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Biomedical subjects

A K Sil

Publications and source records attributed to A K Sil.

5 recordsLinked to original sources

Childhood blindness in India.

To date there are no published studies on blindness in children or on its incidence. Recently information on the causes of blindness in children identified by community based rehabilitation programmes in two states of India has provided very useful population based data. Prevalence and magnitude of blindness in children in India, avoidable causes and control of blindness in children at the primary, secondary and tertiary levels of health care are discussed in this article along with probable areas of research.

Blindness↗

Vectors allowing amplified expression of the Saccharomyces cerevisiae Gal3p-Gal80p-Gal4p transcription switch: applications to galactose-regulated high-level production of proteins.

The Gal4, Gal80, and Gal3 proteins of Saccharomyces cerevisiae constitute a galactose-responsive regulatory switch for GAL gene promoters. The low cellular levels of these proteins have hampered mechanistic studies and limit the utility of the GAL gene promoters for high-yield production of endogenous and exogenous proteins. We have constructed two new vectors, pMEGA2 and pMEGA2-DeltaURA3, that increase the level of the Gal4p-Gal80p-Gal3p switch proteins under conditions that preserve the Gal3p-Gal80p-Gal4p stoichiometries required for normal switch function. Cells carrying pMEGA2 show 15- to 20-fold more Gal4p and 30- to 40-fold more Gal3p and Gal80p than cells lacking pMEGA2. These high levels of Gal4p, Gal80p, and Gal3p do not perturb the integrity of galactose-inducible regulation. Cells that carry pMEGA2 exhibit normal galactose-induction kinetics for the chromosomal MEL1 gene expression and normal, albeit slower, log-phase growth. Insertion of the MEL1 gene into pMEGA2 provides a 24- to 30-fold increase in the Mel1 protein. Cells carrying a 2-microm-based URA3-selectable plasmid containing a GAL1pro:lacZ reporter gene and a second plasmid, pMEGA2-DeltaURA3, produce 12-fold more beta-galactosidase than cells carrying only the GAL1pro:lacZ reporter plasmid. The performance of the MEGA plasmids in providing amplified production of the Gal3, Gal80, and Gal4 proteins should prove useful in investigations of the mechanistic aspects of these transcription switch proteins and in work aimed at achieving high-level, galactose-regulatable production of proteins in yeast.

DNA, Recombinant↗

Regional variation in blindness in children due to microphthalmos, anophthalmos and coloboma.

BACKGROUND: The prevalence and causes of blindness in children vary widely between regions. Few epidemiological data are available on the relative importance of the major congenital anomalies of the globe (i.e., microphthalmos, anophthalmos, coloboma) as causes of blindness in children. The aim of this study was to determine the re-gional variation in the proportion of severe visual impairment and blindness due to congenital abnormalities of the globe in children in schools for the blind and in those identified through Community Based Rehabilitation programs. Other objectives were to estimate the prevalence of blindness due to major congenital abnormalities, and to investigate their etiology. METHODS: Data on the causes of blindness in children were collected between 1990 and 1998 using standard methods, definitions and reporting form in 26 countries. Children were examined in schools for the blind and in Community Based Rehabilitation programs. RESULTS: Of 7,113 children aged 3-15 years with severe visual impairment and blindness examined, 762 (10.7%) had microphthalmos, 161 (2.3%) had anophthalmos, and 96 (1.3%) had coloboma. There are large regional differences in the proportion of severe visual loss in blind school children, ranging from 1.4% in Cuba to 33.2% in Sri Lanka. Severe visual loss due to congenital abnormalities of the globe is estimated to affect between 0.4 and 16.2/100,000 children in the countries studied. An underlying cause could not be identified in 84.2%. CONCLUSIONS: Major congenital abnormalities of the globe are important causes of severe visual loss in children, particularly in Asian countries. Further research into etiology is warranted in order to plan prevention programs.

Adolescent↗

The Gal3p-Gal80p-Gal4p transcription switch of yeast: Gal3p destabilizes the Gal80p-Gal4p complex in response to galactose and ATP.

The Gal3, Gal80, and Gal4 proteins of Saccharomyces cerevisiae comprise a signal transducer that governs the galactose-inducible Gal4p-mediated transcription activation of GAL regulon genes. In the absence of galactose, Gal80p binds to Gal4p and prohibits Gal4p from activating transcription, whereas in the presence of galactose, Gal3p binds to Gal80p and relieves its inhibition of Gal4p. We have found that immunoprecipitation of full-length Gal4p from yeast extracts coprecipitates less Gal80p in the presence than in the absence of Gal3p, galactose, and ATP. We have also found that retention of Gal80p by GSTG4AD (amino acids [aa] 768 to 881) is markedly reduced in the presence compared to the absence of Gal3p, galactose, and ATP. Consistent with these in vitro results, an in vivo two-hybrid genetic interaction between Gal80p and Gal4p (aa 768 to 881) was shown to be weaker in the presence than in the absence of Gal3p and galactose. These compiled results indicate that the binding of Gal3p to Gal80p results in destabilization of a Gal80p-Gal4p complex. The destabilization was markedly higher for complexes consisting of G4AD (aa 768 to 881) than for full-length Gal4p, suggesting that Gal80p relocated to a second site on full-length Gal4p. Congruent with the idea of a second site, we discovered a two-hybrid genetic interaction involving Gal80p and the region of Gal4p encompassing aa 225 to 797, a region of Gal4p linearly remote from the previously recognized Gal80p binding peptide within Gal4p aa 768 to 881.

Adenosine Triphosphate↗