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Biomedical subjects

J L Peters

Publications and source records attributed to J L Peters.

At least 19 recordsLinked to original sources

Predicting haloperidol treatment response in chronic schizophrenia.

The study attempted to identify pretreatment characteristics of chronic schizophrenic patients that would predict remission in psychosis and amount of clinical improvement after treatment with haloperidol. Thirty-five acutely relapsed schizophrenic patients were entered into a blind 6-week treatment protocol. Pretreatment measures were assessed for prediction of both remission status (dichotomous) and for correlations with change in psychopathology (continuous). Later age of onset and higher plasma homovanillic acid values were significant predictors of remission status (model 1). However, higher cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol, as well as indices of normal neurodevelopment, predicted larger changes in psychopathology. The results indicate that the definition of drug response determines the predictive variables. Dopaminergic activity seems to relate to the ability to reach remission, while noradrenergic activity relates to symptom intensity and reduction. In addition to catecholamine activity, neurodevelopmental changes determine response to haloperidol.

Adult

Regulatory effects of endogenous interleukin-1 receptor antagonist protein in immunoglobulin G immune complex-induced lung injury.

IL-1 receptor antagonist (IL-1Ra) has regulatory effects on IL-1 activity both in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered human IL-1Ra suppressed neutrophil recruitment and ensuing lung injury. In this study, we sought to determine if endogenous rat IL-1Ra might regulate this lung-inflammatory response. By Northern blot analysis of lung mRNA and Western analysis of bronchoalveolar lavage (BAL) fluids, rat IL-1Ra expression was found to increase during development of inflammation in IgG immune complex-mediated alveolitis. By immunostaining, alveolar macrophages and recruited neutrophils were the apparent sources of IL-1Ra. In vivo blocking of endogenous IL-1Ra resulted in a 53% increase in lung vascular permeability and a 180% increase in BAL fluid neutrophils. In companion studies, a significant increase in IL-1beta was found, whereas no significant change in TNF-alpha activity was observed. Whereas the in vivo regulatory effects of IL-1R appear to be limited to IL-1beta, IL-10 regulates both IL-1beta and TNF-alpha in this model, reflected by a 48% increase in BAL IL-1beta in rats treated with anti-IL-10. These findings suggest that IL-1Ra is an intrinsic regulator of inflammatory injury after deposition of IgG immune complexes and that it regulates production of IL-1beta.

Alveolitis, Extrinsic Allergic

Monitoring body-core temperature from the trachea: comparison between pulmonary artery, tympanic, esophageal, and rectal temperatures.

INTRODUCTION: We designed an endotracheal tube (ETT) for acquiring body-core temperature from the trachea. This ETT had two temperature sensors, one attached to the inside surface of the cuff, the other mounted on the ETT shaft underneath the cuff. The ETT was evaluated in vitro and in dogs to determine: 1) optimal position of temperature sensors and 2) the responsiveness, accuracy, and resistance to ventilatory artifacts. METHODS: In vitro. An artificial trachea assessed the response-time and accuracy of ETT temperature sensors to abrupt temperature changes and ventilatory flow-rates. In vivo. Body temperature in 5 dogs was lowered to approximately 26 degrees C then elevated toward 39 degrees C using a heat exchanger during carotid-jugular bypass. ETT temperature measurements were compared simultaneously with those from the artificial trachea (in vitro) or from the pulmonary artery, tympanic cavity, esophagus, and rectum of dogs using dry and humidified gas. RESULTS: Cuff temperature sensor responded quickly and accurately to temperature changes and was less prone than the tube sensor to ventilatory and humidity artifacts. During carotid-jugular bypass, in vivo tube and cuff mean temperatures averaged 1.4 degrees C and 0.36 degree C lower, respectively, than pulmonary artery temperatures. There were no statistical differences (P > 0.05) between cuff temperatures and those measured from the pulmonary artery, tympanic cavity, esophagus, and rectum. Heating and humidifying the inspiratory gas of dogs with a water-bath humidifer or heat moisture exchanger (HME) had minimal effects on the cuff temperature sensor. An in-line HME increased in vivo tube temperature from baseline values by 1.13 +/- 0.80 degree C, while cuff temperature increased by 0.21 +/- 0.24 degree C. CONCLUSION: The cuff of the ETT is a reliable site for measuring body-core temperature in intubated patients.

Animals

Predicting duration of clinical stability following haloperidol withdrawal in schizophrenic patients.

Although chronic maintenance antipsychotic drug treatment is the most effective way of preventing relapse in schizophrenic patients, it is not very successful. A considerable number of patients relapse on medication, and many others do not take their medications as prescribed after leaving the hospital. Unfortunately, clinicians are not able to identify how long patients will remain clinically stable after drug discontinuation. To develop a model consisting of behavioral and monoaminergic variables to identify the risk of symptom exacerbation, we obtained in the week prior to haloperidol discontinuation global behavioral ratings and cerebrospinal fluid (CSF) values for monoamine metabolites in a sample of 109 DSM-III-R schizophrenic patients. Patients were followed until specific criteria for increases in psychosis were met for up to 1 year and then returned to antipsychotic drug treatment. Cox regression analysis identified predictors of the survival function, or the probability of relapse at a given time drug free. The best model indicated that increased psychosis, decreased anxiety, an increased CSF homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) ratio, and decreased CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) prior to haloperidol withdrawal were associated with early increases in psychosis. Our study indicates that it is possible to identify those patients who are more likely to remain clinically stable without medication. When the model is validated, it will help clinicians assess the relapse risk over time, lower doses in treatment-resistant patients, and possibly determine the optimal time for aftercare visits following hospital discharge.

Adult

Porcine somatotrophin differentially down-regulates expression of the GLUT4 and fatty acid synthase genes in pig adipose tissue.

The present study was conducted to determine whether porcine somatotropin (pST) differentially regulates expression of the GLUT4 and fatty acid synthase (FAS) genes in pig adipose tissue. Three different experiments were conducted in which pigs were treated daily with different doses of pST for different time periods (7 or 14 d and from 60 to 90 kg of body wt). In these experiments, pST significantly and consistently decreased FAS mRNA levels (80%, 66% and 85%, respectively); however, GLUT4 mRNA was not affected by pST in two of the three experiments, and in the one showing an effect (Experiment 2), the decrease was less than observed for FAS (44%). Because of these results, we conducted subsequent experiments to see if the effects of pST on glucose metabolism in cultured pig adipose tissue (48 h) differed when glucose concentrations were changed from 1 to 5 mmol/L. These studies revealed that the antagonistic effect of pST on insulin action was more potent when glucose transport was saturated (5 mmol/L) than when glucose concentration limited glucose entry into the cell (1 mmol/L). In summary, these results suggest that the effects of pST on glucose transport in pig adipocytes are secondary to changes elicited by the hormone on intracellular glucose use for lipogenesis. When considered in the context of the decrease previously observed in glucose transport in pig adipocytes, the findings reported herein suggest that pST acts to decrease GLUT4 protein activity and/or distribution between the plasma membrane and the intracellular pool with little alteration in GLUT4 gene expression or total cell GLUT4 protein.

Actins

Developmental and light-regulated expression of individual members of the light-harvesting complex b gene family in Pinus palustris.

Angiosperms requires light for multiple aspects of chloroplast development, including chlorophyll synthesis and induction of expression of the mRNAs encoding the major polypeptides of the light-harvesting complex of photosystem II (Lhcb genes). In contrast, many conifers, including pines, firs, and spruces, can accumulate chlorophyll and the light-harvesting chlorophyll a/b-binding proteins of photosystem II in complete darkness. To understand the factors responsible for the regulation of expression of individual Lhcb mRNAs in the pine Pinus palustris, we have prepared sequence-specific cDNA probes for each of three family members, Lhcb1*Pp1, Lhcb2*Pp1, and Lhcb2*Pp2, and have studied the expression of two of these, Lhcb1*Pp1 and Lhcb2*Pp2, in detail. The levels of expression of each sequence were disparate, and Lhcb1*Pp1-encoded transcripts were the most abundant in the light. Both Lhcb1*Pp1 and Lhcb2*Pp2 mRNAs were expressed in stems and cotyledons, but Lhcb1*Pp1 mRNA was present at about 10-fold lower levels in stems than in cotyledons, in contrast to Lhcb2*Pp2 mRNA, which was expressed at higher levels in stems than in cotyledons. Both Lhcb1*Pp1 and Lhcb2*Pp2 mRNAs were absent in embryos but were expressed during seedling development. The levels increased with age in both the light and the dark and in both cases were about 2-fold higher in the light than in the dark. Despite the expression of Lhcb1*Pp1 and Lhcb2*Pp2 mRNAs during development in darkness, the levels of both mRNAs increased in dark-grown seedlings given red light in the low fluence range within 2 h of treatment.

Amino Acid Sequence

The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription.

The present study was conducted to determine the chronic effects of porcine growth hormone administration on fatty acid synthase (FAS) mRNA abundance and gene transcription in growing rats. Growth hormone treatment increased growth rate approximately 27% (P<0.01). Porcine growth hormone decreased FAS mRNA levels by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not affect mRNA abundance or transcription rate of another insulin-regulated gene, phosphoenolpyruvate carboxykinase. In summary, our results have established that chronic treatment with growth hormone decreases FAS mRNA by decreasing the transcription rate of the gene. Furthermore, they suggest that the effects of growth hormone are specific and are not mediated by general changes in insulin-responsive gene expression in liver.

Animals

Behavioral vs biochemical prediction of clinical stability following haloperidol withdrawal in schizophrenia.

BACKGROUND: We sought to identify haloperidol-treated subjects who relapsed within 6 weeks of placebo replacement and those who did not, using multivariate analysis. METHODS: In the week prior to discontinuation of haloperidol treatment, global behavioral ratings and a lumbar puncture for cerebrospinal fluid monoamine metabolities were obtained in 88 patients with chronic schizophrenia. Logistic regression analyses were used to evaluate two competing models of relapse prediction. The models were then compared using receiver operating characteristic analysis and a final combined model was derived. RESULTS: The behavioral model was less variable in its prediction than the cerebrospinal fluid monoamine model. The final model consisted of increased psychosis, decreased anxiety, higher cerebrospinal fluid homovanillic acid levels, and lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels. CONCLUSIONS: Several monoamine systems are involved in psychotic relapse within 6 weeks of haloperidol withdrawal. Future studies of relapse prediction should include both clinical and biological measures to fully assess relapse risk.

Adult

Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status.

OBJECTIVE: Interleukin-2, traditionally viewed as solely involved in immunological events, has recently been shown to exert profound effects on the development and regulation of the central nervous system. This study examined the relationships between interleukin-2 in the CSF and plasma of schizophrenic patients and clinical measures, including relapse and medication status. Plasma and CSF interleukin-1 alpha levels were also measured to ascertain the specificity of changes in cytokine levels. METHODS: Seventy-nine physically healthy male patients with schizophrenia (DSM-III-R) received diagnostic evaluation and behavioral ratings. Haloperidol treatment was withdrawn for up to 6 weeks and patients were evaluated for symptom recurrence. CSF and plasma were obtained by established procedures before haloperidol withdrawal (N = 79) and after (N = 64). RESULTS: CSF levels of interleukin-1 alpha decreased significantly after haloperidol withdrawal but showed no relation to clinical status. In contrast, levels of CSF interleukin-2 were associated with recurrence of psychotic symptoms. Relapse-prone patients, examined both while medicated and after drug withdrawal, had significantly higher levels of CSF interleukin-2 than patients who did not relapse. CSF interleukin-2 level during haloperidol treatment was a significant predictor of worsening in psychosis. CONCLUSIONS: Levels of interleukin-2, a molecule that plays both neurodevelopmental and neuroregulatory roles, may have a role in relapse in schizophrenia. Levels of CSF interleukin-2 appear to be affected by relapse mechanisms, while peripheral blood levels are not. These changes are specific to interleukin-2, since levels of interleukin-1 alpha were affected by medication withdrawal but not by change in clinical state.

Adult

Involvement of N-methyl-D-aspartate receptor using excitatory amino acid neurotransmitters in control of pulsatile secretion of LH during sexual development in Holstein bull calves.

The neuroendocrine mechanisms underlying the development of pulsatile release of LH in bull calves are poorly understood. The hypothesis that endogenous excitatory amino acids, working through N-methyl-D-aspartate (NMDA) receptors, are involved in the generation of pulsatile LH release during sexual maturation of bull calves was tested. Holstein bull calves were administered i.v. 0.001, 0.01 and 0.1 mg kg-1 body mass of MK-801, a specific noncompetitive NMDA receptor antagonist, on alternate days at 1, 12 and 24 weeks of age (n = 6 per dose), using a replicated 3 x 3 latin square design. Blood samples were obtained from jugular catheters at intervals of 10 min for 2 h before and 2 h after MK-801 treatment at 1 week and for periods of 4 h before and after MK-801 administration at 12 and 24 weeks of age. Plasma concentrations of LH were measured by a specific radioimmunoassay and pulsatile LH secretion was analysed using the Pulsar algorithm. Basal LH secretion at 1 week of age was low but was increased by 12 weeks (0.38 +/- 0.01 versus 1.38 +/- 0.11 ng ml-1; P < 0.001) with the establishment of frequent high amplitude pulses. Mean LH concentrations and pulse amplitude, but not frequency, were lower at 24 than at 12 weeks of age (0.88 +/- 0.08 versus 1.38 +/- 0.11 ng ml-1: P < 0.001, 1.74 +/- 0.14 versus 2.82 +/- 0.36 ng ml-1: P < 0.01, and 1.70 +/- 0.30 versus 1.70 +/- 0.41 in 4 h: P > 0.05, respectively). Administration of MK-801 did not affect LH secretion in 1- and 12-week-old calves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hydrogen peroxide affects specific epithelial subpopulations in cultured rabbit lenses.

PURPOSE: To investigate the effect of hydrogen peroxide on the epithelial cells of cultured rabbit lenses. METHODS: Lenses were cultured in minimum essential medium containing a single dose of 0.03, 0.1, or 0.2 mM H2O2. Three hours later the medium was replaced with peroxide-free minimum essential medium. Lenses were also treated with 0.5 mM 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU) to lower the activity of glutathione reductase and then exposed to 0.03 mM H2O2 maintained nearly constant by glucose oxidase. After H2O2 treatment, lenses were fixed and whole mounts of the epithelium were prepared or lenses were processed for electron microscopy. RESULTS: Cells exposed to a single dose of 0.03 mM H2O2 appeared normal; 0.1 mM H2O2 was not cytotoxic. Exposure to 0.2 mM H2O2 elicited swelling in cells in the pre-equatorial region (30 minutes) followed by the formation of islands of cells in the pre-equatorial region at 1 hour. Central epithelial cells appeared normal at 1 hour, were swollen at 3 hours and dead at 24 hours. By 48 hours, dead cells were found in the pre-equatorial and central regions. Cells in the peripheral region of the epithelium did not exhibit cytotoxicity. If lenses were pretreated with BCNU and then challenged with a maintained level of 0.03 mM H2O2, cytotoxicity was induced in the central and pre-equatorial regions. Cells in the peripheral region survived BCNU-H2O2 treatment. CONCLUSIONS: Cells in the peripheral region of cultured lenses were more resistant to H2O2 cytotoxicity than cells in the central and pre-equatorial regions. The antioxidant defense or repair systems for H2O2-induced damage do not appear to be uniformly distributed in subpopulations of the lens epithelium.

Animals

CSF levels of diazepam-binding inhibitor correlate with REM latency in schizophrenia, a pilot study.

CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.

Adult

Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: comparison of the surface, esophageal, and tracheal electrocardiograms.

INTRODUCTION: We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation. METHODS: Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury. RESULTS: Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at > 300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation. CONCLUSION: Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes.

Animals

Platelet aggregation and dense granule secretion in schizophrenia.

The functional state of platelets and their possible impairment in response to various stimuli were assessed in saline-diluted citrated blood samples of normal male control subjects (n = 27), and in schizophrenic patients with (n = 34) and without (n = 23) haloperidol treatment. In response to collagen, but not to arachidonic acid (AA) and adenosine diphosphate, platelet aggregation (as measured by changes in impedance) was significantly higher in both haloperidol-treated and drug-free schizophrenic patients than in normal control subjects. Comparison of the secretion traces, however, indicated that only AA-induced adenosine triphosphate (ATP) release was significantly lower in haloperidol-treated schizophrenic patients than in normal control subjects. In response to thrombin, collagen, and AA, the mean values of ATP release from drug-free patients were significantly higher than those from the same individuals when they were receiving haloperidol. Furthermore, there was a trend toward increased ATP release (in response to thrombin or collagen) in the nonrelapsed group of drug-free schizophrenic patients as compared with the relapsed group. The collagen-induced platelet aggregation or dense granule secretion in drug-free patients was correlated significantly and negatively with psychosis ratings. Such changes in platelet function of schizophrenic patients were not correlated significantly with daily haloperidol dose, plasma haloperidol levels, age of subjects, age of onset, or duration of illness.

Adenosine Triphosphate

Localization of nicotinic cholinergic receptors in rat brain: autoradiographic studies with [3H]cytisine.

There is a great deal of interest in the role of nicotinic acetylcholine receptors in the central nervous system, although their function is not well understood at present. Currently, central nicotinic receptors can be classified broadly as either alpha-bungarotoxin binding sites with low affinity for acetylcholine agonists, or as high-affinity agonist binding sites with low affinity for alpha-bungarotoxin. Neuronal nicotinic receptors with a high affinity for agonists are distributed widely in the central nervous system. Evidence from molecular biology and electrophysiology suggests that multiple nicotinic receptor types exist in the brain. In this study we have used the agonist [3H]cytisine as a ligand for autoradiography to generate a detailed quantitative map of the high-affinity agonist binding nicotinic receptor in the rat brain. Optimized binding conditions, characterization of the kinetic and equilibrium binding properties, and demonstration of the nicotinic pharmacology of this binding site in tissue sections confirm the usefulness of [3H]Cytisine as a ligand for nicotinic receptor autoradiography. [3H]Cytisine autoradiography provides excellent anatomic resolution with very low non-specific binding. This property has allowed us to describe variations in receptor density within subnuclei and gradients of receptor density in larger brain regions. Data from several studies suggest that the predominant high-affinity agonist binding nicotine receptor in the central nervous system is composed of the alpha 4 and beta 2 subunits. The data in the current study are consistent with the suggestion that [3H]cytisine labels only the alpha 4 beta 2 nicotinic receptor with high affinity, offering the possibility of localizing a specific nicotinic receptor subtype in the central nervous system. In summary, we characterize the optimum experimental conditions for the use of [3H]cytisine in tissue section autoradiography. [3H]Cytisine proves to be an excellent marker for nicotinic cholinergic receptors with a very high affinity and very low background. We provide a detailed quantitative characterization of nicotinic receptor density in the rat central nervous system and we find there are significant variations and gradients in receptor density within specific brain regions, including subregions previously thought to be homogeneous.

Alkaloids

Noradrenergic activity and prediction of psychotic relapse following haloperidol withdrawal in schizophrenia.

OBJECTIVE: The purpose of this study was to develop a model based on the authors' previous studies to identify which neuroleptic-treated schizophrenic patients are at risk of early relapse following drug withdrawal. METHOD: Clinical and CSF monoamine-related variables obtained for 50 male haloperidol-treated, schizophrenic patients were used in a logistic regression model to identify those who relapsed (N = 24) within 6 weeks after placebo substitution and those who did not (N = 26). RESULTS: The oral dose of haloperidol, weight, CSF norepinephrine, 3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By including the interactions of paranoia subscale by CSF norepinephrine and anxiety by CSF norepinephrine, the model correctly identified 20 relapsers and 23 nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively. CONCLUSIONS: Increased noradrenergic activity during chronic dopamine blockade may be an episode marker and may predict relapse within 6 weeks following haloperidol withdrawal in schizophrenia. Effective relapse prediction models have important practical implications for the treatment of schizophrenia and the understanding of the psychotic relapse process.

Adult

Age-related changes in the secretion of LH in vivo and in vitro in infantile and prepubertal Holstein bull calves.

The objectives of this study were (i) to determine whether age-related changes in the secretion of LH are associated with alterations in secretory activity or numbers of gonadotrophs, and (ii) to determine whether gonadotrophs obtained from the pars distalis and pars tuberalis undergo similar age-related changes in function. Blood samples were collected from Holstein bull calves every 15 min for 12 h at < 1, 12, and 42 weeks of age (n = 5 per age group) to characterize the secretion of LH. Calves were killed 3-5 days later. The pars distalis and pars tuberalis were enzymatically dispersed into suspensions of single cells. Cells from the pars distalis were (i) extracted with 0.01 mol NaHCO3 l-1, (ii) fixed for immunocytochemical analysis, and (iii) cultured in six-well plastic plates at a density of 500,000 cells per well in media containing 2.5% homologous calf serum for 18 and 72 h. Cells from the pars tuberalis were cultured as for pars distalis cells. As expected, LH pulse frequency increased (P < 0.01) between one and 12 weeks of age and then declined. The percentage of cells from the pars distalis containing immunoreactive LH averaged 8.4%, and did not change with age. The mass of the pars distalis and the total number of cells recovered increased with age (P < 0.05); consequently, the number of gonadotrophs recovered also increased. The initial content of LH of pars distalis cells changed with age and was greatest at 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging