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Biomedical subjects

V Iyer

Publications and source records attributed to V Iyer.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Testing of cerebral autoregulation in head injury by waveform analysis of blood flow velocity and cerebral perfusion pressure.

Thirty five head injured patients were subjected to day-by-day monitoring of intracranial pressure (ICP), arterial blood pressure (ABP) and blood flow velocity (FV) in middle cerebral artery. Parameters describing cerebral autoregulation: flow velocity time average, systolic, diastolic values, pulsatility index (PI), estimate of cerebrovascular resistance (CVR = CPP/FV) etc. were analyzed as functions of CPP (ABP-ICP). The results show that for CPP below 55 mmHg the evidence of exhausted autoregulation can be observed in FV, CVR, PI. The method is helpful in assessment ot the optimal level of CPP in order to reduce the probability of ischaemic brain insults.

Blood Flow Velocity↗
PubMed1994

Frequency-dependent properties of cerebral blood transport--an experimental study in anaesthetized rabbits.

Carotid arterial blood pressure and blood flow velocity in the basilar artery were studied in nine New Zealand rabbits under general anaesthesia. The cerebrovascular impedances for mean and maximal flow velocity were defined as the ratios of the respiratory and pulse waveforms of arterial blood pressure and blood flow velocities. The absolute values of these impedances were expressed and analysed as functions of frequency. Both functions decreased as frequency increased, demonstrating that a pulsatile blood movement need a lower energy expenditure than a continuous one. A minimum absolute value of impedance for flow velocity mean was found near 2.5-4 Hz in each rabbit. The impedance for mean flow velocity could be modelled by a second-order circuit, whereas the distribution of impedance for the maximal velocity had a more uniform character and could be approximated by a first-order model. A method of assessment of changes in cerebrovascular resistance using frequency properties of calculated impedance was proposed.

Animals↗
PubMed1994

A role for osmotic stress-induced proteins in the osmotolerance of a nitrogen-fixing cyanobacterium, Anabaena sp. strain L-31.

The molecular basis of tolerance to osmotic stress was investigated with a cyanobacterium, Anabaena sp. strain L-31. The inherent osmotolerance of this strain (50% growth inhibition at 350 mM sucrose) was enhanced by adaptation with 100 mM sucrose for 30 min. Addition of 10 mM KNO3 during growth also conferred significant osmoprotection, but addition of 3 mM NH4Cl did not. Exposure of cells to 350 mM sucrose induced the expression of at least 12 osmotic-stress-induced proteins (OSPs) within 30 min, in the molecular mass range of 11.5 to 84 kDa. Exposure of cells to 100 mM sucrose or to 10 mM nitrate also induced all the OSPs, but addition of ammonium did not. The observed correspondence between the presence of OSPs and osmotolerance strongly suggests a role for OSPs in osmotolerance of Anabaena sp. strain L-31.

Anabaena↗
PubMed1993

Differential responses of nitrogen-fixing cyanobacteria to salinity and osmotic stresses.

Two nitrogen-fixing Anabaena strains were found to be differentially tolerant to salinity and osmotic stresses. Anabaena torulosa, a brackish-water, salt-tolerant strain, was relatively osmosensitive. Anabaena sp. strain L-31, a freshwater, salt-sensitive strain, on the other hand, displayed significant osmotolerance. Salinity and osmotic stresses affected nitrogenase activity differently. Nitrogen fixation in both of the strains was severely inhibited by the ionic, but not by the osmotic, component of salinity stress. Such differential sensitivity of diazotrophy to salinity-osmotic stresses was observed irrespective of the inherent tolerance of the two strains to salt-osmotic stress. Exogenously added ammonium conferred significant protection against salinity stress but was ineffective against osmotic stress. Salinity and osmotic stresses also affected stress-induced gene expression differently. Synthesis of several proteins was repressed by salinity stress but not by equivalent or higher osmotic stress. Salinity and osmotic stresses induced many common proteins. In addition, unique salt stress- or osmotic stress-specific proteins were also induced in both strains, indicating differential regulation of protein synthesis by the two stresses. These data show that cyanobacterial sensitivity and responses to salinity and osmotic stresses are distinct, independent phenomena.

Journal Article↗
PubMed1992

Use of human data in quantitative risk assessment of carcinogens: impact on epidemiologic practice and the regulatory process.

Epidemiologic data are increasingly being used to assess cancer risk from chemicals as their value is recognized and as more and better studies become available. Weight-of-evidence approaches are now available for classifying the experimental and epidemiological evidence regarding human carcinogenicity. When the human data are extensive and of good quality, they should be given substantial weight in assessing risk. Both the positive and the negative epidemiologic data should be used in a quantitative risk assessment (QRA), because only then can an unbiased risk assessment be derived. Good-quality epidemiological studies are those with sound methodology, lack of bias, long enough follow-up times to observe a carcinogenic response, adequate exposure information, and dose-response information. Before a lack of carcinogenicity can be inferred, it is essential that the exposures be of substantial duration and intensity, and that the number of exposed persons be reasonably large. Epidemiologists need to give more attention to exposure assessment, because lack of quantitative exposure information is often the limiting factor that prevents the use of epidemiologic data in QRA. Development of methods to estimate historical workplace exposure intensities from surrogate industrial hygiene variables should receive high research priority, since they have the potential to increase the usefulness in QRA of many epidemiologic studies that have limited exposure information. Several frequently used surrogates for exposure measurements have limitations or pitfalls in their use. In particular, the use of "ever/never" exposed has a large potential to produce falsely negative results by means of a "dilution" effect, especially in the common case where the exposure distribution is skewed. Duration of exposure (rather than duration x intensity) may also give misleading results. There is little information to suggest that synergistic exposures to multiple toxicants in an industrial environment are likely to invalidate QRAs, probably because few studies have identified a group of workers with major workplace exposures to multiple carcinogens that cause the same type of cancer. Most of the interactive effects which have been identified to date are between smoking and some occupational carcinogen, so this possibility needs careful evaluation for smoking-related diseases. It is important to evaluate dose-response gradients in a QRA to obtain maximum precision and accuracy in the resulting risk coefficient. The analysis should take into account an appropriate cancer induction period. Various methods to account for cancer induction times are compared; those that incorporate a lag period or model the induction-time distribution are superior to other methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinogens↗
PubMed1990

Diesel exhaust exposure and bladder cancer risk.

A total of 136 cases of men with urinary bladder cancer and 272 matched hospital controls were examined for potential exposure to diesel exhaust. A lifetime occupational history was obtained for all subjects in the study and assessment of exposure to diesel exhaust was based on the job titles of the subject and self-reported exposure. The risk was assessed by odds ratios, with adjustment for confounding variables, in particular cigarette smoking. There was no evidence of elevated risk in occupations with possible or probable exposure (the ORs adjusted for smoking were 1.1. and 0.9 respectively). Truck driving alone was also not associated with elevated risk (adjusted OR = 0.5). There was a weak positive crude association with any exposure, including self-reports (OR = 1.4); however after adjustment for smoking, the estimate did not retain statistical significance (OR = 1.2, 95% CI = 0.8-2.0). This study provides little to support the hypothesis of an excess of bladder cancer risk from occupational exposure to diesel exhaust.

Aged↗
PubMed1989

Effect of diltiazem on 2,4-D-induced myotonia in rats.

Myotonia is characterized by prolonged contraction (delay in onset of relaxation) of skeletal muscle fibers with characteristic electromyographic findings. Calcium channel blocking drugs may be expected to reduce myotonia, should they promote the onset of relaxation in a contracted skeletal muscle. This study was aimed at evaluating the effect of diltiazem, a calcium channel blocking agent, on myotonia induced by 2,4-dichlorophenoxyacetic acid (2,4-D). In rat diaphragm, exposed to 2.5 mM 2,4-D in a tissue bath, myotonia was quantified by documenting the contraction time in response to direct stimulation with supramaximal electric stimuli. At the peak of myotonia, different concentrations of diltiazem were added to the tissue bath and the effect on evoked contraction studied over a period of 6 minutes. A concentration of 5 x 10(-5) M was found to be the most effective, causing a decrease in contraction time of more than 90% in 3 minutes in 100% of specimens (n = 7). The above findings raise the possibility of using diltiazem as an antimyotonic agent.

2,4-Dichlorophenoxyacetic Acid↗