Biomedical subjects

A Lal

Publications and source records attributed to A Lal.

At least 37 records · Page 2Linked to original sources

PubMed2001

A database for regional gene expression in the human brain.

Alterations in gene expression levels have been widely studied for various neurological diseases, but few studies have sought to characterize genome-wide gene expression patterns from various regions of the normal brain. A sensitive method for quantifying transcript levels, Serial Analysis of Gene Expression (SAGE), was used to assay expression levels in white matter, thalamus, and cerebellum from the same normal brain, obtained by rapid autopsy. The complete dataset for these SAGE libraries are posted on the Cancer Genome Anatomy Project sponsored SAGEmap website where library comparisons can be made, or the data downloaded for local analysis. The expression of several region-specific genes--neurogenic differentiation 1 (cerebellum), cocaine- and amphetamine-regulated transcript (thalamus), and neurogranin (white matter)--was confirmed using quantitative fluorescent real-time RT-PCR. Further informatics analysis of the data yielded a list of brain-specific genes. The database formed by this analysis provides a means to investigate the expression status of genes involved in the region specific functions of the normal brain. These normal brain gene expression levels also are useful for comparison to pathological expression levels and a sensitive means to determine gene expression in a normal adult brain prior to formulating therapeutic strategies.

Journal Article↗

PubMed2001

Beyond pancreatic cancer: irinotecan and gemcitabine in solid tumors and hematologic malignancies.

Non-platinum combinations including gemcitabine and irinotecan (Gemzar; Eli Lilly and Company, Indianapolis, IN) for the management of a variety of malignancies have started to emerge. Gemcitabine and irinotecan are well-tolerated single agents, each with a broad spectrum of antitumor activity. Preclinical data suggests synergy for the two drugs when used in combination. A phase I trial has defined a well-tolerated combination regimen using both drugs on a day-1, -8 schedule every 3 weeks. Phase II data suggest activity for the combination in pancreatic cancer, and a phase III trial of the two-drug combination versus gemcitabine alone is underway in previously untreated pancreatic cancer patients. Other phase II trials evaluating the impact of this combination on a variety of other tumors, such as non-small cell lung, small cell lung, breast, colorectal, and non-Hodgkin's lymphoma, are either forthcoming or in progress. Semin Oncol 28 (suppl 10):34-43.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Molecular characterization of cryptosporidium oocysts in samples of raw surface water and wastewater.

Recent molecular characterizations of Cryptosporidium parasites make it possible to differentiate the human-pathogenic Cryptosporidium parasites from those that do not infect humans and to track the source of Cryptosporidium oocyst contamination in the environment. In this study, we used a small-subunit rRNA-based PCR-restriction fragment length polymorphism (RFLP) technique to detect and characterize Cryptosporidium oocysts in 55 samples of raw surface water collected from several areas in the United States and 49 samples of raw wastewater collected from Milwaukee, Wis. Cryptosporidium parasites were detected in 25 surface water samples and 12 raw wastewater samples. C. parvum human and bovine genotypes were the dominant Cryptosporidium parasites in the surface water samples from sites where there was potential contamination by humans and cattle, whereas C. andersoni was the most common parasite in wastewater. There may be geographic differences in the distribution of Cryptosporidium genotypes in surface water. The PCR-RFLP technique can be a useful alternative method for detection and differentiation of Cryptosporidium parasites in water.

Animals↗

PubMed2001

Pharmaceutical drug promotion: how it is being practiced in India?

The pharmaceutical industries (PI) throughout the World are heavily involved in aggressive drug promotions, with a clear aim to change the prescribing habits of physicians and to encourage the self-medication of patients. Broadly, drug promotion refers to all the informational and persuasive activities of the PI, the effect of which is to induce prescription, supply, purchase, and use of medicinal drugs. It includes the activities of medical representatives, drug advertisements to physicians, provision of gifts and samples, drug package inserts, direct-to-consumer advertisements, periodicals, telemarketing, holding of conferences, symposium and scientific meetings, sponsoring of medical education and conduct of promotional trials. The PI has the right to promote its products, but it should do so in a fair, accurate, and ethical manner. The promotional claims need to be reliable, truthful, informative, balanced, up-to-date, and capable of substantiation in good taste. However, now a days, whilst the promotional methods have become very sophisticated and effective, it was found that while promoting their products, the PI does not adhere to these ethical principles. Hence, in most situations, these lead to irrational use of drugs. This unfortunate situation could be tackled only by the multiple prong strategy involving government, PI, doctors, medical associations and consumers. The government is required to formulate some guidelines in addition to developing their own code. The doctors and consumers are required to be educated on the promotional practices and abuses committed by the PI and different ways to tackle those. Various medical and consumer groups should also intervene to improve the scenario of promotion.

Advertising↗

PubMed2001

Status of lifestyle modifications in hypertension.

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.

Alcohol Drinking↗

PubMed2000

Genes expressed in human tumor endothelium.

To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.

Biomarkers, Tumor↗

PubMed2000

Differential expression in an antisense MYCN neuroblastoma model.

BACKGROUND: A previously published antisense MYCN-expressing model system was utilized to identify genes whose expression is altered by the down-regulation of MYCN by AS MYCN. RESULTS: Differential display comparing nontransfected human NB NBL-S cells to three AS MYCN-expressing cell lines (NBAS-4, -5, and -6) yielded nine differentially expressed cDNAs designated NDDE:1-9, for MYCN-dependent differential expression genes. A GenBank search revealed matches for seven of the nine cDNAs. Differential expression was confirmed for five of the cDNAs by Northern blot analysis. RESULTS: NDDE:8 is up-regulated in the AS MYCN-expressing clones and shares homology with the EB1 clone p53-induced gene (PRG3). NDDE:2 is up-regulated in the high-expressing N-myc protein NBL-S cells and shares homology with a 27 kD heat shock protein PAN1 clone. Further analysis of all five cDNAs might further elucidate the targets of MYCN in NB.

Antisense Elements (Genetics)↗

PubMed2000

Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol.

The antipyretic effect of nimesulide has not been adequately compared with paracetamol and ibuprofen-paracetamol combination in children. Hence, a randomized, double blind, and parallel groups' design and multicenter study was conducted on children with respiratory tract infections. Eighty-nine patients with temperatures above 38.5 degrees C were randomly administered nimesulide (1.5 mg/kg/dose), paracetamol (10.0 mg/kg/dose), or ibuprofen-patients combination (10.0 mg/kg/dose), thrice daily for five days. The axillary temperature was recorded at the baseline and at different time intervals post administration of drugs. The hematological and biochemical investigations were performed at the basal level and at the end of the treatment period. The adverse drug reactions were monitored during the trial. All the drugs produced a significant fall in temperature as compared to their respective basal values (p < 0.001). However, on looking at the change in temperatures at different time intervals from the respective basal levels, no significant difference was found among all the drugs. Surprisingly, nimesulide had a tendency to raise serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase levels as compared to its baseline values. There was no marked adverse effect of the drugs on other hematological and biochemical parameters investigated. No other serious adverse reaction occurred in the study. Ibuprofen-paracetamol combination, nimesulide, and paracetamol had almost similar antipyretic effects in children.

Acetaminophen↗

PubMed2000

Molecular and phylogenetic analysis of Cryptosporidium muris from various hosts.

Isolates of Cryptosporidium muris and C. serpentis were characterized from different hosts using nucleotide sequence analysis of the rDNA 18S and ITS1 regions, and the heat-shock (HSP-70) gene. Phylogenetic analysis confirmed preliminary evidence that C. muris is not a uniform species. Two distinct genotypes were identified within C. muris; (1) C. muris genotype A; comprising bovine and camel isolates of C. muris from different geographical locations, and (2) C. muris genotype B comprising C. muris isolates from mice, a hamster, a rock hyrax and a camel from the same enclosure. These 2 genotypes may represent separate species but further biological and molecular studies are required for confirmation.

Animals↗

PubMed2000

An outbreak of cryptosporidiosis linked to a foodhandler.

In September and October 1998, a cryptosporidiosis outbreak occurred on a Washington, DC, university campus. In a case-control study of 88 case patients and 67 control subjects, eating in 1 of 2 cafeterias was associated with diarrheal illness (P<.001). Morbidity was associated with eating dinner on 22 September (odds ratio, 8.1; 95% confidence interval, 3.4-19.5); weaker associations were found for 6 other meals. Cryptosporidium parvum was detected in stool specimens of 16 (70%) of 23 ill students and 2 of 4 ill employees. One ill foodhandler with laboratory-confirmed C. parvum prepared raw produce on 20-22 September. All 25 Cryptosporidium isolates submitted for DNA analysis, including 3 from the ill foodhandler, were genotype 1. This outbreak illustrates the potential for cryptosporidiosis to cause foodborne illness. Epidemiologic and molecular evidence indicate that an ill foodhandler was the likely outbreak source.

Adolescent↗

PubMed2000

Identifying potential tumor markers and antigens by database mining and rapid expression screening.

Genes expressed specifically in malignant tissue may have potential as therapeutic targets but have been difficult to locate for most cancers. The information hidden within certain public databases can reveal RNA transcripts specifically expressed in transformed tissue. To be useful, database information must be verified and a more complete pattern of tissue expression must be demonstrated. We tested database mining plus rapid screening by fluorescent-PCR expression comparison (F-PEC) as an approach to locate candidate brain tumor antigens. Cancer Genome Anatomy Project (CGAP) data was mined for genes highly expressed in glioblastoma multiforme. From 13 mined genes, seven showed potential as possible tumor markers or antigens as determined by further expression profiling. Now that large-scale expression information is readily available for many of the commonly occurring cancers, other candidate tumor markers or antigens could be located and evaluated with this approach.

Algorithms↗

PubMed2000

Cryptosporidium meleagridis in an Indian ring-necked parrot (Psittacula krameri).

OBJECTIVE: To perform a morphological and genetic characterisation of a Cryptosporidium infection in an Indian ring-necked parrot (Psittacula krameri) and to compare this with C meleagridis from a turkey. DESIGN: Tissue and intestinal sections from an Indian ring-necked parrot were examined microscopically for Cryptosporidium. The organism was also purified from the crop and intestine, the DNA extracted and a portion of the 18S rDNA gene amplified, sequenced and compared with sequence and biological information obtained for C meleagridis from a turkey as well as sequence information for other species of Cryptosporidium. RESULTS: Morphological examination of tissue sections from an Indian ring-necked parrot revealed large numbers of Cryptosporidium oocysts attached to the apical border of enterocytes lining the intestinal tract. Purified Cryptosporidium oocysts measured about 5.1 x 4.5 microns, which conformed morphologically to C meleagridis. The sequence obtained from this isolate was identical to sequence information obtained from a C meleagridis isolate from a turkey. CONCLUSION: Cryptosporidium meleagridis was detected in an Indian ring-necked parrot using morphological and molecular methods. This is the first time that this species of Cryptosporidium has been reported in a non-galliform host and extends the known host range of C meleagridis.

Animals↗

PubMed2000

Cryptosporidium spp. in domestic dogs: the "dog" genotype.

Genetic and phylogenetic characterization of Cryptosporidium isolates at two loci (18S rRNA gene and heat shock gene) from both Australian and United States dogs demonstrated that dog-derived Cryptosporidium isolates had a distinct genotype which is conserved across geographic areas. Phylogenetic analysis provided support for the idea that the "dog" genotype is, in fact, a valid species.

Animals↗

PubMed2000

Molecular characterization of Cryptosporidium isolates obtained from human immunodeficiency virus-infected individuals living in Switzerland, Kenya, and the United States.

A total of 22 Cryptosporidium isolates from human immunodeficiency virus-infected patients from Kenya, Switzerland, and the United States were examined at three genetic loci: the 18S ribosomal DNA, HSP-70, and acetyl coenzyme A synthetase genes. Four distinct Cryptosporidium genotypes were identified: (i) the Cryptosporidium parvum "human" genotype, (ii) the C. parvum "cattle" genotype, (iii) Cryptosporidium felis, and (iv) Cryptosporidium meleagridis. This is the first report of C. meleagridis in a human host. These results and those of others indicate that immunocompromised individuals are susceptible to a wide range of Cryptosporidium species and genotypes. Future studies are required to understand the full public health significance of Cryptosporidium genotypes and species in immunocompromised hosts.

AIDS-Related Opportunistic Infections↗

PubMed2000

Detection of the Cryptosporidium parvum "human" genotype in a dugong (Dugong dugon).

The Cryptosporidium "human" genotype was identified in a paraffin-embedded tissue section from a dugong (Dugong dugon) by 2 independent laboratories. DNA sequencing and polymerase chain reaction/restriction fragment length polymorphism analysis of the 18S ribosomal RNA gene and the acetyl CoA synthethase gene clearly identified the genotype as that of the Cryptosporidium variant that infects humans. This is the first report of the human Cryptosporidium genotype in a nonprimate host.

Acetate-CoA Ligase↗

PubMed1999

A public database for gene expression in human cancers.

A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE) the user can compare transcript populations between any of the posted libraries. As an initial demonstration of the database's utility, gene expression in human glioblastomas was compared with that of normal brain white matter. Of the 47,174 unique transcripts expressed in these two tissues, 471 (1.0%) were differentially expressed by more than 5-fold (P<0.001). Classification of these genes revealed functions consistent with the biological properties of glioblastomas, in particular: angiogenesis, transcription, and cell cycle related genes.

Brain↗

PubMed1999

Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis.

We have isolated a full-length cDNA clone encoding a human alpha1, 2-mannosidase that catalyzes the first mannose trimming step in the processing of mammalian Asn-linked oligosaccharides. This enzyme has been proposed to regulate the timing of quality control glycoprotein degradation in the endoplasmic reticulum (ER) of eukaryotic cells. Human expressed sequence tag clones were identified by sequence similarity to mammalian and yeast oligosaccharide-processing mannosidases, and the full-length coding region of the putative mannosidase homolog was isolated by a combination of 5'-rapid amplification of cDNA ends and direct polymerase chain reaction from human placental cDNA. The open reading frame predicted a 663-amino acid type II transmembrane polypeptide with a short cytoplasmic tail (47 amino acids), a single transmembrane domain (22 amino acids), and a large COOH-terminal catalytic domain (594 amino acids). Northern blots detected a transcript of approximately 2.8 kilobase pairs that was ubiquitously expressed in human tissues. Expression of an epitope-tagged full-length form of the human mannosidase homolog in normal rat kidney cells resulted in an ER pattern of localization. When a recombinant protein, consisting of protein A fused to the COOH-terminal luminal domain of the human mannosidase homolog, was expressed in COS cells, the fusion protein was found to cleave only a single alpha1,2-mannose residue from Man(9)GlcNAc(2) to produce a unique Man(8)GlcNAc(2) isomer (Man8B). The mannose cleavage reaction required divalent cations as indicated by inhibition with EDTA or EGTA and reversal of the inhibition by the addition of Ca(2+). The enzyme was also sensitive to inhibition by deoxymannojirimycin and kifunensine, but not swainsonine. The results on the localization, substrate specificity, and inhibitor profiles indicate that the cDNA reported here encodes an enzyme previously designated ER mannosidase I. Enzyme reactions using a combination of human ER mannosidase I and recombinant Golgi mannosidase IA indicated that that these two enzymes are complementary in their cleavage of Man(9)GlcNAc(2) oligosaccharides to Man(5)GlcNAc(2).

Amino Acid Sequence↗

PubMed1999

Alpha-mannosidases involved in N-glycan processing show cell specificity and distinct subcompartmentalization within the Golgi apparatus of cells in the testis and epididymis.

The Golgi apparatus is enriched in specific enzymes involved in the maturation of carbohydrates of glycoproteins. Among them, alpha-mannosidases IA, IB and II are type II transmembrane Golgi-resident enzymes that remove mannose residues at different stages of N-glycan maturation. alpha-Mannosidases IA and IB trim Man9GlcNAc2 to Man5GlcNAc2, while alpha-mannosidase II acts after GlcNAc transferase I to remove two mannose residues from GlcNAcMan5GlcNAc2 to form GlcNAcMan3GlcNAc2 prior to extension into complex N-glycans by Golgi glycosyltransferases. The objective of this study is to examine the expression as well as the subcellular localization of these Golgi enzymes in the various cells of the male rat reproductive system. Our results show distinct cell-and region-specific expression of the three mannosidases examined. In the testis, only alpha-mannosidase IA and II were detectable in the Golgi apparatus of Sertoli and Leydig cells, and while alpha-mannosidase IB was present in the Golgi apparatus of all germ cells, only the Golgi apparatus of steps 1-7 spermatids was reactive for alpha-mannosidase IA. In the epididymis, principal cells were unreactive for alpha-mannosidase II, but they expressed alpha-mannosidase IB in the initial segment and caput regions, and alpha-mannosidase IA in the corpus and cauda regions. Clear cells expressed alpha-mannosidase II in all epididymal regions, and alpha-mannosidase IB only in the caput and corpus regions. Ultrastructurally, alpha-mannosidase IB was localized mainly over cis saccules, alpha-mannosidase IA was distributed mainly over trans saccules, and alpha-mannosidase II was localized mainly over medial saccules of the Golgi stack. Thus, the cell-specific expression and distinct Golgi subcompartmental localization suggest that these three alpha-mannosidases play different roles during N-glycan maturation.

Animals↗