Role of Fe2+ in oxygen sensing in the carotid body.
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Biomedical subjects
Publications and source records attributed to A Roy.
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Deletion in the 22.9 -Mb chromosomal (chr.) 8p21.3-23 region has been shown to be necessary for the development of breast carcinoma (CaBr). In this study, we have attempted to detect the minimal deleted region(s) in the chr.8p21.3-23 region in 62 primary breast lesions having 56 CaBr tumors and six other breast lesions of Indian patients using 15 microsatellite markers. The loss of heterozygosity (LOH) was observed for at least one marker in 96.4% (54/56) of the CaBr samples. Three discrete minimal deleted regions with high frequencies of LOH (39-65%) were identified in the chromosomal 8p23.1-23.2 (D1), 8p23.1 (D2) and 8p 21.3-22 (D3) regions within 2.03, 0.41, 2.47 Mb, respectively. No significant correlation was observed with the high deleted regions and the different clinicopathological parameters. Interestingly, 51.8% (29/56) CaBr samples showed either loss of chr.8p or interstitial deletions in this arm, indicating the importance of chr.8p in the development of CaBr. The pattern of allelic loss in the bilateral lesions had indicated that the lesions were clonal in origin and probably the deletion in the D3 region was the early event among the D1-D3 regions. Thus, our data have indicated that the D1-D3 regions could harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CaBr.
OBJECTIVES: We have been done the detailed deletion mapping of chromosome (chr.) 8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well as studied the mechanism of activation of c-myc gene, located at chr.8q24.1, by analyzing the amplification/rearrangement/HPV integration within approximately 580 kb of c-myc locus in uterine cervical carcinoma (CaCx) of Indian patients. The association between the deletions in chr.8p21.3-23 and alterations in the c-myc locus has also been analyzed. METHODS: The deletion mapping of chr.8p21.3-23 was done by 15 microsatellite markers and the alterations in the c-myc locus were analyzed by Southern hybridization using the pal-1/c-myc/mlvi-4/HPV 16/18 probes in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical carcinoma. The alterations in chr.8p/q have been correlated with the different clinicopathological parameters. RESULTS: Three discrete minimal deleted regions with high frequencies of loss of heterozygosity (LOH) (37-43%) were identified in the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41-4.62 Mb. The deletion in the D1 region was significantly associated with the deletion in the D2 region (P = 0.03), whereas the deletion in D2 was marginally associated with the deletion in the D3 region (P = 0.07). The alterations in the c-myc locus were seen in 43% of the samples. About 35% of the samples showed coalterations in both arms of chr.8. No significant association was observed with the alterations in chr.8p/q as well as with the different clinicopathological parameters. CONCLUSIONS: The deletions in chr.8p21.3-23 and the alterations in the c-myc locus are independently associated with the development of CaCx. The D1-D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the development of this tumor. The c-myc gene was activated by amplification/rearrangement at the pal-1/c-myc/mlvi-4 loci as well as HPV integration in the pal-1 locus in this tumor.
OBJECTIVE: To examine whether childhood trauma effect the age of first attempting suicide and the number of attempts. METHOD: One thousand twelve hundred and eighty substance dependent patients were interviewed about whether or not they had ever attempted suicide, the age of first attempt and the number of attempts. Patients completed the Childhood Trauma Questionnaire - 34 item version. RESULTS: Five hundred and thirty-eight patients (42%) had attempted suicide. Significantly more of the patients who had attempted suicide were female. Patients who had made three or more attempts had significantly higher childhood trauma scores than patients who had made two attempts, who had higher scores than patients who had made one attempt, who had higher scores than patients who had never attempted. Patients who first attempted suicide before the age of 20 years had significantly higher childhood trauma scores than patients who first attempted after 20 years of age. CONCLUSION: Childhood trauma may be a determinant of the age of onset of suicidal behavior and of the number of suicide attempts.
BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood. MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure. RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination. CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.
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The hypothesis that an increase in intracellular calcium [Ca(2+)](c) in carotid body (CB) glomus cells will cause enhanced afferent carotid sinus nerve (CSN) activities was tested in the rat CB in-vitro with the use of extracellular ATP. ATP caused a dose dependent [Ca(2+)](c) increase in identified glomus cells. A major part of total [Ca(2+)](c) increase (2/3) was due to the [Ca(2+)] influx. The rest of [Ca(2+)](c) increase (1/3) was due to the release of [Ca(2+)] from the endoplasmic reticulum (ER) [Ca(2+)] stores, and it was inhibited by the pretreatment of cells with cyclopiazonic acid (CPA), an intracellular Ca(2+)-ATPase blocker. Suramin, a purinergic P(2) receptor membrane blocker, blocked [Ca(2+)] influx due to ATP in the presence of extracellular [Ca(2+)]. Perfusion with 5 and 10 microM ATP stimulated CSN activities in both normoxia (Nx) and hypoxia (Hx). Above that level, 100 microM ATP induced slight initial stimulation in CSN activities which were subsided subsequently in Nx and partly diminished in Hx, while 500 microM ATP completely inhibited CSN activities in Nx and Hx after a slight initial stimulation. Electrophysiological measurements of the glomus cell membrane potential in the presence of ATP (100 microM) during Nx indicated cellular enhanced outward K(+) current and hyperpolarization, suggesting potential mechanism for the inhibition of CSN activities. Thus, ATP dependent linear increases in [Ca(2+)](c) did not give rise to a corresponding increase in CSN activities, contravening the normally expected increase in CSN activities following [Ca(2+)](c) rise.
Carotid body chemosensory activities were measured before and after 0.2, 5,6 and 7 h of sustained isocapnic (PaCO(2) approximately equal to 30 Torr) hypoxia (PaO(2) approximately equal to 43 Torr) in the cats (n=7). The activity increased from 5.4 impsec(-1) at 0.2 h to about 13 impsec(-1) at 7 h. This increase in chemosensory activities were due to both an augmented sensitivity and to a long-term facilitation and not due to arterial [H(+)] changes.
Citrus tristeza virus (CTV) is an aphid-transmitted closterovirus, which causes one of the most important citrus diseases worldwide. Isolates of CTV differ widely in their biological properties. CTV-infected samples were collected from four locations in India: Bangalore (CTV-B), Delhi (CTV-D), Nagpur (CTV-N), and Pune (CTV-P), and were maintained by grafting into Kagzi lime ( Citrus aurantifolia (Christm. Swing.). All isolates produced typical vein clearing and flecking symptoms 6-8 weeks after grafting. In addition, CTV-B and CTV-P isolates produced stem-pitting symptoms after 8-10 months. The CTV coat protein gene (CPG) was amplified by RT-PCR using CPG specific primers, yielding an amplicon of 672 bp for all the isolates. Sequence analysis of the CPG amplicon of all the four Indian isolates showed 93-94% nucleotide sequence homology to the Californian CTV severe stem pitting isolate SY568 and 92-93% homology to the Japanese seedling yellows isolate NUagA and Israeli VT p346 isolates. In phylogenetic tree analysis, Indian CTV isolates appeared far different from other isolates as they formed a separate branch. Comparison among the Indian isolates was carried out by restriction analysis and restriction fragment length polymorphism (RFLP). Specific primers to various genome segments of well-characterized CTV isolates were used to further classify the Indian CTV isolates.
OBJECTIVES: Evaluate the safety and effectiveness of quinacrine for non-surgical female sterilization in five different protocols. METHODS: The 5 trials were conducted sequentially. The first and largest, with 985 cases, tested the use of a curved inserter to place a 50 mg dose of quinacrine near each tubal ostia. The next 3 trials were carried out to determine the effect of adjunct procedures on the efficacy of the standard recommended protocol. The three adjuncts were 75 mg of intrauterine diclofenac, 10 mg medroxyprogesterone IM and either 10 mg of atropine IM or 20 mg of hyoscine butylbromide IM The final trial focused on the currently recommended protocol. RESULTS: The 100 mg dose placed at the tubal ostia with the curved inserter resulted in a failure rate of 9.0% at 20 years. Diclofenac or medroxyprogesterone did not improve efficacy over quinacrine alone. Atropine or hyoscine butylbromide substantially diminished the effectiveness of the quinacrine. The failure rate with the standard protocol in our series of 122 cases was 0.8% at 3.5 years. Side effects were minor. There were no deaths nor serious complications with any of these protocols. DISCUSSION: All 5 protocols appeared to be safe and the standard one was the most effective.
OBJECTIVE: To examine the risk factors for suicidal behaviour in human immunodeficiency virus (HIV) positive patients. METHOD: HIV substance dependent positive patients who had attempted suicide were compared with HIV substance dependent positive patients who had never attempted suicide for suicide risk factors. RESULTS: Among the 149 HIV positive patients examined almost half had attempted suicide. Significantly more HIV positive patients who had attempted suicide were female. Attempters were significantly younger than non-attempters. Significantly more of the attempters had a family history of suicidal behaviour. Attempters also reported significantly more childhood trauma, scored significantly higher for neuroticism, had experienced significantly more comorbidity with depression, and more of them had received antidepressant medication. CONCLUSION: These data suggest that both distal and proximal risk factors are involved in suicidal behaviour in HIV positive substance dependent patients.
Classification and regression tree methods represent a potentially powerful means of identifying patterns in exposure data that may otherwise be overlooked. Here, regression tree models are developed to identify associations between blood concentrations of benzene and lead and over 300 variables of disparate type (numerical and categorical), often with observations that are missing or below the quantitation limit. Benzene and lead are selected from among all the environmental agents measured in the NHEXAS Region V study because they are ubiquitous, and they serve as paradigms for volatile organic compounds (VOCs) and heavy metals, two classes of environmental agents that have very different properties. Two sets of regression models were developed. In the first set, only environmental and dietary measurements were employed as predictor variables, while in the second set these were supplemented with demographic and time-activity data. In both sets of regression models, the predictor variables were regressed on the blood concentrations of the environmental agents. Jack-knife cross-validation was employed to detect overfitting of the models to the data. Blood concentrations of benzene were found to be associated with: (a) indoor air concentrations of benzene; (b) the duration of time spent indoors with someone who was smoking; and (c) the number of cigarettes smoked by the subject. All these associations suggest that tobacco smoke is a major source of exposure to benzene. Blood concentrations of lead were found to be associated with: (a) house dust concentrations of lead; (b) the duration of time spent working in a closed workshop; and (c) the year in which the subject moved into the residence. An unexpected finding was that the regression trees identified time-activity data as better predictors of the blood concentrations than the measurements in environmental and dietary media.
AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. CONCLUSION: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.
BACKGROUND: Genetic instability of chromosome 11 is a frequent event in many solid tumours, including head and neck squamous cell carcinoma (HNSCC). AIMS: To perform allelic imbalance analysis of cytogenetically mapped altered regions of human chromosome 11 in patients with HNSCC from eastern India. METHODS: Genomic alterations were investigated using highly polymorphic microsatellite markers in both HNSCC and leukoplakia tissues. RESULTS: Microsatellite markers D11S1758 from 11p13-15 and D11S925 from 11q23.3-24 had the highest frequency (38% and 32%, respectively) of loss of heterozygosity among all the markers analysed. Allelic loss at the marker D11S925 was seen in both leukoplakia and in all stages of HNSCC tumour tissues suggesting that it is an early event in HNSCC tumorigenesis. Microsatellite size alteration was also found to be high (> 20%) in several markers. In leukoplakia samples microsatellite instability was seen at a higher frequency than loss of the allele, indicating such alterations might initiate the process of tumorigenesis in HNSCC. CONCLUSIONS: The high rate of chromosomal alterations at 11q21-24 in HNSCC suggests the presence of a putative tumour suppressor gene in this region.
BACKGROUND: Deletions in chromosome 3 occur frequently in uterine cervical carcinoma (CA-CX). The common consensus regions deleted during CA-CX development are not well defined, and have not been correlated with tumour progression. AIMS: To define specific regions of chromosome 3 deleted during development of CA-CX and to correlate these with clinicopathological data. METHODS: Deletion mapping of chromosome 3 was done in seven cervical intraepithelial neoplasia (CIN) and 43 primary CA-CX samples using 20 highly polymorphic microsatellite markers. RESULTS: Deletions of chromosome 3 were significantly associated with tumour progression. High frequencies (33-53%) of loss of heterozygosity (LOH) were found in 3p26.1, 3p22.3, 3p21.2, and 3p13, suggesting the location of putative tumour suppressor genes (TSGs) in these regions. Among these four regions, deletions in 3p21.2 were suggested to occur early during CA-CX development. A significant correlation was found between LOH at 3p26.1 and 3p22.3 with tumour progression from stage I/IIB to stage III/IV. No association was found with the highly deleted regions and human papillomavirus positivity, parity, or menopausal status. Microsatellite size alteration was seen in only seven of the samples. However, rare biallelic alterations were seen in and around the highly deleted regions. Loss of normal copy of chromosome 3 and interstitial alterations in chromosome 3p were seen in some samples. CONCLUSION: These four regions on chromosome 3p may be differentially deleted during specific stages of CA-CX development. The putative TSGs located in these regions may have a cumulative effect on tumour progression.
In the deletion mapping of chromosome (chr) 9 in head and neck lesions of the Indian patient population by microsatellite markers, we have identified four discrete areas (D1-D4) with high loss of heterozygosities (LOHs) viz. 9p24-p23 (D1), 9p22-p21 (D2), 9q11-q13 (D3) and 9q22.3 (D4) regions. The deletions in D2 and D4 regions were suggested to be essential for the development of dysplastic lesions of head and neck, whereas the deletions in D1 and D3 regions were responsible for progression of the dysplastic lesions to early invasive head and neck squamous cell carcinoma (HNSCC). The microsatellite size alterations (MAs) were observed in the chromosomal 9pter-p23, 9p22-p21(D2), 9q13 and 9q21.1-q21.2 regions with gradual increase during progression of the tumor. Additional chromosomal alterations like loss of normal copy of chr.9 and biallelic alterations were also seen in our samples. There is a correlation between HPV infection with TNM stages, histopathological grades and LOHs at D1 and D4 regions. Whereas tobacco habit is associated with the occurrence of LOHs at D1 and LOHs / MAs at D2 region.
BACKGROUND & OBJECTIVES: Deletions in chromosome 8 (chr.8) have been shown to be necessary for the development of head and neck squamous cell carcinoma (HNSCC). Attempts have been made in this study to detect the minimal deleted region in chr.8 associated with the development of HNSCC in Indian patients and to study the association of clinicopathological features with the progression of the disease. METHODS: The deletion mapping of chr.8 was done in samples from 10 primary dysplastic lesions and 43 invasive squamous cell carcinomas from the head and neck region of Indian patients to detect allelic alterations (deletion or size alteration) using 12 highly polymorphic microsatellite markers. The association of the highly deleted region was correlated with the tumour node metastasis (TNM) stages, nodal involvement, tobacco habit and human papilloma virus (HPV) infection of the samples. RESULTS: High frequency (49%) of loss of heterozygosity (LOH) was seen within 13.12 megabase (Mb) region of chromosomal 8p21.3-23 region in the HNSCC samples, whereas the dysplastic samples did not show any allelic alterations in this region. The highest frequency (17%) of microsatellite size alterations (MA) was observed in the chr.8p22 region. The loss of short arm or normal copy of chr.8 and rare bi-allelic alterations were seen in the stage II-IV tumours (939, 5184, 2772, 1319 and 598) irrespective of their primary sites. The highly deleted region did not show any significant association with any of the clinical parameters. However, HPV infection was significantly associated (P < 0.05) with the differentiation grades and overall allelic alterations (LOH/MA) of the samples. INTERPRETATION & CONCLUSION: Our data indicate that the 13.12 Mb deleted region in the chromosomal 8p21.3-23 region could harbour candidate tumour suppressor gene(s) (TSGs) associated with the progression anti invasion of HNSCC tumours in Indian patients.
Eradication of malaria in Southeast Asian countries is still a distant goal, due to the absence of a simple, rapid and inexpensive diagnostic technique. Here, an immunosensor for the photometric detection of malaria, the malaria-detecting immunosensor (MDI), is developed to detect Plasmodium falciparum malarial antibodies in human blood. The method uses the principle of laser light-scattering by latex bead agglutinates in media monitored by a light-detecting device. Agglutination is induced by mixing antigen-coated latex beads with serum antibodies. Immunoreactions are measured in terms of the Tyndall effect in the transmitted beam detected by photodiodes. MDI sensitivity and specificity are compared with the results of enzyme-linked immunoabsorbent assay and laser light-scattering immunoassay techniques, which show that it is a good and sensitive monitoring device.