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Biomedical subjects

S Maitra

Publications and source records attributed to S Maitra.

At least 19 recordsLinked to original sources

Foreign body mimicking a nasal bone fracture.

Nasal foreign bodies are common in young children and are typically the result of intranasal placement by the child. The authors report a case of an extranasal foreign body in an adult, which presented as a nasal fracture following trauma to the nose. This uncommon presentation, previously unreported in the literature, highlights the importance of careful history taking in cases of nasal trauma and of thorough wound exploration if any penetrative injury is found.

Adult↗

Smoking can be good for you.

Smoking is without doubt one of the greatest causes of avoidable illness and death in the modern world. Most well known is the relationship between smoking and numerous cancers, cerebrovascular and cardiovascular disease. Smoking and most especially nicotine, are, however, sometimes beneficial in certain diseases, including Parkinson's, Alzheimer's, allergic alveolitis, nausea and vomiting of pregnancy, pre-eclampsia, fibroids, carcinoma of body of uterus, ulcerative colitis, pyoderma gangrenosum, aphthous stomatitis and ulceration, pemphigus, herpes simplex and acne. In the immensely justifiable enthusiasm to discredit this dangerous activity, the mechanisms behind these beneficial effects tend to have been un-discussed or ignored. It is the aim of this paper to spur interest in the reasons for these effects. If the mechanisms are elucidated, therapeutic advances may be possible.

Journal Article↗

Forty years of solitude: life-history divergence and behavioural isolation between laboratory lines of Drosophila melanogaster.

The study of the early stages of speciation can benefit from examination of differences between populations of known history that have been separated for a short time, such as a few thousands of generations. We asked whether two lines of Drosophila melanogaster that were isolated more than 40 years ago have evolved differences in life-history characters, or have begun to evolve behavioural or postzygotic isolation. One line, which is resistant to DDT, showed lower egg production and a shorter lifespan than a susceptible line. These differences are not a pleiotropic effect of resistance because they are not attributable to the chromosome that contains the resistance factors. The two lines have begun to become behaviourally isolated. Again, the isolation is not attributable to genes on the chromosome that contains resistance factors. The lines show only prezygotic isolation; there is no evidence of reduced fitness of F1 or F2 hybrids. These lines and others like them, should be excellent subjects for analyses of genetic changes that could lead to speciation.

Age Factors↗

Role of two plasma vitellogenins from Indian major carp (Cirrhinus mrigala) in catfish (Clarias batrachus) vitellogenesis.

Complete vitellogenesis (synthesis and incorporation of vitellogenin, Vg) in the female catfish, Clarias batrachus, during different reproductive phases (preparatory, prespawning, and postspawning) of its annual ovarian cycle is induced by administering heterologous Vg (semipurified; ULT-I and purified; HA-I and HA-II) isolated from the Indian major carp, mrigal (Cirrhinus mrigala). During the prespawning period, ULT-I, which contains both HA-I and HA-II, showed a dose-dependent response in relation to the induction of complete vitellogenesis in female catfish. In the preparatory period, daily treatment with 1 mg of ULT-I for 12 days resulted in an increase in plasma Vg level, ovarian weight, and number of stage-II (vitellogenic) oocytes along with the appearance of stage III (fully formed) yolky oocytes. In the prespawning period, 12-day administration of HA-I at the dose level of 0.5 mg/fish/day enhanced complete vitellogenesis in intact female catfish and induced Vg synthesis in hypophysectomized female catfish, whereas HA-II, at the same dose level, could only stimulate Vg synthesis, indicating their different roles during vitellogenesis. The results so far obtained may be due to the estradiol-17beta contamination in the Vg fractions. Estimation of E(2) in ULT-I, HA-I, and HA-II by E(2) ELISA indicates that HA-II contains only a small amount (106 pg/mg protein). Therefore, daily treatment with 1 mg each of delipidated ULT-I and HA-I for 12 days could synthesize very little Vg, whereas intact ULT-I at the same dose level induced not only a high plasma Vg level but also increased GSI, indicating the importance of lipid in the native molecule for the induction of vitellogenesis. During postspawning period, administration of HA-I (0.5 mg/fish/day for 21 days) to reproductively regressed female catfish pretreated with HA-II (10 microg/fish/day for 7 days) and maintained at a long photoperiod (LD 14:10) and high temperature (30 degrees ), induced complete vitellogenesis.

Animals↗

Increased mortality of elderly female peritoneal dialysis patients with diabetes--a descriptive analysis.

Three recent studies using registry data from the United States, in comparing the mortality risks between peritoneal dialysis (PD) and hemodialysis (HD), have consistently found that elderly diabetic women on PD have a higher mortality risk as compared with their counterparts on HD. Though the cause for this observation is not clear, the phenomenon may be unique to the United States. Alternatively, a selection bias impossible to decipher may be at work in these studies, as none of them have data on comorbidity, nutrition, or adequacy of dialysis. Finally, the possibility that elderly diabetic women are, for some reason, more vulnerable to the ill effects of peritoneal dialysis should be considered. We report here a retrospective analysis of 47 diabetic women, above 55 years of age, with end-stage renal disease, who were started on PD and who later died on dialysis. The primary outcome of interest was cause of death. Demographic details about the patients, comorbid conditions, dialysis adequacy, and biochemical parameters at the start of PD were noted. Death in these patients was attributed mainly to vascular causes, and there appeared to be a high prevalence of peripheral vascular disease. Infection was the next major cause of death, being the primary cause in 14 patients. Of these, only 5 patients had peritonitis. On a Cox regression analysis, only patient age and duration of diabetes at onset of dialysis were found to be predictive of vascular death. No factor was found to be predictive of death from infection. It appears that elderly diabetic women on PD die mainly of the long-term complications of diabetes.

Aged↗

Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster.

The expression of two second chromosome-linked cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster was measured in various strains. Six different strains, including ry(506) and 91-C, showed low or undetectable levels of CYP6A2 and CYP6A8 mRNAs, suggesting that low expression is the wild-type phenotype of Cyp6a2 and Cyp6a8 genes. In the 91-R and MHIII-D23 strains, however, both these genes are overexpressed. In order to examine the genetic basis of Cyp6a2 and Cyp6a8 expression, CYP6A2 and CYP6A8 RNA levels were measured in the F1 hybrids of overproducer (91-R and MHIII-D23) and underproducer (ry(506) and 91-C) strains. Results showed that the total amounts of CYP6A2 and CYP6A8 mRNAs in the F1 hybrids were lower than half the amounts of these RNAs found in the overproducer parental strains. This suggested that the underproducer strains carry loci which downregulate Cyp6a2 and Cyp6a8 gene expression. To determine the chromosome linkage of these loci, several stocks homozygous for the second chromosome of overproducer 91-R strain and, therefore, homozygous for the Cyp6a2-91R and Cyp6a8-91R alleles were synthesized. The third chromosomes in all these stocks were from the underproducer ry(506) strain. The levels of expression of both Cyp6a2-91R and Cyp6a8-91R genes in these three stocks were significantly lower than that observed in the 91-R strain. One of these stocks, named iso-2, showing reduced expression, was used to synthesize two new isogenic stocks by resubstituting the third chromosome of ry(506) origin with third chromosomes of the 91-R strain. Expression of both Cyp6a2-91R and Cyp6a8-91R alleles was found to be much higher in these two resubstituted isogenic stocks than in the progenitor iso-2 stock. Taken together, these results suggest that the second chromosome-linked Cyp6a2 and Cypa8 genes are regulated by loci present on the third chromosome, and the wild-type function of these loci is to repress these two Cyp genes. The data also suggest that Cyp6a2 and Cyp6a8 overexpression in the 91-R and MHIII-D23 strains is more likely due to mutation in the repressor locus (or loci) rather than in the cis-regulatory sequences of the Cyp6a2 and Cyp6a8 genes.

Alleles↗

BSAP can repress enhancer activity by targeting PU.1 function.

PU.1 and BSAP are transcription factors crucial for proper B-cell development. Absence of PU.1 results in loss of B, T, and myeloid cells, while absence of BSAP results in an early block in B-cell differentiation. Both of these proteins bind to the immunoglobulin kappa chain 3' enhancer, which is developmentally regulated during B-cell differentiation. We find here that BSAP can repress 3' enhancer activity. This repression can occur in plasmacytoma lines or in a non-B-cell line in which the enhancer is activated by addition of the appropriate enhancer binding transcription factors. We show that the transcription factor PU.1 is a target of the BSAP-mediated repression. Although PU.1 and BSAP can physically interact through their respective DNA binding domains, this interaction does not affect DNA binding. When PU.1 function is assayed in isolation on a multimerized PU.1 binding site, BSAP targets a portion of the PU.1 transactivation domain (residues 7 to 30) for repression. The BSAP inhibitory domain (residues 358 to 385) is needed for this repression. Interestingly, the coactivator protein p300 can eliminate this BSAP-mediated repression. We also show that PU.1 can inhibit BSAP transactivation and that this repression requires PU.1 amino acids 7 to 30. Transfection of p300 resulted in only a partial reversal of PU.1-mediated repression of BSAP. When PU.1 function is assayed in the context of the immunoglobulin kappa chain 3' enhancer and associated binding proteins, BSAP represses PU.1 function by a distinct mechanism. This repression does not require the PU.1 transactivation or PEST domains and cannot be reversed by p300 expression. The possible roles of BSAP and PU.1 antagonistic activities in hematopoietic development are discussed.

B-Lymphocytes↗

Patients on chronic peritoneal dialysis for ten years or more in North America.

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9 kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year, and duration of hospitalization was 4.8 +/- 3.7 days per patient-year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.

Adolescent↗

Constitutive and barbital-induced expression of the Cyp6a2 allele of a high producer strain of CYP6A2 in the genetic background of a low producer strain.

The levels of one or more cytochrome P450 (CYP) enzymes and the respective mRNAs are found to be higher in insecticide-resistant insects than in susceptible insects. To understand better how insects regulate the levels of CYPs, we examined the expression of the Cyp6a2 gene in various strains of Drosophila melanogaster. We also took a transgenic approach to understand the molecular mechanisms that are involved in strain variation of Cyp6a2 expression. RNA blot analysis showed that the constitutive expression of Cyp6a2 varies from strain to strain; the level of CYP6A2 mRNA is barely detectable in the underproducer ry506 strain, whereas it is very high in the overproducer 91-R and MHIII-D23 strains. The long terminal repeat (LTR) of mobile element 17.6 that is found in the 3' untranslated region (UTR) of the Cyp6a2 gene of some strains does not appear to have any role on the steady-state CYP6A2 mRNA level. We also found that the Cyp6a2 gene is inducible by barbital in 91-R, ry506 as well as 91-C, which carries an LTR insertion. To examine the genetic background of the underproducer ry506 strain with respect to Cyp6a2 expression, we transformed the ry506 strain with the Cyp6a2 allele of the overproducer 91-R strain (Cyp6a2-91 R) and measured the constitutive and barbital-induced expression of the Cyp6a2-91 R transgene in the transformed flies. The Cyp6a2-91 R transgene carrying 129 bp of DNA upstream of the ATG codon did not show any constitutive or barbital-induced expression in the ry506 host genome. However, transgenes with 1331 and 985 bp upstream DNA showed similar levels of constitutive expression that were higher than that of the endogenous Cyp6a2 gene of the ry506 host strain, but lower than the expression of the same gene in the 91-R strain. Both these transgenes, with 1331 and 985 bp upstream DNA, also showed induction with 0.1 M barbital. DNA sequence analysis revealed that in both 91-R and ry506, the upstream DNA between +1 and -985 bp contains a distal and a proximal group of three potential barbie boxes, i.e. cis-elements that are thought to be involved in barbiturate-mediated induction of CYP genes. Except for four bases located near the distal cluster of barbie boxes and two other bases, the base sequence of the upstream DNA is identical in ry506 and 91-R strains. These results suggest that the underproducer ry506 strain has the trans-regulatory factors to support constitutive and induced expression of the Cyp6a2-91 R allele carrying DNA between -129 and -1331 bp regions. Possible reasons for low constitutive expression of the endogenous Cyp6a2 gene and moderate level of expression of the Cyp6a2-91 R allele in the ry506 genetic background are discussed.

Alleles↗

Right hemisphere damage impairs the ability to process emotional expressions of unusual faces.

Patients with focal brain damage, right and left hemisphere damage, and nonpatient controls were asked to match photographs of emotion expressions that were depicted in unusual (line drawings, strange, and schematic) and normal (usual) representations of faces with the target emotion expressions of normal face. Nonpatient controls were significantly superior to right hemisphere damaged patients in matching photographs of emotion expressions that were depicted in line drawings of normal face and schematic face.

Adult↗

Can fingernail creatinine concentrations be used to predict duration of azotemia?

Clinical use of fingernail creatinine estimation to predict duration of azotemia is yet to be validated. We studied the fingernail creatinine concentrations in 48 subjects: seven controls, nine with acute renal failure, five with rapidly progressive glomerulonephritis, 12 with chronic renal failure and 15 with end-stage renal failure on maintenance hemodialysis. The creatinine concentration in aqueous eluates of powdered nail clippings was determined by the alkaline picrate reaction. The mean fingernail creatinine concentration was significantly higher in patients with chronic renal failure (93.7 +/- 83.7 micrograms/g) and end-stage renal disease on maintenance hemodialysis (118.4 +/- 46.8 micrograms/g) as compared to those with acute renal failure (36.6 +/- 23.7 micrograms/g) and rapidly progressive glomerulonephritis (35.8 +/- 20.6 micrograms/g). The creatinine concentrations did not differ significantly between normal subjects (27.2 +/- 28.7 micrograms/g) and those with acute renal failure and rapidly progressive glomerulonephritis. However because of large variability in the values of fingernail creatinine concentrations within each group, the test lacked specificity. Therefore, this investigation is an unreliable indicator of duration of azotemia in individual patients and is not likely to be of much clinical use.

Acute Kidney Injury↗

Three second chromosome-linked clustered Cyp6 genes show differential constitutive and barbital-induced expression in DDT-resistant and susceptible strains of Drosophila melanogaster.

The level of expression of the Cyp6a2 gene is much higher in the DDT-resistant 91-R strain than in the susceptible 91-C strain of Drosophila melanogaster (Waters et al. (1992b) Proc. Natl. Acad. Sci. USA, 89, 4855-4859). To understand the role of Cyp6a2 and related genes in insecticide resistance, we have isolated and characterized two new Cyp6 genes from the 91-R strain. The polypeptides encoded by these two genes, Cyp6a8 and Cyp6a9, show 77 and 75% amino acid sequence similarity, and 60 and 55% identity with Cyp6a2 of D. melanogaster, respectively. In the genome, Cyp6a8 and Cyp6a9 genes are closely clustered within 4 kb and map at region 51C of the second chromosome. In between them another Cyp gene is present which is more related to Cyp6a9 than to Cyp6a8. The Cyp6a8 gene which is transcriptionally highly active in 91-R, moderately active in ry506 and silent in the 91-C strain hybridizes with 2.0- and 1.8-kb RNAs. Two different-sized RNAs, 2.1 and 1.8 kb, also hybridize with the Cyp6a9 and/or Cyp6a9-related genes. While the level of 2.1-kb RNA is similar in all three strains, the level of 1.8-kb RNA is highest in the 91-R strain and barely detectable in 91-C strain. Transgenic experiments showed that a 8.3-kb BamHI fragment contains the cis-regulatory elements for the expression of both Cyp6a8 and Cyp6a9-related genes. Barbital induces all these genes in all three strains and increases the levels of the two Cyp6a8 transcripts and the 1.8-kb RNA produced by the Cyp6a9 and/or Cyp6a9-related genes. Expression of the Cyp6a8 gene is down-regulated in the hybrids of 91-R and 91-C strains despite the fact that the hybrids carry one copy of the highly active allele of the Cyp6a8 gene of the 91-R strain. Based on these results we propose that the Cyp6a8 gene in 91-C strain may be turned off by an active repressor which might be inhibited by barbital treatment. In the 91-R strain, the putative repressor may be defective, allowing high level of constitutive expression of the Cyp6a8 gene.

Amino Acid Sequence↗

Development of a screening set for new (CAG/CTG)n dynamic mutations.

The expansion of a (CAG/CTG)n triplet repeat has been found to be associated with at least seven genetic diseases, suggesting that this mechanism of disease may be fairly common. To accelerate the discovery of new loci containing (CAG/CTG)n triplet expansions, we have isolated numerous genomic clones containing this class of repeats. We have developed 338 sequence-tagged sites (STSs) containing (CAG/CTG)n repeat sequences. Two hundred ninety-nine STSs were unambiguously assigned to chromosomes, and 89 of the total were assigned to YACs. The 141 STSs that were developed based on (CAG/CTG)n repeats of at least seven units were genotyped on four reference CEPH individuals to estimate their polymorphic quality.

Base Sequence↗

Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states: gene structure and 5'-flanking sequence.

The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3-fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position -1641). A consensus glucocorticoid response element is located at base pair -1552, a 9/10 match of the insulin response sequence is located at position -1449, and a 7/8 match of the cAMP response element is located at position -164.

Amino Acid Sequence↗

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Animals↗