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Biomedical subjects

R H Oliver

Publications and source records attributed to R H Oliver.

8 recordsLinked to original sources

Depletion of Raf-1 protooncogene by geldanamycin causes apoptosis in human luteinized granulosa cells.

OBJECTIVE: To investigate the hypothesis that epidermal growth factor (EGF) signaling in luteinized granulosa cells works through Raf-1 and mitogen-activated protein (MAP) kinases and that depletion of Raf-1 by geldanamycin will inhibit the signaling pathway and cause apoptosis. DESIGN: Laboratory study. SETTING: University of Minnesota. PATIENT(S): Human luteinized granulosa cells from IVF patients. INTERVENTION(S): The cells were treated with vehicle (DMSO), 0.5 microM of geldanamycin, 10 ng/mL of EGF, and geldanamycin + EGF. MAIN OUTCOME MEASURE(S): Radiochemical MAP kinase assay, Western blotting, confocal microscopy, and flow cytometry. RESULT(S): Geldanamycin treatment depleted Raf-1 and lowered MAP kinase activity in luteinized granulosa cells. EGF treatment increased MAP kinase phosphorylation and translocation of the phosphorylated MAP kinase to the nucleus. Geldanamycin blocked this effect. Cleavage of caspase-3, the executioner protein in apoptosis, into an active 17 kD fragment was observed by Western blotting in geldanamycin-treated cells. Finally, by flow cytometry we observed significantly increased percentages of subdiploid apoptotic nuclei in geldanamycin-treated cells. CONCLUSION(S): In human luteinized granulosa cells, EGF works through Raf-1, and MAP kinase and depletion of Raf-1 by geldanamycin resulted in decreased MAP kinase activity, increased activated caspase-3, and, ultimately, apoptosis.

Apoptosis↗

Induction of apoptosis in luteinized granulosa cells by the MAP kinase kinase (MEK) inhibitor PD98059.

Our objective is to test the hypothesis that inhibition of mitogen-activated protein (MAP) kinase kinase (MEK) with PD98059 in human luteinized granulosa cells will block epidermal growth (EGF)-stimulated MAP kinase activity and induce apoptosis. Luteinized granulosa cells from human in vitro fertilization aspirates were cultured and treated with the following: (1) vehicle; (2) PD98059; (3) EGF; (4) PD98059 + EGF. Treatment with PD98059 suppressed MAP kinase activity, inhibited MAP kinase phosphorylation by Western blot analysis, blocked nuclear translocation of phosphorylated MAP kinase by confocal microscopy, and increased percentages of subdiploid apoptotic nuclei by flow cytometry. Our data are the first evidence that a relationship may exist between the MAP kinase pathway and control of apoptosis in human luteinized granulosa cells. These results support the hypothesis that suppression of the MAP kinase pathway may lead to apoptosis in these cells.

Apoptosis↗

Estrogen receptor alpha and beta expression in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women.

OBJECTIVE: To assess the expression of messenger RNA (mRNA) for estrogen receptors alpha and beta in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women. DESIGN: In vitro experiment. SETTING: Academic research environment. PATIENT(S): Sixteen consecutively seen women who underwent hysterectomy. INTERVENTION(S): Samples of anterior vaginal walls and uterosacral ligaments were obtained during hysterectomy. MAIN OUTCOME MEASURE(S): Reverse transcriptase-polymerase chain reaction analysis for estrogen receptor mRNA. RESULT(S): Messenger RNA transcripts for estrogen receptor alpha were present in all samples of vaginal walls (16/16) and uterosacral ligaments (16/16). Estrogen receptor beta mRNA was detected in all samples of vaginal walls from premenopausal women (12/12) but in none of those from postmenopausal women (0/4). Estrogen receptor beta mRNA was found in most samples of uterosacral ligaments from premenopausal women (10/12) and in some of those from postmenopausal women (2/4). CONCLUSION(S): Estrogen receptors alpha and beta were expressed in the vaginal walls and uterosacral ligaments of premenopausal and postmenopausal women. Estrogen receptor beta was absent from the vaginal walls of postmenopausal women.

Adult↗

Housing and appendicitis in Anglesey.

STUDY OBJECTIVE: The aim was to test the hypothesis that provision of household amenities such as domestic hot water systems and bathrooms changed hygiene which thereby triggered the epidemic of appendicitis in Anglesey after the second world war. DESIGN: The study was a cross sectional survey with histories of housing and appendicectomy obtained from Anglesey residents by postal questionnaire. The main outcome measure was reported appendicectomy. SETTING: Four general practices in Anglesey. SUBJECTS: 2531 men and women born during 1923-62 and randomly selected from age-sex registers. Overall response rate was 73.7%. MAIN RESULTS: Subjects born into households with amenities--piped water, hot water systems, and bathrooms had, if anything, a reduced risk of appendicectomy. However, those who subsequently moved to houses that lacked amenities were at significantly higher risk than people born into houses without amenities who later acquired them. CONCLUSIONS: Provision of household amenities was not the important trigger to the epidemic of appendicitis which occurred in Anglesey after the second world war. Rather, the trigger may have been reduction in domestic crowding caused by the falling birth rate. Findings among those who moved house support other evidence that after infancy household amenities protect against appendicitis and contributed to the fall in appendicitis rates in Anglesey after 1965.

Adult↗

Appendicitis epidemic following introduction of piped water to Anglesey.

The extension of piped water supplies in Anglesey, North Wales, 30 years ago and the consequent introduction of domestic hot water systems was followed by an epidemic of appendicitis. This occurred while appendicitis rates were falling elsewhere in Britain. The diet of Anglesey is unremarkable. This is further evidence that epidemics of appendicitis occur during the transition to 'western' hygiene, an important component of which is the provision of domestic hot water systems and fixed baths.

Age Factors↗

Exsanguination in a Jehovah's Witness.

A case is reported in which death occurred after a patient's adamant refusal to accept blood transfusion, despite prompt control of blood loss. The management of this situation is discussed. Reconstitution of the circulating volume was followed by survival for 2 hours after surgery. The haemoglobin level fell to 1.8 g/dl.

Adult↗