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Biomedical subjects

J A Bauer

Publications and source records attributed to J A Bauer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential control during maximal concentric and eccentric loading revealed by characteristics of the electromyogram.

Maximal eccentric loading has been associated with higher levels of spindle afferent activity but lower levels of integrated EMG as compared to maximal concentric loading. Elbow flexor EMG was recorded from 17 subjects during concentric (CONC) and eccentric (ECC) elbow flexion at 70 degrees s(-1) using a Kin-Com dynamometer. We hypothesized that peak EMG amplitude would be more sensitive to fluctuations in facilitation by the spindle primary afferents via the segmental stretch reflex pathway, and that the mean EMG would be more reflective of the ongoing level of muscle activation. A ratio of peak to mean EMG (P/M EMG ratio) was predicted to be larger during maximal eccentric loading than maximal concentric loading. The peak EMG (P<0.013) and the P/M EMG ratio (P<0.001) were significantly greater during the ECC condition than the CONC condition. In a subgroup of three subjects who underwent 3 weeks of eccentrically biased weight training, EMG, peak torque and torque variability were assessed before and after training. P/M EMG ratio decreased, while peak torque and torque variability increased following the training. Differences in the P/M EMG ratio appear to reflect differences in the way eccentric and concentric muscle actions are controlled and do not simply represent less control during the eccentric task.

Adult↗
PubMed2000

Endothelial dysfunction and peroxynitrite formation are early events in angiotensin-induced cardiovascular disorders.

Angiotensin II (ANG II) is a well-established participant in many cardiovascular disorders, but the mechanisms involved are not clear. Vascular cell experiments suggest that ANG II is a potent stimulator of free radicals such as superoxide anion, an agent known to inactivate nitric oxide and promote the formation of peroxynitrite. Here we hypothesized that ANG II reduces the efficacy of NO-mediated vascular relaxation and promotes vascular peroxynitrite formation in vivo. ANG II was infused in rats at sub-pressor doses for 3 days. Systolic blood pressure and heart rate were unchanged on day 3 despite significant reductions in plasma renin activity. Thoracic aorta was isolated for functional and immunohistochemical evaluations. No difference in isolated vascular contractile responses to KCI (125 mM), phenylephrine, or ANG II was observed between groups. In contrast, relaxant response to acetylcholine (ACh) was decreased sixfold without a change in relaxant response to sodium nitroprusside. Extensive prevalence of 3-nitrotyrosine (3-NT, a stable biomarker of tissue peroxynitrite formation) immunoreactivity was observed in ANG II-treated vascular tissues and was specifically confined to the endothelium. Digital image analysis demonstrated a significant inverse correlation between ACh relaxant response and 3-NT immunoreactivity. These data demonstrate that ANG II selectively modifies vascular NO control at sub-pressor exposures in vivo. Thus, endothelial dysfunction apparently precedes other established ANG II-induced vascular pathologies, and this may be mediated by peroxynitrite formation in vivo. Wattanapitayakul, S., Weinstein, D. M., Holycross, B. J., Bauer, J. A. Endothelial dysfunction and peroxynitrite formation are early events in angiotensin-induced cardiovascular disorders.

Acetylcholine↗
PubMed2000

Nitrotyrosine causes selective vascular endothelial dysfunction and DNA damage.

Vascular endothelial dysfunction is recognized as a contributor to a wide array of cardiovascular disease states, but the initiating events involved are incompletely defined. Elevated plasma levels of free 3-nitro-L-tyrosine (3NT, biomarker of peroxynitrite formation) have been measured in settings of endothelial dysfunction, but its pathologic significance is unknown. We tested the hypothesis that clinically demonstrated concentrations of 3NT can induce vascular and endothelial dysfunction in vitro. Further studies evaluated involvement of DNA fragmentation and/or apoptosis as a potential mechanism. Preincubation of rat thoracic aorta segments with 3NT (100, 250 microM) resulted in selective, concentration-dependent impairment of acetylcholine (ACH) maximal response, with no change in KCL, phenylephrine, nitroprusside, or ACH EC50 effects (ACH Emax, 53+/-2, 42+/-5, 31+/-2%; Control, 100 microM, 250 microM 3NT). Vascular segments treated with 3NT also demonstrated concentration-dependent DNA damage, assessed using DNA nick-end labeling techniques (TUNEL staining), compared with control (TUNEL-positive nuclei/linear mm: 5.4+/-1.2, 13.7+/-1.2, 16.9+/-3.2; Control, 100 microM, 250 microM 3NT), which was confined to the endothelial layer. Equimolar tyrosine had no significant effects. Frequency of positively stained nuclei was statistically correlated to extent of endothelial dysfunction (p < 0.01). Free 3NT is apparently more than a benign biomarker in vivo, and may contribute to vascular endothelial dysfunction through promotion of DNA damage and/or apoptosis.

Acetylcholine↗
PubMed2000

Digital imaging analysis for the study of endotoxin-induced mitochondrial ultrastructure injury.

Primary defects in mitochondrial function have been implicated in over 100 diverse diseases. In situ, mitochondria possess unique and well-defined morphology in normal healthy cells, but diseases linked to defective mitochondrial function are characterized by the presence of morphologically abnormal and swollen mitochondria with distorted cristae. In situ study of mitochondrial morphology is established as an indicator of mitochondrial health but thus far assessments have been via subjective evaluations by trained observers using discontinuous scoring systems. Here we investigated the value of digital imaging analysis to provide for unbiased, reproducible, and convenient evaluations of mitochondrial ultrastructure. Electron photomicrographs of ileal mucosal mitochondria were investigated using a scoring system previously described by us, and also analyzed digitally by using six digital parameters which define size, shape, and electron density characteristics of over 700 individual mitochondria. Statistically significant changes in mitochondrial morphology were detected in LPS treated animals relative to vehicle control using both the subjective scoring system and digital imaging parameters (p < 0.05). However, the imaging approach provided convenient and high throughput capabilities and was easily automated to remove investigator influences. These results illustrate significant changes in ileal mucosal mitochondrial ultrastructure during sepsis and demonstrate the value of digital imaging technology for routine assessments in this setting.

Analog-Digital Conversion↗
PubMed2000

Endotoxin-induced ileal mucosal injury and nitric oxide dysregulation are temporally dissociated.

Despite recent investigations, the mechanisms responsible for intestinal epithelial injury during endotoxemia remain unclear. The present study tests the hypothesis that epithelial necrosis and/or apoptosis correlate with nitric oxide (NO) dysregulation in a nonischemic model of sepsis-induced ileal injury. To test this hypothesis, a well-established in situ, autoperfused, feline ileal preparation was employed. After endotoxin (lipopolysaccharide [LPS], 3 mg/ kg, intravenously; n = 9) or vehicle (control; n = 5) treatment, ileal segments were obtained at baseline, 2 and 4 h for simultaneous evaluations of cellular and mitochondrial ultrastructure, immunoprevalence of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (a stable biomarker of peroxynitrite), and histochemical evidence of apoptosis. Epithelial necrosis was prominent by 2 h post-LPS, despite unaltered global ileal tissue oxygen content, blood volume, and blood flow. Significant evidence of apoptosis and increases in the immunoprevalence of iNOS and 3-nitrotyrosine were not evident until 4 h post-LPS. These results suggest that the early ileal mucosal necrosis may be due to LPS-induced activation of inflammatory pathways and/or microcirculatory disturbances, whereas NO dysregulation may participate in later events, including protein nitration and epithelial apoptosis.

Animals↗
PubMed2000

An insole pressure measurement system: repeatability of postural data.

This study analyzed the ability of an in-shoe plantar pressure measurement system to provide repeatable measurements of postural sway data for both healthy and clinical patients. Each participant's in-shoe pressure data were recorded for three trials during each test session during quiet stance. Healthy individuals (n = 9) participated on three consecutive days while clinical participants (n = 5) were tested on one day. Nine response variables were measured to assess their postural stability. Intrasubject measures were evaluated using the Kerlinger reliability procedure. Values provided directly by the Parotec System for a single day of testing yielded the following average coefficients: r = 0.95 (left), r = 0.97 (right) with mean coefficient values from the three day tests of: r = 0.98 (left), r = 0.98 (right). Variables calculated from raw data on a single day produced mean coefficients of: r = 0.77 (left), r = 0.76 (right) and over three days of: r = 0.65 (left), r = 0.66 (right). The ability to record highly reproducible data of postural sway parameters should assist clinicians to treat patients more confidently for balance deficiencies.

Biomechanical Phenomena↗
PubMed2000

Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice.

Selective cardiotoxicity of doxorubicin remains a significant and dose-limiting clinical problem. The mechanisms involved have not been fully defined but may involve the production of reactive oxygen species and/or alteration of cardiac energetics. Here, we tested the hypotheses that doxorubicin causes left ventricular dysfunction in mice and is associated with dysregulation of nitric oxide in cardiac tissue, leading to the accumulation of 3-nitrotyrosine (a biomarker of peroxynitrite formation). Animals were dosed with doxorubicin (20 mg/kg i.p.), and left ventricular performance was assessed in vivo using M-mode and Doppler echocardiography. Five days after doxorubicin administration, left ventricular fractional shortening, cardiac output, and stroke volume parameters were significantly reduced relative to control values (30.0 +/- 3.6 versus 46.1 +/- 1. 6%, 8.9 +/- 0.9 versus 11.5 +/- 0.6 ml/min, and 21.2 +/- 0.1 versus 29.5 +/- 0.1 microl for doxorubicin versus control, P <.05). Statistically significant (P <.05) increases in the immunoprevalence of myocardial inducible nitric oxide synthase (33 +/- 18 versus 9 +/- 2%, via quantitative image analysis) and 3-nitrotyrosine formation (56 +/- 24 versus 0.3 +/- 0.4%) were also observed after doxorubicin. Correlation analyses revealed a highly significant inverse relationship between left ventricular fractional shortening and cardiac 3-nitrotyrosine immunoprevalence (P <.01). No such relationship was observed for inducible nitric oxide synthase. Western blot analyses of cardiac myofibrillar fractions revealed extensive nitration of an abundant 40-kDa protein, shown to be the myofibrillar isoform of creatine kinase. These data demonstrate that alteration of cardiac nitric oxide control and attendant peroxynitrite formation may be an important contributor to doxorubicin-induced cardiac dysfunction. Furthermore, nitration of key myofibrillar proteins and alteration of myocyte energetics are implicated.

Animals↗
PubMed1999

Differential subcellular distribution of neurolysin (EC 3.4.24.16) and thimet oligopeptidase (EC 3.4.24.15) in the rat brain.

Immunohistochemistry was used to analyze the rat brain distribution of thimet oligopeptidase and neurolysin. Both enzymes appear ubiquitously distributed within the entire rat brain. However, neuronal perikarya and processes stained for neurolysin, while intense nuclear labeling was only observed for thimet oligopeptidase. These data suggest that neurolysin and thimet oligopeptidase, endopeptidases sharing several functional and structural similarities, are present in distinctive intracellular compartments in neuronal cells.

Animals↗
PubMed1999

Analysis of isobutyl nitrite inhalant in rat and human blood: application for pharmacokinetic investigations.

Organic nitrites have been used therapeutically for the treatment of angina pectoris and as diagnostic agents for the evaluation of cardiac heart murmurs. In addition, these highly volatile vasodilators are being used as inhalant drugs of abuse. We developed a gas chromatographic assay using electron capture detection for the analysis of a representative nitrite inhalant, isobutyl nitrite (ISBN), in rat and human whole blood. Unconventional sampling and processing techniques were required because of the high volatility and chemical instability of nitrites in biological fluids. Our method produced a mean recovery of ISBN from rat blood of about 86% over a concentration range of 1.0 to 400 ng/ml. The inter-day coefficient of variation was below 15% at the lowest quantifiable concentration of 1 ng/ml ISBN in rat blood. In this report, we applied the analytical method to obtain new pharmacokinetic information about ISBN. Results show that rats inhaling 900 ppm ISBN for 45 min produced steady-state blood concentrations of about 290 ng/ml, and a rapid elimination half-life of 1.4 min.

Administration, Inhalation↗
PubMed1999

Diminished nitric oxide production following administration of transforming growth factor-beta1 using a noninflammatory wound repair model.

The effects of transforming growth factor-beta1 (TGF-beta1) on systemic nitric oxide (NO) production and wound repair were evaluated using a noninflammatory mouse perforated mesentery connective tissue repair model. Urinary nitrates were monitored as a measure of NO production. TGF-beta1 [bovine serum albumin (BSA) carrier and TGF-beta1 BSA carrier free] were administered on days 0 and 1 and were evaluated in mice over a 10-day period. A significant decrease in the average postwounding urinary nitrate levels compared to prewounding levels was observed within the TGF-beta1 treatment group animals (P </= 0.001) with an insignificant change for the phosphate-buffered saline control animals (P </= 0.10). Additionally, TGF-beta1-treated animals showed significant connective tissue repair compared to controls without a concurrent increase in postwounding urinary nitrate levels, supporting the noninflammatory nature of the perforated mesentery model. Our findings suggest that an unforseen consequence of TGF-beta1 administration is diminished basal nitric oxide production. When using TGF-beta1 in a wound repair or other therapeutic model, the administration of an exogenous NO donor compound may be necessary in order to ensure homeostasis, thereby avoiding undesired physiological consequences due to diminished basal NO production.

Animals↗
PubMed1999

Electromyographic patterns of individuals suffering from lateral tennis elbow.

This study investigated the applicability of using surface electromyography (EMG) as a tool for differentiating between persons suffering from lateral tennis elbow and the healthy age-matched adults. Temporal muscle activation patterns of the tennis elbow group were evaluated to determine if they varied between subject groups and if noted variations might be interpreted as arresting or exacerbating the injury. Sixteen subjects (Healthy Controls, n = 6; Tennis Elbow, n = 10) were tested under simulated tennis playing conditions. All subjects were males (Healthy group (CON) 38.8 +/- 13.1, Injured group (INJ) 40.8 +/- 10.8 yrs). EMG response data, temporal and spatial muscle activities, of the forearm extensors (Ext), the forearm flexors (Flex) and the triceps (Tri) were recorded for each subject during a single test session using all combinations of three different velocities on three different racket head impact locations. Data were collected at a frequency of 1000 Hz. Statistical analysis was performed using a 2 x 3 x 3 (Health status x Impact velocity x Impact location) ANOVA with repeated measures. Results indicated statistically significant differences (p < 0.05) between the CON and INJ subject groups for the response variables associated with forearm extensor muscle activation. During simulated play, the INJ group employed an earlier, longer, and greater activation of Ext than the CON group, such changes may be considered detrimental to the healing process. These results support the use of surface EMG to quantify differences in muscle activation strategies employed by individuals suffering from soft tissue muscle microtrauma injuries and healthy controls.

Adult↗
PubMed1999

Origin of sensory and autonomic innervation of the rat temporomandibular joint: a retrograde axonal tracing study with the fluorescent dye fast blue.

Previous studies that have used retrograde axonal tracers (horseradish peroxidase alone or conjugated with wheat germ agglutinin) have shown that the temporomandibular joint (TMJ) is supplied with nerve fibers originating mainly from the trigeminal ganglion, in addition to other sensory and sympathetic ganglia. The existence of nerve fibers in the TMJ originating from the trigeminal mesencephalic nucleus is unclear, and the possible innervation by parasympathetic nerve fibers has not been determined. In the present work, the retrograde axonal tracer, fast blue, was used to elucidate these questions and re-evaluated the literature data. The tracer was deposited in the supradiscal articular space of the rat TMJ, and an extensive morphometric analysis was performed of the labeled perikaryal profiles located in sensory and autonomic ganglia. This methodology permitted us to observe labeled small perikaryal profiles in the trigeminal ganglion, clustered mainly in the posterior-lateral region of the dorsal, medial, and ventral thirds of horizontal sections, with some located in the anterior-lateral region of the ventral third. Sensory perikarya were also labeled in the dorsal root ganglia from C2 to C5. No labeled perikaryal profiles were found in the trigeminal mesencephalic nucleus. On the other hand, autonomic labeled perikaryal profiles were distributed in the sympathetic superior cervical and stellate ganglia, and parasympathetic otic ganglion. Our results confirmed those of previous studies and also demonstrated that: (i) there is a distribution pattern of labeled perikaryal profiles in the trigeminal ganglion; (ii) some perikaryal profiles located in the otic ganglion were labeled; and (iii) the trigeminal mesencephalic nucleus did not show any retrogradely labeled perikaryal profiles.

Amidines↗
PubMed1999

Vascular peroxynitrite formation during organic nitrate tolerance.

Nitroglycerin (NTG) is an important cardiovascular agent, but tolerance during continuous administration limits its clinical utility. Increased vascular superoxide production may mediate nitrate tolerance via a reduction in nitric oxide availability. Because superoxide anion and nitric oxide react avidly to form peroxynitrite, an aggressive cellular toxicant that nitrates protein tyrosine residues, we tested the hypotheses that protein nitration, indicative of peroxynitrite formation, occurs during vascular tolerance, and that protein nitration participates in tolerance development. Preincubation of rat thoracic aorta segments with NTG (22 microM, EC(95) for 30 min) caused a significant shift in NTG relaxation response (EC(50); 6.7 +/- 1.7 versus 0.50 +/- 0.13 microM, NTG versus vehicle, p <.05). After functional evaluations, tissues were fixed in formalin for immunohistochemistry and digital image analysis. NTG-induced vascular tolerance was associated with increased immunoprevalence of 3-nitrotyrosine (3NT, stable biomarker of protein nitration; 11.41 +/- 2.48 versus 0.04 +/- 0.02% positive pixels, NTG versus vehicle, p < .05). Staining was observed throughout vascular smooth muscle layers. Addition of 500 microM free tyrosine to the preincubation medium did not alter tolerance development (NTG EC(50) 6.5 +/- 3.0 microM) but abolished 3NT immunoprevalence (0.16 +/- 0.10%). No significant relationship between NTG potency and 3NT immunoprevalence was observed. These data support the hypothesis that protein nitration occurs during nitrate vascular tolerance, however, it apparently does not mediate this phenomenon.

Animals↗
PubMed1998

The distribution of melanin-concentrating hormone in the monkey brain (Cebus apella).

Melanin-concentrating hormone was identified in the brain of Cebus monkey using immunohistochemical and in situ hybridization. MCH-immunoreactive neurons were found in the lateral hypothalamus and dorsolateral zona incerta. MCH-ir fibers were seen in the medial mammillary nucleus, and in the median eminence, and very few fibers in the globus pallidus. This is the first report describing the MCH-ir cell and fiber distribution in the monkey brain.

Animals↗
PubMed1998

Hydroxocobalamins as biologically compatible donors of nitric oxide implicated in the acceleration of wound healing.

In the late 1970s, research was unfolding that implicated nitric oxide involvement in the process of vasodilation. By 1986, research culminated in the identification of nitric oxide as the endothelium-derived relaxing factor responsible for the maintenance of vascular tone, thus implicating nitric oxide as a potential wound-healing agent. Biomedical researchers involved in wound-healing research quickly embraced the utility of developing a polymeric donor of nitric oxide which would enhance the wound-healing process. Several synthetic nitric oxide donors have been developed, dubbed 'NONOates', which have achieved great success in delivering nitric oxide to wounds. However, the impact on wound healing has been ambiguous and deemed antagonistic to the immune system in some cases. The propensity for the immune system to reject 'non-self' is a major factor in evaluating the usefulness of synthetic polymeric nitric oxide donors. The necessity of natural-product nitric oxide donors is apparent when examining the complications which are possible in a synthetic delivery system. Given the affinity nitric oxide has for transition metals, and the biological availability of transition-metal-centered products in vivo, it seems logical to pursue a transition-metal nitric oxide donor which is biologically friendly. Vitamin B12a (hydroxocobalamin), a natural product, offers an ideal environment to serve as a donor of nitric oxide.

Animals↗
PubMed1998

The urea cycle as a source of nitric oxide implicated in the pathogenesis of insulin-dependent diabetes mellitus.

Diabetes mellitus has long been considered an autoimmune disorder whereby the immune system attacks pancreatic tissue, destroying the insulin-producing cells of the pancreas. In this way, diabetes mellitus may be the only metabolic disorder in which the disease state is in no way related to any metabolic pathway. The specific role that nitric oxide plays in the pathogenesis of diabetes mellitus has yet to be established. However, researchers have shown that nitric oxide will independently destroy the beta cells (insulin-producing cells) of the pancreas in the absence of any pathogenic mediators. It is my hypothesis that a breakdown in the urea cycle (via activation of nitric oxide synthase (NOS)), a primary metabolic pathway, whereby nitric oxide production is competitively favored over urea production, is responsible for generating the major source of pathogenic nitric oxide resulting in the death of the beta cells of the pancreas.

Animals↗
PubMed1998

Synthesis, characterization and nitric oxide release profile of nitrosylcobalamin: a potential chemotherapeutic agent.

Nitrosylcobalamin, a vitamin B12-based, non-toxic carrier of nitric oxide (NO), has been synthesized, isolated and characterized in vitro. A UV/Vis analysis was performed confirming the reduction of the cobalt atom of hydroxocobalamin (vitamin B12a) with the binding of NO, causing a shift in the absorption spectra of CO3+ (lambdamax=530) to CO2+ (lambdamax=500) with the formation of nitrosylcobalamin. The extinction coefficient (epsilonmax) of nitrosylcobalamin, as calculated, was 4.8 (mM(-1), cm(-1)). An IR analysis determined the v(NO) vibrational frequency at 1652 cm(-1), supporting the binding of NO and suggesting a bent bonding geometry. NO release was maximized utilizing acidic conditions (pH 4.9, 32 degrees C) with a cumulative release of about 4610 nmol of NO in 675 h (calculated half-life of 210 h), representing 39% NO loading based on 11,890 nmol NO, theoretically possible (one NO per molecule of hydroxocobalamin). The cumulative NO release followed first-order kinetics and was pH dependent. NO release was minimal at pH 6.0 and 7.4 (37 degrees C), and undetected at pH 10 (37 degrees C). The possibility for nitrosylcobalamin to deliver NO (the active chemotherapeutic agent) to neoplastic cells is suggested because tumor cells, specifically leukemia cells, possess surface cell receptors for vitamin B12 which is readily utilized in the cellular proliferation process. Nitrosylcobalamin may offer a 'drug targeting' approach as a potential, biologically compatible and selective chemotherapeutic agent.

Antineoplastic Agents↗