The Role of the Membrane Potential of Endothelial and Smooth Muscle Cells in the Regulation of Coronary Blood Flow

Membrane Potential of Coronary Endothelial and Smooth Muscle Cells. In the mammalian heart the supply of oxygen and energy-rich substrates through the coronary arterioles is continuously adapted to the variations of cardiac work. The coronary resistance arteries and the surrounding myocardium form a functional unit with multiple interactions between coronary endothelial cells, smooth muscle cells, perivascular nerves, and cardiac muscle cells. We describe the mechanisms underlying the electrical and chemical communication between the different cell types, the ionic channels contributing to the resting potential of endothelial and smooth muscle cells, and the mechanisms responsible for modulation of the resting potential. The main conclusion of our analysis is that the membrane potential of coronary endothelial and smooth muscle cells is one of the major determinants of coronary blood flow, and that modulation of the membrane potential provides a way to dilate or constrict coronary resistance arteries. It is proposed that the membrane potential of the myo-endothelial regulatory unit, i.e., of the endothelial cells and the underlying smooth muscle cells in the terminal arterioles, may function as an integrator of the numerous local and global vasodilator and constrictor signals that provide for the adaptation of coronary blood flow to the metabolic demands of the heart.     

Why did persons invited to train in cardiopulmonary resuscitation not do so?

All citizens (N = 22066) aged 16 to 65 of a medium-sized Belgiantown were personally invited to CPR training sessions held intheir neighbourhood. 1152 responded by attending a trainingsession. Those who did not so respond were surveyed (randomsample N=600) for reasons of their not coming. The sample fittedwell with census data for gender, age and suburb location butnot for job, because retired persons and women at home wereover represented. 123 persons did not want to answer the questions. 116 personssaid they were already trained in CPR, 276 said they would accepton a future occasion and 82 said they would not. Three personsdid not answer this question. There was no discrimination for job, gender and suburb locationbetween those who did and did not accept a future training opportunity,nor was the existence of a heart patient among relatives. Theolder the person, the less inclined was that person to participatein CPR training (age effect x² = 17.17, d.f. = 9, P<0.05).The 276 who accepted future training, chose their workplace(221) and/or their social meeting place (club etc.) as the placewhere this future training should be held. We suggest that CPR training is well accepted and that the trainingopportunities should be given at places of work and social gatherings.     

Prognostic relevance of ubiquitin C-terminal hydrolase L1 (UCH-L1) mRNA and protein expression in breast cancer patients

Purpose

The ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the family of deubiquitinating enzymes. It is overexpressed in various tumour entities and associated with metastases formation in some solid tumours. However, only limited information about its role in breast cancer is available. The aim of this study was to examine the UCH-L1 expression in primary breast cancer and to determine its relevance as a potential prognostic marker.

Methods

We investigated both UCH-L1 mRNA expression in microarray data from 182 primary mammary carcinomas and UCH-L1 protein expression using a tissue microarray containing samples from 1,622 breast cancer patients.

Results

With both methods, high UCH-L1 expression correlated significantly with negative oestrogen receptor and progesterone receptor status and advanced tumour stage. Moreover by Kaplan–Meier analysis, high UCH-L1 mRNA and protein expression correlated with a significantly shorter overall survival.

Conclusion

The data of our study suggest that high levels of UCH-L1 expression indicate a more aggressive tumour behaviour and might represent a potential target in breast cancer treatment.     

Comparison of microarray-based RNA expression with ELISA-based protein determination of HER2, uPA and PAI-1 in tumour tissue of patients with breast cancer and relation to outcome

Purpose  

Prognostic and predictive markers in breast cancer are currently determined by single analysis of protein amounts. If RNA-based multi-gene analyses enter clinical practice, simultaneous determination of currently established markers like human epidermal growth factor receptor 2 (HER2), urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) would represent an elegant simplification. To investigate the correlation between RNA and protein levels, we assessed HER2, uPA and PAI-1 in patients with breast cancer. In addition, we evaluated the influence of these factors on patient outcome.     

Management of patients in Germany with suspected viral haemorrhagic fever and other potentially lethal contagious infections

Patients suffering from viral haemorrhagic fevers must be handled specifically. The clinical diagnosis of these diseases in the initial stage is difficult because early symptoms are non specific. In Germany, specific diagnosis is available at two diagnostic centres with biosafety level 4 facilities. Five high security infectious disease isolation units for patient care are available in Munich, Leipzig, Hamburg, Berlin, and Frankfurt. In addition, a corresponding number of centres of competence are established to offer support and advice to the hospitals initially treating the patients and to the local public health officers. The decentralisation of these centres of competence is recommended to allow for more timely and reactive responses to VHF epidemic threats. The risk categorisation for contacts has proved to be very useful in practice.     

Physician‐Assisted Suicide Attitudes of Older Mexican‐American and Non‐Hispanic White Adults: Does Ethnicity Make a Difference?

Little is known about attitudes toward physician‐assisted suicide (PAS) in various ethnic groups. This study compares attitudes held by older Mexican Americans and non‐Hispanic whites and examines subject characteristics that may influence their responses. A convenience sample of 100 older Mexican Americans and 108 non‐Hispanic whites (n=208) aged 60 to 89 were recruited from four primary care community‐based practice sites in San Antonio, Texas. Interview items measured attitudes toward PAS, cognitive status, functional status, and religiosity. Older Mexican Americans (52.7%) reported stronger agreement than non‐Hispanic whites (33.7%) with PAS. Male sex (odds ratio (OR)=2.62, 95% confidence interval (CI)=1.09–6.35) predicted agreement with legalization in Mexican Americans, whereas lower religiosity scores (OR=0.84, 95% CI=0.75–0.94) were predictive of agreement in older non‐Hispanic whites. This study is the first to find positive attitudes among community‐dwelling older Mexican Americans toward PAS that are higher than those of older non‐Hispanic white adults. Sex and religious views were important determinants of positive attitudes toward PAS. Larger, more‐generalizable studies should be conducted to confirm the attitudinal patterns that have been identified in this study.     

Different prevalences of Plasmodium vivax phenotypes VK210 and VK247 associated with the distribution of Anopheles albimanus and Anopheles pseudopunctipennis in Mexico

The geographic distribution of Plasmodium vivax circumsporozoite protein phenotypes from patient blood used to infect colonized Anopheles albimanus and An. pseudopunctipennis was investigated in southern Mexico. Parasite phenotype types were determined in blood samples by a polymerase chain reaction and oligoprobe hybridization or by immunofluorescent assay of sporozoites. The proportion of infected mosquitoes and the number of oocysts per mosquito confirmed previous in vitro observations indicating that An. albimanus is more susceptible to VK210 and that An. pseudopunctipennis is more susceptible to VK247. All patients living on the coast were infected with VK210 and most patients living above 170 meters above sea level had VK247. Both phenotypes infected patients from intermediate altitudes. These results concur with the distribution of the anophelines, indicating that An. albimanus is the main vector of the phenotype VK210, but that An. pseudopunctipennis transmits both phenotypes. These conditions have direct implications on parasite transmission rates and malaria epidemiology in Mexico.     

Short report: failure to select for chloroquine- or mefloquine-resistant Plasmodium berghei through drug pressure in Anopheles stephensi mosquitoes

We investigated whether chloroquine- or mefloquine-resistant Plasmodium berghei could be selected through drug pressure applied during continuous cyclical transmission in Anopheles stephensi mosquitoes. Mosquitoes were infected by feeding them on mice previously inoculated with a drug-sensitive clone of P. berghei ANKA. Mosquitoes ingested mefloquine or chloroquine with the infectious blood-meal, or by feeding on a drug-treated (uninfected) mouse 4 or 10 days after the infectious blood-meal. Twenty-two days after being infected, mosquitoes transmitted sporozoites to uninfected mice. Blood from these animals was used to infect naive mice that were then used to reinitiate the mouse/mosquito/mouse cycle. A total of 20 passages through mosquitoes were completed while under drug pressure. Drug-resistance levels were assessed in the initial clone and after 20 passages through mosquitoes. None of 18 "sub-clones" of parasites showed significant increases in chloroquine or mefloquine resistance, suggesting that exposure of sporogonic stage Plasmodium to chloroquine or mefloquine will not result in the development of drug resistance.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.