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1.
Curr Pharm Biotechnol ; 3(2): 141-50, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12022257

RESUMO

The human genome sequence has given us the view of the internal genetic scaffold around which human life is molded. We have inherited this heritage from our ancestors and through it we are connected to all life on earth. The sequencing of the human genome, amongst others, has led to the newer areas of healthcare and medicine. The human population is heterogeneous and consists of populations of immense ethnic diversity. There are considerable allelic differences between human populations as well as individuals within each ethnic group as a result of molecular heterogeneity of the genome. This, in turn, is responsible for differential allelic expression of genes endowing them with polymorphic characters. The molecular diversity within genes is responsible amongst others, of disease resistance or susceptibility or for that matter drug response. The objective of this article is to understand the nuances of the genetic repertoire and correlate it with disease gene identification, genes that have been or can be used as drug targets, identify candidate genes for drug development and recent trends in drug discovery. As regular clinical trials for drugs does not take into account the ethnic variations, it sometimes results in the differential response with respect to the efficacy and/or adverse reaction of the drug. Therefore the diverse ethnic populations of the world pose a challenge to the pharma industry. The concept of the personal medicine seems to be the answer to this problem. But it is a Herculean task requiring immense innovation in technology, is time consuming and is not a financially viable proposition at this point of time. An alternate approach would be to divide the populations in genetic cohorts and design drugs according to their genetic profile and haplotype. In addition, the ethical and legal bindings have also to be taken into consideration.


Assuntos
Genoma Humano , Farmacogenética/métodos , Animais , Terapia Genética/métodos , Humanos , Tecnologia Farmacêutica/métodos
2.
Indian J Exp Biol ; 36(2): 136-47, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9754041

RESUMO

Role of free calcium and calcium binding protein calmodulin as signal molecule in cellular regulation is well established in eukaryotes. However, reports on Ca(2+)-dependent processes and their inhibition by calcium and/or calmodulin antagonists indicate towards the presence of calmodulin in prokaryotes as well. The common evolutionary origin of pro- and eukaryotes and many examples of evolutionary conservation of structure and functions support the contention of such conservation of the role of Ca2+ and calmodulin. Eukaryotic calmodulin (CaM) contains four structurally and functionally similar Ca2+ domains named I, II, III and IV. Each Ca2+ binding loop consists of 12 amino acid residues with ligands arranged spatially to satisfy the octahedral symmetry of Ca2+ binding. Plant calmodulin differ from vertebrate ones in 13 to 14 amino acid positions of which nine occur at -COOH- terminal half. Differences between protozoan and mammalian CaM also occur mostly in the same half. Isolation and characterization, although to a little extent, of CaM-like proteins from bacteria and cyanobacteria and their comparison with CaMs from diverse origin suggest high degree of conservation. Non-bulky amino acids like glycine, alanine and serine with low specific rotation are present in greater number in the primitive form of calmodulin and have been significantly reduced in highly evolved form of calmodulin, suggesting that their requirement was insignificant and were eliminated from EF hand structure during evolution. However, amino acids like glutamate/glutamine and aspartate/asparagine were highly conserved and did not show any major change in their frequency since their positions are too significant in calcium binding domain. While the number of positively charged amino acids like arginine and leucine was increased, histidine containing weakly ionized group and having a significant buffering capacity was reduced to a major extent, further suggesting that the acidic nature of calmodulin protein has been maintained during evolution. Thus it is now clear that the entire superfamily of Ca2+ binding proteins have arisen from a common genetic ancestry. Two successive tandem duplications of gene encoding a single domain containing protein of 30-40 residues gave rise to a four domain molecule from which this family was then derived.


Assuntos
Cálcio/metabolismo , Calmodulina/genética , Sequência de Aminoácidos , Calmodulina/química , Calmodulina/metabolismo , Sequência Conservada , Células Procarióticas
3.
Indian J Exp Biol ; 35(2): 103-10, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9315216

RESUMO

Lectins are structurally diverse, carbohydrate binding proteins that bind reversibly to specific mono- or oligosaccharides. Their abundance in the plant kingdom suggest that they have diverse roles to perform. They serve as recognition factor between symbiotic nitrogen fixing bacteria and host plants, as a deterrent to phytopathogens like fungi, insects, and animals, as storage protein and as an aid in sexual reproduction in Chlamydomonas, amongst others. The possible application of lectins as a factor in increasing soil fertility and as a biopesticide by genetically engineered organisms is yet to be fully explored by the biotechnologists. However, they are being used by the biomedical scientists and biochemists in blood typing and stimulation of cells for chromosome analysis and gene mapping, in cell separation, identification of complex glycoproteins and typing of bacteria. Cell targeting by lectins in cancer therapy is still in its infancy. This review gives an insight into the potential of these wonder biomolecules in agriculture, biochemistry, cell biology and medicine for the benefit of mankind.


Assuntos
Lectinas , Plantas/química , Biotecnologia , Lectinas de Plantas
4.
Cytobios ; 73(293): 115-20, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8319497

RESUMO

Chorionic villus sampling (CVS) has proved to be an elegant and safe technique for prenatal diagnosis of genetic diseases during the first trimester of pregnancy. Despite a number of obvious advantages, the wide application of direct cytogenetic analysis of CVS has been hampered by serious technical problems involving large numbers of incomplete metaphases and poor chromosome morphology. A chromosome preparation technique direct from CVS has been devised which involves modifications in the hypotonic and dissociation stages. It yielded satisfactory results in fifteen samples within 24 h of sampling. It is suggested that this simple, modified technique can provide complete chromosomal analysis within a short time for prenatal diagnosis of genetic diseases, and may be used as a routine method in cytogenetic laboratories.


Assuntos
Amostra da Vilosidade Coriônica/métodos , Doenças Genéticas Inatas/diagnóstico , Diagnóstico Pré-Natal/métodos , Adulto , Feminino , Técnicas de Preparação Histocitológica , Humanos , Gravidez
5.
Indian J Exp Biol ; 30(12): 1203-5, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1294485

RESUMO

Mitogenic potential of the partially purified lectin from P. vulgaris isolated by ammonium sulphate precipitation was assessed by lymphocyte transformation test (LTT) and was compared with three commercially available phytohemagglutinins (PHA). The blast inducing capacity and mitotic index analysis revealed that this preparation has potential to be used in the indigenous commercial production of PHA which is routinely used for human chromosomal studies from the peripheral blood culture at, at present, is imported.


Assuntos
Fabaceae/química , Ativação Linfocitária , Linfócitos/imunologia , Fito-Hemaglutininas/isolamento & purificação , Plantas Medicinais , Relação Dose-Resposta a Droga , Humanos , Índice Mitótico , Lectinas de Plantas
6.
Indian J Exp Biol ; 29(2): 116-9, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1869293

RESUMO

Phytohaemagglutinin obtained from P. vulgaris is a commonly used mitogen in lymphocyte cultures. The mitogenic potential of different cultivars of P. vulgaris vary. The present investigation encompasses the characterization of partially purified lectins from two varieties of P. vulgaris on the basis of their protein profile, lymphocyte transformation test by light and scanning electron microscopy and incorporation of radioactive thymidine.


Assuntos
Ativação Linfocitária/efeitos dos fármacos , Fito-Hemaglutininas/farmacologia , Células Cultivadas , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/ultraestrutura , Fito-Hemaglutininas/isolamento & purificação
7.
Hum Genet ; 84(2): 172-6, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2298454

RESUMO

A chromosomal survey using standard lymphocyte cultures employing different media and G-banding techniques was initiated in 1984. This study became particularly important following the tragic gaseous exposure of the population in Bhopal at midnight on 2 December 1984. We have been able to formulate a chromosomal profile for each person whom we have studied; during 1986-1988, 154 persons were examined twice. Among seemingly normal individuals, as many as 20% might possess some chromosomal abnormality; of these, 50% may develop, at a later date, some kind of pathological complication (such as tumours, recurrent abortion or transmission of defects to their offspring). The people exposed to methyl isocyanate have repeatedly shown Robertsonian translocations, mostly in acrocentric chromosomes 13 and 21. Other types of translocations have been studied among all exposed (53) and normal (101) persons; the involvement of chromosomes 5, 9, 11, 14 and 16 is statistically significant (P = less than 0.001). One of the major clinical symptoms is dyspnoea; we have estimated that almost all seriously dyspnoeic patients have developed at least two categories of chromosomal aberrations, one of which is Robertsonian translocation, in at least 10% metaphases. Our chromosomal survey will be of significance because we are able to identify people with chromosomal aberrations that might be correlated with future pathological consequences of the accident. The "chromosomal load" that can be sustained with an apparently normal phenotype can also be measured.


Assuntos
Acidentes de Trabalho , Aberrações Cromossômicas , Cianatos/intoxicação , Desastres , Intoxicação por Gás/genética , Isocianatos , Feminino , Humanos , Índia , Cariotipagem , Linfócitos/ultraestrutura , Masculino
8.
Clin Genet ; 37(1): 69-73, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1967991

RESUMO

A 35-year-old, rare male pseudohermaphrodite with inguinal hernia, testis, fallopian tube and uterus, symptoms referrable to persistent Mullerian duct syndrome, is described. The patient has a 46,XY karyotype in 50% of metaphases, while the remaining metaphases show premature cnetromeric divisions and hypoploid counts.


Assuntos
Centrômero , Cromossomos , Transtornos do Desenvolvimento Sexual/diagnóstico , Ductos Paramesonéfricos/anormalidades , Células Cultivadas , Criptorquidismo/complicações , Transtornos do Desenvolvimento Sexual/complicações , Transtornos do Desenvolvimento Sexual/genética , Hérnia Inguinal/complicações , Cariotipagem , Linfócitos/ultraestrutura , Masculino , Síndrome , Translocação Genética
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