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Biomedical subjects

H Li

Publications and source records attributed to H Li.

At least 865 records · Page 48Linked to original sources
PubMed1999

Growth hormone as a cytokine.

1. The growth hormone (GH) receptor was the first of the class 1 cytokine receptors to be cloned. It shares a number of structural characteristics with other family members and common signalling mechanisms based on common usage of the Janus kinase 2 (JAK2). 2. Growth hormone receptor activation is initiated by GH-induced homodimerization of receptor molecules. This has enabled the creation of specific hormone antagonists that block receptor dimerization. 3. The details of the transcription factors used by the activated receptor are being revealed as a result of promoter analyses and electrophoretic mobility gelshift analysis. 4. Growth hormone receptors are widespread and their discovery in certain tissues has led to the assignment of new physiological roles for GH. Some of these involve local or paracrine roles for GH, as befits its cytokine status. 5. Four examples of such novel roles are discussed. These are: (i) the brain GH axis; (ii) GH and the vitamin B12 axis; (iii) GH in early pre-implantation development; and (iv) GH in development of the tooth. 6. We propose that the view that GH acts through the intermediacy of insulin-like growth factor-1 is simplistic; rather, GH acts to induce an array of growth factors and their receptors and the composition of this array varies with tissue type and, probably, stage of development.

Animals↗
PubMed1999

Inhibition of intimal lipid deposition in human apolipoprotein A1 transgenic mice.

1. Southern blot confirmed the emergence of the human apolipoprotein A1 (h-apoA1) gene (four to 15 copies) in newborn transgenic mice. The inheritance pattern of h-apoA1 transgene in three generations of progeny was compatible with a single autosomal integration site. 2. Northern blot showed h-apoA1 mRNA expressed mainly in liver, kidney and aorta. The total plasma apoA1 (murine plus human) level was significantly increased to 58 and 118 in transgenic mice without or under zinc induction, respectively. The majority was h-apoA1. Plasma lecithin:cholesterol acyltransferase activity was positively correlated with h-apoA1 levels in transgenic mice (r = 0.43; P < 0.01). 3. After a high cholesterol intake for 14 weeks, the incidence of fatty streak at the aortic sinus was 40% in transgenic mice and 80% in controls. Expression of platelet-derived growth factor-B, c-myc and c-fos proteins was much weaker in smooth muscle cells at the aortic sinus in transgenic mice.

Animals↗
PubMed1999

Regrowth of axons into the distal spinal cord through a Schwann-cell-seeded mini-channel implanted into hemisected adult rat spinal cord.

Schwann cells (SCs) have been shown to be a key element in promoting axonal regeneration after being grafted into the central nervous system (CNS). In the present study, SC-supported axonal regrowth was tested in an adult rat spinal cord implantation model. This model is characterized by a right spinal cord hemisection at the eighth thoracic segment, implantation of a SC-containing mini-channel and restoration of cerebrospinal fluid circulation by suturing the dura. We demonstrate that a tissue cable containing grafted SCs formed an effective bridge between the two stumps of the hemicord 1 month after transplantation. Approximately 10 000 myelinated and unmyelinated axons (1 : 9) per cable were found at its midpoint. In addition to propriospinal axons and axons of peripheral nervous system (PNS) origin, axons from as many as 19 brainstem regions also grew into the graft without additional treatments. Most significantly, some regenerating axons in the SC grafts were able to penetrate through the distal graft-host interface to re-enter the host environment, as demonstrated by anterograde axonal labelling. These axons coursed toward, and then entered the grey matter where terminal bouton-like structures were observed. In channels containing no SCs, limited axonal growth was seen within the graft and no axons penetrated the distal interface. These findings further support the notion that SCs are strong promotors of axonal regeneration and that the mini-channel model may be appropriate for further investigation of axonal re-entry, synaptic reconnection and functional recovery following spinal cord injury.

Animals↗
PubMed1999

The additive genetic gamma frailty model for linkage analysis of age-of-onset variation.

Age of onset is a key factor in the linkage analysis of many complex diseases. Current methods in nonparametric linkage analysis are mainly concentrated on the affected relative pairs or affected family members with age of onset information either ignored or taken into account by specifying age-dependent penetrances for liability classes. On the other hand, gamma frailty models were developed in the biostatistics literature to model familial aggregation of age of onset. However, these frailty models cannot be used directly for linkage analysis. This paper extends the gamma frailty model by incorporating inheritance vector information and provides a semiparametric approach for linkage testing. For a given inheritance vector at the putative disease locus, we construct an additive genetic gamma frailty for each individual within a nuclear family and use the Cox proportional hazard model to model age of onset. We derive the conditional hazard ratio parameter for sib pairs and define a likelihood ratio based LOD score statistic under our model. The EM algorithm is used for estimating the parameters and the maximum likelihood functions. Simulated data sets are used to illustrate these new statistical methods.

Age Factors↗
PubMed1999

p53 induction by tumor necrosis factor-alpha and involvement of p53 in cell death of human oligodendrocytes.

Oligodendrocytes (OLs) and their myelin membranes are the primary targets in the autoimmune disease multiple sclerosis (MS). The inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated as a mediator of OL cell injury. TNF-alpha is detectable within MS lesions and induces apoptosis of mature human OLs in vitro. One possible mechanism by which TNF-alpha mediates cell death is through the activation of c-jun N-terminal kinase (JNK). We have previously shown that treatment of human OLs with TNF-alpha leads to activation of JNK. Here we provide evidence that p53, a regulator of the cell cycle and apoptosis, is a mediator of TNF-alpha-induced apoptosis of OLs. Although p53 was undetectable by western blot analysis in adult human OLs, its levels increased within 24 h after TNF-alpha treatment (100 ng/ml). The induced p53 was immunolocalized to the nucleus prior to the appearance of significant numbers of apoptotic cells. Overexpression of p53 by adenovirus-mediated gene transfer into human OLs in vitro resulted in marked apoptosis as revealed by in situ cleavage of DNA (TUNEL positive), decreased mitochondrial function, and release of lactate dehydrogenase into the culture medium. These in vitro studies demonstrate that increased p53 levels are associated with apoptosis of human OLs. The findings further implicate p53 as a target for the JNK pathway activated during TNF-alpha-mediated cell death of human adult OLs.

Adenoviridae↗
PubMed1999

EGF promotes development of a differentiated trophoblast phenotype having c-myc and junB proto-oncogene activation.

Human placental cytotrophoblast cells differentiate by a process of fusion into a syncytium. This process is stimulated by EGF but also occurs spontaneously at a slower rate in cultured cytotrophoblast cells. To determine nuclear proto-oncogene changes mediating these events, c-myc, c-fos, c-jun and junB were measured in spontaneously differentiating cells and in cells exposed to EGF. c-myc showed a transient rise in expression at 4-8 h with augmented expression by EGF, occurring even in the absence of serum or attachment. c-myc and c-jun declined during culture, but c-fos and particularly junB showed increased expression by day 3 with marked responses to EGF stimulation. Syncytia induced to form by EGF exposure for 48 h demonstrated marked junB expression after rechallenge with 40 min EGF exposure, but negligible responses of c-fos and c-jun. c-myc showed increased expression after 6 h EGF exposure throughout the culture period and in syncytia. The results indicate EGF promotes a syncytial phenotype characterized by c-fos and junB expression during syncytial formation. EGF continues to elicit junB and c-myc responsiveness in more mature syncytium, indicative of continued EGF actions which may include acting as a survival factor, as an hCG secretagogue, and as an inducer of continued development of the syncytium.

Cell Adhesion↗
PubMed1999

Changing sexual attitudes and behaviour in China: implications for the spread of HIV and other sexually transmitted diseases.

In Imperial China sexual behaviour was regarded as an indispensable activity to reach harmony with the universe, through the unity of the interaction of two opposing forces: yin and yang. Sexual intercourse was accepted when linked to procreation within a family context, while an individual's sexuality was not considered important. Homosexuality was tolerated although not advocated, while masturbation was denounced. Since the One Child Family and Open Door policies in the 1970s and the economic reforms of the 1980s, attitudes towards sexuality in China have changed. Premarital sex has become widely accepted among young people and people in China are now more tolerant toward extramarital sex. Nowadays young people consider that love should dominate marriage and the quality of an individual's sex life is currently more valued than it used to be. Attitudes towards masturbation have become more tolerant and though homosexuality has been hidden by society for a long time, in recent years it has begun to be considered as a legitimate lifestyle choice. Attitudes towards sex and sexual behaviour have become recognized as an individuals' responsibility as long as no offence occurs against society or the interests of other individuals, resulting in the recognition of diversity of sexual behaviour. As part of the changing attitudes to sex and sexual behaviour, heterosexual transmission is becoming the most important route of HIV transmission in China. This is complicated by the internal migration of an estimated 120 million labourers moving from the countryside to the cities as the result of economic reforms, most of whom are sexually active young men. Unless addressed directly, these factors may add to the estimated 300,000 HIV-infected Chinese, further fuelling an already rapidly spreading epidemic. The ramifications of the Chinese HIV epidemic will not only be felt within China, but also within the surrounding Asian countries thereby fuelling the HIV pandemic.

Attitude to Health↗
PubMed1999

Prevention by aspirin and its combination with alpha-difluoromethylornithine of azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E2 levels in rat colon.

The dose-response relationship in male F344 rats was determined for the ability of aspirin administered in the diet to prevent azoxymethane (AOM)-induced colon cancer and aberrant crypt foci (ACF) and to reduce prostaglandin E2 (PGE2) levels. Starting at either 7 or 22 weeks of age, the rats received aspirin. All rats received two doses of AOM (15 mg/kg each on days 7 and 14) and were killed on day 36. The lowest concentrations of aspirin to prevent ACF or reduce PGE2 levels were 600 and 400 mg/kg, respectively. To evaluate the prevention of tumors, rats received either 0 or 400 mg/kg aspirin for a total of 39 weeks with AOM (30 mg/kg) administered 7 days after the start of treatment. Aspirin had no effect on the yield of colon tumors. In a second experiment, rats started to receive 0, 200, 600 or 1800 mg/kg aspirin or 1000 mg/kg alpha-difluoromethylornithine (DFMO) +/- aspirin. Eight and 15 days later, all the rats received 15 mg/kg AOM. Eleven weeks later, animals that were receiving the control diet started to receive 0, 200, 600 or 1800 mg/kg aspirin; 1000 or 3000 mg/kg DFMO; or 1000 mg/kg DFMO + 200 or 600 mg/kg aspirin. The animals were killed 32 weeks later. DFMO effectively reduced the yield of colon tumors when administered starting either before or after AOM while aspirin was much weaker. The combination of aspirin + DFMO administered after AOM was synergistic. Both aspirin and DFMO decreased the Mitotic Index, while apoptosis was increased only by DFMO. Our results demonstrated that aspirin and DFMO could prevent colon cancer when administered after AOM. Furthermore, aspirin reduced ACF, PGE2 levels and mitosis at concentrations that did not prevent cancer. In contrast, the ability to enhance apoptosis did correlate with the prevention of cancer.

Animals↗
PubMed1999

Determination of the urinary benzene metabolites S-phenylmercapturic acid and trans,trans-muconic acid by liquid chromatography-tandem mass spectrometry.

To investigate how various levels of exposure affect the metabolic activation pathways of benzene in humans and to examine the relationship between urinary metabolites and other biological markers, we have developed a sensitive and specific liquid chromatographic-tandem mass spectrometric assay for simultaneous quantitation of urinary S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA). The assay involves spiking urine samples with [13C6]S-PMA and [13C6]t,t-MA as internal standards and clean up of samples by solid-phase extraction with subsequent analysis by liquid chromatography coupled with electrospray-tandem mass spectrometry-selected reaction monitoring (LC-ES-MS/MS-SRM) in the negative ionization mode. The efficacy of this assay was evaluated in human urine specimens from smokers and non-smokers as the benzene-exposed and non-exposed groups. The coefficient of variation of runs on different days (n = 8) for S-PMA was 7% for the sample containing 9.4 microg S-PMA/l urine, that for t,t-MA was 10% for samples containing 0.07 mg t,t-MA/l urine. The mean levels of urinary S-PMA and t,t-MA in smokers were 1.9-fold (P = 0.02) and 2.1-fold (P = 0.03) higher than those in non-smokers. The mean urinary concentration (+/-SE) was 9.1 +/- 1.7 microg S-PMA/g creatinine [median 5.8 microg/g, ranging from not detectable (1 out of 28) to 33.4 microg/g] among smokers. In non-smokers' urine the mean concentration was 4.8 +/- 1.1 microg S-PMA/g creatinine (median 3.6 microg/g, ranging from 1.0 to 19.6 microg/g). For t,t-MA in smokers' urine the mean (+/-SE) was 0.15 +/- 0.03 mg/g creatinine (median 0.11 mg/ g, ranging from 0.005 to 0.34 mg/g); the corresponding mean value for t,t-MA concentration in non-smokers' urine was 0.07 +/- 0.02 mg/g creatinine [median 0.03 mg/g, ranging from undetectable (1 out of 18) to 0.48 mg/g]. There was a correlation between S-PMA and t,t-MA after logarithmic transformation (r = 0.41, P = 0.005, n = 46).

Acetylcysteine↗
PubMed1999

Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice.

How aggregates of polyglutamine proteins are involved in the neurological symptoms of glutamine repeat diseases is unknown. We show that huntingtin aggregates are present in the neuronal processes of transgenic mice that express exon 1 of the Huntington's disease (HD) gene. Unlike aggregates in the nucleus, these neuropil aggregates are usually smaller and are not ubiquitinated. Electron microscopy reveals many neuropil aggregates in axons and axon terminals. Huntingtin aggregates in the axon terminal are co-localized with some synaptic vesicles, implying that they may affect synaptic transmission and neuronal communication. The formation of neuropil aggregates is highly correlated with the development of neurological symptoms. The present study raises the possibility that neuropil aggregates may cause a dysfunction in neuronal communication and con-tribute to the neurological symptoms of HD.

Animals↗
PubMed1999

A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to standard care for the relief of pain and dysfunction in elderly patients with osteoarthritis (OA) of the knee. METHODS: Seventy-three patients with symptomatic OA of the knee were randomly assigned to treatment (acupuncture) or standard care (control). Analysis was performed on last score carried forward to account for patients who dropped out before completion. Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne indices at baseline and at 4, 8 and 12 weeks. Patients in the control group were offered acupuncture treatment after 12 weeks. The data for these patients are pooled with those from the original acupuncture group for within-group analysis. RESULTS: Patients randomized to acupuncture improved on both WOMAC and Lequesne indices compared to those who received standard treatment alone. Significant differences on total WOMAC Scale were seen at 4 and 8 weeks. There appears to be a slight decline in effect at 4 weeks after cessation of treatment (12 weeks after first treatment). No adverse effects of acupuncture were reported. CONCLUSION: These data suggest that acupuncture is an effective and safe adjunctive therapy to conventional care for patients with OA of the knee.

Acupuncture Analgesia↗
PubMed1999

Indefatigable CA1 sector neuroprotection with mild hypothermia induced 6 hours after severe forebrain ischemia in rats.

Considerable controversy exists about whether postischemic hypothermia can permanently salvage hippocampal CA1 neurons or just postpone injury. Studies of very brief cooling in rat have found transient benefit, whereas experiments in gerbil using protracted hypothermia report lasting protection. This discrepancy might be because of the greater efficacy of longer cooling or it might, for example, represent an important species difference. In the present study, a 48-hour period of mild hypothermia was induced starting 6 hours after 10 minutes of severe four-vessel occlusion ischemia in rats. Untreated normothermic ischemia resulted in total CA1 cell loss (99%), whereas delayed hypothermia treatment reduced neuronal loss to 14% at a 28-day survival. In unregulated rats, brain temperature spontaneously fell during ischemia, and stayed subnormal for an extended period after ischemia. This mild cooling resulted in more variable and less severe CA1 injury (75%). Finally, vertebral artery cauterization under halothane anesthesia caused an approximately 2 degrees C drop in brain temperature for 1 hour, but prevention of this hypothermia did not significantly affect CA1 damage. In summary, protracted postischemic hypothermia provided robust and long-term CA1 protection in rat. These results encourage the clinical assessment of prolonged hypothermia and its use as a model to understand ischemic CA1 injury.

Animals↗
PubMed1999

Growth factors and extracellular signal-regulated kinase in vascular smooth muscle cells of normotensive and spontaneously hypertensive rats.

OBJECTIVE: Transforming growth factor-beta1 (TGF-beta1) stimulates vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR), but inhibits cell growth in normotensive Wistar- Kyoto (WKY) rats. The present study was undertaken to test the hypothesis that TGF-beta1 might differentially modulate the activities of mitogen-activated protein (MAP) kinase family members (ERK, JNK and p38) in vascular smooth muscle cells of SHR and WKY rats. METHODS: MAP kinase activity was measured from cultured vascular smooth muscle cells in response to TGF-1 by specific substrate phosphorylation of myelin basic protein, GST-c-Jun and GST-ATF2. RESULTS: Exposure of cultured vascular smooth muscle cells from SHR or WKY rats to TGF-beta1 resulted in a marked increase in the activity of ERK, but not of JNK or p38. The increase of ERK activity stimulated by TGF-beta1 appeared similar in time course and extent in both WKY and SHR cells, with increased activity peaking at 15 min of incubation. Epidermal growth factor (EGF) also stimulated the activity of ERK, in both WKY and SHR cells, but nor of JNK or p38, with stimulation of ERK activity by EGF occurring more rapidly in SHR cells than in those from WKY rats. Co-incubation of SHR cells with TGF-beta1 and EGF showed additive effect on ERK activity. CONCLUSIONS: The results provide the first evidence that TGF-beta1 activates ERK in vascular smooth muscle cells of both normotensive and hypertensive rats. The matching response of ERK activation to TGF-1 in SHR cells suggests that the MAP kinase-signaling pathway remains largely unchanged in the regulation of vascular smooth muscle growth by TGF-1 in spontaneously hypertensive rats.

Animals↗
PubMed1999

Cocaine induced apoptosis in rat testes.

PURPOSE: Exposure of rats to chronic cocaine results in disruption of spermatogenesis including reduction of germ cells. However, the cellular mechanism responsible for the testicular damage in testes is still unknown. We have studied the role of apoptosis in cocaine induced testicular damage. MATERIALS AND METHODS: Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg./kg. body weight) subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed at 15, 30, 60, and 90 days of cocaine administration. In situ detection of germ cells with DNA strand breaks in paraffin-embedded testicular section (5 microm.) was achieved by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labeling (TUNEL) method. DNA fragmentation was also determined by gel electrophoresis. RESULTS: Apoptotic cells were found in the spermatocytes and spermatogonia of germinal epithelium. Less than 7% of seminiferous tubule cross sections showed a high level of apoptosis (> or =3 apoptotic cells per tubule) in control animals compared with experimental group where 25% of the tubules showed a high level of apoptosis (p<0.05). The number of apoptotic cells was significantly increased by 15 days, peaked at 30 days and persisted up to 90 days of cocaine exposure when compared with controls (p<0.05). DNA isolated from the cocaine treated testes displayed a clear ladder pattern whereas the DNA from controls did not. CONCLUSIONS: The experimental results presented here suggest that cocaine exposure leads to significant apoptosis in rat testes and the mechanism of cocaine induced testicular injury may be related to the induction of apoptosis.

Animals↗
PubMed1999

Relationship of human papillomavirus to Schneiderian papillomas.

OBJECTIVES/HYPOTHESIS: To classify a large group of Schneiderian papillomas (SPs) into their histologic subtypes and to determine the incidence of human papillomavirus (HPV) in each subtype. STUDY DESIGN: Pathologic review and polymerase chain reaction-based (PCR-based) examination of archived tissue. METHODS: Slides of 114 tumors diagnosed as Schneiderian, inverting, fungiform, or cylindric cell papillomas, or any associated carcinomas, were examined by a head and neck pathologist. Using PCR, consensus primers for the L1 region of HPV were used to determine the presence of HPV in the tumors. This was also performed on normal turbinate control specimens. RESULTS: Eighty-two (78%) were the inverting subtype, 21 (20%) the fungiform subtype, and 2 (2%) the cylindric cell type. Nine tumors were diagnosed as either verrucous or squamous cell carcinoma. Eighty-eight percent of the tumors had DNA of sufficient quality to be amplified using PCR. Of these, 5 of 69 (6.8%) inverting, 17 of 17 (100%) fungiform, and 0 of 2 cylindric cell papillomas were positive for HPV. One of nine (11.1%) cancers was positive for HPV. No normal turbinate tissue contained HPV. HPV types 6b and 11 accounted for all cases of fungiform papillomas. Of the five HPV-positive inverting papillomas, three had HPV type 11 and two had HPV type 16. The single carcinoma containing HPV contained HPV type 18. CONCLUSIONS: The histologic subtype of SPs is important, as their etiologies appear to be different. HPV 6b and 11 appear to be involved in all cases of fungiform papillomas but are only rarely involved in cases of inverting or cylindric cell papillomas. HPV 16 may rarely play a role in cases of inverting papillomas, and HPV 16 and 18 may be involved in a subset of cases of carcinomas originating in an inverting papilloma.

DNA, Neoplasm↗
PubMed1999

A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis.

Recent studies have reported and provided nucleotide sequence data from divergent isolates of hepatitis E virus (HEV), including isolates from North America and Africa. Sera were investigated from 29 Chinese patients with a diagnosis of acute hepatitis and who were negative for hepatitis viruses A-E by serology (HEV was excluded by testing for IgG antibody only). To determine whether some patients were infected with HEV but had yet to seroconvert to antibody positivity, RT-PCR was carried out with primers designed within conserved sequences of the HEV open reading frame (ORF) 1 and ORF2 regions. Fifteen patients were found to harbour sequences related to HEV. Analysis of the HEV products revealed that nucleotide sequences from nine of the sera closely matched Burmese-like HEV sequences (more than 92% nucleotide identity across ORF1 and 88% in ORF2). The remaining six HEV isolates were similar to each other but divergent from all other known HEV sequences (74 to 83% nucleotide identity in ORF1 or ORF2). Phylogenetic analysis suggests that the six divergent isolates represent a fourth genotype of HEV, distinct from the previously described Burmese, Mexican and United States variants (genotypes 1, 2 and 3). This novel variant, referred to here as the Chinese genotype (genotype 4), may be responsible for a significant proportion of cases of acute hepatitis in China, as seen by the fact that 40% of the HEV-infected patients in this study were genotype 4 positive.

Acute Disease↗
PubMed1999

Control of pollen tube tip growth by a Rop GTPase-dependent pathway that leads to tip-localized calcium influx.

We have shown that Rop1At, a pollen-specific Rop GTPase that is a member of the Rho family of small GTP binding proteins, acts as a key molecular switch controlling tip growth in Arabidopsis pollen tubes. Pollen-specific expression of constitutively active rop1at mutants induced isotropic growth of pollen tubes. Overexpression of wild-type Arabidopsis Rop1At led to ectopic accumulation of Rop1At in the plasma membrane at the tip and caused depolarization of pollen tube growth, which was less severe than that induced by the constitutively active rop1at. These results indicate that both Rop1At signaling and polar localization are critical for controlling the site of tip growth. Dominant negative rop1at mutants or antisense rop1at RNA inhibited tube growth at 0.5 mM extracellular Ca(2+), but growth inhibition was reversed by higher extracellular Ca(2+). Injection of anti-Rop antibodies disrupted the tip-focused intracellular Ca(2+) gradient known to be crucial for tip growth. These studies provide strong evidence for a Rop GTPase-dependent tip growth pathway that couples the control of growth sites with the rate of tip growth through the regulation of tip-localized extracellular Ca(2+) influxes and formation of the tip-high intracellular Ca(2+) gradient in pollen tubes.

Arabidopsis↗