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A Lal

Publications and source records attributed to A Lal.

At least 19 recordsLinked to original sources
PubMed2002

An international database and integrated analysis tools for the study of cancer gene expression.

Researchers working collaboratively in Brazil and the United States have assembled an International Database of Cancer Gene Expression. Several strategies have been employed to generate gene expression data including expressed sequence tags (ESTs), serial analysis of gene expression (SAGE), and open reading-frame expressed sequence tags (ORESTES). The database contains six million gene tags that reflect the gene expression profiles in a wide variety of cancerous tissues and their normal counterparts. All sequences are deposited in the public databases, GenBank and SAGEmap. A suite of informatics tools was designed to facilitate in silico analysis of the gene expression datasets and are available through the NCI Cancer Genome Anatomy Project web site (http://cgap.nci.nih.gov).

DNA, Complementary↗
PubMed2001

Transcriptional response to hypoxia in human tumors.

BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy. To investigate the mechanisms by which cancer cells adapt to hypoxia, we looked for novel hypoxia-induced genes. METHODS: The transcriptional response to hypoxia in human glioblastoma cells was quantified with the use of serial analysis of gene expression. The time course of gene expression in response to hypoxia in a panel of various human tumor cell lines was measured by real-time polymerase chain reaction. Hypoxic regions of human carcinomas were chemically marked with pimonidazole. Immunohistochemistry and in situ hybridization were used to examine gene expression in the tumor's hypoxic regions. RESULTS: From the 24 504 unique transcripts expressed, 10 new hypoxia-regulated genes were detected-all induced, to a greater extent than vascular endothelial growth factor, a hypoxia-induced mitogen that promotes blood vessel growth. These genes also responded to hypoxia in breast and colon cancer cells and were activated by hypoxia-inducible factor 1, a key regulator of hypoxic responses. In tumors, gene expression was limited to hypoxic regions. Induced genes included hexabrachion (an extracellular matrix glycoprotein), stanniocalcin 1 (a calcium homeostasis protein), and an angiopoietin-related gene. CONCLUSIONS: We have identified the genes that are transcriptionally activated within hypoxic malignant cells, a crucial first step in understanding the complex interactions driving hypoxia response. Within our catalogue of hypoxia-responsive genes are novel candidates for hypoxia-driven angiogenesis.

Blotting, Western↗
PubMed2001

Evidence for clonal propagation in natural isolates of Plasmodium falciparum from Venezuela.

We have analyzed 75 isolates of Plasmodium falciparum, collected in Venezuela during both the dry (November) and rainy (May-July) seasons, with a range of genetic markers including antigen genes and 14 random amplified polymorphic DNA (RAPD) primers. Thirteen P. falciparum stocks from Kenya and four other Plasmodium species are included in the analysis for comparison. Cross-hybridization shows that the 14 RAPD primers reveal 14 separate regions of the parasite's genome. The P. falciparum isolates are a monophyletic clade, significantly different from the other Plasmodium species. We identify three RAPD characters that could be useful as "tags" for rapid species identification. The Venezuelan genotypes fall into two discrete genetic subdivisions associated with either the dry or the rainy season; the isolates collected in the rainy season exhibit greater genetic diversity. There is significant linkage disequilibrium in each seasonal subsample and in the full sample. In contrast, no linkage disequilibrium is detected in the African sample. These results support the hypothesis that the population structure of P. falciparum in Venezuela, but not in Africa, is predominantly clonal. However, the impact of genetic recombination on Venezuelan P. falciparum seems higher than in parasitic species with long-term clonal evolution like Trypanosoma cruzi, the agent of Chagas' disease. The genetic structure of the Venezuelan samples is similar to that of Escherichia coli, a bacterium that propagates clonally, with occasional genetic recombination.

Animals↗
PubMed2001

Has the ban on smoking in New South Wales restaurants worked? A comparison of restaurants in Sydney and Melbourne.

OBJECTIVE: To evaluate compliance with a legislative ban on smoking inside restaurants by comparing smoking in Sydney restaurants (where it is legally banned) with smoking in Melbourne restaurants (not subject to a legal ban). DESIGN AND PARTICIPANTS: Unobtrusive observational study of restaurant patrons, and interviews with restaurant staff, carried out by 159 volunteers. SETTING: 78 Sydney restaurants with smoke-free indoor environments (as required by legislation) and 81 Melbourne restaurants not subject to legislation preventing smoking. The study took place from 20-31 October 2000. INTERVENTION: Legislation to ban smoking in indoor areas of restaurants was introduced in New South Wales in September 2000 (about six weeks before our study). OUTCOMES: Observed incidents of smoking inside restaurants; staff attitudes to the ban; customer satisfaction as indicated by comments to staff; staff perceptions of restaurant patronage. RESULTS: No restaurant patrons were seen smoking in 78 Sydney restaurants during 156 hours of observation of 2,646 diners, compared with 176 smokers among 3,014 Melbourne diners over 154 hours of observation. Thirty-one per cent (24/78) of Sydney restaurants had experienced smokers attempting to smoke indoors after the legislation was introduced; 6% (5/78) reported instances of smokers refusing to stop smoking when asked; 79% (62/78) of restaurants had received favourable comments from patrons about the smoke-free law; 81% (63/78) of restaurant staff interviewed either supported or strongly supported the law. Since introduction of the legislation, 76% of restaurants reported normal trade, 14% increased trade, and 9% reduced trade. CONCLUSIONS: Smoke-free restaurants do not require "smoking police" to enforce bans, present few ongoing difficulties for staff, attract many more favourable than unfavourable comments from patrons, and do not adversely affect trade.

Attitude↗
PubMed2001

Detection of minimal residual disease in peripheral blood prior to clinical relapse of childhood acute lymphoblastic leukaemia using PCR.

Submicroscopic evidence of persistent minimal residual disease (MRD) in first remission bone marrow samples from children with acute lymphoblastic leukaemia (ALL) indicates a high risk of clinical relapse. Since microscopic evidence of leukaemic lymphoblasts is often present in the peripheral blood in the weeks before clinical presentation at diagnosis or relapse, peripheral blood may be used instead of bone marrow to detect MRD in ALL patients. We examined a median of 0.165 microg (from 1.0-2.0x10(4)cells) genomic DNA from archived peripheral blood smears collected 8-16 months prior to clinical relapse in eight children with ALL for evidence of MRD. We used the polymerase chain reaction and primers designed to identify clonal antigen receptor gene rearrangements. Among the seven patients with bone marrow relapse, MRD was detected at a median of 1.2 months (0-8 months) prior to clinical relapse, indicating that MRD in the peripheral blood may be a late event in the course of leukaemic relapse. A prospective MRD study in ALL patients analysing larger numbers of peripheral blood cells will be needed to evaluate the utility of peripheral blood over bone marrow for MRD testing in childhood ALL.

Child↗
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↗