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Biomedical subjects

R Amin

Publications and source records attributed to R Amin.

At least 19 recordsLinked to original sources
PubMed2006

Adaptive control of laser modal properties.

An adaptive optical system for precise control of a laser beam's mode structure has been developed. The system uses a dynamic lens based on controlled optical path deformation in a dichroic optical element that is heated with an auxiliary laser. Our method is essentially aberration free, has high dynamic range, and can be implemented with high average power laser beams where other adaptive optics methods fail. A quantitative model agrees well with our experimental data and demonstrates the potential of our method as a mode-matching and beam-shaping element for future large-scale gravitational wave detectors.

Journal Article↗
PubMed2005

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗
PubMed2005

Lymphoproliferative disorder of the airway of an adolescent without immunodeficiency.

Epstein-Barr virus (EBV) is a ubiquitous viral pathogen in humans that has a unique ability to immortalize B-cells. In immunosuppressed individuals, EBV can produce non-neoplastic lymphoproliferative disorders involving various organs. We describe a case report of EBV-associated lymphoproliferative disorder in an immunocompetent 14-year-old male. The case provides a description of EBV-associated lymphoproliferation affecting the upper and lower respiratory tract. The massive submucosal infiltration of B-cells in the lingual tonsils, trachea, and bronchi produced near-complete airway obstruction resulting in tracheotomy. Neither surgical reduction of lingual tonsils nor treatment with steroids was of benefit. An extensive evaluation for immunodeficiency and neoplasia was normal. Treatment with rituximab, an anti-CD20 antibody, resulted in near-complete resolution of the infiltrative process, sufficient to allow decannulation. Rituximab is a treatment option for the rare occurrence of non-neoplastic, EBV-associated, lymphoproliferative disorders.

Adolescent↗
PubMed2005

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗
PubMed2005

Longitudinal relation between limited joint mobility, height, insulin-like growth factor 1 levels, and risk of developing microalbuminuria: the Oxford Regional Prospective Study.

AIMS: To determine risk factors for development of microalbuminuria (MA) in relation to detection of limited joint mobility (LJM+) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) subjects. METHODS: A total of 479 T1DM subjects diagnosed <16 years were followed from diagnosis of diabetes with annual assessments consisting of assessment of LJM, measurement of HbA1c and insulin-like growth factor 1 (IGF-1), and three urine samples for albumin:creatinine ratio (ACR). RESULTS: After a median follow up of 10.9 years, 162 subjects (35.1%) developed LJM at median age 13.0 years and duration 5.2 years. More subjects developed LJM after compared to before puberty (67.6 v 32.4%). In LJM+ compared to LJM- subjects, HbA1c (mean 10.1 (SD 1.6) v 9.6 (1.4) %)) and ACR levels (median 1.1 (range 0.2-242.9) v 0.9 (0.4-70.7) mg/mmol) were higher, and in a Cox model probability of developing LJM was related to puberty and higher HbA1c levels. ACR levels were higher after detection of LJM compared to before (median 1.2 (range 0.4-102.6) v 0.8 (0.2-181.9) mg/mmol). Probability of developing MA was related to puberty, HbA1c, female sex, and presence of LJM (a 1.9-fold increased risk). Both LJM and MA were associated with lower height SDS (LJM: mean 0.0 (SD 1.0) v 0.2 (1.1); MA: 0.0 (1.0) v 0.2 (SD 1.0)) and lower IGF-1 levels. CONCLUSION: The development of LJM was associated with an increased risk of microalbuminuria, independent of glycaemic control. Risk for both microalbuminuria and LJM was associated with puberty, reduced growth, and reduced IGF-1 levels, and may indicate underlying shared pathogenic mechanisms.

Adolescent↗
PubMed2003

The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Growth hormone hypersecretion in Type 1 diabetes could exacerbate insulin resistance and contribute to declining glycaemic control. Our aim was to determine the effects of specific growth hormone blockade on insulin sensitivity and lipolysis in young adults with Type 1 diabetes. METHODS: We studied the effects of two doses of a specific growth hormone antagonist (B2036-PEG; Somavert, Pharmacia Corporation, Milton Keynes, UK) on insulin sensitivity in seven young adults (17-22 yrs, 3M) with Type 1 diabetes. Subjects received 5 and 10 mg B2036-PEG, in random order for 3 weeks, with a 3-week washout. At baseline and following each treatment block, an overnight (03:00 to 08:00 h) insulin infusion for euglycaemia (5 mmol/l), followed by two-step hyperinsulinaemic euglycaemic clamp, using [6,6 2H2] glucose and 2H5 glycerol to measure glucose and glycerol turnover was performed. RESULTS: Compared to baseline, overnight insulin requirements decreased with both doses: (means+/-SEM) 0.34+/-0.02 mU/Kg/min vs 0.25+/-0.01 (5 mg) (p=0.04), and 0.24+/-0.01 (10 mg) (p=0.004). IGF-I (ng/ml) decreased following 10 mg [223.5+/-23.9 vs 154.6+/-28.1 (p=0.005], but not 5 mg. Mean overnight non esterified fatty acid concentrations (mmol/l) decreased with 10 mg [0.51+/-0.04 vs 0.38+/-0.04 (p=0.03)], as did beta-hydroxybutyrate (mmol/l); [0.31+/-0.04 vs 0.15+/-0.02 (p=0.004)]. Glycerol production rate, an index of lipolysis, was lower following 10 mg (p=0.04), but insulin sensitivity during the clamp did not change with either dose. CONCLUSION/INTERPRETATION: Treatment with both doses of B2036-PEG reduced overnight insulin requirements. The 10 mg dose suppressed lipolysis and reduced IGF-I. Failure to show enhanced insulin sensitivity during the clamp with the 10 mg dose could reflect opposing actions of growth hormone and IGF-I.

Adolescent↗
PubMed2003

Relation between insulin kinetics and insulin sensitivity in pregnancy.

BACKGROUND: Different time-concentration profiles of plasma insulin following insulin modification of a frequently sampled intravenous glucose-tolerance-test (FSIVGTT) were observed in a study investigating maternal metabolism and fetal macrosomia. We aimed to investigate whether these differences were related to the volume of distribution of insulin, insulin clearance, or both. DESIGN: Forty-four women were studied between 33 and 35 weeks' gestation using an insulin-modified FSIVGTT. Specific insulin was assayed with an enzyme-linked immunosorbent assay. Insulin sensitivity was calculated using the minimal model and the homeostasis model assessment (HOMA). The volume of distribution and clearance of insulin were calculated from measurements between 2 and 155 min after insulin modification using a one-compartment model. RESULTS: In accordance with the method for deriving the volume of distribution, there was a significant negative correlation between the increment in insulin concentration and the volume of distribution (rho=-0.92, P<0.0001). The insulin increment was also related negatively to the clearance of insulin (rho=-0.88, P<0.0001). There was a significant correlation between the volume of distribution and both the insulin sensitivity index (rho=0.56, P<0.0001) and HOMA-%S (rho=0.30, P=0.048), and between the clearance of insulin and both the insulin sensitivity index (rho=0.83, P<0.0001)) and HOMA-%S (rho=0.34, P=0.025). CONCLUSION: The different time-concentration profiles of plasma insulin resulted from differences in the volume of distribution and clearance of insulin. There was a correlation between insulin kinetics and the insulin sensitivity index. Further research is required to investigate possible mechanisms by which insulin kinetics may be related to insulin sensitivity.

Enzyme-Linked Immunosorbent Assay↗
PubMed2003

Evaluation of hospitalized infants and young children with bronchiolitis - a multi centre study.

Four hundred and twenty nine young children with bronchiolitis admitted consecutively in different hospitals of Bangladesh were evaluated. Three hundred and forty eight children studied for their putative risk factors, clinical profile, management and the outcome. Both cases and controls were examined for respiratory syncytial virus (RSV) antibody status. The diagnosis of bronchiolitis was made on the basis of first attack of wheeze in previously healthy children below two years of age. Detailed history including the possible risk factors, the management and daily follow-up on the ward and the outcome at discharge were documented through a structured questionnaire. Chest x-ray was done in each case to find out the radiological changes. Blood of 266 patients and 30 controls were studied for RSV IgM and IgG antibody by ELISA. There were 66% male and 34% female children. The median age of the children was 3.0 months and 82.7% were below 6 months of age. Most of the babies were born term (88%), with ABW (73%), by normal vaginal delivery (88%). Exclusive or predominant breast-feeding were given in 72% cases. The location of the patient was rural in 55% cases. Around half of the parents were illiterate or slightly educated (up to 5 years schooling) fathers 46.5% and mothers 56% and majority of the parents were poor (74%). In 52% cases the number of family members in one room were four or more. Half of the parents (52%) were smokes and there was atopy in 26.5% families. The clinical features of bronchiolitis were mostly cough (99%), respiratory distress (97%), feeding difficulty (93%) and fast breathing (96%) (median RR 68/min). Fever (1000F or more) was in only 33% cases, though parents complained in 90% cases. All children (100%) had wheeze and crackles in lungs in 96% cases. Liver could be palpable in 83% and spleen in 42% cases. Important radiological features were increased translucency (96%), increased interstitial markings (87%), hyperinflation (75%) and streaky densities (61%). In 69.6% cases TLC was 12,000 or less and only 15% with a neutrophil fraction greater than 60%. Children were positive for IgM antibody in 43.6% cases and both IgM and IgG in 5.3% cases. The main modalities of treatment were antibiotics (99%) (Ampicillin, 76%), oxygen therapy (83%), nebulised salbutamol (76%) and intravenous fluid (51%). The median duration of hospital stay was 4 days. Most of the children were discharged with improvement (96%) with 2% mortality. Not a single case was diagnosed as bronchiolitis in hospitals outside Dhaka. Cefrtiaxone (72.5%) and parenteral steroids (70.5%) were the mainstay of therapy there.

Bronchiolitis↗
PubMed2002

Inhibitors of post-translational modifications of G-proteins as probes to study the pancreatic beta cell function: potential therapeutic implications.

It is well established that glucose-induced insulin secretion involves generation of intracellular second messengers. Using specific inhibitors of guanosine triphosphate [GTP] biosynthesis [e.g., mycophenolic acid; MPA], we have identified a permissive role for GTP in glucose-stimulated insulin secretion. While the exact site of action for GTP within the islet beta cell remains to be identified and defined, recent evidence from several laboratories, including our own, indicate that it could involve activation of GTP-binding proteins [G-proteins]. These studies have identified both trimeric and monomeric forms of G-proteins within the pancreatic beta cell. Recent data also indicate that these G-proteins, specifically the monomeric G-proteins and the gamma subunits of trimeric G-proteins undergo a series of posttranslational modifications at their C-terminal cysteine. Such modifications include, isoprenylation, carboxyl methylation and palmitoylation. These modification steps appear to be essential for translocation of these proteins to the membrane sites for interaction with their respective effector proteins. This review primarily focuses on recent findings that clearly support the viewpoint that these posttranslational modification steps not only play obligatory roles in fuel-induced insulin secretion, but also in cytokine-mediated apoptotic demise of the beta cell. In this review, we also attempted to describe those findings involving the use of specific inhibitors for each of these pathways, and it is our hope that these aspects of beta cell metabolism and function generate interest in development of therapeutic intervention modalities to states of perturbed insulin release.

Apoptosis↗
PubMed2002

IL-1beta-induced nitric oxide release from insulin-secreting beta-cells: further evidence for the involvement of GTP-binding proteins.

Recently, we have demonstrated regulatory roles for G-proteins (e.g., H-Ras) in IL-1beta induced NO release from HIT-T15 cells. Herein, we report a similar regulatory mechanism for IL-1beta induced NO release from RIN5F and INS-1 cells. Our data indicate that functional inactivation of Ras, either by Clostridial toxins or by specific inhibitors of Ras function, results in a significant inhibition in IL-1beta induced NO release, suggesting that activation of specific G-proteins is essential for IL-1beta induced NO release. In the present study, we report possible loci where IL-1beta treatment might result in functional activation of these G-proteins. For example, IL-1beta treatment resulted in significant reduction in (high-and low-affinity) GTPase activities in lysates derived from normal rat islets; such a scenario might lead to retention of candidate G-proteins in GTP-bound, active conformation. Further, IL-1beta treatment increased the G-protein carboxyl methyl transferase activity as well as carboxyl methylation of endogenous beta-cell proteins; such a modification has been shown to increase the membrane association and interaction of these G-proteins with their respective effector proteins. Also, we report immunologic localization of H-Ras regulatory proteins including its nucleotide exchange factor (GRF-1) and its effector protein (eg., Raf-1) in isolated beta-cells. Together, our data indicate localization, and regulation by IL-1beta, of specific enzymes that are critical to activation of G-proteins. Based on these preliminary findings, we propose a model for the involvement of G-proteins in IL-1beta induced NO release and subsequent demise of the pancreatic beta-cell.

Animals↗
PubMed2001

Positive modulation by Ras of interleukin-1beta-mediated nitric oxide generation in insulin-secreting clonal beta (HIT-T15) cells.

In the present study, we have shown that exposure of insulin-secreting clonal beta (HIT-T15) cells to interleukin-1beta (IL-1beta) results in a time- and concentration-dependent increase in nitric oxide (NO) release. These effects by IL-1beta on NO release were mediated by induction of inducible nitric oxide synthase (iNOS) from the cells. Preincubation of HIT cells with Clostridium sordellii lethal toxin-82, which irreversibly glucosylates and inactivates small G-proteins, such as Ras, Rap, Ral, and Rac, but not Cdc42, completely abolished IL-1beta-induced NO release. Pre-exposure of HIT cells to C. sordellii lethal toxin-9048, which monoglucosylates and inhibits Ras, Cdc42, Rac, and Rap, but not Ral, also attenuated IL-1beta-mediated NO release. These data indicate that activation of Ras and/or Rac may be necessary for IL-1beta-mediated NO release. Preincubation of HIT cells with C. difficile toxin-B, which monoglucosylates Rac, Cdc42, and Rho, had no demonstrable effects on IL-mediated NO release, ruling out the possibility that Rac may be involved in this signaling step. Further, two structurally dissimilar inhibitors of Ras function, namely manumycin A and damnacanthal, inhibited, in a concentration-dependent manner, the IL-1beta-mediated NO release from these cells. Together, our data provide evidence, for the first time, that Ras activation is an obligatory step in IL-1beta-mediated NO release and, presumably, the subsequent dysfunction of the pancreatic beta cell. Our data also provide a basis for future investigations to understand the mechanism of cytokine-induced beta cell death leading to the onset of insulin-dependent diabetes mellitus.

Animals↗
PubMed2000

Pseudohypoparathyroidism--another monogenic obesity syndrome.

Obesity is a common feature of pseudohypoparathyroidism (PHP) type 1a, but is usually associated with short stature. We describe two children referred because of hyperphagia and excessive weight gain from early infancy. Tall stature in both children initially confounded the diagnosis of PHP, but on follow-up both children developed the typical hormonal abnormalities and Case 2 developed typical skeletal features of Albright hereditary osteodystrophy. PHP type 1a is caused by germline loss of function mutations in the alpha subunit of GS, the ubiquitously expressed G protein that couples many hormone receptors to the adenylate cyclase second messenger system. Recent evidence suggest that the hypothalamic GS protein coupled melanocortin-4 receptor (MC4R) may mediate the central effects of leptin on inhibition of satiety. Similar patterns of infancy onset hyperphagia, excessive weight gain and tall stature are seen in subjects with congenital leptin deficiency and in subjects with MC4R mutations. We suggest that the genetic mutations in GSalpha which underlie PHP type 1a may also directly result in severe obesity. This diagnosis should be considered in any child with a history of hyperphagia and early onset morbid obesity.

Child, Preschool↗
PubMed1999

Intramedullary spinal metastasis from carcinoma of the cervix.

Intramedullary spinal metastases are rare and prior to the availability of MRI were seldom diagnosed antemortem. Lung and breast carcinoma are the most common primary sources. Cervical carcinoma is the least likely source of intramedullary spinal metastases. A case of intramedullary spinal metastases is described in a 29-year-old woman with squamous cell carcinoma of the cervix.

Adult↗
PubMed1999

Perianal Paget's disease.

Perianal Paget's disease is rare. Unlike Paget's disease of the nipple, which is always associated with a subjacent breast adenocarcinoma, perianal Paget's disease is not always associated with a subjacent or visceral malignancy. The treatment recommendation in nearly all reported cases has been surgical excision. Radiation therapy is seldom used as a curative treatment. A case of perianal Paget's disease is described in whom radiation therapy was used with a curative intent after four unsuccessful surgical resections.

Aged↗