Gene expression of LDL receptor, HMG-CoA reductase, and cholesterol-7 alpha-hydroxylase in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic lipid profile and an increased risk of ischaemic cardiovascular disease. The associated hyperlipidaemia is reportedly ameliorated by erythropoietin (Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed a high- protein diet exhibited increased activities of hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND METHODS: This study was designed to examine the effects of naturally progressing CRF of longer duration as well as those of Epo therapy on gene expressions of the key factors involved in hepatic cholesterol metabolism, i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group (given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated normal controls. They were allowed free access to regular rat chow and studied 6 weeks after surgery. Liver mRNAs and protein mass or activities of the above factors were studied. RESULTS: Plasma cholesterol concentration was significantly increased in the CRF group (P < 0.001) and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were similar to those of the normal control group representing an inappropriate response to the associated hypercholesterolemia. Epo therapy led to partial amelioration of CRF- associated hypercholesterolaemia with no discernible effect on hepatic tissue expression of the above factors.      

Improving survival and limb salvage in patients with aortic graft infection

A 15-year experience with 38 aortic graft infections, including 15 patients with graft enteric fistulas, is reviewed in order to analyze modern-day surgical results utilizing extra-anatomic bypass and aortic graft excision. Perioperative mortality was 14% during the most recent 7-year interval, which was a notable improvement compared with the earlier time interval (p = 0.06). Extended follow-up of the perioperative survivors demonstrated a 77% cumulative 5-year survival and a 76% cumulative 5-year limb salvage rate. Subsequent axillofemoral graft infection occurred in 22% of survivors and resulted in a significantly higher amputation rate compared with those patients with no axillofemoral graft infection (p less than 0.001). The results suggest good perioperative and long-term survival in patients with aortic graft infection, with excellent limb salvage if subsequent axillofemoral graft infection can be avoided.     

Transmitter release from presynaptic terminals of electric organ: inhibition by the calcium channel antagonist omega Conus toxin

Cholinergic synaptosomes from electroplax of the ray Ommata discopyge release both ATP and ACh when depolarized with high K+ concentration in the presence of Ca2+. Others have shown that the ATP and ACh are released in the molar ratio found in isolated synaptic vesicles. Thus, it is assumed that the release of ATP reflects exocytosis of synaptic vesicles, and that transmitter release can be indirectly monitored by assaying ATP release. We present further evidence for this assumption and examine the effects of presynaptic neurotoxins on this ATP release. As expected for transmitter release, we find that depolarization-evoked ATP release is supported by Sr2+ and Ba2+ and is inhibited by the Ca channel antagonists Co2+ and Mn2+. Likewise, the presynaptic toxins omega-CmTX and omega-CgTX, omega peptides from the venom of the marine snails Conus magus and Conus geographus, respectively, inhibit 80% of the depolarization-evoked ATP release. Half-maximal inhibition of ATP release occurs with approximately 0.5 microM of either toxin. The toxins' effects are reversible, and when toxin is washed away, the time dependence of recovery of release is approximately first order and half complete within 40 min with omega-CmTX and 15 min with omega-CgTX. The Ca2+ ionophore A23187 induces Ca2+-dependent ATP release from resting synaptosomes. As would be expected of a Ca channel antagonist, omega-CmTX does not affect this ionophore-induced release. Leptinotarsin-d (LPTd), a putative Ca channel agonist from the Colorado potato beetle, evokes Ca2+-dependent ATP release from resting synaptosomes. omega-CmTX does not block LPTd-evoked release of ATP, which suggests that omega-CmTX and LPTd act at different sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic significance of immunoglobulin M antibodies to Toxoplasma gondii detected after separation of immunoglobulin M from immunoglobulin G antibodies.

Failure to demonstrate immunoglobulin M (IgM) antibodies by indirect immunofluorescence (IgM-IFA) in sera from some patients with acute acquired toxoplasmosis has recently been attributed to an inhibitory effect of high titers of IgG antibodies in these sera (Pyndiah et al. J. Clin. Microbiol. 9:170-174, 1979). To confirm these findings and define their importance for diagnosis, we used gel filtration to separate IgM from IgG antibodies in a series of sera that were negative in the IgM-IFA test. A total of 68 sera were from patients with acquired toxoplasmosis, 13 were from uninfected adults, 13 were from infants with congenital toxoplasmosis, and 7 were from uninfected neonates. Of the 68 sera from patients with acquired toxoplasmosis, IgM preparations (from the separated sera) were positive in the IgM-IFA test in 36 (53%). There was a significant (P = 0.00003) association between high titers of IgM-IFA antibodies in the IgM preparations (corrected for dilution of IgM antibodies by the gel filtration procedure) and recent acquisition of infection. IgM antibodies were also detected in 5 (38%) of the IgM preparations of 13 sera from congenitally infected infants but not in any of the IgM preparations of sera from uninfected neonates. IgG antibodies to Toxoplasma gondii were shown to interfere with demonstration of IgM antibodies in the IgM-IFA test. Treatment of sera with protein A resulted in greater dilution of IgM antibodies and less efficient separation of IgM from IgG antibodies than did separation of sera by gel filtration. Treatment of sera with protein A did not result in increased detection of IgM antibodies to T. gondii. Testing of IgM preparations (obtained by gel filtration) resulted in a significant increase in sensitivity of the IgM-IFA test for the diagnosis of recently acquired and congenital toxoplasmosis.     

Comparison of ejection fraction and Goldman risk factor analysis to dipyridamole-thallium 201 studies in the evaluation of cardiac morbidity after aortic aneurysm surgery

Associated coronary artery disease is the critical factor that influences early and late mortality after abdominal aortic aneurysm surgery. Dipyridamole-thallium 201 scintigraphy, left ventricular ejection fraction, and Goldman risk factor analysis have been suggested as preoperative noninvasive screening methods to detect significant coronary artery disease. In this series of 95 elective abdominal aortic aneurysm repairs dipyridamole-thallium 201 scintigraphy was highly predictive of the absence of perioperative cardiac morbidity (96% specificity, 44/46 normal scans, no cardiac morbidity), whereas ejection fraction (73% specificity, 31/42 normal ejection fraction, no cardiac morbidity) and Goldman risk factor analysis (84% specificity, 44/51 class I, no cardiac morbidity) were less. Furthermore, thallium redistribution on dipyridamole-thallium 201 scintigraphy leading to coronary angiography identified a significant number of patients with occult coronary artery disease who required preoperative coronary revascularization (8%, 8/95) and might have remained undetected on the basis of left ventricular ejection fraction or Goldman risk factor analysis. Finally, fixed thallium deficit, which some investigators have interpreted as a low probability finding for cardiac morbidity, was associated with a higher than expected incidence of cardiac complications. Forty-six percent (7/15) of all postoperative cardiac complications (three myocardial infarctions, three ischemic events, one death) occurred in patients with abdominal aortic aneurysms with fixed deficits. This suggests that patients with fixed deficits on dipyridamole-thallium 201 scintigraphy should be considered for later "delayed" (4 hours) thallium images or coronary angiography or both.     

Haemoptysis in healthy children due to unsuspected foreign body

Abstract: Haemoptysis in otherwise healthy children is an uncommon event. Two cases of massive haemoptysis, subsequently requiring lobectomy, are discussed. In each case, foreign vegetable matter was identified despite previously normal bronchoscopy and minimal changes on chest radiograph.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.