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Biomedical subjects

L Edwards

Publications and source records attributed to L Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1995

Crystallization and analysis of the subunit assembly and quaternary structure of imidazoleglycerol phosphate dehydratase from Saccharomyces cerevisiae.

Imidazoleglycerol phosphate dehydratase (IGPD) from Saccharomyces cerevisiae has been crystallized in the presence of a range of divalent cations using the hanging-drop method of vapour diffusion with ammonium sulfate or polyethylene glycol (PEG) 4000 as the precipitants. X-ray precession photographs have established that the crystals formed with ammonium sulfate (form A) belong to the space group F432, with cell parameter a = 177.5 A and a single subunit in the asymmetric unit. A preliminary data set collected to 6 A resolution on a two-detector San Diego Multiwire area detector has established that the crystals formed with PEG 4000 (form B) belong to either of the special pair of space groups I23 or I2(1)3, with cell parameter a = 131.0 A. A self-rotation function has been calculated using these data and indicates that the cell axes show pseudo fourfold symmetry consistent with a dimer in the asymmetric unit in this crystal form. Light-scattering studies indicate that in the presence of Mn(2+) and a number of other divalent cations IGPD undergoes assembly to a particle of molecular weight approximately 500 kDa. Given the subunit molecular weight of 23 kDa together with the symmetry of the crystals it would indicate that the most likely quaternary structure for this enzyme is based on a 24-mer in 432 symmetry.

Journal Article↗
PubMed1993

Gastrointestinal symptoms in Parkinson disease: 18-month follow-up study.

In a recent study we identified abnormal salivation, dysphagia, nausea, constipation, and defecatory dysfunction as those gastrointestinal (GI) symptoms associated with Parkinson disease (PD) and characterized their relationship to PD severity and therapy. In this study, we re-evaluated these symptoms and their relationship to parameters of PD 18 months later. Sixty-six percent of the original participants responded. Over the 18 months, 68% of originally untreated PD subjects commenced anti-PD therapy. Abnormal salivation, dysphagia, nausea, constipation, and defecatory dysfunction were again identified as those GI symptoms more common in PD. Constipation increased both in severity and frequency. Comparison of GI symptom scores and parameters of PD dysfunction failed to reveal significant progression of either GI symptomatology or PD dysfunction, or the development of new GI symptoms over the 18-month period. This study validates our GI dysfunction assessment system and confirms abnormal salivation, dysphagia, nausea, constipation, and defecatory function as those GI symptoms truly associated with PD. A direct relationship between PD and its related GI symptoms is again supported.

Aged↗
PubMed1993

Characteristics of the inhibition of human promyelocytic leukaemia HL60 cell growth by S-D-lactoylglutathione in vitro.

The mechanism of the inhibition of proliferation of human leukaemia 60 (HL60) cells by S-D-lactoylglutathione in vitro was investigated. The median inhibitory concentration IC50 value was 66 microM (95% C.I. 50-87 microM; n = 18). The inhibition of leukaemia cell growth required exposure of HL60 cells to S-D-lactoylglutathione (and metabolites) for 12 h, with maximum growth inhibition achieved after 24 h. Removal and replacement of culture medium within the initial 12 h of culture prevented inhibition of growth and toxicity. S-D-lactoylglutathione was consumed within the initial 3 h of culture. Pretreatment of culture medium containing 10% foetal calf serum for 3 h produced no subsequent inhibition of HL60 cell growth. Incubation of HL60 cells in culture medium with low serum content (5% v/v) produced a decreased rate of cell proliferation and a decreased response to S-D-lactoylglutathione. S-D-lactoylglutathione inhibited uptake of 3H-thymidine into DNA in the third hour of culture where the median inhibitory concentration IC50 value was 74 microM (95% C.I. 51-102; n = 10). The mechanism of inhibition of HL60 cell growth by S-D-lactoylglutathione is unknown but may be cell cycle related, mediated by inhibition of DNA synthesis and involve an active metabolite which may be removed and/or inactivated by a change in culture medium.

Cell Division↗
PubMed1992

Therapeutic response to somatostatin analogue, BIM 23014, in metastatic prostatic cancer.

Metastatic prostate cancer is well known to respond to hormonal manipulations, but once progression occurs new treatment modalities are required. Specific and systemic antitumour therapy is preferable to local treatments such as radiotherapy in such patients. The finding that somatostatin analogue, BIM 23014, inhibits prostatic tumour growth in animal models is of great interest. We treated 25 poor risk patients with progressive metastatic prostate cancer. Sixteen had also failed to respond to 'total androgen blockade'. Two patients have achieved a partial remission, one of which is maintained at over 30 months, and three had stable disease for over 6 months. Side effects have consisted of mild diarrhoea and abdominal cramp in the first few days of treatment in a minority of the patients. These results are encouraging and further randomized studies are in progress.

Aged↗
PubMed1992

Selective memory for sensory and affective information in chronic pain and depression.

Mood congruity effects in induced mood states and affective disorders are well established. Recent evidence suggests that a similar process occurs in chronic pain patients, although the extent to which the memory bias is a consequence of the affective or sensory state of the subject in this group is unknown. In this study selective memory for sensory and affective pain-related information was investigated in depressed and non-depressed chronic pain patients and depressed psychiatric patients. A recall test comprising sensory, affective and neutral adjectives matched for frequency was followed by a recognition task, where the words of the recall test were randomized with an equal number of new adjectives matched for word type and frequency. Comparison of the three patient groups with normal controls revealed specific recall biases directly related to pain and depression in both chronic pain groups and the controls. Contrary to expectations, the depressed psychiatric patients failed to show a recall bias for affective adjectives: the possibility of cognitive avoidance as an explanation for this is discussed. Signal detection analysis of the recognition results suggested that selective memory in chronic pain and depression may to some extent be accounted for by differences in 'true memory', the contribution of response bias remaining less clear.

Adult↗
PubMed1992

Acceleration of alveolar type II cell differentiation in fetal rhesus monkey lung by administration of EGF.

To examine the effect of epidermal growth factor (EGF) on lung parenchymal maturation in fetal rhesus monkey, recombinant human EGF was administered intraperitoneally (IP) at 66 mg/kg body wt over a 7-day period into the fetal peritoneal cavity alone or IP and into the amniotic fluid (AF) simultaneously. The saline carrier was injected IP and AF into control (CO) fetuses. The body weights of the IP + AF group were significantly larger than CO. Overall lung growth, measured as wet lung weight or fixed volume of the right cranial lobe, was unchanged. Fixed lung volume per gram body weight was significantly lower for both IP + AF and IP compared with CO. Morphogenesis of lung parenchyma, measured as percent parenchymal airspace or airspace size, was unchanged. Alveolar type II cell ultrastructure was significantly altered by EGF treatment; volume fraction of cytoplasmic glycogen was 50% less and lamellar bodies threefold greater for IP + AF and IP groups compared with CO. Total phospholipid content of AF was not altered, but relative percentages of different phospholipids were changed by EGF treatments; phosphatidylinositol was significantly reduced, and phosphatidylglycerol was significantly elevated. The lecithin-to-sphingomyelin ratio was unchanged. Surfactant apoprotein A concentration in AF was significantly elevated and was detected by immunoperoxidase in more cuboidal alveolar cells in EGF-treated animals when compared with CO. We conclude that exogenous EGF administered in the last trimester of pregnancy accelerates structural and functional cytodifferentiation of the alveolar type II cell in fetal primates. These maturational changes occur in the absence of significant alterations in overall lung growth or morphogenesis of the gas exchange area.

Amniotic Fluid↗
PubMed1992

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

Adult↗
PubMed1992

Reiter's syndrome of the vulva. The psoriasis spectrum.

BACKGROUND: Reiter's syndrome is a disease characterized by crusted, scaling, acral and genital plaques; urethritis or cervicitis; and arthritis, which occur in genetically susceptible patients in response to any of many infections. This disease rarely occurs in women, and specific characterizations of vulvar and cervical lesions are rare. OBSERVATIONS: We describe a 39-year-old woman with a history of mucocutaneous candidiasis that was refractory to oral ketoconazole therapy. She presented with well-demarcated, erythematous, crusted plaques over the vulva, hands, and feet, as well as with cervical lesions and a history of conjunctivitis and iritis. Following the biopsy of characteristic skin lesions, recognition of systemic signs, and cultures that were negative for yeast, her condition was diagnosed as Reiter's syndrome. CONCLUSIONS: Reiter's syndrome of the vulva, vagina, and cervix may not be recognized because of its uncommon occurrence in women and the physician's consequent unfamiliarity with its clinical appearance in the genital area. This disease and pustular psoriasis share many common features and exist on a spectrum. A high index of suspicion and correlation of the many facets of the disease will better enable the clinician to make this diagnosis.

Adult↗
PubMed1992

Desquamative vulvitis.

The typical appearance of inflammatory and bullous diseases may be changed when they occur on the vulva. The moist, warm, occluded environment produces a tendency for the thin skin of the vulva to erode and scar, resulting in a common final appearance often characterized by loss of the labia minora and agglutination of the clitoral hood. The most common diseases that may produce desquamative vulvitis include lichen sclerosus, lichen planus, immunobullous diseases, contact dermatitis, erythema multiforme, lupus erythematosus, and squamous cell carcinoma in situ. The differentiating characteristics and treatment of these diseases are discussed in this article.

Adult↗
PubMed1992

Vulvar cicatricial pemphigoid as a lichen sclerosus imitator. A case report.

Because vulvar lichen sclerosus is very common, a clinician confronted with hypopigmentation and agglutination of the labia minora is tempted to make a diagnosis of the disease without the benefit of a skin biopsy or a careful examination of other epithelial surfaces. Unfortunately, that clinical picture is also consistent with the end stage of several other diseases, including cicatricial pemphigoid (benign mucous membrane pemphigoid), as demonstrated by a case of cicatricial pemphigoid affecting the vulva.

Administration, Oral↗