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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 487 records · Page 27Linked to original sources

Regional variability of lung inflammation in cystic fibrosis.

Chest radiography in patients with cystic fibrosis (CF) frequently shows more severe changes in the upper lobes. We performed bronchoalveolar lavage (BAL) on 12 clinically stable, young adult patients with CF to determine whether inflammation varies significantly among geographically distinct areas of the lung. We found that absolute numbers of neutrophils were generally greater in BAL fluid from the upper lobe (25.7 +/- 7.9 x 10(5) neutrophils/ml [mean +/- SEM]) of the right lung than that obtained from the right lower lobe (6.8 +/- 2.8 x 10(5) neutrophils/ml; p < 0.01). The mean value of unopposed neutrophil elastase activity in upper-lobe BAL fluid (227 +/- 91 nmol peptide hydrolyzed/ml/min) was also significantly greater than that in lower-lobe BAL fluid (84 +/- 43 nmol/peptide hydrolyzed/ml/ min; p < 0.01), and similar differences were found for myeloperoxidase activity and DNA content. Neutrophil influx and unopposed neutrophil elastase for a given region correlated inversely with lung function or percentage of ideal body weight, and upper-versus lower-lobe differences were more pronounced in subjects with better preservation of lung function. Our findings suggest that regional variation in inflammation must be considered when utilizing BAL to study lower respiratory tract inflammation in CF or to monitor responses to therapeutic interventions that can potentially diminish lung inflammation. Our findings may also have implications for the study of the natural history of lung inflammation and infection in neonates, infants, and young children with CF.

Adult↗

Prophyromonas gingivalis fimbriae mediate coaggregation with Streptococcus oralis through specific domains.

Fimbriae are major adhesive components on the cell surface of Prophyromonas gingivalis. In this study, we evaluated the role of fimbriae in coaggregation with Streptococcus oralis. Fimbriae purified from P. gingivalis competitively inhibited the coaggregation by 100% at a concentration of 50 micrograms/mL. On the other hand, the same amount of lipopolysaccharide isolated from P. gingivalis was inhibited by only 25% of the level of the fimbriae. A fimA-inactivated mutant of P. gingivalis failed to show distinct coaggregation activity. Fimbriae added to a solution of various strains of streptococci caused their self-aggregation at a concentration of 10 to 30 micrograms/mL. The self-aggregation induced by fimbriae was inhibited by lambda-arginine (20 to 40 mM/L). Iodinated fimbriae reacted with S. oralis cells immobilized on the nitrocellulose membrane, and 100 degrees C heating of the cells diminished the binding abilities. Recombinant fimbrillin (r-Fim, corresponding to whole residues 1 to 337 of native fimbrillin) of P. gingivalis also showed 100% inhibition of the coaggregation. The r-Fim variant (residues 1 to 286) lacking the C-terminal 51 residues was as inhibitory as r-Fim. However, the variant (residues 1 to 265) without the C-terminal 72 residues lost 77% of the inhibitory activity. These findings suggested that residues 266 to 286 contain a domain involved in the coaggregation of P. gingivalis with S. oralis. Inhibition by three polypeptides corresponding to residues 266 to 286, 266 to 337, and 287 to 337 was studied. Peptides 266 to 286 and 266 to 337 inhibited by 96 and 100%, respectively, at a concentration of 1.5 nmol/mL. Peptide 287 to 337 also showed a significant inhibitory effect but to a slightly lesser extent than that of peptide 266 to 286. P. gingivalis fimbriae appear to be involved in coaggregation with streptococci, probably through an adhesive protein molecule(s) of the latter, and the fimbriae possess several domains in the C-terminal residues 266 to 337 for interaction with S. oralis.

Bacterial Adhesion↗

Analysis of the role of E2A-encoded proteins in insulin gene transcription.

Pancreatic beta-cell type-specific transcription of the insulin gene is mediated, in part, by factors in the basic helix-loop-helix (bHLH) family that act on a site within the insulin enhancer, termed the E1-box. Expression from this element is regulated by a heteromeric protein complex containing ubiquitous (i.e. the E2A- and HEB-encoded proteins) and islet-enriched members of the bHLH family. Recent studies indicate that the E2A- and HEB-encoded proteins contain a transactivation domain, termed AD2, that functions more efficiently in transfected beta-cell lines. In the present report, we extend this observation by demonstrating that expression of full-length E2A proteins (E47, E12, and E2/5) activates insulin E element-directed transcription in a beta-cell line-selective manner. Stimulation required functional interactions with other key insulin gene transcription factors, including its islet bHLH partner as well as those that act on the RIPE3b1 and RIPE3a2 elements of the insulin gene enhancer. The conserved AD2 domain in the E2A proteins was essential in this process. The effect of the E2A- and HEB-encoded proteins on insulin gene expression was also analyzed in mice lacking a functional E2A or HEB gene. There was no apparent difference in insulin production between wild type, heterozygote, and homozygous mutant E2A or HEB mice. These results suggest that neither the E2A- or HEB-encoded proteins are essential for insulin transcription and that one factor can substitute for the other to impart normal insulin E1 activator function in mutant animals.

Animals↗

Placement of endosseous implants in grafted alveolar clefts.

OBJECTIVE: The purpose of this study was to determine the optimal timing for placement and to evaluate short- and long-term outcomes of endosseous implants in bone-grafted alveolar clefts. DESIGN: Fourteen patients who underwent alveolar cleft bone grafting (ACBG) and closure of an oronasal fistula followed by restoration of the missing lateral incisor tooth using endosseous implants (EI) were studied. The oronasal fistulae were closed using local flaps, and the alveolus was grafted with fresh autogenous iliac marrow. Endosseous implants were placed a minimum of 4 months following ACBG. The average age at ACBG was 20.35 years (range, 12-65 yr), and at implant placement 22.2 years (range, 15-66 yr). It was necessary to regraft the alveolar cleft region in six patients to provide adequate bone volume for implant placement. Those who required alveolar regrafting had an increased mean interval between the initial ACBG and planned implant placement compared to the patients with adequate bone available for implant placement 26.4 months (range, 4-46 mo) versus 15.75 months (range, 4-36 mo). RESULTS: Twenty-nine implants were placed in 14 patients, 9 outside of the cleft region and 20 in grafted alveolar clefts. Eighteen of 20 (90%) implants in the bone-grafted alveolar clefts have been successfully restored. The mean follow-up after implant placement was 39.1 months (range, 1-54 mo), and after restoration 28.5 months (range, 1-47 mo). CONCLUSIONS: Endosseous implants can be placed in bone-grafted alveolar clefts. Consideration should be given to the adequacy of graft volume and ridge morphology at the time of ACBG. The interval between ACBG and implant placement is important. The greater the interval beyond 4 months, the more likely there will be inadequate bone volume to accept an implant.

Adolescent↗

Hypobaric hypoxia and hedonic matrix in rats.

This study was carried out to evaluate the effect of continuous exposure to hypobaric hypoxia on the feeding behavior and taste responses of rats, under simulated conditions of a high altitude (HA) of 7,620 m for 21 h a day and consecutively for 18 d, which more closely resembles actual field conditions. Their food, water intake and body weight were recorded daily, and blood sugar was estimated once a week. All the parameters were recorded for a period of 18 d each, before, during, and after exposure to simulated HA. The results show a decrease in daily food and water intake and body weight, and mild hypoglycemia during hypoxic exposure. Single-bottle and two-bottle tests showed a preference for sweet solutions over water, citric acid, sodium chloride, and quinine sulfate during exposure. The two-bottle test showed a preference for glucose over calorically-inert saccharine. The continuous exposure in this study produced qualitatively similar but quantitatively accentuated results as compared to intermittent 6 h exposure contiguously for 21 d. High-altitude stress appears to influence food intake such that sensory cues assume greater significance during feeding behavior.

Altitude↗

MR imaging of tubercular spinal arachnoiditis.

OBJECTIVE: The purpose of our study was to examine the spectrum of abnormalities seen on MR imaging in patients with tubercular spinal arachnoiditis. MATERIALS AND METHODS: A retrospective analysis of MR findings in 22 cases of tubercular spinal arachnoiditis was carried out. The diagnosis had been established on the basis of clinical features, evidence of associated tubercular meningitis or of tubercular spondylitis, and CSF analysis. RESULTS: Nineteen (86%) patients had involvement of more than one spinal region, with the dorsal region being most commonly involved. CSF showed increased signal intensity on T1-weighted images in 17 (77%) patients, leading to complete loss of cord-CSF interface in seven patients and shaggy cord outline in 10 patients. As suggested by increased signal intensity on T2-weighted images, we saw cord involvement in 18 (82%) patients. Three of these patients had evidence of cord cavitation. Other findings seen on unenhanced images were CSF loculations in five patients, nodules in subarachnoid space in six patients, and clumping of cauda equina nerve roots in six patients. Contrast-enhanced studies were available in 20 patients. Meningeal enhancement was seen in 16 (80%) of 20 patients, and nerve root enhancement was seen in six (30%) patients. Cord enhancement was seen in four (20%) of 20 patients. Enhancement was observed along the surface of the cord in two of these patients, whereas the other two patients showed central enhancement. Associated findings were tubercular spondylitis in two patients, basal exudate in eight patients, and intracranial granulomas in five patients. CONCLUSION: MR imaging revealed several pathologic changes that occur in patients with tubercular spinal arachnoiditis and, hence, may play an important role in the diagnosis of this entity.

Adult↗

Imaging appearance of pachymeningeal tuberculosis.

OBJECTIVE: The purpose of our study was to examine imaging findings in patients with pachymeningeal tuberculosis. Imaging studies of seven patients with pachymeningeal tuberculosis were retrospectively reviewed. The diagnosis had been established on the basis of histopathology in three patients and response to antitubercular treatment in four patients. CONCLUSION: Tuberculosis can lead to localized or diffuse involvement of the pachymeninges. Most of the focal lesions were seen as en plaque, homogeneous, uniformly enhancing, dural-based masses. The lesions appeared hyperdense on plain CT scans, isointense to brain parenchyma on T1-weighted MR images, and isointense to hypointense on T2-weighted MR images. One patient had diffuse sheet-like thickening of the pachymeninges in the right hemicranium, involving both the supratentorial and infratentorial compartments.

Adult↗

Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol.

The effect of the method of insulin administration on insulin sensitivity estimates from the insulin modified minimal model (MINMOD) protocol was evaluated using the tolbutamide-boosted protocol as a reference. The study included 21 nondiabetic men ages 40 +/- 2 years (mean +/- SE) with a BMI of 26.6 +/- 1.1 kg/m2. Each subject underwent four frequently sampled intravenous glucose tolerance tests (FSIGTT), one with tolbutamide and three with the same insulin dosage (0.03 U/kg) given as a bolus or infusion over 5 or 10 min. The insulin sensitivity index (SI) of each subject was calculated from each FSIGTT with MINMOD. Insulin sensitivity indexes from the four FSIGTTs were highly correlated (r > 0.85, P < 0.001). SI(insulin) from the bolus and the 5- and 10-min infusion protocols were similar, but were 21 +/- 5, 29 +/- 5, and 23 +/- 4% lower than SI(tolbutamide), respectively. SG(tolbutamide) and SG(insulin) were not different among the four protocols and were significantly correlated (r > 0.55, P < 0.01). Thus the tolbutamide and insulin protocols must not be used interchangeably in any single cross-sectional or longitudinal study. When the same insulin dosage is used, the method of its administration has no bearing on insulin sensitivity estimates from the insulin-modified FSIGTT. The same method of insulin administration should be used, however, in any single study for purpose of standardization.

Adult↗

Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and adults.

The use of methanol as a component of automobile fuel will increase perinatal exposures in the general population. Few studies have addressed questions concerning neurotoxicity stemming from such exposures. In the current study, four cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a control group, were exposed to 4500 ppm methanol vapor in Rochester-type inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure continued for both dams and pups through Postnatal Day 21 (PND 21) to model gestational and neonatal toxicity in humans. Several behavioral procedures were used to assess exposure effects in the offspring. Male-female littermates were studied whenever possible to examine sex differences, with one pair from a litter for each procedure. Exposure to methanol did not affect suckling latency and nipple attachment on PND 5 or performance on an aversive olfactory conditioning procedure on PND 10. Exposure to methanol did alter performances in a motor activity procedure. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control group pups. Two operant conditioning procedures, not used previously in this context, assayed other littermates as adults. A fixed ratio schedule required the rat to rotate a running wheel a specified number of revolutions to obtain food-pellet reinforcers. When the fixed ratio requirement changed, number of responses (revolutions) per 1-hr session displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. Compared to initial baseline performances, methanol-exposed males showed decreases, and methanol-exposed females increases, in the rate of running. A stochastic spatial discrimination procedure permitted subjects to respond on any three levers, with the probabilities of food-pellet delivery determined by the location of the preceding response. A reinforcement matrix defined the response sequence required to maximize reinforcements. When the matrix was changed, the methanol-exposed subjects responded less efficiently at asymptotic levels of performance than controls. Across procedures, developmental exposure to 4500 ppm methanol vapor was associated with subtle behavioral changes in both neonates and adults.

Administration, Inhalation↗

Cultivation of Mycobacterium tuberculosis from pleural tissue and its histopathology in suspected cases of tuberculous pleural effusion.

The majority of idiopathic pleural effusion are considered to be of tuberculous etiology. The culture of bacilli provide most authentic evidence of disease process. This study was carried out on 21 cases of suspected tuberculous pleural effusion. The pleural fluid and tissue was subjected for smear examination, and cultivation of tubercle bacilli along with pleural biopsy. Overall the diagnosis could be made out of 8 (38.09%) cases. The cultivation of Mycobacterium tuberculosis from pleural tissue was more sensitive (33.33%) as compared to histopathology (19.05%). However, the triad of cultivation of Mycobacterium tuberculosis from pleural tissue, pleural histopathology and pleural fluid smear examination or culture should be done in each suspected case of tuberculous effusion.

Adolescent↗

Ovarian cancer patients with high CA-125 but no symptoms--should antiangiogenic treatments be considered?

In ovarian cancer patients, the duration of complete response after successful cancer chemotherapy is often short-lived. During that time period, patients usually receive no further maintenance therapy. Ovarian cancer patients in complete remission, however, often begin to show steady increases in their plasma levels of cancer antigen CA-125, 4-6 months before the recurrence of clinical symptoms. For these individuals, we are proposing the administration of angiogenesis inhibitors as a maintenance therapy. Although, in ovarian cancer, CA-125 provides a unique opportunity in identifying those patients requiring further treatment, this concept could be applied to other forms of cancer as other prognostic indicators become available.

Antineoplastic Agents↗

Trabeculectomy with mitomycin-C for postkeratoplasty glaucoma: a preliminary study.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of trabeculectomy with mitomycin-C in the management of postkeratoplasty glaucoma. PATIENTS AND METHODS: Included in this study were 16 eyes of 16 patients who underwent trabeculectomy with mitomycin-C for medically uncontrolled postkeratoplasty glaucoma, each having at least 6 months of follow-up. RESULTS: The mean pretrabeculectomy intraocular pressure (IOP) with maximal medical therapy was 34.6 mm Hg (range 24-45 mm Hg). The mean IOP following trabeculectomy with mitomycin-C was 14.2 mm Hg (range 8-36 mm Hg) by the end of a mean follow-up of 14.2 months (range 8-32 months). Fourteen eyes (87.5%) had complete success, 1 eye (6.25%) had qualified success, and 1 eye (6.25%) had failure. All the patents had the same or better visual acuity, compared with the preoperative value. None of the patients had postoperative complications, such as shallow anterior chamber, epithelial defect, or hypotony. CONCLUSIONS: Trabeculectomy with mitomycin-C is a safe and effective modality in the management of medically uncontrolled postkeratoplasty glaucoma.

Administration, Topical↗

Efficacy of alpha,beta-arteether in acute uncomplicated P. falciparum malaria.

A phase-III clinical trial was conducted in 50 patients (42M + 8F) with acute uncomplicated falciparum malaria from Delhi during the period of September to November 1995. Their mean age was 27.2 years, and the mean parasitaemia on day 0 was 0.65%. Patients were hospitalized and treated with a new ethyl derivative of artemisinin developed at CDRI called alpha, beta-arteether, at the dosage of 150 mg l/M for three consecutive days. Peripheral smears were examined every day for 4 days and then weekly up to 28 days. The results of the study showed that the mean parasite and fever clearance times were respectively 19.94 +/- 6.87 and 37.81 +/- 21.67 hours. Within 48 h, 70% of the cases became afebrile and the peripheral smear was negative in 100% of the cases. The drug was well tolerated. Three cases (6%) had recrudescence within 28 days. It is concluded that alpha, beta-arteether is a safe, effective and rapidly acting antimalarial.

Adolescent↗

High altitude effects on human taste intensity and hedonics.

BACKGROUND: The study was conducted on human volunteers taken to 3500 m altitude for a period of 3 wk. METHODS: Subjects rated four compounds representing sweet, salty, sour and bitter taste, and the hedonic matrix in terms of taste threshold, taste intensity, and taste hedonicity were recorded using category scale. Blood sugar levels were estimated weekly. RESULTS: An increase in the taste thresholds for glucose and sodium chloride was shown while quinine sulphate and citric acid thresholds recorded a decrease. The taste intensity ratings showed a linear relationship with increasing logarithmic molar concentrations of each solution, as compared with taste hedonicity which showed an inverted 'U' type function. The blood picture did not reveal any change in the blood sugar level. All the parameters recorded at high altitude (HA) showed a tendency to return to basal values after reinduction to sea level. CONCLUSION: The study suggests that HA hypoxic stress brings about changes in the hedonic responses, primarily an increased palatibility for sweetness; we speculate that the mechanism may be anorexia-linked nutritional stress.

Adult↗

The possible role of adrenergic component in ischemic preconditioning.

The role of adrenergic mechanism in the cardioprotective effect of ischemic preconditioning against ischemia-reperfusion induced injury in in vivo dog heart and isolated rat heart was investigated. Anesthetized dogs were subjected to LAD coronary artery ligation for 60 min followed by reperfusion for 4 h. Preconditioning protocol was 5 min of ischemia followed by reperfusion for 10 min. Rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 30 min. Preconditioning protocol was 5 min global ischemia followed by reperfusion for 5 min repeated four times. Infarct size, electrocardiographic changes and release of LDH were estimated to assess the extent of cardiac injury. Preconditioning reduced the infarct size, ST segment elevation and prevented the loss of R wave. Prazosin attenuated the cardioprotective effect of preconditioning in dog. Preconditioning conferred protection against ischemia-reperfusion induced cardiac injury and reperfusion-induced arrhythmias in isolated rat heart. Reserpine pretreatment attenuated this protective effect of preconditioning on reperfusion-induced arrhythmias. These observations suggest the involvement of adrenergic mechanism in the cardioprotective and antiarrhythmic effect of ischemic preconditioning in dog and rat species respectively.

Adrenergic Uptake Inhibitors↗