Protective effect of the Nramp1 BB genotype against Brucella abortus in the water buffalo (Bubalus bubalis)

We tested 413 water buffalo cows (142 cases and 271 controls) for the presence of anti-Brucella abortus antibodies (by the skin test, the agglutination test, and the complement fixation test) and the Nramp1 genotype (by capillary electrophoresis). Four alleles (Nramp1A, -B, -C, and -D) were detected in the 3' untranslated region of the Nramp1 gene. The BB genotype was represented among only controls, providing evidence that this genotype confers resistance to Brucella abortus. The monocytes from the BB (resistant) subjects displayed a higher basal level of Nramp1 mRNA and a lower number of viable intracellular bacteria than did the monocytes from AA (susceptible) subjects. The higher basal level of the antibacterial protein Nramp1 most probably provides the BB animals with the possibility of controlling bacteria immediately after their entry inside the cell.     

The relationship between socioeconomic status, ethnicity, and cigarette smoking in urban adolescents

BACKGROUND: This study examined the relationship between community-level and school-level socioeconomic status indicators and current cigarette smoking among urban adolescents, and examined whether the socioeconomic status-cigarette smoking relationship was similar for African Americans and Whites. METHODS: Participants were 3,813 seventh-graders recruited in a large school system in the United States. Independent variables included median income and mean education within zip codes of participants' residence, percentage of participants receiving lunch at reduced or no cost at school level, and ethnicity. The dependent variable was current smoking status (never smoked vs smoking one or more cigarettes per month). RESULTS: Whites were significantly more likely than African Americans to smoke cigarettes. There was a main effect of education and lunch at reduced or no cost on cigarette smoking. Mean education by zip code was inversely associated with cigarette smoking, and lunch at reduced or no cost was directly associated with cigarette smoking. There was a significant interaction between income and ethnicity. Median income by zip code was directly associated with cigarette smoking among African Americans. CONCLUSIONS: Our findings suggest that smoking prevention efforts in this population should take both socioeconomic status and ethnicity into account.     

A Phase 1/2a Follistatin Gene Therapy Trial for Becker Muscular Dystrophy

Becker muscular dystrophy (BMD) is a variant of dystrophin deficiency resulting from DMD gene mutations. Phenotype is variable with loss of ambulation in late teenage or late mid-life years. There is currently no treatment for this condition. In this BMD proof-of-principle clinical trial, a potent myostatin antagonist, follistatin (FS), was used to inhibit the myostatin pathway. Extensive preclinical studies, using adeno-associated virus (AAV) to deliver follistatin, demonstrated an increase in strength. For this trial, we used the alternatively spliced FS344 to avoid potential binding to off target sites. AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections. Cohort 1 included three subjects receiving 3 × 10¹¹ vg/kg/leg. The distance walked on the 6MWT was the primary outcome measure. Patients 01 and 02 improved 58 meters (m) and 125 m, respectively. Patient 03 showed no change. In Cohort 2, Patients 05 and 06 received 6 × 10¹¹ vg/kg/leg with improved 6MWT by 108 m and 29 m, whereas, Patient 04 showed no improvement. No adverse effects were encountered. Histological changes corroborated benefit showing reduced endomysial fibrosis, reduced central nucleation, more normal fiber size distribution with muscle hypertrophy, especially at high dose. The results are encouraging for treatment of dystrophin-deficient muscle diseases.     

Ultrastructural study of autologous cultivated conjunctival epithelium.

BACKGROUND AND OBJECTIVE: This report is one of the first in the literature on the attempted cultivation and clinical application of human conjunctival epithelium. The authors investigated the possibility of restoring severely damaged ocular surface with autologous cultivated conjunctival epithelium. PATIENTS AND METHODS: The conjunctival cells needed for the experiment were harvested from six patients with oculopalpebral diseases. Confluent epithelial sheets were developed from each biopsy specimen. The new epithelium was then implanted on the patients' or donors' eye surface. RESULTS: The histologic examination showed a pluristratified squamous non-keratinized epithelium lying on a basement membrane and with a lamina propria of well-vascularized connective tissue. Normal ultrastructural characteristics were evident on electron microscopy. CONCLUSION: The cultivation of autologous conjunctival cells may be a good option for rapid and safe repair of large single or bilateral conjunctival defects, as an alternative to heterotopic or allogenic grafts.