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Biomedical subjects

J Fang

Publications and source records attributed to J Fang.

At least 145 records · Page 8Linked to original sources
PubMed1999

Intrapreoptic microinjection of GHRH or its antagonist alters sleep in rats.

Previous reports indicate that growth hormone-releasing hormone (GHRH) is involved in sleep regulation. The site of action mediating the nonrapid eye movement sleep (NREMS)-promoting effects of GHRH is not known, but it is independent from the pituitary. GHRH (0.001, 0. 01, and 0.1 nmol/kg) or a competitive antagonist of GHRH (0.003, 0.3, and 14 nmol/kg) was microinjected into the preoptic area, and the sleep-wake activity was recorded for 23 hr after injection in rats. GHRH elicited dose-dependent increases in the duration and in the intensity of NREMS compared with that in control records after intrapreoptic injection of physiological saline. The antagonist decreased the duration and intensity of NREMS and prolonged sleep latency. Consistent alterations in rapid eye movement sleep (REMS) and in brain temperature were not found. The GHRH antagonist also attenuated the enhancements in NREMS elicited by 3 hr of sleep deprivation. Histological verification of the injection sites showed that the majority of the effective injections were in the preoptic area and the diagonal band of Broca. The results indicate that the preoptic area mediates the sleep-promoting activity of GHRH.

Animals↗
PubMed1999

Conformational analysis of an alpha-galactosyl trisaccharide epitope involved in hyperacute rejection upon xenotransplantation.

alpha-Galactosyl epitopes are carbohydrate structures bearing an alpha-Gal-(1-->3)-Gal terminus (alpha-Gal epitopes). The interaction of these epitopes on the surface of animal cells with anti alpha-Gal antibodies in human serum is believed to be the main cause in antibody-mediated hyperacute rejection in xenotransplantation. In this paper, conformational analysis of an N-linked alpha-D-Galp-(1-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp trisaccharide epitope was conducted in terms of each monosaccharide residue conformation, primary hydroxymethyl group configuration, and interglycosidic conformations. Selective 2D J-delta INEPT experiments have been carried out at three different temperatures to evaluate three-bond, long-range 13C-1H coupling constants for the crucial alpha-(1-->3) linkage. The NMR experimental data were complemented by theoretical calculations. The flexibility and dynamics of the trisaccharide have been studied by Metropolis Monte Carlo simulations. Ensemble-averaged three-bond, long-range 13C-1H coupling constants and nuclear Overhauser effects were in good agreement with the experimental data. The alpha-(1-->3) glycosidic linkage has shown a restricted flexibility as indicated by NMR spectroscopy and molecular modeling.

Galactose↗
PubMed1999

Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study.

BACKGROUND: In a recent acute study, amantadine was found to have antidyskinetic effect against levodopa-induced motor complications in patients with Parkinson disease. The longevity of this effect was not addressed but is of interest in light of the controversy in the literature regarding the duration of amantadine's well-established antiparkinsonian action. OBJECTIVE: To determine the duration of the antidyskinetic effect of amantadine in advanced Parkinson disease. DESIGN: One year after completion of an acute, double-blind, placebo-controlled, crossover study, patients returned for re-evaluation of motor symptoms and dyskinesias using a nonrandomized, double-blind, placebo-controlled follow-up paradigm. SETTING: National Institutes of Health Clinical Center. PATIENTS: Seventeen of the original 18 patients with advanced Parkinson disease complicated by dyskinesias and motor fluctuations participated in this study; 1 was lost to follow-up. Thirteen of the 17 individuals had remained on amantadine therapy for the entire year. INTERVENTIONS: Ten days prior to the follow-up assessment, amantadine was replaced with identical capsules containing either amantadine or placebo. MAIN OUTCOME MEASURES: Parkinsonian symptoms and dyskinesia severity were scored using standard rating scales, while subjects received steady-state intravenous levodopa infusions at the same rate as 1 year earlier. RESULTS: One year after initiation of amantadine cotherapy, its antidyskinetic effect was similar in magnitude (56% reduction in dyskinesia compared with 60% 1 year earlier). Motor complications occurring with the patients' regular oral levodopa regimen also remained improved according to the Unified Parkinson's Disease Rating Scale (UPDRS-IV). CONCLUSION: The beneficial effects of amantadine on motor response complications are maintained for at least 1 year after treatment initiation.

Amantadine↗
PubMed1999

Contextual determinants of female-female mounting in laboratory rats.

Female-female mounting is widespread among mammalian species, but little is known about the proximal function of this behaviour. While such mounting is often regarded as a 'masculine' trait, its widespread occurrence may indicate that it serves specific functions within the context of female-female social behaviour. We valuated female mounting behaviour in Long-Evans rats in standard observation chambers and in a seminatural enclosure. Under these conditions, we examined a number of potential factors that might influence mounting, including the oestrous cycle, social hierarchy, familiarity and male presence. The female's mounting was not influenced by her own oestrous cycle, but did vary with the oestrous cycle of the stimulus female. Socially dominant females mounted significantly more than subordinate females, and mounting by the dominant female was most frequent when the subordinate female was sexually receptive. Females mounted (and fought with) unfamiliar females significantly more than they did with familiar cagemates. Female-female mounting was dramatically reduced when males were present. Further testing showed that female mounting did not affect the induction of the progestational state of pregnancy, suggesting that female mounting does not function as a pseudomale behaviour that can substitute for genital stimulation provided by the male. Based on these data, female mounting does not appear to function as a sexual behaviour per se, but may serve as a form of female social behaviour related to maintenance of the female's social status within female groups. In this regard, the results of this study suggest that female mounting is part of the normal female's complex behavioural repertoire and does not necessarily reflect masculinization of some underlying neural substrate. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Cardiovascular mortality of Chinese in New York City.

To determine cardiovascular disease mortality among Chinese migrants in New York City and compare it to both that of residents in China and whites in New York City, mortality records for 1988 through 1992 for New York City and the 1990 US census data for New York City were linked. Age-specific death rates for urban China, reported by the World Health Organization, were used for comparison. The results show that male and female Chinese residents in New York City had lower mortality rates for all causes and total cardiovascular disease than did either New York City whites or Chinese in China. Coronary heart disease deaths among New York City Chinese were intermediate between Chinese in China (lowest) and New York City whites (highest). Stroke death rates for New York City Chinese were substantially lower than those in China and, in general, were similar to those for New York City whites. However, New York City Chinese had higher death rates for hemorrhagic stroke and lower for atherosclerotic stroke than did New York City whites. In conclusion, cardiovascular mortality rates among Chinese migrants in New York City fall below those of both Chinese in China and whites in New York City.

Adult↗
PubMed1999

Growth-promoting effect of recombinant human growth hormone and stanozolol in girls with Turner syndrome.

Ten girls with Turner syndrome were treated with a combination therapy of recombinant human growth hormone (R-hGH) and low dose stanozolol for a period of 8 to 36 months. The results showed that when compared with the growth rate before the treatment, the growth rates after treatment with R-hGH and stanozolol showed a sustained increase, reaching 9.0 +/- 1.9 cm/year during the first year of treatment; the height age increase by 2.5 +/- 0.8 years while the bone age increase were 1.0 +/- 0.7 years; and the predicted final adult height at the end of the first year of the treatment increased to 149.4 +/- 6.1 cm compared to their original mean of 142.8 +/- 4.2 cm. We are led to conclude that therapy with R-hGH in combination with stanozolol can increase the growth velocity and significantly increase the predicted adult height of children with Turner syndrome.

Adolescent↗
PubMed1999

Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4.

Risperidone is a relatively new antipsychotic drug that has been reported to improve both the positive and the negative symptoms of schizophrenia and produces relatively few extrapyramidal side effects at low doses. Formation of 9-hydroxyrisperidone, an active metabolite, is the most important metabolic pathway of risperidone in human. In the present study, in vitro metabolism of risperidone (100 microM) was investigated using the recombinant human cytochrome P450 (CYP) enzymes CYP1A1, CYP1A2, CYP2C8, CYP2C9-arg144, CYP2C9-cys144, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 supplemented with an NADPH-generating system. 9-Hydroxyrisperidone was determined by a new HPLC method with an Hypersil CN column and a UV detector. Of these enzymes, CYPs 2D6, 3A4 and 3A5 were found to be the ones capable of metabolising risperidone to 9-hydroxyrisperidone, with activities of 7.5, 0.4 and 0.2 pmol pmol(-1) CYP min(-1), respectively. A correlation study using a panel of human liver microsomes showed that the formation of 9-hydroxyrisperidone is highly correlated with CYP2D6 and 3A activities. Thus, both CYP2D6 and 3A4 are involved in the 9-hydroxylation of risperidone at the concentration of risperidone used in this study. This observation is confirmed by the findings that both quinidine (inhibitor of CYP2D6) and ketoconazole (inhibitor of CYP3A4) can inhibit the formation of 9-hydroxyrisperidone. Furthermore, inducers of CYP can significantly increase the formation of 9-hydroxyrisperidone in rat. The formation of 9-hydroxyrisperidone is highly correlated with testosterone 6beta-hydroxylase activities, suggesting that inducible CYP3A contributes significantly to the metabolism of risperidone in rat.

Animals↗
PubMed1999

Food restriction alters the diurnal distribution of sleep in rats.

The purpose of the present study was to determine the effects of restricting food and water intake to the light period on sleep and brain temperature (Tbr). Sprague-Dawley male rats were anesthetized and provided with electrodes and thermistors for electroencephalographic (EEG) and Tbr recordings. Baseline recordings were performed after a 3-week recovery period. After baseline recordings, access to food and water was restricted (FWR) to the light period for 29 days. During FWR, the diurnal distribution of rapid-eye-movement sleep (REMS) and Tbr were reversed, while the distribution of non-REMS (NREMS) between the dark and light periods was attenuated. Daily food and water intake, body weight, and the diurnal distribution of EEG slow-wave activity within NREMS remained unchanged. In a separate study, sham-operated and pinealectomized rats were studied in a similar manner. The sleep responses of pinealectomized and sham-operated rats to FWR were similar. Further, FWR did not affect melatonin levels in the sham-operated rats, thereby suggesting that the pineal gland does not mediate the effects of FWR on sleep.

Animals↗
PubMed1999

Why we sleep: a theoretical view of sleep function.

We propose that sleep begins within small groups of highly interconnected neurons and is characterized by altered input --> output (i-->0) relationships for any specific neuronal group. Further, experimental findings suggest that growth factors, released locally in response to neuronal activity, and acting in paracrine and autocrine fashions, induce the altered i-->0 relationships. These growth factors also act to provide the structural basis for synapses. Thus, we envision that sleep mechanisms (neural use-dependent induction of growth factors and their subsequent effects on i-->0 relationships) cannot be separated from sleep function (growth factor-induced synaptic sculpturing). This mechanism/firnction is envisioned to take place in all areas of the brain, including sleep regulatory circuits as well as throughout the cortex. Finally, the "sleep" of neuronal groups (altered i-->o relationships) is coordinated by the known sleep regulatory circuits and activational-projection systems in the brain. The theory extends and integrates existing sleep theories to cover a broader range of phenomena.

Journal Article↗
PubMed1999

Metabolism, pharmacogenetics, and metabolic drug-drug interactions of antipsychotic drugs.

1. Antipsychotic drugs are extensively metabolised by cytochrome P450 (CYP) enzymes. 2. Dispositions of a number of antipsychotic drugs have been shown to cosegregate with polymorphism of CYP2D6. 3. Metabolic drug-drug interactions have frequently been observed when antipsychotics are coadministered with other drugs. 4. Many antipsychotic drugs are converted to active metabolites which can contribute to the therapeutic or side effects of the parent drug. 5. Information concerning the individual CYP isoenzymes involved in the metabolism of antipsychotic drugs is important for the safe clinical use of this group of drugs.

Antipsychotic Agents↗
PubMed1999

Current understanding of chemokine involvement in allograft transplantation.

Multiple studies have demonstrated that chemokines play an essential role in regulating and co-ordinating the infiltration of leucocytes into allografts. Chemokines are expressed in skin, liver, heart, and kidney allografts following initial engraftment, ischemic injury, viral infection, and acute and chronic rejection. To date, most of our understanding of chemokine biology has been generated from studies of animal models of transplantation and little is known about the role of chemokines in human allograft rejection. Chemokines may play important mechanistic roles in transplant rejection, in the development of graft arteriosclerosis, and in chronic sclerosing cholangiopathy. Furthermore, these molecules may serve as sensitive diagnostic indicators for the analysis of rejection, including chronic rejection or other forms of graft dysfunction. Lastly, it is possible that chemokine-targeted therapy might become a feasible option for the treatment of allograft rejection.

Animals↗
PubMed1999

Humoral regulation of physiological sleep: cytokines and GHRH.

Interleukin-1, tumour necrosis factor, and growth hormone releasing hormone form part of the humoral mechanisms regulating physiological sleep. Their injection enhances non-rapid-eye-movement sleep whereas their inhibition reduces spontaneous sleep and sleep rebound after sleep deprivation. Changes in their mRNA levels and changes in their protein levels in the brain are consistent within their proposed role in sleep regulation. Furthermore, results from transgenic and mutant animals also are suggestive of their role in sleep regulation. The sites responsible for the growth hormone releasing hormone somnogenic activity seem to reside in the anterior hypothalamus/basal forebrain. Somnogenic sites for interleukin-1 and tumour necrosis factor likely include the anterior hypothalamus, but also may extend beyond that area. These substances elicit non-rapid-eye-movement sleep via a biochemical cascade that includes other known sleep regulatory substances.

Animals↗
PubMed1999

IGF binding protein-1 (IGFBP-1) is preferentially associated with the fetal-facing basal surface of the syncytiotrophoblast in the human placenta.

IGF receptors are expressed in a spatially polarized manner on the syncytiotrophoblast cell membrane. We therefore examined the hypothesis that IGFBPs expressed at the maternal-fetal interface interact with distinct surfaces of the syncytiotrophoblast membrane to modulate IGF function. Membrane vesicles were prepared specifically from the maternal-facing, microvillous membrane (MVM) and the fetal-facing, basal membrane (BM) surfaces of the syncytiotrophoblast. The association of IGFBPs with each membrane preparation was determined by ligand blot analysis. A doublet migrating at 38/42 kD was detected in both MVM and BM preparations. Selective immunoprecipitation followed by ligand blot analysis identified this IGF binding species as IGFBP-3. Additionally, a protein migrating at approximately 29 kD was associated primarily with the BM. This protein was identified as IGFBP-1 by both immunoprecipitation and ligandblotting techniques. Non-denaturing PAGE revealed five distinct bands corresponding to different degrees of phosphorylation. The phosphorylation pattern of BM-associated IGFBP-1 was identical to that of native IGFBP-1 in amniotic fluid. Immunohistological analysis of term placenta revealed IGFBP-1-specific staining of the syncytiotrophoblast and the fetal capillary/pericapillary bed. The localization of IGFBP-1 to a distinct compartment within the fetal placenta, not in proximity to the syncytiotrophoblast type I IGF receptor, suggests it may play a role in regulating/targeting IGF activity within the stromal compartment or by exerting IGF-independent effects on the basal surface of the syncytiotrophoblast. The nature of its binding to the BM has not been determined.

Female↗
PubMed1999

Interleukin-10 inhibits spontaneous sleep in rabbits.

Proinflammatory cytokines, including interleukin-1beta(IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in sleep regulation. IL-10 is an anti-inflammatory cytokine that inhibits proinflammatory cytokine production. We hypothesized that IL-10 could attenuate sleep. Thirty-one male rabbits were used. Three doses of IL-10 (5 ng, 50 ng, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-10 (250 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were given to the same rabbits on different days. The two highest doses of IL-10 significantly inhibited spontaneous nonrapid eye movement sleep if IL-10 was given during the light cycle. The highest dose of IL-10 (250 ng) also significantly decreased rapid eye movement sleep. IL-10 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-10 provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiologic sleep.

Analysis of Variance↗
PubMed1999

Decomposition of multiunit electromyographic signals.

We have developed a comprehensive technique to identify single motor unit (SMU) potentials and to decompose overlapped electromyographic (EMG) signals into their constituent SMU potentials. This technique is based on one-channel EMG recordings and is easily implemented for many clinical EMG tests. There are several distinct features of our technique: 1) it measures waveform similarity of SMU potentials in the wavelet domain, which gives this technique significant advantages over other techniques; 2) it classifies spikes based on the nearest neighboring algorithm, which is less sensitive to waveform variation; 3) it can effectively separate compound potentials based on a maximum signal energy deduction algorithm, which is fast and relatively reliable; and 4) it also utilizes the information on discharge regularities of SMU's to help correct possible decomposition errors. The performance of this technique has been evaluated by using simulated EMG signals composed of up to eight different discharging SMU's corrupted with white noise, and also by using real EMG signals recorded at levels up to 50% maximum voluntary contraction. We believe that it is a very useful technique to study SMU discharge patterns and recruitment of motor units in patients with neuromuscular disorders in clinical EMG laboratories.

Action Potentials↗
PubMed1999

Somnogenic relationships between tumor necrosis factor and interleukin-1.

Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines. They also induce each other's production and both induce nuclear factor kappa B activation, which in turn enhances IL-1 and TNF transcription. We hypothesized that TNF and IL-1 could influence each other's somnogenic actions. To test this hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on spontaneous sleep and on sleep rebound after sleep deprivation in rabbits. Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits with the combination of TNFRF and IL-1RF also significantly attenuated sleep rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate physiological sleep.

Animals↗
PubMed1999

Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits.

Various growth factors are involved in sleep regulation. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family; it and its receptors are found in normal brain. Furthermore, cerebral cortical levels of BDNF mRNA have a diurnal variation and increase after sleep deprivation. Therefore, we investigated whether BDNF would promote sleep. Twenty-four male Sprague-Dawley rats (320-380 g) and 25 male New Zealand White rabbits (4.5-5.5 kg) were surgically implanted with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and, on a separate day, one of the following doses of BDNF: 25 or 250 ng in rabbits; 10, 50, or 250 ng in rats. The EEG, brain temperature, and motor activity were recorded for 23 h after the intracerebroventricular injections. BDNF increased time spent in non-rapid eye movement sleep (NREMS) in rats and rabbits and REMS in rabbits. Current results provide further evidence that various growth factors are involved in sleep regulation.

Animals↗