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Biomedical subjects

J H Williams

Publications and source records attributed to J H Williams.

At least 109 records · Page 6Linked to original sources
PubMed1994

Skeletal muscle overload upregulates the sarcoplasmic reticulum slow calcium pump gene.

Functional data suggest that the kinetics of force production and relaxation are slowed in hypertrophied skeletal muscle because of chronic overload. The purpose of this study was to determine whether gene expression of the slow/cardiac isoform of the sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) pump is upregulated in overloaded fast-twitch plantaris muscles. Increased active muscle loading was induced in rat plantaris muscles bilaterally by surgical removal of gastrocnemius and soleus muscles. Mass of the plantaris muscle was 80% greater 5 wk after surgery than in age-matched unoperated control rats (P < 0.05). Expression of the slow pump mRNA was 135% greater in hypertrophied muscles, as determined from autoradiograms of Northern blots with use of a cDNA probe specific for the slow/cardiac isoform. A monoclonal antibody (7E6) was used to quantify slow Ca2+ pump in SR vesicles with use of Western blot analysis. Densitometry of blots showed that the relative expression of the slow pump protein was 130% greater in hypertrophied plantaris muscles. Expression of the fast SR Ca2+ pump protein isoform, assessed using monoclonal antibody A52, was 25% less in hypertrophied than in control muscles. The Ca2+ uptake rate and ATPase activity of SR vesicles was approximately 15% lower in hypertrophied plantaris muscles (P < 0.05). Differential phospholamban expression could not account for changes in SR Ca2+ handling, because it could not be detected in rat slow- or fast-twitch skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Intratracheal injection of LPS and cytokines. V. LPS induces expression of LIF and LIF inhibits acute inflammation.

Lipopolysaccharide (LPS) injected into the trachea of rats was found to induce the secretion of leukemia inhibitory factor (LIF) into bronchoalveolar lavage (BAL) fluid with a maximum expression of LIF after 2-12 h. The acute pulmonary neutrophilic inflammation caused by the intratracheal injection of bacterial endotoxin (LPS) could be inhibited by the intratracheal coinjection of recombinant LIF. Compared with intratracheal injection of LPS alone, intratracheal coinjection of LIF and LPS decreases the number of BAL neutrophils obtained 6 h later by approximately 50% (P < 0.0001). LIF decreased the amount of the proinflammatory cytokine tumor necrosis factor (TNF), but not the amount of the anti-inflammatory cytokine interleukin (IL)-6, in the BAL fluid of LPS-injected rats. Similarly, intravenous LIF was found to decrease TNF expression, but increase IL-6 expression, in the serum of rats receiving intravenous LPS. Intravenous LIF, even in the absence of LPS, was found to cause IL-6 expression. In conclusion, intratracheal LPS initiates the secretion of endogenous LIF into the alveolar space where LIF may contribute to the downregulation of LPS-initiated acute neutrophilic inflammation by downregulating expression of TNF. LIF may down-regulate LPS-initiated TNF expression at least in part indirectly by upregulating expression of IL-6, a cytokine known to downregulate LPS-initiated TNF expression.

Acute Disease↗
PubMed1994

Eccentric contraction-induced injury in normal and hindlimb-suspended mouse soleus and EDL muscles.

The primary objective of this study was to compare the magnitude of injury in mouse extensor digitorum longus (EDL) and soleus muscles induced by high-force eccentric contractions. A second objective was to study the effect of altering the daily loading of the muscles through hindlimb suspension (HS) on the injury. One of two protocols was performed in vitro: 1) 15 eccentric contractions (n = 20: 10 EDL and 10 soleus muscles) or 2) 15 isometric contractions (n = 20: 10 EDL and 10 soleus muscles). After the protocol, the decrements in contractile performance and lactate dehydrogenase (LDH) release were measured at 15-min intervals over 1 h. Immediately after the eccentric contraction protocol, markedly greater decrements in maximal isometric tetanic force (Po) occurred in the normal EDL than in the normal soleus muscles (60.7 +/- 4.2 vs. 7.6 +/- 2.1%, P < or = 0.0001). LDH release immediately after the eccentric contraction protocol was 2.7-fold greater in the normal EDL than in the normal soleus muscles. To investigate the role of recent loading of the muscles in the injury, EDL (n = 9) and soleus (n = 10) muscles from mice subjected to HS for 14 days performed the eccentric contraction protocol. HS resulted in greater decrements in contractile performance for the soleus muscles (decreases in Po immediately after the protocol for HS and normal soleus muscles were 31.0 +/- 1.8 and 7.6 +/- 2.1%, respectively; P < or = 0.0001) but not for the EDL muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Significant gastric reflux of technetium-99m-MIBI in SPECT myocardial imaging.

We present a case in which significant gastric reflux of 99mTc-methoxy isobutylisonitrile (MIBI) was observed in a patient who underwent stress/rest 99mTc-MIBI SPECT myocardial perfusion imaging for suspected coronary artery disease. The intense gastric activity partially obscured myocardial uptake of 99mTc MIBI, particularly in the inferolateral wall of the left ventricle. The presence of significant gastric activity should be considered when performing SPECT myocardial imaging with 99mTc MIBI, and, where necessary, steps should be taken to minimize this activity prior to commencing acquisition.

Adult↗
PubMed1993

The effect of indomethacin on the circulatory and plasma noradrenaline responses to cold pressor testing in normal subjects.

Prostaglandins may alter neuronal noradrenaline release or vascular responsiveness to sympathoexcitation. The purpose of this study was to determine if indomethacin, a prostaglandin synthesis inhibitor, influences the sympathetic and circulatory adjustments to a commonly utilized laboratory stressor in the clinical assessment of autonomic function, the cold pressor test. Venous plasma noradrenaline levels (n = 8), mean arterial pressure and heart rate (n = 10) were measured in healthy male subjects during immersion of the non-dominant hand in cold water (1 degree C) for 90 s. The subjects were given either placebo or indomethacin (100 mg) in a double-blind manner. The order of administration was counterbalanced and a 1 week period was given for systemic clearance of the drug. The absolute level of mean arterial pressure was elevated during the resting control period after indomethacin treatment (88 in placebo vs. 92 mmHg in indomethacin). Both heart rate and venous plasma noradrenaline levels were similar between trials during the resting control period. Mean arterial pressure and heart rate increased similarly during cold pressor testing in both indomethacin and placebo. Venous plasma noradrenaline levels increased during cold pressor testing 162 +/- 39 vs. 200 +/- 69 pg/ml in indomethacin vs. placebo (p > 0.05), respectively. In addition, perceived pain (peak level = 7 +/- 1 vs. 6 +/- 1 units; indomethacin vs. placebo, respectively) was not different between the trials. These results suggest that administration of indomethacin in a maximal single therapeutic dose, does not affect the sympathetic nervous system or circulatory responsiveness to cold pressor testing. It may not be necessary to discontinue indomethacin prior to autonomic function testing.

Adult↗
PubMed1993

Effects of rotation discipline on medical student grades in obstetrics and gynecology throughout the academic year.

OBJECTIVES: Our purpose was to determine whether the sequence of rotation disciplines taken can effect medical student examination scores on the National Board of Medical Examiners Subject Exam score for obstetrics and gynecology. STUDY DESIGN: A retrospective study was conducted of 439 student files for the academic years 1987 through 1991. The final clerkship grades and subject examination scores for internal medicine, pediatrics, psychiatry, surgery, and obstetrics and gynecology were reviewed. RESULTS: It was determined that completion of internal medicine or surgery before obstetrics and gynecology yielded higher scores in obstetrics and gynecology (p < 0.00001), with the largest improvement (from 533 to 586) observed when obstetrics and gynecology followed the internal medicine rotation. CONCLUSION: The sequence of rotation can affect scores on the National Board of Medical Examiners subject examination in obstetrics and gynecology. The largest improvement in student scores was observed when obstetrics and gynecology followed the internal medicine or surgery clerkships.

Curriculum↗
PubMed1993

5,7-Dihydroxytryptamine lesions in the fornix-fimbria attenuate latent inhibition.

When animals are preexposed to a stimulus without consequence they are subsequently slower to associate this stimulus with an important event, such as footshock. This retarding effect of stimulus preexposure is called latent inhibition and can be demonstrated in a variety of classical and instrumental paradigms and in a wide range of species, including man. Latent inhibition is disrupted in acute schizophrenics and by amphetamine treatment in both rat and man. The present study investigated the role of hippocampal 5HT terminals in latent inhibition using a conditioned suppression procedure with male Sprague-Dawley rats. Microinjections of 5,7-dihydroxytryptamine in the fornix-fimbria significantly reduced hippocampal indoleamine levels and attenuated latent inhibition of conditioned suppression. This finding supports the hypothesis that the destruction of mesolimbic 5-hydroxytryptamine terminals reduces latent inhibition. This result is discussed in terms of the possible involvement of reduced serotonergic function in schizophrenic attentional disorder. In addition to the predicted lesion effect, biochemical analyses indicated that experimental treatments in the latent inhibition procedure altered neurotransmitter turnover: utilization ratios for 5-hydroxytryptamine and/or dopamine were increased in preexposed relative to nonpreexposed animals in four of the six brain regions sampled.

5,7-Dihydroxytryptamine↗
PubMed1993

The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent.

At room temperature (23 degrees C-25 degrees C), the induction of long-term potentiation (LTP) in area CA1 of slices from young male Sprague-Dawley rats was depressed by preincubation with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NA, 100 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). The D isomers were ineffective under the same conditions. Hemoglobin (20 microM) reduced but did not completely block LTP. Neither L-NA (at concentrations up to 1 mM) nor hemoglobin (20 microM) had any significant effect on LTP in slices from adult rats at room temperature, or in young rats at 29 degrees C-30 degrees C. These results suggest that nitric oxide is unlikely to play a role in the induction of LTP under physiological conditions.

Aging↗
PubMed1993

Experimental model of bladder outflow tract obstruction in the guinea-pig.

Bladder outflow tract obstruction was produced in immature female guinea-pigs. Obstruction caused an increase in voiding pressure and bladder weight and a decrease in bladder compliance. No change occurred in the sensitivity of obstructed detrusor strips to exogenous agonists, but the force of contraction and response to electrical stimulation of the intrinsic nerves were less than in the strips from controls. The response of strips from sham-operated animals to exogenous agonists and to electrical stimulation was greater than that from obstructed animals. The effects of length and tension could not account for the in vitro responses from obstructed animals. Histology after obstruction showed muscle hypertrophy, connective tissue infiltration and decrease in nerve density. Many of the changes resembled those seen in the obstructed human bladder.

Adenosine Triphosphate↗
PubMed1993

Effect of indomethacin on the pressor responses to sustained isometric contraction in humans.

The purpose of this study was to test the hypothesis that prostaglandins participate in metaboreceptor stimulation of the pressor response to sustained isometric handgrip contraction in humans. To accomplish this, mean arterial pressure, heart rate (n = 10), and plasma norepinephrine levels (n = 8) were measured in healthy male subjects during sustained isometric handgrip at 40% of maximal voluntary contraction force to exhaustion and during a period of postcontraction muscle ischemia. The subjects were given a double-blind and counterbalanced administration of placebo or a single 100-mg dose of indomethacin. A period of 1 wk was allowed for systemic clearance of the drug. Mean arterial pressure increased 25 +/- 5 vs. 22 +/- 4 mmHg during the final minute of isometric handgrip contraction and 26 +/- 2 vs. 21 +/- 5 during the last minute of postcontraction muscle ischemia in the placebo vs. the indomethacin trial (P > 0.05), respectively. Heart rate was increased 21 +/- 4 vs. 17 +/- 3 beats/min during the final minute of isometric handgrip contraction in the placebo vs. the indomethacin trial (P > 0.05), respectively, and returned to control values during postcontraction muscle ischemia. Plasma norepinephrine levels increased 343 +/- 89 vs. 289 +/- 89 pg/ml after isometric handgrip contraction and 675 +/- 132 vs. 632 +/- 132 pg/ml after postcontraction muscle ischemia (P > 0.05) in the placebo vs. the indomethacin trial, respectively. These results suggest that prostaglandin inhibition does not significantly modulate muscle contraction-induced stimulation of mean arterial pressure, heart rate, or plasma norepinephrine levels.

Adult↗
PubMed1993

Fatigue-induced alterations in Ca2+ and caffeine sensitivities of skinned muscle fibers.

The purpose of this investigation was to examine the Ca2+ and caffeine sensitivities of skinned skeletal muscle fibers after fatigue. Single frog semitendinosus fibers were chemically skinned in either a rested state or after tetanic contractions (80 Hz, 100 ms) evoked at 2 s-1 for 5 min. This protocol reduced tetanic force to 1.8 +/- 0.2% of control. Maximal Ca(2+)-activated force (F0, 20 degrees C) was not significantly different between rested and fatigued fibers. However, the concentration of Ca2+ required to evoke 50% of F0 was significantly lower in the fatigued fibers (1.80 +/- 0.18 vs. 1.33 +/- 0.16 microM; P < 0.05), an effect that persisted as the skinned fiber was allowed to incubate in the relaxing solution for > 90 min. The addition of caffeine (25 mM) after Ca2+ loading of the sarcoplasmic reticulum (SR) for periods of 5-30 s (0.25 microM free [Ca2+]) evoked smaller contractures in fatigued fibers than in rested fibers. However, when the loading period was prolonged (60-240 s), force developed after caffeine application was not significantly different between conditions. This suggests that the rate, but not the maximal capacity of Ca2+ loading by the SR, is reduced by fatigue. After Ca2+ loading (120 s), the minimal caffeine concentration required to evoke a contracture in fatigued fibers (5.7 +/- 0.3 mM) was significantly greater than that of control fibers (3.1 +/- 0.4 mM), an effect that persisted with prolonged incubation of the skinned fibers. In addition, the rate of force increase in response to 8 mM caffeine was reduced in fatigued fibers by 41%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Activated pulmonary vascular neutrophils as early mediators of endotoxin-induced lung inflammation.

Pulmonary vascular sequestration of leukocytes has been reported to increase in some models of lung injury, including that induced by gram-negative bacterial lipopolysaccharide (LPS). Neutrophils recruited to the lung likely participate in LPS-induced lung inflammation and associated injury, but the functional activities of these pulmonary vascular neutrophils have not been directly assessed. In the current study, cells were recovered by pulmonary vascular lavage (PVL) of isolated rat lungs, harvested 2 h after intravenous infusion of LPS (3 mg/kg) or saline in intact rats, at which time LPS-induced neutrophil recruitment to the lung could be appreciated histologically but not by airway lavage. Relative concentrations of leukocytes recovered from the pulmonary vasculature by PVL were compared with those present in circulating blood, normalizing for lavage dilution on the basis of erythrocyte counts. Excess neutrophils, lymphocytes, monocytes, and eosinophils were recovered from the pulmonary vasculature of controls, and LPS infusion increased recovery of neutrophils (most prominently), lymphocytes, and monocytes. Compared with cells recovered from controls, PVL neutrophils from LPS-infused animals were primed for increased zymosan-stimulated superoxide generation, determined by ferricytochrome C reduction, and were more adherent to nylon wool columns. Northern blots of extracted RNA demonstrated that LPS infusion also upregulated interleukin-1 beta (IL-1 beta) mRNA expression in PVL leukocyte samples, but not BAL or circulating blood samples. Ficoll-hypaque separation demonstrated that the LPS-induced IL-1 beta signal in PVL leukocytes was derived primarily from polymorphonuclear rather than mononuclear leukocytes. In conclusion, all circulating leukocyte populations are sequestered in rat lungs, and LPS increases pulmonary vascular sequestration of leukocytes, recruiting most prominently an activated pool of neutrophils that are more adherent, primed for increased oxygen radical production, and expressing increased IL-1 beta message. These findings suggest a more prominent role than previously appreciated for sequestered neutrophils in sepsis-induced lung inflammation.

Animals↗
PubMed1993

Effect of ibuprofen use on muscle soreness, damage, and performance: a preliminary investigation.

Twenty subjects were randomly assigned to: 1) prophylactic ibuprofen (N = 5) [400 mg TID initiated 4 h before collection of baseline data and strenuous eccentric exercise bout], 2) therapeutic ibuprofen (N = 5) [400 mg TID initiated 24 h after baseline], 3) placebo (N = 5), or 4) control (N = 5). Muscle soreness perception, plasma creatine kinase, knee extensor torque, and EMG of the quadriceps were evaluated at baseline, 24, and 48 h. The prophylactic ibuprofen group had between 40 and 50% less muscle soreness perception and significantly less decline in isometric, concentric, and eccentric torque at 24 h compared with the other three groups (P < 0.05). At 48 h both prophylactic and therapeutic ibuprofen had significantly less muscle soreness perception and decline in torque than the placebo and control groups (P < 0.05). There was no difference between the amount of muscle damage between the four groups at 24 and 48 h. Vastus medialis and lateralis EMG magnitude decreased across time. Vastus lateralis EMG magnitude had significantly less decline from baseline for prophylactic ibuprofen compared with the other three treatments at 24 h, while both prophylactic and therapeutic ibuprofen had significantly less decline at 48 h. These data indicate that a prophylactic dosage of ibuprofen does not prevent CK release from muscle, but does decrease muscle soreness perception and may assist in restoring muscle function.

Adolescent↗
PubMed1993

Emphysematous cystitis in a non-diabetic cat.

Emphysematous cystitis in man and domestic animals is reviewed. A case of emphysematous cystitis occurring 5 d after standard therapy for urethral obstruction in a non-diabetic male Siamese-cross cat is described. Escherichia coli was isolated, and the cystitis resolved after antibiotic therapy.

Amoxicillin↗
PubMed1993

Contractile properties of skinned fibers from hypertrophied skeletal muscle.

We have previously shown deficits in specific tension (N.cm-2) in whole hypertrophied skeletal muscle (18-30%). The purpose of the present study was to determine if this intrinsic deficit exists in chemically skinned, hypertrophied single fibers, and also to measure their Ca2+ sensitivity. One group of rats (N = 4) had bilateral surgical ablation of the gastrocnemius and soleus muscles, and another group (N = 4) had the gastrocnemius and plantaris muscles ablated to induce hypertrophy in the plantaris and soleus muscles, respectively. Thirty days after surgery five fibers were dissected and analyzed from each of eight muscles per group, including control muscles. In hypertrophied plantaris and soleus muscles, fiber cross-sectional area (CSA) was 20% and 29% greater, respectively, than control values. Maximal Ca2+ activated tension (Po, pCa 4.5) was 15% greater in hypertrophied plantaris fibers and 18% greater in hypertrophied soleus fibers compared with respective control values (P < 0.05). Therefore, Po expressed per fiber CSA was slightly depressed (3-8%) in both plantaris and soleus fibers (P < 0.05). Regarding Ca2+ sensitivity, the Ca2+ concentration to elicit 50% of Po (i.e., pCa50) was significantly lower in hypertrophied soleus (58%) and plantaris (29%) fibers. This leftward shift in the force-pCa curve reflects greater Ca2+ sensitivity in hypertrophied fibers. Since the single fiber Po/CSA was only slightly decreased, these data suggest that during tetanic stimulation of whole muscle Ca2+ delivery to the contractile apparatus may be impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Besnoitiosis in a horse.

Besnoitiosis was confirmed in a pony which presented with inspiratory dyspnoea, scleroderma and ventral oedema. Numerous cysts were visible in the sclerae. Histological examination of the skin confirmed the presence of numerous cysts. The parasite could not be transmitted by subcutaneous injection of homogenised skin from the infected horse to rabbits and a horse. Ultrastructural morphology of the crescent-shaped bradyzoites was not compatable with Besnoitia besnoiti or B. jellisoni and it is proposed that the infection was caused by B. bennetti.

Animals↗
PubMed1992

W-7, a calmodulin antagonist, and contracture of malignant hyperthermia susceptible skeletal muscle.

1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7 released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10 microM W-7 was irreversible in that the SR was unable to re-sequestor calcium after exposure to the drug. 4. The release of calcium by W-7 was not prevented by exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM). 5. Calcium release by W-7 appears to be independent of calmodulin inhibition.

Animals↗