Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.     

Immunoglobulin M antibody responses to Mycobacterium ulcerans allow discrimination between cases of active Buruli ulcer disease and matched family controls in areas where the disease is endemic

Buruli ulcer disease (BUD) is an emerging disease caused by Mycobacterium ulcerans. In the present study we have characterized the serological reactivities of sera from volunteer case patients with laboratory-confirmed BUD and controls living in three different regions of Ghana where the disease is endemic to determine if serology may be useful for disease confirmation. Our results showed highly reactive immunoglobulin G (IgG) responses among patients with laboratory-confirmed disease, healthy control family members of the case patients, and sera from patients with tuberculosis from areas where BUD is not endemic. These responses were represented by reactivities to multiple protein bands found in the M. ulcerans culture filtrate (CF). In contrast, patient IgM antibody responses to the M. ulcerans CF (MUCF) proteins were more distinct than those of healthy family members living in the same village. A total of 84.8% (56 of 66) of the BUD patients exhibited strong IgM antibody responses against MUCF proteins (30, 43 and 70 to 80 kDa), whereas only 4.5% (3 of 66) of the family controls exhibited such responses. The sensitivity of the total IgM response for the patients was 84.8% (95% confidence interval [CI], 74.3 to 91.6%), and the specificity determined with sera from family controls was 95.5% (95% CI, 87.5 to 98.4%). These studies suggest that the IgM responses of patients with BUD will be helpful in the identification and production of the M. ulcerans recombinant antigens required for the development of a sensitive and specific serological assay for the confirmation of active BUD.     

Relationship of internalized racism to abdominal obesity and blood pressure in Afro-Caribbean women

Racism is associated with increased psychosocial stress and blood pressure in blacks. However, little is known of the relationship of racism to other features of insulin resistance syndrome. This study examined the relationship of internalized racism to abdominal obesity and elevated blood pressure in a population of black Caribbean women aged 20-55 years. One hundred thirty-three randomly selected women from the island of Barbados comprised the study sample. Data collected included anthropometric and blood pressure measurements, and information about internalized racism, anxiety, and depression. The stress measures including anxiety, depression, and internalized racism were significantly correlated with waist circumference (r = .25, r = .21, and r = .25). After adjusting for age, education, anxiety, and depression, internalized racism remained significantly correlated with waist circumference. The odds ratio associated with development of abdominal obesity among those with high internalized racism (OR = 2.4 [95% CI, 1.1,5.3]) was significant (P < .05) after adjusting for age, education, and body mass index. Blood pressure was not independently related to internalized racism. Studies comparing black-white differences in diseases for which abdominal obesity is a risk factor (eg, diabetes and cardiovascular disease) should take into account the potential role of internalized racism in defining the differences between ethnic groups.     

The 11q13 amplicon of a mammary carcinoma cell line

Fifteen to 20% of breast carcinomas show amplification of genes located at 11q13. The HST/FGFK and INT2 fibroblast growth factor (FGF)-related genes and the BCL1 locus are usually present in the amplification units. We have investigated the structure and chromosomal location of the 11q13 amplicon of the MDA-MB-134 mammary carcinoma cell line by using in situ chromosomal and pulsed field gel hybridizations. The results indicate that a limited number of amplification units are involved in the constitution of an extended chromosomal region located on 11q. These units do not show any important rearrangement over rather large distances around the HST/INT2 and BCL1 loci.     

Affective and Behavioral Stress Outcomes in Alzheimer's Caregivers

Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring.     

Immunologic events in pigeon breeders'' disease

The immunologic and physiologic status of a group of symptomatic and asymptomatic pigeon breeders was studied in an attempt to define the immunologic events occurring in pigeon breeders' disease. Antibody activity to antigen(s) present in pigeon dropping extract (PDE) and pigeon serum (PS) was detected in the serum of both symptomatic and asymptomatic breeders. Antibody activity, however, tended to be greater in the symptomatic pigeon breeders. When subjects were challenged with PS via aerosol, serum complement activity became depressed only in asymptomatic patients. Cellular hypersensitivity to antigens present in PDE was detected in vitro in peripheral lymphocyte populations of 4 of 5 symptomatic breeders and in none of the asymptomatic breeders; cellular hypersensitivity to antigens in PS was not demonstrated in any of the individuals tested. These findings indicate that cell-mediated hypersensitivity, as well as humoral immunologic processes, may be involved in the pathogenesis of the hypersensitivity pneumonitis found in pigeon breeders.     

Tardive dyskinesia successfully treated with alprazolam

Tardive dyskinesia is a disorder secondary to prolonged treatment (from 18 months to 3 years) with antipsychotic agents, affecting approximately 15% to 20% of patients. Tardive dyskinesia is characterized by difficulty controlling involuntary movements of the small muscle groups, producing tic-like reactions, muscle rigidity, and difficulty maintaining muscle tone. It is a chronic and unrelenting disorder which may be permanent if not successfully treated. The mechanism of action is thought to be secondary to dopamine hypersensitivity resulting from prolonged deprivation of dopamine on the part of dopamine-sensitive receptors. Theoretically, these receptors have been deprived of the neurotransmitter by chronic treatment with antipsychotic drugs, which are recognized as dopamine-blocking agents. We present a case in which alprazolam was successfully used in treating tardive dyskinesia.