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Biomedical subjects

P L Johnson

Publications and source records attributed to P L Johnson.

At least 19 recordsLinked to original sources

Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs.

Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.

Adrenergic alpha-Antagonists↗

Meat quality traits were unaffected by a quantitative trait locus affecting leg composition traits in Texel sheep.

A QTL affecting leg muscle and fat traits has been identified within the New Zealand Texel population. The QTL maps to a region on OAR 2 with a two-marker haplotype test established at markers BULGE20 and BM81124. These markers encompass the likely position of Growth Differentiation Factor 8 (GDF8). The pleiotropic effects of this QTL on meat quality traits are tested. Objective measures of meat quality including pH, color (L*, a*, and b*), and tenderness (as assessed by Warner-Bratzler shear force measurements) were assessed on longissimus and semi-membranosus muscles of 540 progeny from six Texel sires. Four of these sires were subsequently identified as segregating for leg muscle and fat traits. For these segregating sires, comparison of progeny that had inherited the favorable haplotype from their sire with those that had received the alternate haplotype revealed no significant differences in the meat quality traits assessed. This finding suggests that the muscling QTL does not have pleiotropic effects on meat quality. A general scan for meat quality QTL was carried out using genotype data for eight markers from FCB128 to RM356 flanking 122cM of OAR 2 using Haley-Knott regression. This analysis revealed two QTL for a single sire. A QTL detected in the region of Marker INRA40 for color L* mapped to a site close to the muscling QTL, but there was evidence to suggest it is at a distinct locus. The QTL in the region of Marker RM356 might map distal to Marker RM356, as no peak was observed. This QTL, which seems to affect pH, color a*, color b*, and Warner-Bratzler shear measurements, requires further characterization.

Animals↗

A directed search in the region of GDF8 for quantitative trait loci affecting carcass traits in Texel sheep.

A directed search for QTL affecting carcass traits was carried out in the region of growth differentiation factor 8 (GDF8, also known as myostatin) on ovine chromosome 2 in seven Texel-sired half-sib families totaling 927 progeny. Weights were recorded at birth, weaning, ultrasound scanning, and slaughter. Ultrasonic measures of LM cross-sectional dimensions and s.c. fat above the LM were made, with the same measurements made on the LM after slaughter. Following slaughter, linear measurements of carcass length and width were made on all carcasses, and legs and loins from 540 lambs were dissected. Genotyping was carried out using eight microsatellite markers from FCB128 to RM356 on OAR 2 and analyzed using Haley-Knott regression. There was no evidence for QTL for growth rates or linear carcass traits. There was some evidence for QTL affecting LM dimensions segregating in some sire families, although it was not consistent between ultrasound and carcass measures of the same traits. There was strong and consistent evidence for a QTL affecting muscle and fat traits in the leg that mapped between markers BM81124 and BULGE20 for the four sires that were heterozygous in this region, but not for the three sires that were homozygous. The size of the effect varied across the four sires, ranging from 0.5 to 0.9 of an adjusted SD for weight-adjusted leg muscle traits, and ranging from 0.6 to 1.2 of an adjusted SD for weight-adjusted leg fat traits. The clearest effect shown was for multivariate analysis combining all leg muscle and fat traits analyzed across sires, where the -log(10) probability was 14. Animals carrying the favorable haplotype had 3.3% more muscle and 9.9% less fat in the leg relative to animals carrying other haplotypes. There was evidence for a second peak in the region of marker TEXAN2 for one sire group. It seems that a QTL affecting muscle and fat traits exists within the New Zealand Texel population, and it maps to the region of GDF8 on OAR2.

Adipose Tissue↗

Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts.

Transmembrane voltage-sensitive fluorescence measurements are limited by baseline drift that can obscure changes in resting membrane potential and by motion artifacts that can obscure repolarization. Voltage-dependent shift of emission wavelengths may allow reduction of drift and motion artifacts by emission ratiometry. We have tested this for action potentials and potassium-induced changes in resting membrane potential in rabbit hearts stained with di-4-ANEPPS [Pyridinium, 4-(2-(6-(dibutylamino)-2-naphthalenyl) ethenyl)-1-(3-sulfopropyl)-, hydroxide, inner salt] using laser excitation (488 nm) and a two-photomultiplier tube system or spectrofluorometer (resolution of 500-1,000 Hz and <1 mm). Green and red emissions produced upright and inverted action potentials, respectively. Ratios of green emission to red emission followed action potential contours and exhibited larger fractional changes than either emission alone (P < 0.001). The largest changes and signal-to-noise ratio (signal/noise) were obtained with numerator wavelengths of 525-550 nm and denominator wavelengths of 650-700 nm. Ratiometry lessened drift 56-66% (P < 0.015) and indicated decreases in resting membrane potential. Ratiometry lessened motion artifacts and increased magnitudes of deflections representing phase-zero depolarizations relative to total deflections by 123-188% in intact hearts (P < 0.02). Durations of action potentials at different pacing rates, temperatures, and potassium concentrations were independent of whether they were measured ratiometrically or with microelectrodes (P > or = 0.65). The ratiometric calibration slope was 0.017/100 mV and decreased with time. Thus emission ratiometry lessens the effects of motion and drift and indicates resting membrane potential changes and repolarization.

Animals↗

Reversal of impaired oxidative phosphorylation and calcium overloading in the skeletal muscle mitochondria of CHF-146 dystrophic hamsters.

Membrane-mediated excessive intracellular calcium accumulation (EICA) and diminished cellular energy production are the hallmarks of dystrophic pathobiology in Duchenne and Becker muscular dystrophies. We reported reversal of respiratory damage and Ca(2+)-overloading in the in vitro cardiac mitochondria from CHF-146 dystrophic hamsters (DH) with hereditary muscular dystrophy (Bhattacharya et al., 1993). Here we studied respiratory dysfunctions in the skeletal muscle mitochondria from young and old DH, and whether these abnormalities can be reversed by reducing [Ca2+] in the isolation medium, thereby lowering intramitochondrial Ca(2+)-overloading. Age- and sex-matched CHF-148 albino normal hamsters (NH) served as controls. As an index of EICA and cellular degeneration, Ca and Mg levels were assayed in the skeletal muscle and mitochondria. Mitochondria from young and old DH, isolated without EDTA (BE medium), revealed poor coupling of oxidative phosphorylation, diminished stimulated oxygen consumption rate, and lower respiratory control ratio and ADP/O ratios, compared to NH. Incorporation of 10 mM EDTA (Bo medium) in the isolation medium restored mitochondrial functions of the dystrophic organelles to a near-normal level, and reduced Ca(2+)-overloading. The mitochondrial Ca level in DH was significantly higher than in NH, irrespective of the medium. However, compared to Bo medium, the dystrophic organelles isolated in BE medium had lower Ca levels and markedly improved oxidative phosphorylation as seen in NH. Muscle Ca contents in the young and old DH were elevated relative to NH, showing a positive correlation with the increased mitochondrial Ca(2+)-sequestration. Dystrophic muscle also revealed Ca deposition with an abundance of Ca(2+)-positive and necrotic myofibers by light microscopy, and intramitochondrial Ca(2+)-overloading by electron microscopy, respectively. However, Mg levels in the muscle and mitochondria did not alter with age or dystrophy. These data parallel our observations in the heart, and suggest that functional impairments and Ca(2+)-overloading also occur in the skeletal muscle mitochondria of DH, and are indeed reversible if EICA is regulated by slow Ca(2+)-channel blocker therapy (Johnson and Bhattacharya, 1993).

Adenosine Diphosphate↗

Correlation of gallbladder ejection fraction with pathologic grade for chronic inflammation.

BACKGROUND: The purpose of this study is to define the sensitivity and specificity of the gallbladder ejection fraction (GBEF) for identifying patients with various grades of histologically proven chronic cholecystitis. METHODS: Of 693 consecutive patients who had a scintigraphic GBEF determination at Baptist Medical Center of Oklahoma, 161 subsequently had a cholecystectomy at the same institution. Pathologic material was reassessed by one outside blinded reviewer, who graded the intensity of the inflammation present on a 0 (absent) to 3 (most severe) scale. RESULTS: The least square mean maximum GBEF was 23.7% for those with grade 0, 9.6% for those with grade 3, and 13.9% for those with cholesterolosis. If a normal value for GBEF is set at > 30%, the sensitivity for detecting grade 1, 2, or 3 disease was 84%, and the specificity was 26%. For grade 3 disease alone, the sensitivity was 100%, and the specificity was 26%. CONCLUSIONS: The GBEF is sensitive but not specific for chronic inflammation of the gallbladder. The GBEF appears to be useful as a screening examination in the appropriate clinical setting.

Cholecystitis↗

Reduced sarcolemmal dystrophin distribution and upregulation of utrophin in the cardiac and skeletal muscles of CHF-146 dystrophic hamsters.

Abnormalities in the dystrophic gene product, dystrophin, have been implicated in initiating the primary membrane defect and excessive intracellular calcium accumulation (EICA), which play fundamental pathogenic roles in hereditary muscular dystrophy (HMD). Two other cytoskeletal proteins, spectrin and utrophin, bear remarkable structural and functional homologies to dystrophin. CHF-146 strain dystrophic hamsters (DH), like patients with Duchenne muscular dystrophy (DMD), die prematurely from cardiopulmonary insufficiency, focal myonecrosis, and progressive degeneration of the cardiac and skeletal muscles with EICA. Although DH present a suitable model for HMD, there are controversies concerning their dystrophin and utrophin status. Using immunocytochemistry and Western blotting, we studied dystrophin, spectrin and utrophin anomalies in the cardiac and skeletal muscles of 6-mo-old male DH. Age- and sex-matched CHF-148 strain albino normal hamsters (NH) served as controls. Sarcolemmal dystrophin staining was much weaker and interruptive in the DH. The densitometric analysis of the immunoblots revealed that dystrophin is reduced in DH by 83% in cardiac muscle (p < 0.0001), and by 50% in skeletal muscle (p < 0.0001). We conclude that sarcolemmal dystrophin distribution is markedly reduced and discontinuous in the cardiac and skeletal muscles of DH, with simultaneous upregulation of utrophin and a varied degree of spectrin labelling. This observation suggests that reduced sarcolemmal dystrophin is associated with membrane hyperpermeability, which leads to progressive muscle degeneration via EICA and segmental necrosis in DH. As in DMD, utrophin appears to play an important compensatory role in hamster dystrophinopathy.

Animals↗

Laparoscopy. Gasless vs. CO2 pneumoperitoneum.

OBJECTIVE: To compare gasless laparoscopy with conventional laparoscopy using CO2 pneumoperitoneum. STUDY DESIGN: Women undergoing bilateral laparoscopic tubal coagulation (LTC) were randomly assigned to one of two laparoscopy procedures: (1) a gasless laparoscopy system consisting of an intraabdominal fan retractor and electrically powered mechanical arm, and (2) standard CO2 pneumoperitoneum laparoscopy. The two laparoscopic procedures were compared on the basis of intraoperative visualization, operation duration, procedural difficulty, ventilatory parameters, hemodynamic stability, and postoperative pain and nausea. RESULTS: Significant disadvantages for the surgeon (increased technical difficulty, poorer visualization, longer operative times) and patient (greater postoperative pain and nausea) were seen with the gasless system. Because of these findings, the study was prematurely terminated after only 18 patients had participated. Intraoperative ventilatory and hemodynamic parameters were more stable in the gasless laparoscopy groups; however, the differences were not clinically significant in this population of healthy patients. CONCLUSION: The markedly increased technical difficulty and absence of clear clinical benefits for the healthy patient led to the conclusion that laparoscopy with CO2 pneumoperitoneum is preferable for routine LTC and most laparoscopic procedures in the pelvis. Gasless laparoscopy may be of benefit for the fragile patient with a compromised cardiovascular system who may suffer complications from hypercarbenemia.

Adult↗

Behavioral components of marital satisfaction: an individualized assessment approach.

This study examined the extent to which spousal behaviors, obtained through a daily checklist of marital activities individualized along an importance dimension, related to global and daily marital satisfaction. Eighty-two marital couples completed daily checklists of spousal behaviors for 7 days using either an individualized or a standardized assessment method. The results demonstrated that the individualized measures of daily behavioral events were significantly related to global and daily measures of marital satisfaction and discriminated distressed from nondistressed spouses. Although the individualized method did not correlate with marital satisfaction to a significantly greater degree than the standardized method, the individualized assessment approach provides a valid, viable, and cost-effective alternative for assessing daily spousal events that relate to marital satisfaction.

Adult↗

Evaluation of U.S. Public Health Service programs. Organization and management.

This article provides an overview of evaluation in the Public Health Service (PHS) of the U.S. Department of Health and Human Services. The kinds of evaluation activities are outlined with illustrations of recently completed studies. The overview includes information on resources, policies, and management of evaluations conducted by the various PHS agencies and programs. In particular, the department's new efforts to better disseminate evaluation results through the Internet are described. The article concludes with a discussion of future prospects of how PHS evaluations will play a role in implementation of the Government Performance and Results Act (GPRA).

Computer Communication Networks↗

Effects of accumbens DALA microinjections on brain stimulation reward and behavioral activation in intact and 6-OHDA treated rats.

The effects of bilateral nucleus accumbens microinjections of d-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 micrograms) treated rats. Microinjections of DALA (2.5 micrograms/microliters) in the behavioral activation paradigm had little effect on normal activity; however, DALA administered to 6-OHDA treated rats produced a significant overall increase in locomotion. The 6-OHDA DALA-induced locomotion effect peaked at 2 weeks after 6-OHDA treatment and then returned to baseline levels by week 5 post-treatment. Using LHSS, DALA tested over a range of doses (2.5, 5, 10, 20 micrograms/microliters) displayed a weak biphasic reward effect only at the highest dose, which was characterized by an initial suppression followed by an elevation. DALA significantly depressed initial operant motor/performance in LHSS in a dose dependent fashion. Microinjections of the normally ineffective low dose of DALA (2.5 micrograms/microliters) following accumbens 6-OHDA treatment produced a significant LHSS reward decrease 2 weeks post-treatment, while LHSS motor/performance was relatively unaffected. Results are discussed in terms of opiate-dopamine and limbic-motor interactions.

Animals↗

Pulse oximetry signals local anesthetic-induced methemoglobinemia.

An otherwise healthy patient with a fractured mandible was scheduled to undergo an open reduction under general anesthesia. Just before transport to the operating room, bimaxillary arch bars were placed under local anesthesia with 4% prilocaine and 1:200,000 epinephrine. Although induction of anesthesia and nasoendotracheal intubation were uneventful, pulse oximetry values fell to 89% despite adequate ventilation and an inspired oxygen concentration of 50%. Inquiry by the anesthesiologist and arterial blood gas measurements revealed that methemoglobinemia had developed in response to the large amount 576 mg) of prilocaine administered. A total of 150 mg of methylene blue administered in two doses corrected the problem. The oral surgeon, having recently switched to prilocaine because of a manufacturer's recall of lidocaine, was unaware of the potential of prilocaine to cause this disorder.

Adult↗

Reversal of impaired oxidative phosphorylation and calcium overloading in the in vitro cardiac mitochondria of CHF-146 dystrophic hamsters with hereditary muscular dystrophy.

Membrane-mediated excessive intracellular calcium accumulation (EICA), and diminished cellular energy charge are invariably present in the myocardium of CHF-146 strain dystrophic hamsters (DH) with hereditary muscular dystrophy (HMD) and hypertrophic cardiomyopathy (HC). Therefore, we investigated respiratory dysfunctions and Ca2+ overloading in the isolated cardiac mitochondria from young and old DH, and whether these abnormalities can be reversed by controlling EICA in the in vitro mitochondria upon chelating excessive Ca2+ from the isolation medium with EDTA. Age- and sex-matched CHF-148 strain albino normal hamsters (NH) served as the disease controls. As an index of membrane-mediated EICA and chronic cellular degeneration, Ca and Mg concentrations were quantitated in the ventricular myocardium and in the cardiac mitochondria harvested in two different isolation media. Mitochondria from young and old DH, isolated in the absence of 10 mM EDTA (B0 medium), revealed poor coupling of oxidative phosphorylation, diminished stimulated oxygen consumption rate, and lower respiratory control and ADP/O ratios, than those seen in NH. However, incorporation of 10 mM EDTA in the isolation medium (B medium) restored the mitochondrial functions and reduced massive Ca(2+)-overloading in the dystrophic organelles. Ca concentration in the in vitro mitochondria from DH was significantly higher than in NH, irrespective of the composition of the isolation medium and age of the hamsters. Furthermore, the dystrophic organelles isolated in B medium had a much lower Ca concentration, and markedly improved oxidative phosphorylation as seen in the cardiac mitochondria from NH, compared to those prepared using B0 medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Regulation of membrane-mediated chronic muscle degeneration in dystrophic hamsters by calcium-channel blockers: diltiazem, nifedipine and verapamil.

Membrane-mediated excessive intracellular calcium accumulation (EICA) is a fundamental pathogenetic event associated with chronic muscle degeneration in patients with Duchenne muscular dystrophy (DMD), and in animals with hereditary muscular dystrophy (HMD). Because of potential Ca(2+)-channel blocking properties, we investigated the relative efficacies of chronic diltiazem (DTZM) (50 mg/kg/d), nifedipine (NFDN) (6 mg/kg/d), and verapamil (VPML) (25 mg/kg/d) therapies in reducing EICA and improving dystrophic pathobiology beginning in 30-day-old male BIO-14.6 strain dystrophic hamsters (DH). Each agent, and sterile distilled water as vehicle control, was given in a single daily oral dose for 180 days to four groups each of DH and BIO-F1B strain normal hamsters (NH). Plasma [Ca] and [Mg]; plasma aldolase (ALD), creatine kinase (CK), and lactate dehydrogenase (LDH) activities; relative cardiac hypertrophy and relative soleus hypertrophy; tissue [Ca] and [Mg] of the heart and rectus femoris muscle, histology of rectus femoris, and overall mortality rate were quantitated. Muscle Mg was not modified in DH, or by any of these agents. NFDN produced significant edema in the soleus and myocardium. During the 6-month therapeutic trial, 45% DH and 18% NH died on VPML, 27% DH and 9% NH on NFDN, and 20% DH controls on distilled water, but none on DTZM; suggesting that DTZM treated DH lived longer than DH controls. Relative efficacy in regulating EICA in both the cardiac and skeletal muscles; plasma ALD, CK, and LDH; and improving associated dystrophic pathobiology was found to be DTZM >>> NFDN > VPML. DTZM appears to be the most effective and safest agent in mitigating EICA in cardiac and skeletal muscles, efflux of intracellular enzymes, histopathology of dystrophic muscle with sporadic necrosis, and chronic muscle degeneration in DH with HMD. DTZM therapy also halted the high morbidity and mortality associated with the dystrophic pathobiology inherent in DH.

Animals↗

The magnetic resonance appearance of extraperitoneal bowel perforation: a case report.

The use of magnetic resonance imaging (MRI) for abdominal and gastrointestinal imaging has been quite limited, when compared to its utilization in other organ systems. We present an interesting case of extraperitoneal bowel perforation, which was diagnosed by magnetic resonance (MR). Extraperitoneal bowel perforation is frequently a confusing and difficult diagnosis to make. The multiplanar imaging capability and unique sensitivity of MR to fluid enabled a specific diagnosis to be made in this challenging case.

Abscess↗

Isolation of skeletal muscle mitochondria from hamsters using an ionic medium containing ethylenediaminetetraacetic acid and nagarse.

An improved procedure is reported for the isolation of skeletal muscle mitochondria from hamsters and compared with our previous method. This procedure utilizes 20 mg% Nagarse in an ionic medium containing 100 mM sucrose, 10 mM EDTA, 100 mM Tris-HCl, 46 mM KCl, and 0.5% bovine serum albumin (BSA), at pH 7.4 (medium-B). Oxidative phosphorylation was studied by measuring ADP/O ratio and respiratory control ratio (RCR) using NAD(+)-linked pyruvate-malate (PM), as well as FAD-linked succinate (SUCC) as substrates. The mitochondria isolated in medium-B exhibited high RCR and high ADP phosphorylation capacity, and were superior to those prepared by our previous method. Electron micrographs of organelles isolated in medium-B revealed intact mitochondrial membrane and structural integrity, whereas those isolated with medium-A containing 50 mg% Nagarse depicted considerable damage including swelling, ruptured membrane, and loss of intramitochondrial matrix. Previously, we used a nonionic medium containing 210 mM mannitol, 70 mM sucrose, 0.1 mM EDTA, 10 mM Tris-HCl, 50 mg% Nagarse, and 0.5% BSA, at pH 7.4 (medium-A). Mitochondria isolated with medium-B yielded mean RCR values of 7.3 to 8.3 with PM, and values of 3.7 to 4.7 with SUCC as substrates, compared to 1.6 and 1.8 with PM, and 1.4 and 1.7 with SUCC for the organelles isolated using medium-A, respectively. Likewise, the ADP/O ratios were 2.6 to 2.7 with PM, and 1.6 to 1.7 with SUCC for medium-B preparations, compared to 1.5 and 1.8 with PM and 1.0 and 1.2 with SUCC for medium-A preparations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗