Search PubMed⌕ Search

Biomedical subjects

H Wei

Publications and source records attributed to H Wei.

At least 73 records · Page 4Linked to original sources

Parathyroid hormone-related protein is expressed by transformed and fetal human astrocytes and inhibits cell proliferation.

Parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor are expressed in most normal tissues, including brain, where PTHrP is though to act locally in an autocrine or paracrine fashion. Previous in situ localization studies in adult rodents have documented CNS PTHrP expression in neurons but not in glial cells. However, a recent report describing immunoreactive PTHrP in human astrocytomas suggests that PTHrP expression may be a marker of dedifferentiation and/or malignant transformation in glial cells. To begin to test this hypothesis, constitutive and regulated PTHrP expression were examined in cultured fetal and transformed (U-373 MG) human astrocytes. PTHrP was expressed in untreated fetal astrocytes and U-373 MG cells, as determined by Northern analysis, immunocytochemical staining, and detection of PTHrP(1-84) protein in conditioned media. Epidermal growth factor and tumor necrosis factor, important growth factors in astrocyte development and malignant transformation, stimulated PTHrP expression in both cell types. Treatment of U-373 MG cells or fetal astrocytes with PTHrP(1-34) consistently inhibited cellular proliferation, as measured by [(3)H]-thymidine incorporation. These findings suggest that PTHrP, a peptide whose expression is induced by mitogens in both immature and transformed human astrocytes, may feedback inhibit cellular proliferation, an effect that may be of importance during malignant transformation as well as CNS development. Furthermore, when combined with previous evidence of PTHrP expression by PTH/PTHrP receptor-positive neurons, our demonstration of regulated PTHrP expression by receptor-positive astrocytes identifies PTHrP as a potential peptide mediator of cross-talk between glial cells and neurons.

Astrocytes↗

Whole-body metabolic rate appears to determine the rate of DNA oxidative damage and glycation involved in aging.

While aging has been found to be a multifactorial process, it seems logical that different aging parameters which reflect the deleterious effects of normal basal metabolism should be directly related. Three such putative aging parameters were therefore measured in adult male Fischer 344 rats on three different long-term diets which have been shown to yield different lifespans. It was found that the daily caloric intake per unit organ weight, a measure of whole-body metabolic rate, was directly proportional to: (1) the level of 8-hydroxydeoxyguanosine in skin dermal cells, used as a measure of the rate of DNA oxidative damage; (2) the proportion of hemoglobin that was glycated, used as a measure of the rate of glycation. This appears to be the first evidence suggesting that whole-body metabolic rate plays a role in determining both the rate of DNA oxidative damage and the rate of glycation involved in aging, because whole-body metabolic rate was the only one of these three variables manipulated in the study. The study also found that there were no significant between-group differences in brain, kidney and liver 8-hydroxydeoxyguanosine, suggesting that DNA oxidative damage in non-mitotic and slow-dividing cells is not a reliable linear biomarker of aging.

8-Hydroxy-2'-Deoxyguanosine↗

Event-related brain potentials elicited by a number discrimination task.

To study the number cognition process, we recorded event-related potentials (ERPs) in 14 subjects when they were indicating whether a number pair was the same or not. The two numbers given in sequence were either the same (condition 1) or different (condition 2). After 270 ms following the onset of the second stimulus in condition 2, a negative component N270 was recorded on the scalp with the most negative amplitude at the central and occipital areas. Hemispheric asymmetry was not observed in the potential. This negative component is considered to reflect the mismatching process for numbers in the brain.

Adult↗

beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment.

Treatment of rat pheochromocytoma cells (PC 12) cells with beta-amyloid peptide-(1-42) for 24 h induced a concentration-dependent decrease in cellular redox activity in the dose range of 1 to 20 microM. These effects were markedly attenuated by pretreatment with 2 mM LiCl for 7 days, whereas 1-day pretreatment was ineffective. Measurements of live and dead cells by double-staining with fluorescein diacetate and propidium iodide, respectively revealed that protracted lithium pretreatment attenuated PC 12 cell death induced by beta-amyloid-(1-42) and cerebellar granule cell death induced by beta-amyloid-(25-35). Preceding PC 12 cell death, beta-amyloid peptide elicited a slight decrease in protein levels of Bcl-2. Conversely, 7-day pretreatment with lithium resulted in an approximate doubling of Bcl-2 protein levels in cells treated with or without beta-amyloid peptide-(1-42). Lithium-induced Bcl-2 upregulation was temporally associated with the cytoprotective effects of this drug. Thus, lithium protection against beta-amyloid peptide neurotoxicity might involve Bcl-2 overexpression, and lithium treatment for Alzheimer's disease should be reexamined.

Amyloid beta-Peptides↗

Characterization, chromosomal assignment, and tissue expression of a novel human gene belonging to the ARF GAP family.

We have identified and characterized a novel human ADP-ribosylation factor GTPase-activating protein (ARFGAP1) gene that is related to other members of the ARF GAP family. The full-length cDNA for human ARFGAP1 was cloned following the identification of an EST obtained by large-scale cDNA library sequencing through a Blast search of public databases. Structurally, ARFGAP1 encodes a polypeptide of 516 amino acids, which contained a typical GATA-1-type zinc finger motif (CXXCX(16)CXXC) with the four cysteine residues that are highly conserved among other members of the ARF GAP family. The conserved ARF GAP domain may emphasize the biological importance of this gene. The ARFGAP1 gene, which contained 16 exons ranging from 0.5 to 9.3 kb, was mapped to human chromosome 22q13.2-q13.3 using radiation hybridization and in silico analyses. ARFGAP1 is strongly expressed in endocrine glands and testis. Interestingly, the expression of ARFGAP1 in testis is about sixfold higher than that in ovary, indicating a possible role of ARFGAP1 in the physiological function of sperm. Expression of ARFGAP1 in four human fetal tissues and seven cancer cell lines was also detected.

ADP-Ribosylation Factors↗

No-scalpel vasal sperm aspiration and in vitro fertilization for the treatment of anejaculation.

OBJECTIVES: To evaluate the utility of no-scalpel vasal sperm aspiration and in vitro fertilization for the treatment of male infertility due to anejaculation. METHODS: Vasal aspiration was performed using a no-scalpel technique, and the sperm were used for conventional in vitro fertilization in 1 patient and intracytoplasmic sperm injection in 6 patients. RESULTS: The average total sperm count was 6 x 10(6), with the motility between 20% and 95%. No complications have been observed to date. A high fertilization rate (74.6%) and pregnancy rate (5 of 7) was achieved with subsequent intracytoplasmic sperm injection or in vitro fertilization. CONCLUSIONS: No-scalpel vasal sperm aspiration is a simple, effective alternative to sperm retrieval, especially for anejaculatory males.

Adult↗

Fertilisability of ovine, bovine or minke whale (Balaenoptera acutorostrata) spermatozoa intracytoplasmically injected into bovine oocytes.

This study was conducted to investigate the possibility of using bovine oocytes for a heterologous fertility test by intracytoplasmic sperm injection (ICSI) and to compare the pronuclear formation of ram, bull and minke whale spermatozoa after injection into bovine oocytes. Bovine oocytes were cultured in vitro for 24 h and those with a polar body were selected for ICSI. Frozen-thawed semen from the three species were treated with 5 mM dithiothreitol for 1 h and spermatozoa were killed by storing them in a -20 degrees C refrigerator before use. ICSI was performed using a Piezo system. Three experiments were designed. In experiment 1, a higher (p < 0.05) male pronuclear formation rate was found in the oocytes injected with ram (52.6%) or bull (53.4%) spermatozoa than with minke whale spermatozoa (39.1%). In experiment 2, sperm head decondensation was detected at 2 h after ICSI in the oocytes injected with a spermatozoon of each species. Male pronuclei were first observed at 4 h in the oocytes injected with ram or bull spermatozoa and at 6 h in oocytes injected with minke whale spermatozoa. The mean diameters of male pronuclei derived from both whale and bull spermatozoa were larger than those from ram spermatozoa (30.4 microm and 28.3 microm vs 22.4 microm, p < 0.005). The mean diameter of female pronuclei in the oocytes injected with whale spermatozoa was also larger than with ram spermatozoa (29.3 microm vs 24.7 microm, p < 0.05). The development of male and female pronuclei was synchronous. In experiment 3, ethanol-activated oocytes injected with a spermatozoon from any of the three species achieved significantly higher (p < 0.05-0.001) cleavage rates than control oocytes. Blastocyst formation was only observed when bull spermatozoa were used. The results of this study indicate that dead foreign spermatozoa can participate in fertilisation activities in bovine oocytes after ICSI.

Animals↗

The dissociation of sedative from spinal antinociceptive effects following administration of a novel alpha-2-adrenoceptor agonist, MPV-2426, in the locus coeruleus in the rat.

BACKGROUND: MPV-2426 is a novel alpha-2-adrenoceptor agonist developed for spinal pain therapy. In the present study we characterized its sedative and antinociceptive properties following microinjections into the brainstem and intrathecally at the lumbar spinal cord level. METHODS: Sedative effects of MPV-2426 were assessed in a locomotion measuring device following unilateral microinjection into the locus coeruleus (LC) of the brainstem or 1-2 mm rostral to the LC in rats. Antinociceptive effects induced by MPV-2426 in the brainstem, and for comparison intrathecally at the lumbar spinal cord level, were determined with a tail-flick test. Dexmedetomidine was used as the reference alpha-2-adrenoceptor agonist. RESULTS: MPV-2426 produced a dose-related hypolocomotive/sedative effect, which was significantly stronger following microinjection into the LC than 1-2 mm rostral to the LC. The sedation induced by MPV-2426 was reversed by atipamezole (1 mg/kg s.c.), an alpha-2-adrenoceptor antagonist. The sedative potency of dexmedetomidine, the reference alpha-2-adrenoceptor agonist, was stronger and less dependent on the exact injection site in the brainstem. Following microinjections at sedative doses in the brainstem, only dexmedetomidine produced a significant antinociceptive effect in the tail-flick test. When microinjected into the lumbar spinal cord, MPV-2426 and dexmedetomidine had an equally strong antinociceptive effect in the tail-flick test. CONCLUSION: The results indicate that the sedative potency of MPV-2426 is considerably weaker than that of dexmedetomidine. Additionally, the spread of MPV-2426 within the central nervous system is more limited than that of dexmedetomidine. This could explain why MPV-2426 is sedative only when injected into the LC while antinociceptive effect is obtained when it is injected intrathecally at the lumbar spinal cord level.

Adrenergic alpha-2 Receptor Agonists↗

Neuronal apoptosis induced by pharmacological concentrations of 3-hydroxykynurenine: characterization and protection by dantrolene and Bcl-2 overexpression.

We have studied neurotoxicity induced by pharmacological concentrations of 3-hydroxykynurenine (3-HK), an endogenous toxin implicated in certain neurodegenerative diseases, in cerebellar granule cells, PC12 pheochromocytoma cells, and GT1-7 hypothalamic neurosecretory cells. In all three cell types, the toxicity was induced in a dose-dependent manner by 3-HK at high micromolar concentrations and had features characteristic of apoptosis, including chromatin condensation and internucleosomal DNA cleavage. In cerebellar granule cells, the 3-HK neurotoxicity was unaffected by xanthine oxidase inhibitors but markedly potentiated by superoxide dismutase and its hemelike mimetic, MnTBAP [manganese(III) tetrakis(benzoic acid)porphyrin chloride]. Catalase blocked 3-HK neurotoxicity in the absence and presence of superoxide dismutase or MnTBAP. The formation of H(2)O(2) was demonstrated in PC12 and GT1-7 cells treated with 3-HK, by measuring the increase in the fluorescent product, 2',7'-dichlorofluorescein. In both PC12 and cerebellar granule cells, inhibitors of the neutral amino acid transporter that mediates the uptake of 3-HK failed to block 3-HK toxicity. However, their toxicity was slightly potentiated by the iron chelator, deferoxamine. Taken together, our results suggest that neurotoxicity induced by pharmacological concentrations of 3-HK in these cell types is mediated primarily by H(2)O(2), which is formed most likely by auto-oxidation of 3-HK in extracellular compartments. 3-HK-induced death of PC12 and GT1-7 cells was protected by dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. The protection by dantrolene was associated with a marked increase in the protein level of Bcl-2, a prominent antiapoptotic gene product. Moreover, overexpression of Bcl-2 in GT1-7 cells elicited by gene transfection suppressed 3-HK toxicity. Thus, dantrolene may elicit its neuroprotective effects by mechanisms involving up-regulation of the level and function of Bcl-2 protein.

Animals↗

Pseudoxanthoma elasticum and calcinosis cutis.

A 42-year-old white woman presented with clinical and histologic manifestations of both calcinosis cutis and pseudoxanthoma elasticum: discrete milia-like calcifications at the anterior aspect of the neck, a funduscopic examination with classic eye findings, peripheral vascular disease, and a mottled appearance of the skin at the axillae, groin, and lateral aspects of the neck. A younger sibling had similar skin lesions and deteriorating visual acuity. The patient was normocalcemic and normophosphatemic. This case may represent the coincidental occurrence of two rare entities in the same person or may be suggestive of a pattern of dystrophic calcification associated with pseudoxanthoma elasticum.

Adult↗

Attenuation of ascending nociceptive signals to the rostroventromedial medulla induced by a novel alpha2-adrenoceptor agonist, MPV-2426, following intrathecal application in neuropathic rats.

BACKGROUND: In the current study, the potency and spread of the antinociception induced by MPV-2426, a novel alpha2-adrenoceptor agonist, was characterized in neuropathic and non-neuropathic animals. METHODS: Neuropathy was induced by unilateral ligation of two spinal nerves in the rat. After lumbar intrathecal or systemic administration of MPV-2426, thermally and mechanically evoked responses of nociceptive neurons of the rostroventromedial medulla were recorded during pentobarbitone anesthesia. To obtain a behavioral correlate of neurophysiologic findings, nocifensor reflex responses evoked by thermal and mechanical stimuli were assessed in unanesthetized neuropathic and control animals. RESULTS: After intrathecal administration, MPV-2426 and dexmedetomidine produced a dose-related antinociceptive effect, independent of the submodality of the noxious test stimulus or the pathophysiologic condition. This antinociceptive effect was spatially restricted to the inputs from the lower half of the body, and it was reversed by atipamezole, an alpha2-adrenoceptor antagonist. After systemic administration in non-neuropathic animals, MPV-2426 had no antinociceptive effect on responses to rostroventromedial medulla neurons, whereas systemically administered dexmedetomidine produced a dose-related suppression of nociceptive signals to the rostroventromedial medulla, independent of the site of test stimulation. In a behavioral study, intrathecal MPV-2426 produced a dose-dependent suppression of nocifensor responses evoked by noxious mechanical or heat stimuli, whereas systemic administration of MPV-2426 had no effects. CONCLUSIONS: Intrathecal MPV-2426 has spatially limited antinociceptive properties in neuropathic and non-neuropathic conditions because of its action on spinal alpha2-adrenoceptors. These properties may be advantageous when designing therapy for spatially restricted pain problems.

Adrenergic alpha-2 Receptor Agonists↗

Early-latency somatosensory evoked potentials elicited by electrical acupuncture after needling acupoint LI-4.

The stimulating methods of prior studies on somatosensory evoked potentials (SEPs) elicited by acupoint stimulus had involved surface electrodes, while the clinical practice of acupuncture is mostly performed by inserting the acupuncture needle inside the body. Clinical observations show that there are often some special sensations when LI-4 is needled. To observe if the SEPs produced by acupoint acupuncture had a distinguishing property, we studied the SEPs elicited by electrical acupuncture after the acupuncture needle was inserted into LI-4 and its control point, and then mapped them with the 128-channel Electric Brain Signal Image system. We also compared this to SEPs by median nerve stimuli. Results showed that the most interesting finding was the marked differences of N1-P1 and N2-P2 amplitude between SEPs at LI-4 (SEP-LI) and its control point (SEP-CP), which were in the opposite direction. Marked differences were also found between latencies and amplitudes of the SEPs elicited by acupuncture and by median nerve stimulus (SEP-M). The differences between SEP-LI and SEP-CP might be due to the additional effects of the activation of nerve endings and muscle spindles in LI-4 to the SEPs formed by the activation of superficial and deep radial nerves during electrical acupuncture. The differences between SEPs to acupoint and median nerve stimuli might be mainly due to the different distances from the stimulated regions to the cerebral cortex, the diversity and the number of activated fibers.

Acupuncture Points↗

Intensity-based modal decomposition of optical beams in terms of Hermite-Gaussian functions

We show that when an arbitrary optical beam is decomposed into a superposition of Hermite-Gaussian functions, it is sufficient to record a number of intensity profiles sampled at various transverse planes to uniquely determine the relative modal weights. This result follows from the parity relation and the nature of the Gouy phase, in addition to the orthogonality of the Fourier-transformed intensity profiles associated with the Hermite-Gaussian modes.

Journal Article↗

Promotion of health by soy isoflavones: efficacy, benefit and safety concerns.

Cardiovascular diseases, osteoporosis-related hip fractures, and various cancers of the colon, prostate, uterus, and breast are remarkably less prevalent in Asia than in other industrialized countries. It is believed that the large consumption of soy products in Asian countries is contributory to the reduction of these chronic disorders. Genistein is a major isoflavone found in most soy products and plays an important role in the promotion of human health. Extensive epidemiological, in vitro, and animal studies have been performed, and most studies indicate that genistein has beneficial effects on a multitude of human disorders, including cancers, cardiovascular diseases, osteoporosis, and postmenopausal symptoms. To date, there is an abundance of promising studies supporting genistein's potential uses, but further research is still needed to validate its preventative and therapeutic efficacy. In addition, the adverse effects of genistein have drawn public attention. More studies are required to assess the potential detrimental effect of genistein, and a benefit-risk ratio should be considered before future clinical studies are performed.

Animals↗

Therapeutic developments in peroxisome biogenesis disorders.

Clinically, peroxisome biogenesis disorders (PBDs) are a group of lethal diseases with a continuum of severity of clinical symptoms ranging from the most severe form, Zellweger syndrome, to the milder forms, infantile Refsum disease and rhizomelic chondrodysplasia punctata. PBDs are characterised by a number of biochemical abnormalities including impaired degradation of peroxide, very long chain fatty acids, pipecolic acid, phytanic acid and xenobiotics and impaired synthesis of plasmalogens, bile acids, cholesterol and docosahexaenoic acid. Treatment of PBD patients as a group is problematic since a number of patients, especially those with Zellweger syndrome, have significant neocortical alterations in the brain at birth so that full recovery would be impossible even with postnatal therapy. To date, treatment of PBD patients has generally involved only supportive care and symptomatic therapy. However, the fact that some of the milder PBD patients live into the second decade has prompted research into possible treatments for these patients. A number of experimental therapies have been evaluated to determine whether or not correction of biochemical abnormalities through dietary supplementation and/or modification is of clinical benefit to PBD patients. Another approach has been pharmacological induction of peroxisomes in PBD patients to improve overall peroxisomal biochemical function. Well known rodent peroxisomal proliferators were found not to induce human peroxisomes. Recently, our laboratory demonstrated that sodium 4-phenylbutyrate induces peroxisome proliferation and improves biochemical function (very long chain fatty acid beta-oxidation rates and very long chain fatty acid and plasmalogens levels) in fibroblast cell lines from patients with milder PBD phenotypes. Dietary supplementation and/or modification and pharmacological induction of peroxisomes as treatment strategies for PBD patients will be the subject of this review.

Antineoplastic Agents↗

Pharmacological induction of peroxisomes in peroxisome biogenesis disorders.

Inherited aberrant peroxisome assembly results in a group of neurological diseases termed peroxisome biogenesis disorders (PBDs). PBDs include three major clinical phenotypes that represent a continuum of clinical features from the most severe form, Zellweger syndrome (ZS), through neonatal adrenoleukodystrophy (NALD) to the least severe form, infantile Refsum's disease (IRD). Somatic cell complementation studies have identified 13 PBD complementation groups, each representing a defect in a peroxisomal protein (peroxin) involved in peroxisome biogenesis. Most complementation groups include a range of clinical phenotypes. In this study, peroxisome numbers were determined in fibroblasts from 29 PBD (ZS, NALD, and IRD) patients, with various phenotypes from nine complementation groups, using antibodies against either a peroxisomal membrane protein (anti-Pex14p) or peroxisomal matrix proteins (anti-SKL). A correlation between the number of peroxisomes, determined with either antibody, and PBD phenotype was found, suggesting that induction of peroxisome number might have a favorable effect on PBD. After treatment of PBD fibroblasts with sodium 4-phenylbutyrate, a human peroxisome proliferator, there was an approximate twofold increase in peroxisome number. After 4-phenylbutyrate treatment, an increase in transcription of the adrenoleukodystrophy-related gene and the peroxin gene, PEX11alpha, was found in PBD fibroblasts. In NALD and IRD, but not ZS, fibroblasts there was an increase in very-long-chain fatty acid beta-oxidation and plasmalogen concentrations, and a decrease in very-long-chain fatty acid concentrations. These data suggest that pharmacological agents that induce peroxisome proliferation, such as 4-phenylbutyrate, may have therapeutic potential in the treatment of PBD patients with milder phenotypes (NALD and IRD).

Cells, Cultured↗

Expression of metallothionein in invasive ductal breast cancer in relation to prognosis.

The aim of this study was to assess the presence and clinical significance of metallothionein (MT) in primary invasive ductal carcinoma of the breast. We investigated 96 cases of routinely fixed and paraffin-embedded primary breast carcinomas with the immunohistochemical method. Positive staining for MT was observed in 52.1% of specimen. In most cases both nuclear and cytoplasmic staining was seen. A statistically significant association was found between MT-positive staining and nuclear grade (p < 0.01). MT-positive cases had a significantly poorer prognosis when compared with the MT-negative cases (p < 0.01). We concluded that the MT expression may be of a prognostic value for primary invasive ductal carcinoma of the breast and is possibly an indicator of more aggressive and less differentiated carcinoma cells.

Adult↗