Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors.

OBJECTIVE: Hpr6 (heme-1 domain protein/human progesterone receptor) is one of a family of proteins that are implicated in progesterone metabolism, resistance to genotoxic agents and steroid biosynthesis. Because these processes are frequently misregulated in tumors, we have examined the expression of Hpr6 in a group of clinical tumor samples and cancer cell lines. METHODS: Hpr6 expression was analyzed by Western blot in extracts from breast, cervix, colon and thyroid cell lines and in nonmalignant and adjacent tumor tissue from breast, colon and thyroid. Hpr6 localization was determined by immunofluorescence. RESULTS: Hpr6 expression is significantly elevated in breast tumors in comparison with matched nonmalignant tissue and demonstrated limited overexpression in colon and thyroid tumors. Hpr6 is strongly expressed in a panel of tumor cell lines originating from breast, thyroid and colon. Hpr6 localizes to the perinuclear region of the cell, consistent with a role in cell detoxification, signaling and/or sterol synthesis. CONCLUSIONS: Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism. These are the first studies linking Hpr6 expression to cancer progression and cellular survival. Our results suggest that Hpr6 is an important marker for cancer progression and a potential anticancer therapeutic target.     

The effect of aminophylline on renin release from human chorio-decidua

The effect of aminophylline on renin release from human chorion was investigated by perfusing the tissue with various concentrations of the drug. Buffer containing aminophylline (2 X 10(-6) mol/l) doubled the rate of active and total renin secretion, but a more concentrated solution (10(-5) mol/l) released proportionately less active and total renin although the result was statistically significant. Renin secretion was not altered by aminophylline (5 X 10(-5) mol/l). The pattern of renin release was modulated by concentrations of aminophylline which were at least a 100-fold lower than those required to inhibit cyclic adenosine 3',5'-monophosphate phosphodiesterase. However, as the methylxanthines are potent adenosine receptor antagonists, we suggest that in the human chorion adenosine is a mediator of renin release.     

Applanation tonometer tip sterilization for adenovirus type 8

Eighty-nine ophthalmologists in the Dallas-Fort Worth area were surveyed to find the methods used to sterilize applanation tonometer tips. Sixteen different methods were in use, with the most popular being alcohol wipes (26%) and diluted sodium hypochlorite soak (23%). Six of the most frequently used sterilization techniques were evaluated for removal of type 8 adenovirus applied to sterile tonometer tips. Adenovirus was removed or inactivated from applanation tonometer tip surfaces by using one of the following techniques: soaking inoculated tips for 15 minutes in diluted sodium hypochlorite (1:10 household bleach), 3% hydrogen peroxide, or 70% isopropyl alcohol; or wiping with alcohol "prep pads", 1:1000 merthiolate, or dry tissues.     

微小染色体维持蛋白5和细胞增殖核抗原在肺癌组织中的表达及其临床意义

目的:检测MCM5蛋白和PCNA在肺癌组织中的表达,探讨两者与肺癌各临床病理因素之间的关系及两者相互的联系,从而为评估肺癌的发生发展、预后及治疗提供理论依据。方法:运用免疫组织化学技术分别检测MCM5蛋白和PCNA在68例肺癌组织和20例正常组织中的表达情况,分析其与临床病理因素之间的关系及两者相互的联系。结果:MCM5表达的阳性信号位于细胞核,胞浆无着色。在正常肺组织中,MCM5的表达局限在上皮基底部的1/3至1/2的细胞,在肺癌组织中,MCM5的表达分布广泛,靠近上皮表面的细胞也可见大量表达。(1)正常肺组织和肺癌组织的MCM5的表达的差别有统计学意义(P<0.01)。(2)肺癌中MCM5表达与分化程度、淋巴结转移有显著相关性(P<0.05),与病人年龄、性别无显著相关性(P>0.05)。(3)PCNA的表达与肺癌的分化程度无显著相关性(P>0.05)。(4)在肺正常组织中,PCNA标记指数高于MCM5标记指数,两者具有显著差异性(P<0.05)。在肺癌组织中,PCNA与MCM5标记指数无显著差异性(P>0.05)。结论:(1)在肺组织中,微小染色体维持蛋白5(MCM5)是一种可靠的细胞增殖标志物。根据MCM5染色的组织结构差异和平均光密度能比较准确区分肺正常组织和癌组织。MCM5表达与肺癌的分化程度显著相关,因此MCM5表达可以提示肺癌的恶性程度,有助于临床判断病人的预后以及选择合适的治疗方法。MCM5与其他增殖标志PCNA相比是一种更好的细胞增殖标志物,是肺癌细胞的更好标志和分级指标。(2)PCNA在肺癌组织中过表达,提示PCNA的过表达与肺癌的发生发展关系密切。     

Compliance with zidovudine therapy in patients infected with human immunodeficiency virus, type 1: a cross-sectional study in a municipal hospital clinic.

PURPOSE: To determine the extent of and clinical variables associated with zidovudine compliance. PATIENTS AND METHODS: A survey of 83 patients infected with human immunodeficiency virus (HIV) followed in a municipal hospital clinic was performed. Compliance histories were validated by serum and urine zidovudine levels. Patient characteristics included 46% white, 63% with a history of intravenous drug use, and 59% reporting a diagnosis of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The main outcome measure was greater than 80% compliance with prescribed doses of zidovudine over the previous week. RESULTS: Sixty-seven percent of the study patients reported greater than 80% compliance with prescribed doses of zidovudine over the previous week. The most common explanations given for missing a dose were "forgot to take zidovudine" and "did not have the medication with me." Five variables were independently associated with greater than 80% compliance as determined by stepwise multiple logistic regression: patient belief that zidovudine prolongs life (odds ratio [OR] 9.3, [95% confidence interval (CI) 2.4, 36.7]), a diagnosis of AIDS or ARC (OR 5.5, [CI 1.5, 20.4]), use of a medication timer (OR 4.4, [CI 1.0, 19.1]), no history of intravenous drug use (OR 3.7, [CI 1.0, 14.2]), and taking one to three other medications with zidovudine. CONCLUSIONS: High compliance with zidovudine was achieved by HIV-infected patients in a municipal hospital clinic, many of whom had a history of intravenous drug use. Compliance with zidovudine may be enhanced by a patient's belief that it prolongs life and the use of a medication timer for proper dosing.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.     

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience

Aims/hypothesis

Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes.

Methods

A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month?4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status.

Results

Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4?months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4?months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4?months. No differences in study outcomes were seen by FACI criteria.

Conclusions/interpretation

Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. Trial registration: ClincalTrials.gov: NCT00000620 Funding: The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.     

Pulse Wave Velocity for Assessment of Arterial Stiffness Among People With Spinal Cord Injury: A Pilot Study

Background/Objective: The most significant complication and leading cause of death for people with spinal cord injury (SCI) is coronary artery disease (CAD). It has been confirmed that aortic pulse wave velocity (PVW) is an emerging CAD predictor among able-bodied individuals. No prior study has described PWV values among people with SCI. The objective of this study was to compare aortic (the common carotid to femoral artery) PWV, arm (the brachial to radial artery) PVW, and leg (the femoral to posterior tibial artery) PVW in people with SCI (SCI group) to able-bodied controls (non-SCI group).

Methods: Participants included 12 men with SCI and 9 non-SCI controls matched for age, sex, height, and weight. Participants with a history of CAD or current metabolic syndrome were excluded. Aortic, arm, and leg PVW was measured using the echo Doppler method.

Results: Aortic PVW (mean ± SD) in the SCI group (1,274 ± 369 cm/s) was significantly higher (P < 0.05) than in the non-SCI group (948 ± 110 cm/s). There were no significant between-group differences in mean arm PVW (SCI: 1,152 ± 193 cm/s, non-SCI: 1,237 ± 193 cm/s) or mean leg PVW (SCI: 1,096 ± 1 73 cm/s, non-SCI: 994 ±178 cm/s) values.

Conclusions: Aortic PVW was higher among the SCI group compared with the non-SCI group. The higher mean aortic PVW values among the SCI group compared with the non-SCI group indicated a higher risk of CAD among people with SCI in the absence of metabolic syndrome.