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Biomedical subjects

V Iyer

Publications and source records attributed to V Iyer.

At least 19 recordsLinked to original sources
PubMed2003

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗
PubMed2003

Experience with ketamine and sodium pentobarbital as anesthetics in a rat model of cardiac arrest and resuscitation.

We review 7 years experience with the chest compression model of cardiac arrest and resuscitation, comparing two different anesthetics. Ketamine stimulates cardiac function and only mildly depresses respiration; of the two it provides easier resuscitation. However, ketamine severely depresses brain protein synthesis; in studies using this measure ketamine is unsuitable and another agent must be used. Sodium pentobarbital mildly depresses brain protein synthesis, but depresses both cardiac and respiratory function, making resuscitation more difficult. Use of alternate chest/abdominal pumping (Babbs resuscitation technique), with judicious use of intra-cardiac epinephrine (adrenaline), made resuscitation reliable under sodium pentobarbital as well.

Anesthetics, Dissociative↗
PubMed2002

Correlation between fetal scalp blood samples and intravascular blood pH, pO2 and oxygen saturation measurements.

OBJECTIVE: This study was designed to compare the values of blood gases in local scalp blood, obtained by scalp blood sampling, with direct measurements of fetal preductal arterial blood in fetal sheep. METHODS: Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO2) of 20 to 5% by addition of nitrogen to the inhaled gas mixture. Fetal scalp and arterial blood were sampled simultaneously at maternal FiO2 step intervals after maternal FiO2 and oxygen were stable for > 5 min. Blood pH, pO2 and oxygen saturation were measured and linear regression was performed to determine the correlation between these values. RESULTS: Scalp pH correlated well with arterial pH, whereas scalp pO2, pCO2 and oxygen saturation did not. However, when a secondary analysis was performed taking into account the effects of aerobic contamination, scalp pCO2, pO2 and oxygen saturation became highly correlated with arterial values. CONCLUSIONS: Local scalp blood oxygen saturation correlates highly with fetal preductal arterial values, when physiological artifacts are eliminated. The technique of scalp blood sampling introduces error into oxygenation saturation measurements, owing to difficulties in anaerobic sample collection. These results suggest that continuous measurement of fetal scalp oxygenation by noninvasive oximetry may be superior to direct sampling of scalp blood.

Animals↗
PubMed2000

Oral contraceptive pills for heavy menstrual bleeding.

BACKGROUND: Menorrhagia (heavy menstrual bleeding) is a benign yet debilitating social and health condition. The widely accepted clinical definition of menorrhagia is blood loss of 80ml or more per period. This figure is derived from population studies that have shown that the average blood loss is between 30 and 40ml, and 90% of women have blood losses of less than 80ml. Excessive menstrual bleeding is the commonest cause of iron deficiency in the United Kingdom affecting 20-25% of the fertile female population. Menorrhagia is a common problem accounting for 12% of all gynaecological referral in the UK. Ranges of medical therapies are prescribed in order to reduce excessive menstrual blood loss, including prostaglandin synthetase inhibitors, antifibrinolytics, the oral contraceptive pill and other hormones. The combined oral contraceptive pill (OCP) is claimed to have a variety of beneficial, inducing a regular shedding of a thinner endometrium and inhibiting ovulation thus having the effect of treating menorrhagia and providing contraception. OBJECTIVES: To determine whether: 1. the OCP is an effective medical therapy to reduce menorrhagia in both the short term and long term. 2. the effectiveness of combined oral contraceptive pills (OCP) compared with other medical therapies for the treatment of menorrhagia. 3. OCP is a more cost effective method than any other medical treatments of menorrhagia. 4. OCP has fewer side effects than other drugs used for menorrhagia. SEARCH STRATEGY: All publications which describe randomised trials of OCP for the treatment of menorrhagia were obtained using the search strategy developed by the Menstrual Disorders Group. SELECTION CRITERIA: All randomised controlled comparisons of OCP versus other medical therapies, placebo or no treatment for the treatment of menorrhagia. Women of reproductive years with regular heavy periods, measured either objectively or subjectively and greater than, or equal to, two months follow up. DATA COLLECTION AND ANALYSIS: All assessments of the quality of trials and data extraction were performed unblinded by at least two reviewers. Only one trial met the inclusion criteria and none were excluded. The included trial involved a total of 45 women. MAIN RESULTS: As the trial used a cross-over design, only data from the first treatment period (cycles 3 and 4 ) were analysed. The results from all the three mefanamic acid groups were combined. There was no significant difference in menstrual blood loss (MBL) between those patients treated with the OCP and danazol, mefenamic acid or naproxen. REVIEWER'S CONCLUSIONS: The one small study identified [Fraser 1991] found no significant difference between groups treated with OCP, mefenamic acid, low dose danazol or naproxen. Overall, the evidence from the one study identified [Fraser 1991] is not sufficient to adequately assess the effectiveness of OCP. This review was unable to achieve its stated objectives because of the paucity of the data.

Contraceptives, Oral↗
PubMed2000

Systematic variation in gene expression patterns in human cancer cell lines.

We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo.

Breast↗
PubMed2000

Revision total hip arthroplasty using third-generation cementing technique.

A total of 83 consecutive first-revision total hip arthroplasties were performed in 83 patients using pressurized vacuum-mixed cement, a third-generation cementing technique. At a median follow-up of 3.6 years (range, 1.5-6.3 years), the overall failure rates (radiographic loosening, re-revision, or both) were 39% for the femoral components and 30% for the acetabular components. With definite radiographic loosening as an endpoint, the cement-bone interface achieved was the only significant factor to predict stem durability, with an adjusted odds ratio of 1.8 (95% confidence interval, 1.1-3.0). On the acetabular side, bone stock was the only significant factor, with an adjusted odds ratio of 5.3 (95% confidence interval, 4.0-27.7). In this retrospective cohort study, femoral cement pressurization per se did not appear to improve the results over those of other studies using second-generation techniques.

Adult↗
PubMed2000

Assessment of fetal scalp oxygen saturation determination in the sheep by transmission pulse oximetry.

OBJECTIVE: Electronic fetal heart rate monitoring has an unacceptable false-positive nonreassuring rate, which results in an excess of operative interventions. As a more objective measure of fetal oxygenation, fetal scalp pulse oximetry has been used to assess fetal blood oxygen saturation (SO (2)). The current devices use reflectance oximetry, which has inherent limitations. These include varying depths of signal penetration, variation with position, and potential for optical interference. In this study we evaluated a newly developed transmission pulse oximetry device consisting of transmitter and receiver diodes mounted within the coil of a standard scalp electrode (Spiral O(2)CTG; Respironics Inc, Marietta, Ga). STUDY DESIGN: Six pregnant ewes at 127 to 135 days' gestation (term, 145 days' gestation) were anesthetized, intubated, and prepared with a femoral artery catheter. Fetuses were prepared with brachial artery and jugular vein catheters. Maternal inspired oxygen fraction was titrated from 21% to 3%. Oximetry O(2)CTG devices were positioned on the fetal scalp, and recordings were compared with directly determined fetal arterial pH, PO (2), and SO (2) values. RESULTS: Maternal SaO (2) and PaO (2) ranged from 102% to 16% and 110 to 18 mm Hg, respectively. Fetal SaO (2) and PaO (2) ranged from 76% to 12% and 28 to 8 mm Hg, respectively. There was excellent correlation between direct fetal SaO (2) and scalp SO (2) (r (2) = 0.90; scalp SO (2) = 0.79 SaO (2) + 6.89). With an SaO (2) of <30% as the cutoff point for assessment of fetal compromise, scalp SO (2) measurements had a 94% +/- 10% specificity and a 94% +/- 10% positive predictive value. CONCLUSION: (1) Preliminary studies of the Spiral O(2)CTG sensor demonstrated high correlation of scalp SO (2) with fetal SaO (2). (2) Although potential inaccuracies remain, transmission oximetry may offer potential advantages in consistency, ease of application, and technology with respect to the current reflection oximeter devices.

Animals↗
PubMed1998

Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia.

Fosphenytoin, a water-soluble disodium phosphate ester of phenytoin, is a phenytoin prodrug with similar anticonvulsant properties. In this study, we evaluated its neuroprotective properties in a cardiac arrest-induced global ischemia model. After 12 minute ischemia, Long-Evans hooded rats were resuscitated, given fosphenytoin (30 mg/kg, i.m.) or saline 5 minutes after the ischemic episode, and killed on day 7. Brains were removed, fixed, and vibratome sectioned to assess the numbers of normal appearing CAI pyramidal neurons and for immunohistological staining of glial fibrillary acidic protein (GFAP). After global ischemia, the number of hippocampal CA1 pyramidal neurons decreased significantly (from 14.33 +/- 1.73 to 2.19 +/- 0.16 per 100 micron 2). Most hippocampal CA1 pyramidal neurons showed signs of injury and GFAP immunoreactivity of the region increased. With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90 +/- 0.92), however, GFAP staining was not significantly changed. Our data, although indicating different neuronal and glial responses following fosphenytoin treatment, nevertheless, suggest that fosphenytoin is an effective neuroprotectant against ischemia-induced damage.

Analysis of Variance↗
PubMed1996

Absolute mRNA levels and transcriptional initiation rates in Saccharomyces cerevisiae.

We quantitate the absolute levels of individual mRNAs per yeast cell by hybridizing total yeast RNA with an excess of gene-specific 32P-oligonucleotides, and digesting the resulting RNA-DNA hybrids with S1 nuclease. By comparing the his3 hybridization signal from a known amount of yeast cells to the signal generated by a known amount of his3 RNA synthesized in vitro, we determine that yeast strain KY114 growing in yeast extract/peptone/glucose medium at 30 degrees C contains seven molecules of his3 mRNA per cell. Using a galactose shut-off procedure, we determined that the half-life of his3 mRNA is approximately 11 min under these conditions. From these observations, we calculate that one his3 mRNA molecule is synthesized every 140 s. Analysis of other his3 promoter derivatives suggests that the maximal transcriptional initiation rate in yeast cells is one mRNA molecule every 6-8 s. Using his3 as an internal standard, the number of mRNA molecules per cell have been determined for ded1, trp3, rps4, and gall under a variety of growth conditions. From these results, the absolute mRNA level of any yeast gene can be determined in a single hybridization experiment. Moreover, the rate of transcriptional initiation can be determined for mRNAs whose decay rates are known.

Base Sequence↗
PubMed1996

Audiogenic seizures following global ischemia induced by chest compression in Long-Evans rats.

Transient global ischemia was used to produce a rat model of generalized tonic-clonic epilepsy. Controlled chest compression in ketamine-anesthesized Long-Evans rats produced transient global ischemia by mechanically preventing the heart from pumping blood. Circulation was restored by standard cardiopulmonary resuscitation techniques. With a temporal muscle (skull) temperature of 35 +/- 0.4 degrees C, 75% (76/102) of the rats survived 7 min of chest compression. Generalized seizures could be evoked in 78% (59/76) of the surviving rats by a 60 s exposure to a loud sound (bell, 110 dB) beginning 24 h after the ischemic episode. The seizure patterns seen resembled those described by Maresceaux (1987) for genetically seizure-prone Wistar rats. Susceptibility to sound-induced seizures declined with time, with wide variations in recovery rate between individuals; one rat showed a daily sound-induced seizure for over 5 months. Seizures were attenuated or blocked by treatment with carbamazepine or sodium valproate. This model is similar to the great vessel occlusion model used by Kawai et al. (1995), but is less invasive. We believe it will be useful in the evaluation of therapies for acquired generalized (grand mal) seizures.

Acoustic Stimulation↗
PubMed1995

Cardiac arrest-induced global cerebral ischemia studied in vitro.

The goal of the present study was to characterize the effects of chest compression-induced global cerebral ischemia on the hippocampal slice preparation. One of the characteristics of rats exposed to such cardiac arrest is a high susceptibility to sound-induced seizures. We tested audiogenic seizures as an in vivo indicator of ischemic cerebral damage and as a possible small animal model of epilepsy. The results of these tests were reported elsewhere. Long-Evans male rats (200-350 g) were subjected to 7 min of chest compression sufficient to stop the pumping action of the heart. The rats were then revived using cardiopulmonary resuscitation. Evaluation of cerebral damage following cardiac arrest and resuscitation was performed in vitro, by testing neuronal responses to electrical stimulation in hippocampal slices prepared from these animals. Sham control animals were used for comparisons. Twenty-one to 146 days after rats were chest-compressed, hippocampal slices were prepared. Sham control rats, anesthetized but not chest-compressed, were sacrificed one week later for preparation of slices. Rats in a second group exposed to 7-min chest compression, were sacrificed at different time intervals after their resuscitation (from 1 h to 7 days); hippocampal slices were prepared for electrophysiological analysis of neuronal damage. The results of these studies indicate that 3 weeks or longer after chest compression the evoked CA1 population spike amplitude in hippocampal slices was significantly attenuated; in 60% of these slices an epileptiform response was evoked. An increased proportion of slices prepared from rats 1 to 48 h after chest compression showed an augmentation in the amplitude of the evoked population spike; 72 h and up to 7 days after chest compression, an attenuation in the evoked CA1 population spike amplitude was observed, signaling delayed neuronal damage.

Animals↗
PubMed1995

Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure.

Many yeast promoters contain homopolymeric dA:dT sequences that affect nucleosome formation in vitro and are required for wild-type levels of transcription in vivo. Here, we show that poly(dA:dT) is a novel promoter element whose function depends on its intrinsic structure, not its interaction with sequence-specific, DNA-binding proteins. First, poly(dA:dT) stimulates Gcn4-activated transcription in a manner that is length dependent and inversely related to intracellular Gcn4 levels. Second, Datin, the only known poly(dA:dT)-binding protein, behaves as a repressor through poly(dA:dT) sequences. Third, poly(dG:dC), a structurally dissimilar homopolymer that also affects nucleosomes, has transcriptional properties virtually identical to those of poly(dA:dT). Three probes of chromatin structure including HinfI endonuclease cleavage in vivo indicate that poly(dA:dT) increases accessibility of the Gcn4 binding site and adjacent sequences in physiological chromatin. These observations suggest that, by virtue of its intrinsic structure, poly(dA:dT) locally affects nucleosomes and increases the accessibility of transcription factors bound to nearby sequences.

Base Sequence↗
PubMed1995

Computerised transient hyperaemic response test--a method for the assessment of cerebral autoregulation.

A simple bedside test has been developed to assess the state of autoregulation in subarachnoid haemorrhage patients. Transcranial Doppler was used to measure blood flow velocity in the middle cerebral artery after a brief common carotid compression. Acceleration of blood flow postcompression was interpreted as evidence of intact cerebral autoregulation. A program using the Windows environment was designed for signal analysis of the transient hyperaemic response test (THRT). The flow velocity signal from the TCD was recorded, carotid compression and release automatically detected and the test results immediately displayed and stored in a database. The program was verified in 614 tests; 552 of them were analysed off-line using previously recorded data and 62 on-line during the examination. A significant correlation was found between the results of computerised testing and the patient's neurological state.

Adult↗
PubMed1995

Mechanism of differential utilization of the his3 TR and TC TATA elements.

The yeast his3 promoter region contains two TATA elements, TC and TR, that are differentially utilized in constitutive his3 transcription and Gcn4-activated his3 transcription. TR contains the canonical TATAAA sequence, whereas TC is an extended region that lacks a conventional TATA sequence and does not support transcription in vitro. Surprisingly, differential his3 TATA-element utilization does not depend on specific properties of activator proteins but, rather, is determined by the overall level of his3 transcription. At low levels of transcription, the upstream TC is preferentially utilized, even though it is inherently a much weaker TATA element than TR. The TATA elements are utilized equally at intermediate levels, whereas TR is strongly preferred at high levels of transcription. This characteristic behavior can be recreated by replacing TC with moderately functional derivatives of a conventional TATA element, suggesting that TC is a collection of weak TATA elements. Analysis of promoters containing two biochemically defined TATA elements indicates that differential utilization occurs when the upstream TATA element is weaker than the downstream element. In other situations, the upstream TATA element is preferentially utilized in a manner that is independent of the overall level of transcription. Thus, in promoters containing multiple TATA elements, relative utilization not only depends on the quality and arrangement of the TATA elements but can vary with the overall level of transcriptional stimulation. We suggest that differential TATA utilization results from the combination of an intrinsic preference for the upstream element and functional saturation of weak TATA elements at low levels of transcriptional stimulation.

Base Sequence↗
PubMed1994

Administration of human chorionic gonadotropin affects sleep-wake phases and other associated behaviors in cycling female rats.

We investigated the possible effects of human chorionic gonadotropin (hCG) on sleep-wake phases and other associated behaviors controlled by the medial preoptic area, cerebral cortex and hippocampus. Chronic epidural electroencephalographic (EEG) and temporal muscle electromyographic (EMG) electrodes were placed in cycling female rats. After a week of recovery, rats were injected intraperitoneally at 3.00 pm on the day of proestrus with either saline or highly purified hCG or indomethacin or hCG plus indomethacin. Three hours after injection, EEG, EMG and behavioral activities were recorded for 3.5 h. The administration of hCG increased high and low amplitude sleep, resting phase and decreased active awake phase, walking, sniffing and chewing as compared to the controls. While the administration of indomethacin alone had no effect, coadministration inhibited hCG effects. Medial preoptic area, cerebral cortex and hippocampus contain immunostaining for LH/hCG receptors. The administration of hCG resulted in an increase of immunoreactive PGD2 and a decrease of PGE2 in median preoptic area, cerebral cortex and hippocampus as compared to the controls. In summary, hCG administration affects sleep-wake phases and other associated behaviors in rats which can collectively be described as decreased activity. These effects are probably mediated by increasing PGD2 and decreasing PGE2 in areas of brain which control these activities. The above findings may be relevant to pregnant women who experience decreased activity when hCG is present in the circulation and cerebrospinal fluid.

Alprostadil↗