivations and political efficacy within three AIDS organizations.

Employed quantitative and qualitative data in a contextual examination of participation in three San Francisco-area HIV/AIDS organizations: an urban, gay community-based social change setting; an urban, broadly focused information/referral setting; and a suburban individual support setting. The settings attracted different kinds of volunteers and engaged them differently with the setting, each other, and community. In quantitative analyses external political efficacy (belief in the responsiveness of sociopolitical systems to change efforts) significantly distinguished settings, but was best predicted by setting-moderated relationships to scaled motivations. Qualitative data more clearly illuminated volunteers' motivations for participation, as well as complex, embedded relationships between setting, motivations, attitudes about sociopolitical participation, and personal and community experience and identification. Together the findings underscore three unique but related stories for the three AIDS organizations, and the value of contextual approaches to participation and empowerment.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Metabolism of catecholamines by catechol-O-methyltransferase in cells expressing recombinant catecholamine transporters.

To determine if catechol-O-methyltransferase (COMT) metabolizes catecholamines within cell lines used for heterologous expression of plasmalemmal transporters and alters the measured characteristics of 3H-substrate transport, the uptake of monoamine transporter substrates was assessed in three cell lines (C6 glioma, L-M fibroblast, and HEK293 cells) that had been transfected with the recombinant human transporters. Uptake and cellular retention of 3H-catecholamines was increased by up to fourfold by two COMT inhibitors, tropolone and Ro 41-0960, with potencies similar to those for inhibition of COMT activity, whereas the uptake of two transporter substrates that are not substrates for COMT, [3H]serotonin and [3H]MPP+, was unaffected. Direct measurement of monoamine substrates by HPLC confirmed that tropolone (1 mM) increased the retention of the catecholamines dopamine and norepinephrine, but not the retention of serotonin in HEK293 cells. Saturation analysis of the uptake of [3H]dopamine by C6 cells expressing the dopamine transporter demonstrated that tropolone (1 mM) decreased the apparent Km of transport from 0.61 microM to 0.34 microM without significantly altering the maximal velocity of transport. These data suggest that endogenous COMT activity in mammalian cells may alter neurotransmitter deposition and thus the apparent kinetic characteristics of transport.

Carrier Proteins↗
PubMed1997

Aggression and violence in sport: an ISSP position stand.

Violent and aggressive behaviours have become common in a large variety of sport. The antecedents and consequences of such behaviours are outlined in the position statement issued by the International Society of Sport Psychology (ISSP). The ISSP recommends several actions be taken to minimize such acts in sport and encourages education of young athletes in line with fair-play ethics.

Aggression↗
PubMed1996

The 'destruction box' of cyclin A allows B-type cyclins to be ubiquitinated, but not efficiently destroyed.

The destruction of mitotic cyclins by programmed proteolysis at the end of mitosis is an important element in cell cycle control. This proteolysis depends on a conserved motif of nine residues known as the 'destruction box', which is located 40-50 residues from the N-terminus. The sequences of the A- and B-type destruction boxes are slightly different, which might account for the differences in timing of their destruction. When the cyclin A-type destruction box was substituted for the normal one in cyclin B1 or B2, however, the resulting constructs were unexpectedly stable, although the converse substitution of B-type destruction boxes in cyclin A permitted normal degradation. We compared the ubiquitination of various cyclin constructs, and found that whereas mutation of the highly conserved residues in the destruction box strongly reduced the level of ubiquitinated intermediates, the stable destruction box 'swap' constructs did form such adducts. Thus, while ubiquitination is probably necessary for cyclin destruction, it is not sufficient. We also found that poly-ubiquitinated cyclin derivatives are still bound to p34cdc2, which is not detectably ubiquitinated itself, raising the questions of how cyclin and cdc2 dissociate from one another, and at what stage, in the process of degradation.

Amino Acid Sequence↗
PubMed1996

Treatment of patients with pineoblastoma with high dose cyclophosphamide.

The outcome for patients with pineoblastoma has historically been very poor, with most patients dying of disseminated disease despite irradiation. Furthermore, the low incidence of this tumor has hindered progress toward defining better treatment strategies. Here we report the activity and toxicity of cyclophosphamide administered as a single agent at a dose schedule of 2 g/m2/day for 2 successive days at monthly intervals for a maximum of four courses. Eight patients were evaluated, six newly diagnosed and two recurrent. Amongst the six newly diagnosed patients, there were three patients demonstrating partial responses, and three had stable disease throughout the cyclophosphamide treatment period. All six patients are alive and disease free after further therapy. One patient with recurrent disease demonstrated tumor progression on cyclophosphamide, and the other had stable disease throughout the cyclophosphamide treatment period. Both patients subsequently died of progressive disease. The major toxicity of high dose cyclophosphamide was hematopoietic, with one patient requiring a dose reduction after three courses due to prolonged thrombocytopenia. One patient was also withdrawn from treatment with cyclophosphamide due to impaired pulmonary function. This study demonstrates the activity of high dose cyclophosphamide in the treatment of pineoblastoma and may serve as basis for the design of future studies of this tumor.

Adolescent↗
PubMed1996

Successful treatment of childhood pilocytic astrocytomas metastatic to the leptomeninges with high-dose cyclophosphamide.

Leptomeningeal dissemination of childhood pilocytic astrocytoma (PA) is a rare event with little information available regarding therapy. We report here four children with disseminated PA whom we treated with high doses of cyclophosphamide with clinical benefit. The patients were aged 2.5 to 8 years. Three patients presented with PA localized in the posterior fossa, initially treated with surgical resection (n = 3) and radiotherapy (n = 1). Leptomeningeal dissemination occurred at 32, 44, and 8 months from diagnosis, respectively. The fourth patient presented with an optic pathway tumor with leptomeningeal dissemination at diagnosis. At commencement of cyclophosphamide therapy, disease was present in the subarachnoid space (intracranial, n = 2; spinal, n = 4), cerebral ventricles (n = 2), and primary site (n = 3). Histology was identical at diagnosis and recurrence in the two biopsied cases and cerebrospinal fluid was negative in all cases. Treatment was with cyclophosphamide 4-5 g/m2/cycle given every 4 weeks for a total of two cycles (n = 1) and four cycles (n = 3). One patient achieved disease stabilization (duration 27 months at the time of publication) and three patients experienced significant reductions in tumor burden. Subsequent intrathecal therapy was administered to two patients. Two patients developed disease progression at 10 and 9 months from cessation of chemotherapy. The one re-treated patient responded to further, lower dose, cyclophosphamide. This is the first report of the use of high dose cyclophosphamide for disseminated PA. The recurrence of disease in two cases with a further response to lower dose cyclophosphamide has implications for the optimal duration of therapy for these low grade, aggressive tumors.

Antineoplastic Agents, Alkylating↗
PubMed1996

S-phase and DNA-damage checkpoints: a tale of two yeasts.

Many genes required for the S-phase and DNA-damage checkpoints have been identified in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. This year many checkpoint genes have been sequenced, providing new information about the mechanism of checkpoint control. Several of these genes are conserved between the two yeasts but others are species-specific.

Cell Division↗
PubMed1996

Esophageal intramural pseudodiverticulosis associated with achalasia.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition in which multiple small outpouchings are seen in the wall of the esophagus. Although EIPD is typically associated with esophageal narrowing, only a few cases have been described in which it was associated with esophageal dysmotility. We report the case of a 52-yr-old female who presented with dysphagia and who had EIPD protruding from a 5-cm-long concentric distal esophageal stricture, with a markedly dilated upper and middle third of the esophagus. The short segment of the esophagus between the stricture and the lower esophageal sphincter also was dilated. Barium column was held up above a nonrelaxing lower esophageal sphincter that opened after inhalation of amylnitrate. Esophageal manometry confirmed the presence of vigorous achalasia. Although EIPD has been associated with several other conditions, this is the first report of an association with achalasia.

Deglutition Disorders↗
PubMed1994

Cyclin A and cyclin B dissociate from p34cdc2 with half-times of 4 and 15 h, respectively, regardless of the phase of the cell cycle.

The exchange rate of cyclin A and cyclin B between endogenous p34cdc2 and bacterially expressed GST-cdc2 was measured in concentrated Xenopus egg extracts. The half-lives of the cyclin A.p34cdc2 and the cyclin B.p34cdc2 complexes are estimated as 4 and 15 h, respectively. There is no significant difference in these affinities when they are measured in mitosis, interphase, or during transition between these two states. The tight association between cyclin and p34cdc2 in the cell cycle may be significant for mechanisms of cyclin destruction.

Amino Acid Sequence↗
PubMed1994

Destruction of Xenopus cyclins A and B2, but not B1, requires binding to p34cdc2.

The specific and rapid destruction of cyclins A and B during mitosis is their most remarkable property. A short peptide motif of approximately 10 amino acids near the N-terminus, known as the destruction box, is absolutely required for programmed proteolysis. In this paper we show that although the destruction box is necessary for the degradation of cyclin A, it is not sufficient. Mutant versions of cyclin A that cannot form complexes with p34cdc2 are stable, which we interpret to mean that this cyclin must bind to p34cdc2 in order to undergo programmed proteolysis. Thus, N-terminal fragments of cyclin A containing little more than the destruction box and its surroundings are indestructible. p34cdc2 binding also appears to be required for the destruction of cyclin B2. In contrast, cyclin B1 does not require p34cdc2 binding for specific proteolysis. The systems for the proteolysis of cyclins A, B1 and B2 thus appear to show important differences in the way they recognize their substrates.

Amino Acid Sequence↗
PubMed1994

Radiation tolerance of the transplanted liver. A histopathologic study in three cases.

Three patients with multifocal recurrence of hepatocellular carcinoma following liver transplantation received palliative irradiation. Hyperfractionated irradiation (150 cGy/fraction b.i.d.) was delivered in two cases to the entire liver using parallel opposed oblique portals to a total dose of 30 Gy. Conventional irradiation (180 cGy/fraction) totaling 45 Gy was administered to the liver hilus with concomitant infusional 5-fluorouracil chemotherapy in the third case. Clinicopathologic correlations were performed. At autopsy all patients had massive tumor burden within the liver. Veno-occlusive changes were observed in two patients 1 and 2 months following completion of conventional and hyperfractionated irradiation, respectively. Liver transplantation in these two patients had been performed 18 and 16 months prior to palliative hepatic irradiation. In the third patient, no veno-occlusive changes were pathologically observed at autopsy 1 month after completing hyperfractionated radiation, which was delivered 6 months following liver transplantation. No significant differences in prior immunosuppressive therapy were identified among patients. Veno-occlusive changes are not spared by hyperfractionated radiation. Transplanted livers exhibit responses to radiation similar to those normally observed.

Adult↗
PubMed1994

Effect of exercise on the nasal transmucosal potential difference in patients with cystic fibrosis and normal subjects.

BACKGROUND: Normal subjects have a negative nasal transmucosal potential difference (TPD) at rest which becomes more negative with exercise. Patients with cystic fibrosis have a more negative resting nasal TPD than controls. The present study was designed to determine the effects of exercise on the TPD of patients with cystic fibrosis. METHODS: Seven subjects with cystic fibrosis and seven control subjects had their usual TPD measured at rest, and during and after a 12 minute period on an exercise bicycle designed to produce a pulse rate of 80% of their maximum predicted value. RESULTS: The normal subjects developed a more negative nasal TPD during exercise which returned towards normal at the completion of the rest period. The patients with cystic fibrosis had higher resting values which became less negative during exercise. At the end of the exercise period there was no difference between the two groups. At the end of the recovery period the results for the patients with cystic fibrosis had returned to their resting values. CONCLUSIONS: Exercise reduces the abnormally high resting values for nasal TPD in patients with cystic fibrosis. Elucidation of the mechanism for this change may help to produce functional improvement for patients with this disease.

Adolescent↗
PubMed1994

School consultation and the management of obsessive-compulsive personality in the classroom.

The need for a comprehensive assessment involving areas of ability, personality, and motivation when young people are referred to a mental health service with problems of school failure is discussed. Traits associated with obsessive-compulsive personality style are reviewed, and the impact on school performance explored. Three case examples illustrate the ways this personality style interferes with success in the classroom and the concerns and problems encountered in providing intervention. Particular classroom teaching strategies may assist teacher and student in avoiding these problems. In addition, the benefits of SQ3R, Cornell systems, and cooperative learning are discussed, and warning signals, observable by the teacher, described. The process of mental health consultation, contribution to classroom change, and difficulties encountered along with the advantages of professional partnership in the diagnosis and management of school problems are reviewed.

Adolescent↗
PubMed1993

A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

We have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D13S31 and D13S59. Here we describe the construction of a contig of approximately 4.5 Mb, which spans this region and extends from D13S25 to D13S59. This contig consists of 28 genomic yeast artificial chromosome (YAC) clones. Five critical crossover events have been defined in this interval in two unaffected (Centre d'Etudes du Polymorphisme Humain) and three WND families. The combination of sequence tagged site content mapping of YACs with both polymorphic and nonpolymorphic markers and recombination breakpoint mapping resulted in the following order of polymorphic markers: centromere-RB1-D13S25-AFM205vh2-D13S31-D13S22 7-D13S228-AFM238vc3-D13S133- AFM084xc5-D13S137-D13S169, D13S155-D13S59-telomere. The recombination/physical distance ratio varies from approximately 3000 kb per cM in the region between D13S31 and D13S25 to 6000 kb per cM in the region between D13S31 and D13S59. Three WND families exhibiting recombination between the disease locus and D13S31 or D13S59 were genotyped for additional markers in this region and further refined the location of the WND gene to between D13S155 and D13S133. Nine of the markers in this region of < 1 cM are polymorphic microsatellites (seven have observed heterozygosities of 70% or above) that will be extremely useful in prenatal and preclinical diagnosis of this disease. This physical map is an essential step in the isolation of the WND gene and is a framework for the identification of candidate genes.

Base Sequence↗