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Biomedical subjects

R Watson

Publications and source records attributed to R Watson.

At least 37 records · Page 2Linked to original sources

The role of induction androgen deprivation prior to radical prostatectomy.

In patients with localised prostate cancer and a life expectancy of at least 10 years, radical prostatectomy is increasingly being performed. Pre-operative clinical staging of prostate cancer is, however, inaccurate with around 10-20% of clinical T1, 10-30% of clinical T2a, and 30-60% of clinical T2b cases having tumour at the surgical margin. There is no documented best treatment for patients with a positive surgical margin. Options include close observation, adjuvant radiation therapy or androgen deprivation. The role of induction androgen deprivation has, therefore, evolved in an attempt to improve upon the cure rate for radical prostatectomy, and in this review results from clinical trials are discussed. In the largest United States randomised trial in patients with stage T2b prostate cancer, pre-operative androgen deprivation resulted in a significantly lower rate of positive surgical margins, normalisation of prostate-specific antigen and a decrease in the size of the prostate. Sufficient follow-up is required from all of the completed prospective randomised trials before pre-operative androgen deprivation can be justified in all T2b patients.

Androgen Antagonists

The role of the membrane-spanning domain and stalk region of N-acetylglucosaminyltransferase I in retention, kin recognition and structural maintenance of the Golgi apparatus in HeLa cells.

Using a series of chimeric and truncated N-acetylglucosaminyltransferase I (NAGT I) molecules we have shown that part of the lumenal stalk region is both necessary and sufficient for kin recognition of mannosidase II and retention in the Golgi stack. The membrane-spanning domain was not required for retention, but replacing part or all of this domain with leucine residues did have a dramatic effect on Golgi morphology. In stable cell lines, stacked cisternae were replaced by tubulo-vesicular clusters containing the mutated NAGT I. The loss of stacked cisternae was proportional to the number of leucines used to replace the membrane-spanning domain.

Amino Acid Sequence

Can postmenopausal hormone replacement improve plasma lipids in women with diabetes? The Atherosclerosis Risk in Communities Study Investigators.

OBJECTIVE: to evaluate the association of postmenopausal hormone replacement with plasma lipids in diabetic women. RESEARCH DESIGN AND METHODS: Cross-sectional data from a multiracial population study were used to evaluate the relationship of hormone replacement status with plasma lipids in diabetic (n = 694) versus nondiabetic (n = 5,321) postmenopausal women. RESULTS: Although diabetic women who currently used hormone replacement had higher adjusted mean HDL cholesterol levels than those who did not (56.9 vs. 53.6 mg/dl), they had proportionately lower hormone-related increases in HDL, HDL2, and HDL3 cholesterol than did nondiabetic women (HDL cholesterol 64.9 [current users] vs. 55.7 mg/dl [those who never used hormones]). There was a trend toward greater triglyceride values with hormone replacement in diabetic women (156.6 [current users] vs. 125.4 mg/dl [those who never used hormones]) than in nondiabetic women (143.3 [current users] vs. 123.7 mg/dl [those who never used hormones]). LDL cholesterol and apolipoprotein B levels were lower and apolipoprotein A-I levels were higher with hormone replacement, to a similar degree in diabetic and nondiabetic women. CONCLUSIONS: Diabetic women appear to have a blunted response to the HDL-raising effects of estrogen and an exaggerated hypertriglyceridemic response. This may result in attenuated cardioprotection from postmenopausal hormone replacement therapy and potentially an increased risk of acute pancreatitis from hypertriglyceridemia. The risks and benefits of postmenopausal hormone replacement need to be carefully weighed in diabetic women.

Alcohol Drinking

Dermatomyositis sine myositis: association with malignancy.

OBJECTIVE: To describe dermatomyositis (DM) sine myositis as a distinct diagnostic subclass of DM and the association with malignancy. METHODS: This case series includes all patients presenting to our primary and tertiary care outpatient dermatology department with DM and DM sine myositis between 1986 and 1993. Seven patients were diagnosed with classic DM and 12 with DM sine myositis. We analyzed average age of onset, duration of followup, clinical course, and incidence of associated malignancy in the patients with classic DM and DM sine myositis. RESULTS: No statistically significant differences were found in these 2 groups on examining age at onset and frequency of associated malignancy. Malignancy was diagnosed in 4 of 12 (25%) patients with DM sine myositis followed for a total of 50.8 patient-years (average followup 51 months) and in 2 of 7 (28%) patients with classic DM followed for a total of 20.6 patient-years (average followup 35 months). CONCLUSION: Although these patients with DM are select and few, they demonstrate that DM sine myositis may be quite similar to classic DM. It may be said that like DM, DM sine myositis may represent a paraneoplastic syndrome. DM sine myositis should be added to the currently accepted polymyositis/dermatomyositis classification system, with appropriate emphasis on the potential association with malignancy.

Adult

Evidence for recycling of the resident medial/trans Golgi enzyme, N-acetylglucosaminyltransferase I, in ldlD cells.

ldlD cells, which lack the UDP-Gal/UDP-GalNAc 4-epimerase, were stably transfected with a Myc-tagged version of N-acetylglucosaminyltransferase I (Myc-Glc-NAc-T I). In the absence of GalNAc and Gal, newly synthesized GlcNAc-T I did not acquire O-linked oligosaccharides but was catalytically active and was transported to the Golgi region as defined using both immunofluorescence and immunoelectron microscopy. After addition of cycloheximide to prevent further synthesis, GalNAc and Gal were added, and the unglycosylated GlcNAc-T I was found to acquire mature, O-linked oligosaccharides with a half-time of about 150 min. The addition of these sugars was sensitive to N-ethylmaleimide and okadaic acid, both inhibitors of vesicle-mediated traffic. Together, these results suggest that Myc-Glc-NAc-T I undergoes retrograde transport to the early part of the Golgi apparatus where the first O-linked sugar, GalNAc, is added followed by anterograde transport back to the Golgi stack, where addition of Gal and sialic acid occurs.

Animals