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Biomedical subjects

K A Johnson

Publications and source records attributed to K A Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity.

A newborn rat model of retinopathy of prematurity was used to test the hypothesis that a lack of superoxide dismutase contributes to the retinal vaso-attenuation seen during exposure of the animals to hyperoxic conditions. To determine the endogenous superoxide dismutase activity of the retina under hyperoxic conditions, litters of albino rats were placed in either constant 80% ambient oxygen (constant hyperoxia), or placed in 21% oxygen (room air) immediately after birth. Every other day, for 14 days, several rat pups were sacrificed and their retinas removed for the determination of total superoxide dismutase (SOD) activity and manganese-associated SOD activity. An attempt was made to increase retinal SOD activity by intraperitoneal administration of exogenous SOD encapsulated in polyethylene glycol-modified liposomes. Additional litters were exposed to the same oxygen treatments and supplemented twice daily with either liposome-encapsulated superoxide dismutase in saline or liposomes containing saline without SOD. Animals were sacrificed at various time points for the determination of total superoxide dismutase activity and computer-assisted analysis of vessel density and avascular area. Animals raised in an atmosphere of constant 80% oxygen had significantly reduced levels of retinal superoxide dismutase activity through 6 days of life when compared to their room air-raised littermates. At 6 days of age, daily supplementation with liposome-encapsulated SOD had significantly increased retinal superoxide dismutase activity and reduced oxygen-induced vaso-attenuation as evidenced by increased vessel density and decreased avascular area, when compared to littermates exposed to constant hyperoxia that received control liposomes. Superoxide dismutase had no adverse effects on any of the animals regardless of treatment. Tracing experiments demonstrated that liposomes entered the retina and were found in cells morphologically resembling microglia. Delivery of SOD to the retina via long-circulating liposomes proved beneficial, suggesting that restoration and/or supplementation of endogenous antioxidants in oxygen-damaged retinal tissue is a potentially valuable therapeutic strategy.

Animals↗
PubMed1997

Movement-related potentials in Parkinson's disease. Motor imagery and movement preparation.

Movement-related potentials (MRPs) associated with voluntary movements reflect cortical activity associated with processes of movement preparation and movement execution. Early-stage pre-movement activity is reduced in amplitude in Parkinson's disease. However, it is unclear whether this neurophysiological deficit relates to preparatory or execution-related activity, since previous studies have not been able to separate different functional components of MRPs. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Therefore, MRP components relating to movement preparation and execution may be examined separately by comparing MRPs associated with imagined and actual movements. In this study, MRPs were recorded from 14 subjects with Parkinson's disease and 10 age-matched control subjects while they performed a sequential button-pressing task, and while they imagined performance of the same task. Early-stage pre-movement activity was present in both Parkinson's disease patients and control subjects when they imagined movement, but was reduced in amplitude compared with that for actual movement. Movement execution-related components, arising predominantly from the primary motor cortex, were relatively unaffected in Parkinson's disease subjects. However, motor preparatory processes, probably involving the supplementary motor area, were reduced in amplitude overall and abnormally prolonged, indicating impaired termination following the motor response. Further, this impaired termination of preparatory-phase activity was observed only in patients with more severe parkinsonian symptoms, and not in early-stage Parkinson's disease.

Aged↗
PubMed1997

Reversible cerebral hypoperfusion in Lyme encephalopathy.

Lyme encephalopathy (LE) presents with subtle neuropsychiatric symptoms months to years after onset of infection with Borrelia burgdorferi. Brain magnetic resonance images are usually normal. We asked whether quantitative single photon emission computed tomography (SPECT) is a useful method to diagnose LE, to measure the response to antibiotic therapy, and to determine its neuroanatomic basis. In 13 patients with objective evidence of LE, SPECT demonstrated reduced cerebral perfusion (mean perfusion defect index [PDI] = 255), particularly in frontal subcortical and cortical regions. Six months after treatment with 1 month of intravenous ceftriaxone, perfusion significantly improved in all 13 patients (mean PDI = 188). In nine patients with neuropsychiatric symptoms following Lyme disease, but without objective abnormalities (e.g., possible LE), perfusion was similar to that of the treated LE group (mean PDI = 198); six possible LE patients (67%) had already received ceftriaxone prior to our evaluation. Perfusion was significantly lower in patients with LE and possible LE than in 26 normal subjects (mean PDI = 136), but 4 normal subjects (15%) had low perfusion in the LE range. We conclude that LE patients have hypoperfusion of frontal subcortical and cortical structures that is partially reversed after ceftriaxone therapy. However, SPECT cannot be used alone to diagnose LE or determine the presence of active CNS infection.

Adult↗
PubMed1997

Late-gestation treatment of pregnant cows with trenbolone acetate does not increase subsequent growth of heifer calves.

Fifty crossbred cows (38 multiparous and 12 nulliparous) were used to evaluate in utero androgenization of heifer calves with trenbolone acetate. Three 200-mg trenbolone acetate (Finaplix-H) implants were implanted in the ear of treated cows (n = 24) on d 214 +/- 11 of gestation; the remaining animals (n = 26) were used as controls. Cows' rate of gain, serum levels of trenbolone acetate, gestation length, degree of dystocia, percentage bred back, days until conception, and 24-h milk production were evaluated. Fourteen-day weigh periods until parturition indicated that trenbolone acetate-treated dams had an increased (P < .05) average daily gain (1.05 +/- .1 kg) compared with control cows (.55 +/- .1 kg). Serum concentrations of trenbolone acetate were higher (P < .01) in treated cows with a peak at 9 d after implantation and returned to basal concentrations by d 77. Treatment did not affect degree of dystocia among all cows (P > .05) but seemed to increase (P < .01) the incidence of dystocia in nulliparous cows compared with nulliparous control cows. Gestation length and subsequent fertility were not affected by treatment (P > .05). Similarly, there was no difference in 24-h milk production (P > .05) between treated and control cows. Calf birth weight, phenotypic measurements at birth, vigor, average daily gain, carcass characteristics, and heifer reproductive tract and ovarian weights did not differ with treatment (P > .05). These data showed that late-gestation treatment with 600 mg of trenbolone acetate significantly increased weight gain of dams without demonstrating any androgenizing effects on the growth or physical characteristics of heifer calves.

Anabolic Agents↗
PubMed1997

Resilience to drinking vulnerability in women with alcoholic parents: the moderating effects of dyadic cohesion in marital communication.

Data from a subsample of women (N = 4,235) in two waves of the National Longitudinal Surveys of Youth (NLSY) are used to examine the relationship between parental alcoholism and alcohol use in adult life. Dyadic cohesion in marital communication (frequency of interaction and agreement on substantive issues that affect couples) is investigated as a resilience factor that could potentially mitigate adverse drinking outcomes in adult children of alcoholics (ACAs). A moderated mediation model is estimated using a Two-Stage Least Squares (2SLS) regression analysis. The results indicated that an imputed transmission of risk for drinking vulnerability in women ACAs, controlling for nonACA status, was effectively moderated by positive dyadic interaction.

Adolescent↗
PubMed1997

Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23.

Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are mostly benign, slow-growing tumors of the head and neck region, inherited from carrier fathers in an autosomal dominant fashion subject to genomic imprinting. Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We ascertained a total of 11 North American PGL families and confirmed maternal imprinting (inactivation). In three of six families, linkage analysis provided evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the critical region to an approximately 4.5-Mb interval flanked by markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly different between fathers and children (Wilcoxon rank-sum test, P < .002). Affected children had an earlier age at onset of symptoms in 39 of 57 father-child pairs (chi2 = 7.74, P < .006). However, a more conservative comparison of the number of pairs in which a child had > or = 5 years earlier age at onset (n = 33) vis-a-vis that of complementary pairs (n = 24) revealed no significant difference (chi2 = 1.42, P > .2). Whether these data represent genetic anticipation or ascertainment bias can be addressed only by analysis of a larger number of father-child pairs.

Adolescent↗
PubMed1997

Stability of gamma-glutamyltransferase activity in calf sera after refrigerated or frozen storage.

OBJECTIVES: To examine stability of -glutamyltransferase (GGT) activity in stored serum from neonatal calves. ANIMALS: 10 commercial beef calves between 36 and 60 hours old. PROCEDURE: Serum samples were obtained from the calves, and each sample was divided into 8 aliquots. Serum GGT activity was measured on day 0 (fresh) and days 1, 2, 3, and 4 of refrigerated storage (4 C) and weeks 1, 2, and 3 of frozen storage (-20 C). RESULTS: Serum GGT activities for each of the refrigerated aliquots did not significantly differ from day zero, with serum GGT activity (expressed as a percentage of initial activity) > 99% on all 4 days. Serum GGT activity in frozen aliquots decreased significantly after 1 and 2 weeks of frozen storage, 97 and 98%, respectively; however, this decrease in GGT activity was not biologically significant. The observed GGT activity did not decrease significantly in the samples stored frozen for 3 weeks; these samples retained 99% of initial activity. CONCLUSION: The observed stability of serum GGT activity indicates that serum may be obtained, stored, and batch processed at a later time. This stability during storage is important to the success of a bovine passive transfer monitoring program based on GGT activity.

Animals↗
PubMed1997

Synovial fluid interleukin 6, tumor necrosis factor, and nitric oxide values in dogs with osteoarthritis secondary to cranial cruciate ligament rupture.

OBJECTIVE: To measure and compare values of interleukin 6 (IL-6), tumor necrosis factor (TNF), and nitric oxide (NO) metabolites in synovial fluid from canine joints with osteoarthritis (OA) secondary to naturally acquired cranial cruciate ligament (CCL) rupture and experimental CCL transection. ANIMALS: 57 dogs (clinical group) with OA secondary to CCL rupture; 5 dogs (experimental group) with OA secondary to CCL transection; 19 control dogs with normal joints. PROCEDURE: Joints were radiographed and graded for seventy of OA. Synovial fluid was collected from dogs: at surgery from the clinical group, at 90 days after surgery from the experimental group, and at necropsy from the control group. Activities of IL-6 and TNF, as well as concentration of the NO metabolites (NO2-/NO3-) were measured, and results were reported as mean +/- SEM. RESULTS: IL-6 activity in dogs of the clinical (290 +/- 40 U/ml) and experimental (494 +/- 165 U/ml) groups was greater than that in control dogs (6 +/- 1.6 U/ml; P < 0.05). The TNF values in dogs of the clinical (3.0 +/- 0.5 pg/ml) and experimental (2.0 +/- 0.9 pg/ml) groups were lower than those in control dogs (8.6 +/- 2.3 pg/ml; P < 0.05). The IL-6 values were negatively associated with radiographic score of OA and were positively associated with age (R2 = 26.5%, P < 0.05). CONCLUSION: Dogs with OA secondary to naturally acquired CCL rupture and experimental CCL transection had significantly different alterations in synovial fluid IL-6 and TNF values. The decrease in IL-6 activity with advancing OA was independent of the increase in IL-6 activity with aging. CLINICAL RELEVANCE: IL-6 and TNF may be involved in pathogenesis of OA secondary to naturally acquired and experimentally induced CCL rupture.

Age Factors↗
PubMed1997

Protocol design considerations that relate to demonstrating the safety and effectiveness of chemopreventive agents.

As with other drugs, applications for marketing approval of new chemopreventive agents in the United States must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. Knowledge of a drug's pharmacologic actions and metabolism may benefit protocol design, by identifying the patient populations and dosing schedules associated with a favorable risk/benefit profile. With availability of appropriate preclinical data, including standard assessments of an agent's toxicology, effects on reproductive performance, and genotoxicity, initial Phase I studies of 1-3 months may be performed in normal volunteers or an appropriate higher risk population. For chronic dosing studies of longer duration, preclinical toxicology studies of longer duration are relevant. Enrollment in chemoprevention studies should be directed toward individuals at sufficient risk of developing cancer so that potential benefit may counterbalance the unpredictable and possibly serious adverse effects that may be observed with prolonged administration of a study drug. Phase I and II studies with clinical dosing lasting up to 12 months often afford opportunities to assess drug effect on surrogate endpoint biomarkers that may correlate with endpoints of clinical effectiveness. Phase III and late phase II chemopreventive investigations should routinely utilize a prospective, randomized study design (double-masked and placebo-controlled, when possible). To support marketing approval, there must be evidence that a chemopreventive agent significantly delays or prevents the occurrence of malignancy, with acceptable safety. In some circumstances, modulation of a surrogate marker may provide a basis for marketing approval, before more definitive endpoint data become available. However, the acceptability of a surrogate depends on the nature and quality of the data supporting its predictive value. Given the considerations of large study size, long duration, and high cost that may hamper development of potential agents, studies designed to examine the predictive value of surrogate endpoint biomarkers are of great importance to the future development of chemoprevention research.

Anticarcinogenic Agents↗
PubMed1996

Birth outcomes in pregnant women taking fluoxetine.

BACKGROUND: Although fluoxetine is the most frequently prescribed antidepressant drug in the United States, its safety in pregnant women has not been established. METHODS: From 1989 through 1995, we prospectively identified 228 pregnant women taking fluoxetine. We compared the outcomes of their pregnancies with those of 254 women identified in a similar manner who were not taking fluoxetine. RESULTS: The rate of spontaneous pregnancy loss did not differ significantly between the women treated with fluoxetine and the control women (10.5 percent and 9.1 percent, respectively), nor was the rate of major structural anomalies significantly different (5.5 percent vs. 4.0 percent). Among the 97 infants exposed to fluoxetine who were evaluated for minor anomalies, the incidence of three or more minor anomalies was significantly higher than among 153 similarly examined control infants (15.5 percent vs. 6.5 percent, P=0.03). As compared with the 101 infants exposed to fluoxetine only during the first and second trimesters, the 73 infants exposed during the third trimester had higher rates of premature delivery (relative risk, 4.8; 95 percent confidence interval, 1.1 to 20.8), admission to special-care nurseries (relative risk, 2.6; 95 percent confidence interval, 1.1 to 6.9), and poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding, and jitteriness (relative risk, 8.7; 95 percent confidence interval, 2.9 to 26.6). Birth weight was also lower and birth length shorter in infants exposed fluoxetine late in gestation. CONCLUSION: Women who take fluoxetine during pregnancy do not have an increased risk of spontaneous pregnancy loss or major fetal anomalies, but women who take fluoxetine in the third trimester are at increased risk for perinatal complications.

Abnormalities, Drug-Induced↗
PubMed1996

Interlocking intramedullary nail stabilization of a femoral fracture in a dog with osteomyelitis.

Complications developed in a dog that underwent intramedullary pin and cerclage wire fixation of a comminuted femoral fracture. The fracture was unstable, the intramedullary pin protruded through the skin over the hip, and Staphylococcus sp was isolated from the fracture site. The loose pin was removed, and the fracture was restabilized with a 6.0-mm interlocking intramedullary nail and 3 interlocking screws. Cephalexin was given orally for 6 weeks. Eight weeks after the second surgery, the fracture was healed radiographically. Seventeen months later, the dog had a persistent mild lameness that was associated with low-grade osteomyelitis. The lameness resolved after the implants were removed, and antibiotics were administered. In human beings, interlocking intramedullary nail stabilization is an accepted treatment for open and contaminated fractures. Chronic infection of bone may be attributable to bacteria in biofilm surrounding implants, necessitating implant removal for resolution.

Animals↗
PubMed1996

A polysomnographic study of sleep disturbance in community elderly with self-reported environmental chemical odor intolerance.

Subjective sleep complaints and food intolerances, especially to milk products, are frequent symptoms of individuals who also report intolerance for low-level odors of various environmental chemicals. The purpose of the present study was to evaluate the objective nature of nocturnal sleep patterns during different diets, using polysomnography in community older adults with self-reported illness from chemical odors. Those high in chemical odor intolerance (n = 15) exhibited significantly lower sleep efficiency (p = .005) and lower rapid-eye-movement (REM) sleep percent (p = .04), with a trend toward longer latency to REM sleep (p = .07), than did those low in chemical intolerance (n = 15), especially on dairy-containing as compared with nondairy (soy) diets. The arousal pattern of the chemical odor intolerant group differed from the polysomnographic features of major depression, classical organophosphate toxicity, and subjective insomnia without objective findings. The findings suggest that community elderly with moderate chemical odor intolerance and minimal sleep complaints exhibit objectively poorer sleep than do their normal peers. Individual differences in underlying brain function may help generate these observations. The data support the need for similar studies in clinical populations with chemical odor intolerance, such as multiple chemical sensitivity patients and perhaps certain veterans with "Persian Gulf Syndrome."

Aged↗
PubMed1996

Time-dependent sensitization of plasma beta-endorphin in community elderly with self-reported environmental chemical odor intolerance.

This study examined plasma beta-endorphin as a marker of the physiological stress response in community elderly who were either high (n = 15) or low (n = 15) in self-rated frequency of illness from environmental chemical odors. Individuals who report nonatopic multiple sensitivities to or intolerances for low levels of environmental chemicals also claim high rates of comorbid food sensitivities or intolerances. Subjects gave 9 AM blood samples for plasma beta-endorphin 90 min after ingesting either 1% fat cow's milk or a soy-based nondairy drink, on six different mornings in the laboratory after all-night sleep recordings. The six sessions-were divided into three sets of two successive days each, with each set [involving baseline (ad lib milk), nondairy (soy-based), and dairy diets] separated from the next by 3 weeks. In the chemically tolerant subjects, stably lower beta-endorphin levels suggested that milk may have been a physiologically less stressful beverage than was the soy drink. In contrast, the chemical odor intolerant group exhibited a) increased levels of plasma beta-endorphin averaged over the 6 days (p = .02); and b) marked fluctuations in endorphin from one laboratory day to the next (Group x Diet x Day interaction, p = .005). The findings were consistent with time-dependent, context-dependent sensitization of beta-endorphin in the chemical odor intolerant individuals.

Aged↗
PubMed1996

Mechanism of NO-induced oxidation of myoglobin and hemoglobin.

Nitric oxide (NO) has been implicated as mediator in a variety of physiological functions, including neurotransmission, platelet aggregation, macrophage function, and vasodilation. The consumption of NO by extracellular hemoglobin and subsequent vasoconstriction have been suggested to be the cause of the mild hypertensive events reported during in vivo trials of hemoglobin-based O2 carriers. The depletion of NO from endothelial cells is most likely due to the oxidative reaction of NO with oxyhemoglobin in arterioles and surrounding tissue. In order to determine the mechanism of this key reaction, we have measured the kinetics of NO-induced oxidation of a variety of different recombinant sperm whale myoglobins (Mb) and human hemoglobins (Hb). The observed rates depend linearly on [NO] but show no dependence on [O2]. The bimolecular rate constants for NO-induced oxidation of MbO2 and HbO2 are large (k.ox,NO = 30-50 microM-1 s-1 for the wild-type proteins) and similar to those for simple nitric oxide binding to deoxygenated Mb and Hb. Both reversible NO binding and NO-induced oxidation occur in two steps: (1) bimolecular entry of nitric oxide into the distal portion of the heme pocket and (2) rapid reaction of noncovalently bound nitric oxide with the iron atom to produce Fe(2+)-N=O or with Fe(2+)-O-O delta- to produce Fe(3+)-OH2 and nitrate. Both the oxidation and binding rate constants for sperm whale Mb were increased when His(E7) was replaced by aliphatic residues. These mutants lack polar interactions in the distal pocket which normally hinder NO entry into the protein. Decreasing the volume of the distal pocket by replacing Leu(B10) and Val(E11) with aromatic amino acids markedly inhibits NO-induced oxidation of MbO2. The latter results provide a protein engineering strategy for reducing hypertensive events caused by extracellular hemoglobin-based O2 carriers. This approach has been explored by examining the effects of Phe(B10) and Phe(E11) substitutions on the rates of NO-induced oxidation of the alpha and beta subunits in recombinant human hemoglobin.

Animals↗
PubMed1996

Purification and characterization of two monomeric kinesin constructs.

Steady-state and pre-steady-state kinetic methods were used to analyze two shorter Drosophila kinesin constructs (K341 and K366) in comparison to K401. K341, K366, and K401 represent the kinesin motor domains containing the N-terminal 341, 366, or 401 amino acids, respectively. K401 is dimeric (Kd = 37 +/- 17 nM) whereas both K366 and K341 are monomeric [Correia et al. (1995) Biochemistry 34, 4898-4907]. Like native kinesin and K401, K341 and K366 demonstrate low ATPase activity in the absence of microtubules (0.03 and 0.01 s-1, respectively), and ADP release is rate-limiting during steady-state turnover. Microtubules activate the steady-state ATPase to 84 s-1 for K341 (K(m),ATP = 100 microM; K0.5,MT = 3.2 microM tubulin) and 64 s-1 for K366 (K(m),ATP = 65 microM; K0.5,MT = 2.5 microM tubulin) in comparison to K401 at 20 s-1 (K(m)ATP = 60 microM; K0.5,MT = 1 microM tubulin). The rapid quench experiments for all three constructs show a burst of product formation during the first turnover, indicating the rate-limiting step for the microtubule-activated ATPase occurs after ATP hydrolysis. The interaction of K341 and K366 with the microtubule was analyzed by electron microscopy. The results show that K341 and K366, like K401, bind to the microtubule with an 8 nm axial periodicity. However, the addition of K366 to microtubules resulted in significant aggregation of microtubules. The pre-steady-state kinetic results show that K341 retains the kinetic and structural properties necessary to compare directly the kinetic properties of monomeric and dimeric kinesins, although the microtubule-activated ATPase is significantly faster for the monomeric constructs, suggesting possible interactions in the dimer which inhibit ATP turnover as part of the coupling to force production.

Adenosine Triphosphatases↗