Biomedical subjects

R Mathur

Publications and source records attributed to R Mathur.

At least 19 recordsLinked to original sources

PubMed1997

A cellular model for long QT syndrome. Trapping of heteromultimeric complexes consisting of truncated Kv1.1 potassium channel polypeptides and native Kv1.4 and Kv1.5 channels in the endoplasmic reticulum.

We demonstrated that overexpression of a cRNA encoding a truncated potassium channel polypeptide that contains the NH2 terminus and the first transmembrane segment (Kv1.1N206Tag) abolished the expression of Kv1.1 and Kv1.5 outward currents in Xenopus oocytes (Babila, T., Moscucci, A., Wang, H., Weaver, F. E. & Koren, G. (1994) Neuron 12, 615-626). Recently, we showed that expression of Kv1.1N206Tag in the heart of transgenic mice resulted in the creation of mice with prolongation of the surface electrocardiogram's QT interval (London, B., Han, X., Folco, E. & Koren, G. (1996) Biophys. J. 70, A2601). To study the dominant negative mechanism of Kv1.1N206Tag, we overexpressed it in GH3 cells, a pituitary cell line expressing Kv1. 5 and Kv1.4. RNase protection analysis comparing the steady-state levels of native Kv1.5 and Kv1.1N206Tag transcripts revealed an excess of Kv1.1N206Tag transcript. Immunoprecipitation analysis using 12CA5 monoclonal antibody detected a 25-kDa polypeptide in the transfected cells. The half-life of Kv1.1N206Tag was 2.6 h. Subcellular fractionation of cell lysates labeled with [35S]methionine revealed that Kv1.1N206Tag polypeptide is detectable in the particulate (membranous) fraction, but not in the soluble (cytosol) fraction. A series of double immunoprecipitations with 12CA5 and polyclonal antibodies against Kv1.5 and Kv1.4 revealed that Kv1.1N206Tag forms heteromultimeric complexes with the native Kv1.4 and Kv1.5 polypeptides. The steady-state levels of Kv1.5 were not affected by the overexpression of Kv1.1N206Tag. Immunofluorescence colocalization and confocal microscopy analyses revealed that Kv1.1N206TagFlag did not reach the plasma membrane, and its distribution pattern was characteristic to that of a resident endoplasmic reticulum polypeptide. Our observations establish that the negative effect of Kv1.1N206Tag is mediated by the formation of heteromultimeric complexes with the native channels and by the retention of these complexes in the endoplasmic reticulum.

Animals↗

PubMed1997

Role of the S3-S4 linker in Shaker potassium channel activation.

Structural models of voltage-gated channels suggest that flexibility of the S3-S4 linker region may be important in allowing the S4 region to undergo large conformational changes in its putative voltage-sensing function. We report here the initial characterization of 18 mutations in the S3-S4 linker of the Shaker channel, including deletions, insertions, charge change, substitution of prolines, and chimeras replacing the 25-residue Shaker linker with 7- or 9-residue sequences from Shab, Shaw, or Shal. As measured in Xenopus oocytes with a two-microelectrode voltage clamp, each mutant construct yielded robust currents. Changes in the voltage dependence of activation were small, with activation voltage shifts of 13 mV or less. Substitution of linkers from the slowly activating Shab and Shaw channels resulted in a three-to fourfold slowing of activation and deactivation. It is concluded that the S3-S4 linker is unlikely to participate in a large conformational change during channel activation. The linker, which in some channel subfamilies has highly conserved sequences, may however be a determinant of activation kinetics in potassium channels, as previously has been suggested in the case of calcium channels.

Amino Acid Sequence↗

PubMed1997

Analysis of the Legionella pneumophila fliI gene: intracellular growth of a defined mutant defective for flagellum biosynthesis.

Using a PCR-based strategy and degenerate oligonucleotides, we isolated a Legionella pneumophila gene that showed high sequence similarity to members of the fliI gene family. An insertion mutation that disrupted the fliI open reading frame was recombined onto the L. pneumophila chromosome and analyzed for its effects on production of flagella and intracellular growth. The mutation resulted in loss of surface-localized flagellin protein but had no effect on the ability of the bacteria to grow within cultured cells. Therefore, in spite of the fact that some aflagellar mutations render L. pneumophila unable to grow within macrophages, the isolation of this defined mutant confirms that production of flagella is not required for intracellular growth.

Amino Acid Sequence↗

PubMed1997

A repeat audit of hospital discharge letters in patients admitted with acute asthma.

Subsequent to the implementation of recommendations from a previous audit of acute asthma admission discharge letters from our specialist respiratory unit, a repeat audit of typed discharge letters of 86 patients (33 male, mean age 29 SD 9 years) admitted with acute asthma to the same unit over a 12 month period was performed. There was significant improvement in the discharge letter documentation of precipitating factors (p < 0.001), previous admissions with acute asthma (p < 0.01), admission arterial blood gas analysis (p < 0.001), admission peak flow rates (p < 0.05), discharge peak flow rates (p < 0.001), corticosteroid (p < 0.01) and inhaled beta 2 agonist (p < 0.01) prescription on discharge and on the specification of inhaler delivery device on discharge (p < 0.001). No significant differences in discharge letters were found in the documentation of acute therapy or post discharge follow up plan. The improvement in discharge letter quality was attributed to closing the feed back loop from the previous audit though continuing deficiencies in discharge letter contents have been identified again. These deficiencies need to be rectified and the results reaudited.

Acute Disease↗

PubMed1997

Reaudit of acute asthma admissions using a severity marker stamp and determinants of an outcome measure.

Subsequent to the implementation of a severity marker stamp in case notes, an audit was performed in 86 admissions with acute asthma to a specialist centre over a 12 month period. Compared to previous audit the documentation of severity markers was significantly better (PEFR: 52% vs 83% p = 0.001, Respiratory rate: 44% vs 81% p = 0.001, ABG: 72% vs 80% p = 0.04, air entry: 58% vs 86% p = 0.001, speech: 27% vs 86% p = 0.001, exhaustion: 4% vs 86% p = 0.001). In contrast to the previous audit where no patient received FiO2 > 0.35, 66% of the cases in the repeat audit received FiO2 0.60 (p = 0.001). The mean duration of admission was five days and showed highest partial correlation (r = 0.6) to the time in hours for the pulse to fall to 80/min. Multiple linear regression showed that this was the only variable best predicting the duration of admission (R2 = 0.3). Admission pulse rate (p = 0.04) and serum K+ (p = 0.04) best discriminated between patients admitted for over and under five days. Logistic regression identified only the admission pulse as significant in calculating the odds of the patient staying in the hospital for > 5 days.

Adult↗

PubMed1997

The effect of age, sex, obesity and posture on upper airway size.

Most patients with sleep apnoea/hypopnoea syndrome (SAHS) are middle-aged men. As there are conflicting data on the effects of age and gender on upper airway calibre, we tested the hypothesis that increasing age and the male sex predispose to upper airway narrowing in normal subjects. We measured upper airway calibre using acoustic reflection in 60 men and 54 women (median 35, range 16-74 yrs) both seated and supine. All upper airway dimensions, except oropharyngeal junction (OPJ), decreased with increasing age in both men and women (r > -0.24, p < or = 0.05) while supine (r2 > 0.06). Men had greater changes in airway area at OPJ on lying down (mean (SEM) 0.5 (0.1), 0.2 (0.1) cm2; p < 0.02). Men had greater body mass indices (mean (SD) 26 (4), 24 (4) kg.m-2; p = 0.04), and larger neck circumferences (mean (SD) 38 (3), 33 (2) cm; p < 0.0001) than women. For any body mass index, neck circumference was larger in men than women (p < 0.001). This study shows that upper airway size decreases with increasing age in both men and women, and that men have greater upper airway collapsibility on lying down at oropharyngeal junction than women.

Aging↗

PubMed1997

Exposure effects of static magnetic field on some physiological parameters of developing rats.

Effect of long term exposure of static magnetic field on developing rats is investigated. The animals of either sex were subjected to a field of 1 kg for 120 days after attaining 28 days of their ages. The parameters included for observations were electrocardiogram, motor activity, and organ weights. The electrocardiogram of the experimental animals shows a higher amplitude of R and T waves, lengthening of QT interval and a slowing down of heart rate. The survival time of the two categories of animals was not significantly different. The weights of brain, skull and ovaries found to be significantly less in experimental group, while the motor activity of the corresponding group registered an increase. It is concluded that these are the stressor effects caused due to long duration of exposure to the magnetic field.

Animals↗

PubMed1996

2-buten 4 olide affects feeding behavior of rhesus monkey.

1. Endogenous satiety substance 2-Buten 4 Olide (2-B40- a short chain sugar derivative) effect on feeding behaviour of rhesus monkey was studied. 2. The cannula was implanted in the third ventricle of three, adult, male, rhesus monkeys. 3. Monkeys were conditioned to ingest their daily requirement of food during one hour. 4. Their daily food intake was recorded. 5. Various doses of 2-B40 (1.6, 2.1, 2.7, 4.3, 10.6, 20 and 25 mg)were administered intracerebroventricularly on different days five minutes prior to presentation of food. 6. The effective dose for inducing significant satiety effect was 20.0 mg, while 10.6 mg induced a mild and 25.0 mg a severe effect. 7.However, when administered intraperitoneally 43 mg/kg bw 2-B40 induced satiety effect, but was ineffective in doses of 1.5 to 21.5 mg bw. 8. This study is suggestive of the presence of 2-B40 satiety mechanism in monkeys almost in doses similar to those previously reported for rats.

4-Butyrolactone↗

PubMed1996

Hypolipidaemic effect of fruit juice of Emblica officinalis in cholesterol-fed rabbits.

The lipid lowering and antiatherosclerotic effects of Emblica officinalis (Amla) fresh juice were evaluated in cholesterol-fed rabbits (rendered hyperlipidaemic by atherogenic diet and cholesterol feeding). E. officinalis fresh juice was administered at a dose of 5 ml/kg body weight per rabbit per day for 60 days. Serum cholesterol, TG, phospholipid and LDL levels were lowered by 82%, 66%, 77% and 90%, respectively. Similarly, the tissue lipid levels showed a significant reduction following E. officinalis juice administration. Aortic plaques were regressed. E. officinalis juice treated rabbits excreted more cholesterol and phospholipids, suggesting that the mode of absorption was affected. E. officinalis juice is an effective hypolipidaemic agent and can be used as a pharmaceutical tool in hyperlipidaemic subjects.

Animals↗

PubMed1996

Improved method for study of chromosomes of chorionic villus samples.

Chorionic villus sampling (CVS) offers rapid prenatal diagnosis of chromosomal disorders. We evaluated four methods for chromosomal analysis of chorionic villi (three based on direct preparations and one on long-term culture) in order to define a method which would provide good quality metaphases in sufficient numbers. The direct culturing method using synchronisation and dissociation with dispase was as good as long-term culturing. The optimal period of gestation for study was 10-12 wk.

Chorionic Villi Sampling↗

PubMed1996

Influence of low and high doses of naloxone on tonic pain and motor activity in rats.

Naloxone has been reported to affect pain and locomotor activity differently depending on the dose. The objective of the present investigation was to study the effects of low and high (6 micrograms and 3 mg/kg, s.c.) doses of naloxone (Nx) on formalin-induced pain (tonic pain) and spontaneous motor activity and any correlation between them. The experiments were conducted on adult male Wistar rats. Tonic pain and spontaneous motor activity were recorded by the formalin test and video monitoring respectively. An increase in spontaneous motor activity (locomotion, movements and distance) was observed following formalin injection as compared to basal activity (P < 0.05). Low dose of Nx reduced the pain intensity and also the spontaneous motor activity during the later phase (after 15 min of formalin injection) (P < 0.05). High dose of Nx on the other hand increased the pain intensity but still reduced motor activity (P < 0.05). Both doses of Nx initially produced hyperalgesia (5 min peak). The bidirectional effects of Nx on formalin pain were dissociated from the spontaneous motor behavior of rats. A direct correlation could not be established between pain intensity and spontaneous motor activity.

Animals↗

PubMed1995

Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses.

BACKGROUND: The incidence of thrombotic cardiovascular disease is greater in men than in premenopausal women. Testosterone has been implicated as a significant risk factor for cardiovascular disease and for acute myocardial infarctions and strokes in young male athletes who abuse anabolic steroids. Thromboxane A2 (TXA2) is a vasoconstrictor and platelet proaggregatory agent that has been implicated in the pathogenesis of cardiovascular disease. We therefore tested the hypothesis that testosterone regulates the expression of human platelet TXA2 receptors. METHODS AND RESULTS: In a double-blind, placebo-controlled, randomized, parallel-group study, we determined the effects of testosterone cypionate 200 mg IM given twice, 2 weeks apart, or saline placebo in 16 healthy men. Platelet TXA2 receptor density (Bmax) and dissociation constant (Kd) were measured by use of the TXA2 mimetic 125I-BOP. Platelet aggregation responses to I-BOP and to thrombin and plasma testosterone concentrations were measured before treatment (pretreatment phase), at 2 and 4 weeks (active phase), and again at 8 weeks (recovery phase). Treatment with testosterone was associated with an increase in the Bmax value from 0.95 +/- 0.13 to 2.10 +/- 0.4 pmol/mg protein (n = 9), with a peak effect at 4 weeks (P = .001), returning to baseline by 8 weeks. There was no significant change in Bmax values in the saline-treated group. The Kd values were unchanged. Testosterone treatment was associated with a significant increase in the maximum platelet aggregation response to I-BOP (P < .001) at 4 weeks and returned to baseline at 8 weeks. The EC50 values were not significantly changed. Platelet TXA2 receptor density was positively correlated (r = .56, P < .001, n = 32 measurements) with pretreatment (endogenous) plasma testosterone levels (range, 215 to 883 ng/dL) but not Kd. CONCLUSIONS: Testosterone regulates the expression of platelet TXA2 receptors in humans. This may contribute to the thrombogenicity of androgenic steroids.

Adult↗

PubMed1995

Family studies in patients with the sleep apnea-hypopnea syndrome.

OBJECTIVE: To determine whether familial factors affect development of the sleep apnea-hypopnea syndrome and upper airway caliber. DESIGN: A case-control study. SETTING: Tertiary, referral clinical sleep laboratory. PARTICIPANTS: 51 first-degree relatives of patients with the sleep apnea-hypopnea syndrome and 51 controls matched for age, sex, height, and weight who were drawn at random from a family practice register. To avoid studying the familial nature of obesity, only relatives of index patients with body mass indices less than 30.0 kg/m2 were recruited. MEASUREMENTS: Assessment of sleep-related symptoms; breathing, sleep, and oxygenation patterns on overnight polysomnograms; upper airway dimensions by acoustic reflection; and facial structure by lateral cephalometry. RESULTS: More relatives of patients with the sleep apnea-hypopnea syndrome reported snoring (24 relatives compared with 7 controls; P < 0.001) and daytime sleepiness (28 relatives compared with 16 controls; P = 0.01). Relatives had more apneas and hypopneas per hour (median of 13/h [95% CI, 3 to 82/h] for relatives compared with median of 4/h [CI, 0 to 53/h] for controls; P < 0.001), more arousals from sleep (30/h [CI, 11 to 87/h] for relatives compared with 17/h [CI, 4 to 59/h] for controls; P < 0.001), poorer sleep quality, and more oxygen desaturations. Relatives also had narrower upper airways with retroposed maxillae and mandibles and longer soft palates with wider uvulae. CONCLUSION: The sleep apnea-hypopnea syndrome has a strong familial component. The familial tendency may be caused by differences in facial structure.

Adult↗

PubMed1995

Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate on beryllium-induced biochemical alterations and metal concentration in male rats.

The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.

Animals↗

PubMed1995

Time course of resolution of persistent air leak in spontaneous pneumothorax.

Persistent air leak (PAL) following tube drainage for spontaneous pneumothorax (SP) is a potentially troublesome complication. The optimum time to intervene surgically is not known. We therefore investigated the rate of resolution of PAL (defined as continued air leak at 2 days after tube insertion) in patients treated medically. We retrospectively reviewed the records of 214 patients presenting with SP over 5 yr. One hundred and forty-two (67%) had tube drainage and in 73 (51%) of these a PAL developed. Overall median time to resolution in the 43 patients with PAL treated medically was 8 days from tube insertion, but PAL resolution was longer in those with underlying lung disease (n = 19) than those without such disease (11 days vs. 7 days, P = 0.05). In patients with normal lungs 20/24 had resolved by 9 days but subsequently the rate of resolution was much slower. In those with abnormal lungs only 8/19 had resolved by 9 days (P < 0.05 compared with those with normal lungs) but the rate of resolution in such patients appeared to change little subsequently. The size of the initial SP did not influence the rate of resolution of PAL. For patients with PAL and normal lungs, surgery at 7-9 days from tube insertion would provide a reasonable opportunity for the PAL to resolve with medical treatment. For those with underlying lung disease there is no clear optimal time and decisions need to be taken on an individual basis.

Adolescent↗

PubMed1995

Effect of breathing, pressure and posture on palatoglossal and genioglossal tone.

1. Patency of the upper airway is critical to respiration. Although about half of patients with the sleep apnoea/hypopnoea syndrome obstruct their upper airway at the retropalatal level, the respiratory actions of the palatal muscles have been little studied. We have therefore tested the hypothesis that the nasopharyngeal dilator muscle palatoglossus is activated during inspiration and by negative pressure. 2. Using intramuscular wire electrodes inserted perorally, we have compared the response of palatoglossus and genioglossus to breathing, posture change and airway negative pressure in 10 normal awake subjects before and after topical anaesthesia. The results are expressed as a percentage of maximal electromyogram. Data were analysed by repeated-measures analysis of variance. 3. Inspiratory activity was exhibited by both genioglossus [inspiratory, 10% +/- 2% (SEM); expiratory, 6% +/- 1%, P = 0.001] and palatoglossus (inspiratory, 16% +/- 5%, expiratory, 10% +/- 3%, P = 0.016), but only genioglossus exhibited increased activity on lying (supine 10% +/- 2%, erect 6% +/- 1% maximum, P = 0.01). 4. One hundred milliseconds after negative pressure application, activity increased in both genioglossus (7% +/- 2% and 13% +/- 3% respectively, P = 0.02) and palatoglossus (8% +/- 2% and 23% +/- 6% respectively, P < 0.001). After lignocaine surface anaesthesia to the nose and pharynx both genioglossus and palatoglossus still increased their activity in response to negative upper airway pressure, the extent of the increase being decreased for palatoglossus (P = 0.02) but not for genioglossus. 5. Thus, palatoglossus has respiratory activity and is activated by negative upper airway pressure.

Adult↗

PubMed1995

Frequency of EEG arousals from nocturnal sleep in normal subjects.

Brief arousals are clinically important and increasingly scored during polysomnography. However, the frequency of arousals during routine polysomnography in the normal population is unknown. We performed overnight polysomnography in the 55 of 59 control subjects from a family practice list who were approached and agreed to undergo polysomnography. Awakenings were scored according to the criteria of Rechtschaffen and Kales and briefer arousals according to three different criteria, including the American Sleep Disorders Association (ASDA) definition. There was a mean of 4 [95% confidence interval (CI), 1-15) Rechtschaffen and Kales awakenings per hour, whereas the ASDA definition gave 21 (95% CI, 7-56) per hour slept. Arousal frequencies increased significantly (p < 0.001) with age in our subjects, who ranged from the late teens to early 70s. The high upper limit of the frequency of brief arousals was not altered by exclusion of patients who snored or had witnessed apneas or daytime sleepiness. It is important that those scoring arousals on routine polysomnography recognize that high arousal frequencies occur in the normal population on 1-night polysomnography.

Adult↗

PubMed1995

Lateral condylar fractures of the humerus in children: fixation with partially threaded 4.0-mm AO cancellous screws.

Thirty-seven children with fresh, displaced (more than 2 mm in any direction) fractures of the lateral condyle of the humerus were treated by open reduction and internal fixation with a partially threaded 4.0-mm diameter AO lag screw. They were reviewed at a mean follow-up of 4.8 years. Painless, full-elbow movements were obtained in 36 cases. Delayed union, with loss of 10 degrees of elbow motion, was observed in one case (2.72%). Radiologically, less than 4 degrees of varus deviation, compared with the contralateral side, was found in four cases (10.8%). Mild fishtailing was observed in three cases (8.18%). Nonunion, avascular necrosis or clinically significant premature epiphysial fusion was not observed. Elbow function was excellent, irrespective of minor radiologic abnormalities.

Bone Screws↗