Effect of vitamin D metabolites and analogs on renal and intestinal calbindin-D in the rat

The effects of endotoxin (20 mg kg-1 i.p.) on the mesenteric vascular responses to acetylcholine, bradykinin, sodium nitroprusside, and to transient occlusion of the superior mesenteric artery were examined in rats anesthetized with pentobarbitone. Mesenteric vasodilator responses to close arterial injections of acetylcholine and bradykinin were reduced at 1.5 h after endotoxin and almost abolished by 4 h; responses to sodium nitroprusside were unaffected. Occlusion of the superior mesenteric artery for 30, 60, or 120 s produced, on release of the occlusion, a time-dependent vasodilator response in the mesenteric circulation (post-occlusion hyperemia). This hyperemia was markedly reduced by nitro-L-arginine methyl ester (L-NAME); L-NAME did not modify acetylcholine-induced vasodilation. Endotoxin-pretreatment did not modify mesenteric post-occlusion hyperemia 1.5 h after administration but markedly reduced the response by 2.5 h. The administration of L-NAME to endotoxin-treated rats did not further attenuate the hyperemic responses. Mesenteric vasoconstrictor responses to phenylephrine were not modified by endotoxin, although systemic pressor responses to this agent were impaired. We concluded that endotoxin impairs endothelium and nitric oxide-dependent vasodilator responses in the mesenteric circulation.     

Incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography and impact on subsequent management in patients with or suspected of having myocardial ischemia

We examined 1,159 consecutive patients who underwent adenosine stress dual isotope single-photon emission computed tomography (SPECT) and had follow-up performed at a mean of 27.5 +/- 9.1 months (94% complete) for hard events (cardiac death and myocardial infarction) and referral to cardiac catheterization after nuclear testing. During follow-up, 120 hard events occurred (11.0% hard event rate; 72 cardiac deaths [6.7% cardiac death rate] and 57 myocardial infarctions [5.3% myocardial infarction rate]). Cox proportional hazards analysis revealed that nuclear testing added incremental value after adjusting for clinical and historical variables (global chi-square increased 13 to 98 for cardiac death as the end point, global chi-square increased 19 to 105 for hard events as the end point; p <0.0001 for both). Kaplan-Meier analysis demonstrated that after clinical risk stratification of the patient population, the results of nuclear testing were further able to significantly stratify both low- and intermediate- to high-risk patients. Patients with both normal and mildly abnormal scans were at low risk of cardiac death (<1% cardiac death per year of follow-up) and the risk of events increased significantly with worsening scan result. Multivariable analysis revealed that the only predictor of referral to catheterization was the extent and severity of reversible defect present on the scan. Referral rates to early catheterization were very low in patients with normal scans and increased significantly as a function of worsening scan results. In patients who underwent myocardial perfusion SPECT using adenosine stress, the results of nuclear testing yielded incremental prognostic information and clinically relevant risk stratification. Referring physicians predominantly utilized nuclear information when referring patients to catheterization after nuclear testing and do so at rates comparable with those after exercise SPECT despite the higher risk of events in patients undergoing pharmacologic stress.     

Cisplatin-induced inhibition of p34cdc2 is abolished by 5-fluorouracil

This paper attempts to establish whether dissatisfaction with the artificial limb and/or body image relate to achieved mobility following lower limb amputation in established limb wearers. Patients attending limb fitting clinics (n = 107, 62% male, mean time from amputation 13.9 years; range 1-54) participated. The measures were a specially designed Attitude to Artificial Limbs Questionnaire, a Body Image Questionnaire adapted from an eating disorders instrument including reference to body shape, the Hospital Anxiety and Depression Scale and the Harold Wood Stanmore Mobility Scale. The rehabilitation physician rated prosthetic suitability on a Numerical Rating Scale. The results showed patients were moderately satisfied with their artificial limb, had little experience of body image disruption or distress and there was no overall relationship between these variables and mobility. However, those with a more negative body image were more anxious and in younger patients who sustained more traumatic than vascular amputations, the correlation between body image and mobility was significant, anxiety was higher and physician satisfaction with the prosthesis was lower. It is concluded that body image disruption, anxiety and depression are not common in established limb wearers except in young people with traumatic amputations.     

The 86-kDa subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity

We previously reported the immunopurification of a somatostatin receptor from the human tumoral gastric cell HGT1 using the monoclonal antibody 30F3 (Reyl-Desmars, F., Le Roux, S., Linard, C., Benkouka, F., and Lewin, M. J. M. (1989) J. Biol. Chem. 264, 18789-18795). Screening of a lambda gt11 HGT1-cDNA library with 30F3 led us to isolate a cDNA encoding an 86-kDa polypeptide displaying 100% structural identity with the 86-kDa subunit (p86-Ku) of the Ku autoantigen. Recombinant p86 expressed in Escherichia coli cross-reacted with 30F3 and specifically bound [125I-Tyr11]somatstatin-14. Binding was totally displaced by somatostatin-14, somatostatin-28, and SMS 201-995, with IC50 values of 0.7, 1.0, and 1.2 nM, respectively. In a search for a biological effect associated with binding, we purified a 36-kDa, okadaic acid-sensitive phosphatase (protein phosphatase-2A (PP2A)) from rat gastric cytosol. PP2A catalyzed 32P release from p34cdc2-phosphorylated histone H1. However, PP2A-induced 32P release was concentration dependently inhibited by recombinant p86-Ku, with a decrease in maximal velocity without a change in Km. Steric exclusion high pressure chromatography indicated that the inhibition resulted from direct interaction of the enzyme with p86-Ku. Furthermore, it was antagonized by increased concentrations of somatostatin-14 and prevented by preincubating p86-Ku with 30F3. Given the key role played by PP2A in cell cycle regulation, the current findings suggest that p86-Ku could be a physiological target of somatostatin antiproliferative action.     

The role of ultrasonography in the evaluation of endometrial receptivity following assisted reproductive treatments: a critical review

We set out to estimate the value of ultrasonographic parameters as prognostic indicators of implantation following in-vitro fertilization (IVF) and embryo transfer. Our survey included 414 natural cycles, 3558 cycles following ovarian stimulation for IVF and embryo transfer, and 411 cycles with hormone replacement therapy for oocyte donation, reviewing 27 reports identified in a computerized literature research. The ultrasonographic prognostic indicators for implantation evaluated included peri-ovulatory endometrial thickness and pattern and Doppler measurements of uterine artery blood flow. Topics include: definitions of the ultrasonographic parameters proposed to evaluate uterine receptivity; the clinical context in which they were used; the proposed optimal timing for sonographic evaluation; and, finally, their actual correlation with pregnancy rate following assisted reproductive technologies. For various sonographic parameters, negative predictive value, positive predictive value, sensitivity and specificity were calculated, based on published data. Sonographic parameters had a high negative predictive value and sensitivity, but a limited positive predictive value and low specificity. Several confounding factors may influence the interpretation of reports, and the statistical evaluation sometimes lacks calculation of the positive and negative predictive values of the parameters examined. Although ultrasonographic parameters of endometrial receptivity have a strong negative value in setting some minimum criteria, their value as prognostic indicators for implantation following embryo transfer has yet to be proved.     

Heuristic procedure for the reduction of finite-state machines

A practical technique for the reduction of large finite-state machines is proposed. The method is based on an empirical evaluation of the machine outputs.