Age at arrival and risk of obesity among US immigrants

Although immigrants are a rapidly growing subgroup, little is known about overweight/obesity among the foreign-born in the United States, especially regarding the effect of age at arrival. This study determined whether overweight/obesity prevalence is associated with age at arrival of immigrants to the United States. We analyzed data on 6,421 adult immigrants from the New Immigrant Survey (NIS), a study that is nationally representative of adult immigrants with newly acquired legal permanent residence (LPR). Multiple regression analyses tested the effects of duration of residence and age at arrival on overweight/obesity, defined by BMI of > or = 25 kg/m(2), and self-reported dietary change score. We found the relationship between duration of residence and overweight/obesity prevalence varied by age at arrival (P < 0.001). Immigrants < or = 20-years old at arrival who had resided in the United States > or = 15 years were 11 times (95% confidence interval: 5.33, 22.56) more likely to be overweight/obese than immigrants < 20-years old at arrival who had resided in the United States < or = 1 year. By comparison, there was no difference in overweight/obesity prevalence by duration among immigrants who arrived at >50 years of age. Higher self-reported dietary change is also associated with overweight/obesity. In conclusion, immigrants younger than 20 at arrival in the United States may be at higher risk of overweight/obesity with increasing duration of residence than those who arrive at later ages. Obesity prevention among young US immigrants should be a priority.     

Genetic analysis of HIV-1 subtypes in Nairobi, Kenya

Background

Genetic analysis of a viral infection helps in following its spread in a given population, in tracking the routes of infection and, where applicable, in vaccine design. Additionally, sequence analysis of the viral genome provides information about patterns of genetic divergence that may have occurred during viral evolution.

Objective

In this study we have analyzed the subtypes of Human Immunodeficiency Virus -1 (HIV-1) circulating in a diverse sample population of Nairobi, Kenya.

Methodology

69 blood samples were collected from a diverse subject population attending the Aga Khan University Hospital in Nairobi, Kenya. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs), and used in a Polymerase Chain Reaction (PCR) to amplify the HIV gag gene. The PCR amplimers were partially sequenced, and alignment and phylogenetic analysis of these sequences was performed using the Los Alamos HIV Database.

Results

Blood samples from 69 HIV-1 infected subjects from varying ethnic backgrounds were analyzed. Sequence alignment and phylogenetic analysis showed 39 isolates to be subtype A, 13 subtype D, 7 subtype C, 3 subtype AD and CRF01_AE, 2 subtype G and 1 subtype AC and 1 AG. Deeper phylogenetic analysis revealed HIV subtype A sequences to be highly divergent as compared to subtypes D and C.

Conclusion

Our analysis indicates that HIV-1 subtypes in the Nairobi province of Kenya are dominated by a genetically diverse clade A. Additionally, the prevalence of highly divergent, complex subtypes, intersubtypes, and the recombinant forms indicates viral mixing in Kenyan population, possibly as a result of dual infections.     

Modeling and interactions of Aspergillus fumigatus lanosterol 14-alpha demethylase 'A' with azole antifungals

Recent identification of the sterol 14-alpha demethylase genes (CYP51 A and B) from Aspergillus fumigatus and other species by Mellado et al. (J. Clin. Microbiol. 2001, 39(7), 2431-2438), has opened up possibilities of investigating the interactions of azole antifungals with the enzyme(s) from fungi. This study describes for the first time, a model of the three-dimensional structure of A. fumigatus 14-alpha demethylase (AF-CYP51A), using the crystal structure of Mycobacterium tuberculosis 14-alpha demethylase (PDB code:1EA1) as a template. The paper also describes the various interactions between azole antifungals and the target from A. fumigatus (AF-CYP51A). Quantitative evaluation of these interactions is done using COMBINE analysis to understand contributions of active site residues to ligand activity. It also provides explanation for the activity/inactivity of different ligands for AF-CYP51A.     

Myosin-18B Promotes the Assembly of Myosin II Stacks for Maturation of Contractile Actomyosin Bundles

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Therapeutic Effects of α1-Antitrypsin on Psedumonas aeruginosa Infection in ENaC Transgenic Mice

Cystic fibrosis (CF) is a genetic disease with many airway pathological features, including aberrant epithelial sodium channel (ENaC) function, persistent Pseudomonas aeruginosa (PA) infection and neutrophil-dominant inflammation. PA infection in CF airways is difficult to treat due to antibiotic resistance and other factors. Recently, α1-antitrypsin (A1AT) have been shown to be effective to reduce CF airway PA infection. However, there is a dearth of studies about the mechanisms underlying A1AT’s therapeutic effects. The goal of our study is to provide an animal model of A1AT therapy in CF lungs. ENaC transgenic mice with PA infection were used as a CF-like model. Mice were intratracheally treated with PA or saline (control) in a fibrin plug. Two hours after PA infection, aerosolized A1AT were delivered to mouse lungs once daily. At day 1 and day 3 post PA infection, lung inflammation, PA load as well as host defence protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) were measured. At day 1 post PA infection when A1AT was delivered once to ENaC transgenic mouse lungs, A1AT did not reduce lung inflammation (e.g., neutrophils) and PA load. However, at day 3 post PA infection when ENaC transgenic mice received three repeated A1AT treatments, a significant decrease in airspace inflammation and PA load was observed. Although A1AT prevented the loss of SPLUNC1 in bronchoalveolar lavage fluid of PA-infected wild-type mice, it did not restore SPLUNC1 levels in ENaC transgenic mice. Our current study has provided a valid and quick A1AT therapeutic model in CF-like lungs that may serve as a platform for future mechanistic studies about how A1AT exerts beneficial effects in human CF patients.     

Sintering of wax for controlling release from pellets

The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%–20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusion of ground or emulsified carnauba wax did not sustain the release of theophylline for more than 3 hours. Matrix pellets of theophylline prepared with various concentrations of carnauba wax were sintered thermally at various times and temperatures. In vitro drug release profiles indicated an increase in drug release retardation with increasing carnauba wax concentration. Pellets prepared with ground wax showed a higher standard deviation than did those prepared with emulsified wax. There was incomplete release at the end of 12 hours for pellets prepared with 20% ground or emulsified wax. The sintering temperature and duration were optimized to allow for a sustained release lasting at least 12 hours. The optimized temperature and duration were found to be 100° and 140 seconds, respectively. The sintered pellets had a higher hydrophobicity than did the unsintered pellets. Scanning electron micrographs indicated that the carnauba wax moved internally, thereby increasing the surface area of wax within the pellets. Published: September 14, 2007     

Comparative study of myelodysplastic syndromes and normal bone marrow biopsies with conventional staining and immunocytochemistry

OBJECTIVE: To study the histomorphometric features of megakaryocytic elements in bone marrow trephine biopsies of various subtypes of myelodysplastic syndrome (MDS). STUDY DESIGN: Comparative image morphometry using hematoxylin-eosin-stained and CD 61-stained trephine biopsies was carried out on 40 cases of MDS and 10 normal subjects to analyze the megakaryocytes objectively. The various variables analyzed were number of megakaryocytes and micromegakaryocytes, area, perimeter and diameter of the megakaryocytic elements. RESULTS: The mean number of megakaryocytes was lower in cases of MDS as compared to the normals in all except for a single case of hypoplastic MDS, in which the megakaryocytes were more abundant (3.6 per high-power field [hpf]). No micromegakaryocytes were observed in the 2 cases of chronic myelomonocytic leukemia. The mean area, perimeter and diameter of megakaryocytes decreased significantly on immunostaining with CD 61. CONCLUSION: The mean number of megakaryocytes per hpf was lower in the cases of MDS as compared to normal cases on hematoxylin-eosin. However, on CD 61 staining the number of megakaryocytes per hpf increased in cases of MDS. Micromegakaryocytes were seen in scanty numbers in the normals but increased in MDS cases and increased significantly on CD 61 immunostaining. The mean area, perimeter and diameter of megakaryocytes decreased significantly on immunostaining with CD 61, indicating the increased numbers of micromegakaryocytes in MDS. Hence, immunostaining is an efficient method of detecting increased numbers of megakaryocytes and micromegakaryocytes that would ordinarily be missed by using routine hematoxylin-eosin staining.     

Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose transport and cell division

Protein kinases have a diverse array of functions in bacterial physiology, with a distinct role in the regulation of development, stress responses, and pathogenicity. pknF, one of the 11 kinases of Mycobacterium tuberculosis, encodes an autophosphorylating, transmembrane serine/threonine protein kinase, which is absent in the fast-growing, nonpathogenic Mycobacterium smegmatis. Herein, we investigate the physiological role of PknF using an antisense strategy with M. tuberculosis and expressing PknF and its kinase mutant (K41M) in M. smegmatis. Expression of PknF in M. smegmatis led to reduction in the growth rate and shortening and swelling of cells with constrictions. Interestingly, an antisense strain of M. tuberculosis expressing a low level of PknF displayed fast growth and a deformed cell morphology compared to the wild-type strain. Electron microscopy showed that most of the cells of the antisense strain were of a smaller size with an aberrant septum. Furthermore, nutrient transport analysis of these strains was conducted using 3H-labeled and 14C-labeled substrates. A significant increase in the uptake of D-glucose but not of glycerol, leucine, or oleic acid was observed in the antisense strain compared to the wild-type strain. The results suggest that PknF plays a direct/indirect role in the regulation of glucose transport, cell growth, and septum formation in M. tuberculosis.