Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.     

Application of transcatheter valves for aortic valve replacement in pediatric patients: A case series

• Diabetic patients are frequently affected by coronary artery disease (CAD) and are at increased risk of CAD‐related adverse events, even after drug‐eluting stent (DES) implantation. If currently available DES have similar safety and efficacy in diabetic and nondiabetic patients is still debated.
• This prospective, multicenter registry showed similar 3‐year outcome in patients undergoing different DES implantation, although diabetic patients, especially those requiring insulin treatment, had significantly higher risk of adverse events than nondiabetic patients.
• Specific efforts to improve the performance of DES in diabetic patients are mandatory to adequately address the unsolved issue of diabetic patients affected by CAD.

     

Metabolism of prolactin in mice with a high incidence of mammary tumours: evidence for greater conversion into a non-immunoassayable form.

Monomeric mouse prolactin containing small amounts of 125I-labelled prolactin was administered to adult female mice of a high (C3H/St) and low (C57BL/St) mammary tumour strain. Their endogenous prolactin had been suppressed with 2-bromo-alpha-ergocryptine. The chromatographic profile, on Sephadex G-100, of prolactin in the serum of mice injected with mouse prolactin was compared by direct measurement (radioactivity count) and by radioimmunoassay (RIA) at several intervals after injection. With both methods, the injected hormone was found in the serum in predominantly two molecular sizes, the so-called 'big' and 'little' forms. Although 'little' prolactin in both strains constituted a constant 80% of the total hormone at most intervals by direct measurement, it comprised a comparatively smaller proportion by RIA. In addition, the RIA-determined 'little' prolactin, after reaching maximum levels at 15 min, progressively decreased with time, the decrease being greater in the C3H/St than in the C57BL/St strain. Similar experiments with mouse growth hormone revealed no such discrepancies between the radioactivity counts and the RIA measurements. A fraction of both 'big' and 'little' forms in the C3H/St strain failed to precipitate completely after the material had been incubated with an antiserum to mouse prolactin. These results demonstrate that the prolactin injected into mice is metabolized in serum into two non-immunoreactive forms, one that elutes with the same elution volume on Sephadex G-100 column as the monomer and the other that elutes as the 'big' form. Furthermore, the loss of immunoreactivity of monomeric mouse prolactin is greater in the high-tumour C3H/St strain than in the low-tumour C57BL/St strain. Endogenous immunoreactive prolactin, on the other hand, was found mainly in the 'big' form in the serum of female mice of the C3H/St strain under basal conditions, whereas it was present only in the 'little' form in comparable mice of the C57BL/St strain, even though pituitary extracts of both strains contained mainly the 'little' form. These results support the concept that monomeric prolactin in the systemic circulation of the tumour-prone C3H/St strain is largely in a non-immunoreactive form.     

Unusual dynamics of extinction in a simple ecological model.

Studies on natural populations and harvesting biological resources have led to the view, commonly held, that (i) populations exhibiting chaotic oscillations run a high risk of extinction; and (ii) a decrease in emigration/exploitation may reduce the risk of extinction. Here we describe a simple ecological model with emigration/depletion that shows behavior in contrast to this. This model displays unusual dynamics of extinction and survival, where populations growing beyond a critical rate can persist within a band of high depletion rates, whereas extinction occurs for lower depletion rates. Though prior to extinction at lower depletion rates the population exhibits chaotic dynamics with large amplitudes of variation and very low minima, at higher depletion rates the population persists at chaos but with reduced variation and increased minima. For still higher values, within the band of persistence, the dynamics show period reversal leading to stability. These results illustrate that chaos does not necessarily lead to population extinction. In addition, the persistence of populations at high depletion rates has important implications in the considerations of strategies for the management of biological resources.     

Eating Pathology among Women with Alcoholism and/ or Anxiety Disorders

Two hundred one non-treatment seeking women with alcoholism, anxiety disorders, alcoholism and anxiety disorders, or neither alcoholism nor anxiety disorders were interviewed to assess core psychopathology associated with eating disorders using the Eating Disorders Examination and DSM-IIIR psychiatric diagnoses using the Schedule of Affective Disorders and Schizophrenia-Lifetime version. Alcoholic women had significantly higher mean scores on each of the Eating Disorders Examination subscales of Restraint, Overeating, Eating Concern, Shape Concern, and Weight Concern compared with nonalcoholic women. Women with anxiety disorders had significantly elevated scores on subscales of Overeating, Eating Concern, and Weight Concern compared with women without anxiety disorders. Women with both alcoholism and anxiety disorders had higher rates of bulimia nervosa and/or eating disorder NOS compared with women with either disorder alone. Implications of these findings are discussed in the context of the co-morbid association between alcoholism, eating disorders, and anxiety disorders.     

A community-based, comparative evaluation of direct agglutination and rK39 strip tests in the early detection of subclinical Leishmania donovani infection

In the Indian state of Bihar, the sensitivities and specificities of direct agglutination tests (DAT) and rK39 test strips for the detection of Leishmania donovani infection in humans were explored and found to be generally good (92%-100%). When 172 asymptomatic individuals [16 'case-contacts' who lived in the same households as past or current, confirmed cases of visceral leishmaniasis (VL) and 156 other subjects from neighbouring households] were tested, the same 36 (21%) individuals, including all 16 'case-contacts', were found seropositive using each type of test. When followed-up after 3 months, 18 of the individuals who had been found seropositive in the baseline survey remained seropositive, and eight (44%) of these had developed symptomatic VL, with amastigotes in their splenic aspirates. Seven (44%) of the 16 'case-contacts' but only one (5%) of the other 20 subjects found seropositive at baseline went on to develop VL within 3 months. Although the strip test appeared slightly better than DAT for predicting the development of VL in the 172 subjects, either type of test may be very useful for the early detection of asymptomatic L. donovani infection and thus the identification of those at relatively high risk of developing VL.     

Biodegradable microspheres for protein delivery

In a very short time, since their emergence, the field of controlled delivery of proteins has grown immensely. Because of their relatively large size, they have low transdermal bioavailabilities. Oral bioavailability is generally poor since they are poorly absorbed and easily degraded by proteolytic enzymes in the gastrointestinal tract. Ocular and nasal delivery is also unfavorable due to degradation by enzymes present in eye tissues and nasal mucosa. Thus parenteral delivery is currently most demanding and suitable for delivery of such molecules. In systemic delivery of proteins, biodegradable microspheres as parenteral depot formulation occupy an important place because of several aspects like protection of sensitive proteins from degradation, prolonged or modified release, pulsatile release patterns. The main objective in developing controlled release protein injectables is avoidance of regular invasive doses which in turn provide patient compliance, comfort as well as control over blood levels. This review presents the outstanding contributions in field of biodegradable microspheres as protein delivery systems, their methods of preparation, drug release, stability, interaction with immune system and regulatory considerations.     

A 16/6 idiotype-positive anti-DNA antibody is encoded by a conserved VH gene with no somatic mutation

Recently, the heavy chain of 16/6 idiotype-positive human anti-DNA antibodies was found to be similar, but not identical, to the VH26 gene. We resequenced the VH26 gene and found that its coding sequence is actually identical to the complementary DNA sequence of the anti-DNA antibodies previously described. Together with the previous data, our findings demonstrate that some human autoantibodies are encoded directly by immunoglobulin V region genes, and that these V region genes are remarkably conserved in populations.