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Biomedical subjects

H Li

Publications and source records attributed to H Li.

At least 127 records · Page 7Linked to original sources
PubMed2004

Detection of nitrated benzene metabolites in bone marrow of B6C3F1 mice treated with benzene.

Benzene, a constituent of cigarette smoke, is a human leukemogen and induces bone marrow toxicity. The mechanism of benzene-induced toxicity is not well-established. We hypothesized that relatively high levels of nitric oxide formed in bone marrow can react with oxygen and/or superoxide anion that is generated during redox cycling of ring-hydroxylated benzene metabolites to yield peroxynitrite as well as other NO-derived intermediates. Peroxynitrite can either directly damage cellular macromolecules or form nitrated toxic metabolites. Toward this end, we investigated whether nitro derivatives of benzene are formed in bone marrow of mice treated with benzene. First, we have characterized products formed during activation of benzene in Fenton's system in the absence or presence of NO-releasing compound in vitro by GC/MS. The result of above experiment prompted us to determine whether similar products can be formed in vivo. Groups of B6C3F1 male mice, eight weeks of age, were given a single intraperitoneal dose of [14C]benzene (400 mg/kg body wt, 9.7 mCi/mmol) or an equal dose of unlabeled benzene in corn oil, and the mice were killed 0.5 or 1 h posttreatment. The control group received only vehicle injections. Organic solvent extractable metabolites from bone marrow, liver, lungs, and blood of mice treated with [14C]benzene were identified by comparison of their respective retention times under two different HPLC conditions with authentic standard samples. These metabolites were further characterized by comparison of their GC/MS properties to those of reference standards. Nitro metabolites, namely, nitrobenzene, nitrobiphenyl, and nitrophenol isomers, were detected in the bone marrow of the mice 1 h after benzene treatment. Formation of nitro derivatives in other tissues was either not observed or was significantly less than that formed in bone marrow. This study clearly demonstrates that nitric oxide is a contributor to benzene metabolism and can form nitrated derivatives that may, in part, account for bone marrow toxicity.

Animals↗
PubMed2004

Recombinant adeno-associated virus-mediated kallikrein gene therapy reduces hypertension and attenuates its cardiovascular injuries.

Gene therapy of hypertension requires long-term expression of a therapeutic gene to achieve stable reduction of blood pressure. Human tissue kallikrein (HK) cleaves kininogen to produce a potent vasoactive peptide kinin, which plays an important role in the regulation of the cardiovascular and renal functions. In the present study, we have delivered human kallikrein cDNA with an rAAV vector to explore the potential therapeutic effects of kallikrein on hypertension and related secondary complications. A single tail vein injection of the rAAV-HK vector into the adult spontaneously hypertensive rats resulted in a significant reduction (12.0+/-2.55 mmHg, P<0.05, n=6, ANOVA) of the systolic blood pressure from 2 weeks after vector injection, when compared with the control rAAV-lacZ vector-injected rats. Weekly blood pressure monitoring showed stable hypertension-reduction effect throughout the course of the 20-week experiments. In addition, total urine microalbumin contents decreased as a result of rAAV-HK treatment. Histological analysis of various tissues showed remarkable amelioration of cardiovascular hypertrophy, renal injury and collagen depositions in the rAAV-treated group. Finally, persistent expression of the transgene product HK was confirmed by the enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. We conclude that rAAV-mediated HK delivery rendered a long-term and stable reduction of hypertension and protected against renal injury, cardiac remodeling in the spontaneously hypertensive rat model. Further studies are warranted for the development of a gene therapy strategy for human hypertension.

Animals↗
PubMed2004

Anthropometric predictors of coronary heart disease in Chinese women.

OBJECTIVE: To evaluate the associations of body size and fat distribution with incidence of coronary heart disease (CHD) in Chinese women. DESIGN: Population-based, prospective cohort study. SUBJECTS: A total of 67 334 women aged 40-70 y, who had no prior history of CHD, stroke, and cancer at study recruitment. MEASUREMENTS: Weight, standing and sitting heights, circumferences of waist and hip, and ratios of the anthropometric measurements. OUTCOME: incidence of CHD (non-fatal myocardial infarction (MI) or fatal CHD). RESULTS: After a mean follow-up of 2.5 y (168 164 person-years), there were 70 incident cases of CHD (49 non-fatal MIs and 21 CHD deaths). Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-standing height ratio (WHtR), waist-to-sitting height ratio (WsHtR), and conicity index were all positively associated with the risk of CHD. With the exception of WHR, all other anthropometric indexes only predicted the risk of CHD among women </=55 y of age at enrollment. The relative risks (RRs) between extreme tertiles of BMI were 9.0 (95% CI, 2.0-41.5; P for trend=0.002) for younger women vs 1.3 (0.6-3.0; P for trend=0.83) for older women. Similarly, the RRs for WC, WHtR, WsHtR, and conicity index were 6.1 (1.8-21.4) vs 1.9 (0.6-5.4), 9.4 (2.6-33.8) vs 1.2 (0.5-3.1), 15.2 (3.3-69.1) vs 1.0 (0.4-2.5), and 7.8 (2.2-28.0) vs 0.9 (0.4-2.3) for the young and elderly, respectively. In contrast, the RR for WHR was 3.2 (1.1-9.1) for the young and 2.9 (1.0-8.4) for the elderly. CONCLUSIONS: WHR was positively associated with the risk of CHD in both younger and older women, while other anthropometrics, including BMI, were related to CHD risk primarily among younger women.

Adult↗
PubMed2004

Fluorescence studies of single biomolecules.

Single-molecule fluorescence has the capability to detect properties buried in ensemble measurements and, hence, provides new insights about biological processes. Ratiometric methods are normally used to reduce the effects of excitation beam inhomogeneity. Fluorescence resonance energy transfer is widely used but there are problems in inserting the fluorophores in the correct position on the biomolecule, particularly if the structure is not known. We have recently developed two-colour coincidence single-molecule fluorescence that addresses this problem. This method can be used to determine quantitatively the multimerization states of biomolecules, in solution without separation. The future prospects of single-molecule fluorescence as applied to biological molecules are discussed.

Fluorescence Resonance Energy Transfer↗
PubMed2004

A new single nucleotide polymorphism in the chicken pituitary-specific transcription factor (POU1F1) gene associated with growth rate.

The pituitary-specific transcription factor (POU1F1) is a protein which binds to and transactivates promoters of growth hormone (GH), prolactin (PRL) and thyroid-stimulating hormone chain (TSHB)-encoding genes. Ten chicken populations (n = 662), including six Chinese indigenous breeds, White Leghorn, paternal/maternal lines of brown egg layer and a paternal line of broiler, were used to detect single nucleotide polymorphisms in the pituitary-specific transcription factor gene (PIT1) by means of PCR-SSCP. A nucleotide transversion from adenine (A) to thymidine (T) at position 980 of the open reading frame of the PIT1 cDNA (GenBank accession no. AF029892) was identified. This nucleotide transversion results in an alteration of codon 299 from AAC to ATC, which leads to a change from asparagine (Asn) to isoleucine (Ile) in the POU domain of POU1F1. The distribution of allele and genotype frequencies differed significantly between meat-type chickens (higher frequencies of A and A/A) and layer-type chickens (P < 0.01). Another experimental population with growth records was used to evaluate the relationship between this polymorphism and growth rate. The results revealed a positive relationship between genotype A/A and body weight at 8 weeks of age, indicating that the SNP in PIT1 gene is a potential molecular marker for early growth rate in chicken.

Animals↗
PubMed2004

Assessing health-related quality-of-life in individuals with haemophilia in China.

Haemophilia is a group of inherited, congenital diseases present all through the life. Those disorders are associated with a chronic burden of morbidity punctuated by episodes of acute deterioration in health-related quality-of-life (HR-QL). The significances of assessing HR-QL in individuals with haemophilia as an important component of the clinical database have gained increasing recognition in recent years. To the best of our knowledge, reports on the HR-QL of Chinese patients with haemophilia are not available. The purpose of this paper was to assess the HR-QL of patients with haemophilia in China. In order to do this, 179 patients with haemophilia (age 16-70) were mailed China quality-of-life questionnaire, which was designed specially for this study taking into account the culture characters of Chinese. Compared with the normal male general population, individuals with haemophilia experienced significantly lower levels of HR-QL and within the subgroups of patients, there was a gradation of HR-QL from mild < moderate < severe haemophilia patients. Age, clinical severity, degree of arthropathy, hepatitis status, salary and mean annual expenditure for replacement therapy were predictors of HR-QL. Clinical severity of the disease manifestation rather than the severity of the disease based on molecular classification was a factor that negatively influenced the HR-QL of patients with haemophilia. Arthropathies of patients with haemophilia in China were more severe than that in western countries because of the poorer medical care and were associated with their lower income and therapy cost. A large number of patients never had hepatitis or HIV serological examination. The exact prevalence of hepatitis and HIV was difficult to obtain and the HR-QL of hepatitis and HIV positive patients required further study.

Adolescent↗
PubMed2004

Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products.

BACKGROUND AND OBJECTIVES: Human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. Recent outbreaks of emergent viral pathogens, such as West Nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma-derived products. The purpose of this study was to evaluate the efficacy of current viral inactivation methods for West Nile and vaccinia viruses and to reassess the use of model viruses to predict inactivation of similar viral pathogens. MATERIALS AND METHODS: Virus-spiked product intermediates were processed using a downscaled representation of various manufacturing procedures. Virus infectivity was measured before and after processing to determine virus inactivation. RESULTS: The results demonstrated effective inactivation of West Nile virus, vaccinia virus and a model virus, bovine viral diarrhoea virus, during pasteurization, solvent/detergent treatment and caprylate treatment. Caprylate provided rapid and effective inactivation of West Nile virus, vaccinia virus, duck hepatitis B virus and Sindbis virus. Inactivation of West Nile virus was similar to that of bovine viral diarrhoea virus. CONCLUSIONS: This study demonstrates that procedures used to inactivate enveloped viruses in manufacturing processes can achieve inactivation of West Nile virus and vaccinia virus. In addition, the data support the use of model viruses to predict the inactivation of similar emergent viral pathogens.

Animals↗
PubMed2004

Effects of several Chinese herbal aqueous extracts on human sperm motility in vitro.

The effects of six kinds of aqueous extracts of Chinese herbal medicine (Astragalus membranaceus, Acanthopanacis senticosi, Panax genseng and Ophiopogon japonicus, P. genseng and Aconitum carmichaeli, Salviae miltiorrhiae, Polyporus umbellatus polysaccharide) on sperm motility characteristics of 30 infertile male volunteers were studied in vitro with a computer-assisted sperm analysis at 15, 60 and 180 min after incubated with the drugs. The results showed that per cent viability, number of progressive motile spermatozoa, curvilinear velocity, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. membranaceus (P < 0.05 or < 0.01), per cent viability, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. senticosi (P < 0.05), but all the above were not affected by P. genseng and O. japonicus, P. genseng and A. carmichaeli, S. miltiorrhiae and P. umbellatus polysaccharide. It is suggested that A. membranaceus and A. senticosi can enhance the motility of human spermatozoa in vitro.

Drugs, Chinese Herbal↗
PubMed2004

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Base Sequence↗
PubMed2004

Discovery of binding motif pairs from protein complex structural data and protein interaction sequence data.

Unravelling the underlying mechanisms of protein interactions requires knowledge about the interactions' binding sites. In this paper, we use a novel concept, binding motif pairs, to describe binding sites. A binding motif pair consists of two motifs each derived from one side of the binding protein sequences. The discovery is a directed approach that uses a combination of two data sources: 3-D structures of protein complexes and sequences of interacting proteins. We first extract maximal contact segment pairs from the protein complexes' structural data. We then use these segment pairs as templates to sub-group the interacting protein sequence dataset, and conduct an iterative refinement to derive significant binding motif pairs. This combination approach is efficient in handling large datasets of protein interactions. From a dataset of 78,390 protein interactions, we have discovered 896 significant binding motif pairs. The discovered motif pairs include many novel motif pairs as well as motifs that agree well with experimentally validated patterns in the literature.

Amino Acid Motifs↗
PubMed2004

The prognostic significance of thymidine phosphorylase, thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expressions in breast carcinomas.

Thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been indicated as possible predictive markers for epithelial malignancies. All these three enzymes are actively involved in 5-FU metabolism. In this report, we investigated mRNA expression of these factors with real-time quantitative PCR in a series of 86 micro-selected breast carcinomas and 8 micro-selected tumour-adjacent normal breast epithelial specimens. Highly variable mRNA expressions of these factors were observed in both normal and cancerous samples. TP and TS mRNA expressions in breast carcinomas were elevated, but only TS mRNA expression showed a trend for statistical difference, compared with the expression in normal breast epithelial samples. Although the DPD mRNA expression range in tumours was also elevated, the average mean was reduced in tumours compared to that in normal samples. No association between mRNA expressions of TP, TS and DPD and clinicopathological features such as histological grade, tumour size, node status, S-phase fraction, ploidy, and clinical stage was found. A negative association between DPD mRNA expression and age was, however, revealed. Ten-year follow-up analysis showed no association between TP and DPD mRNA expression and clinical outcome. An high level of TS mRNA expression, however, was associated with a shorter clinical survival, indicating its potential role as a clinical marker in breast carcinoma.

Adult↗
PubMed2003

Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.

Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By 1 month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.

Animals↗
PubMed2003

Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal studies.

We present a high-sensitivity near-infrared optical imaging system for noninvasive cancer detection and localization based on molecularly labeled fluorescent contrast agents. This frequency-domain system utilizes the interferencelike pattern of diffuse photon density waves to achieve high detection sensitivity and localization accuracy for the fluorescent heterogeneity embedded inside the scattering media. A two-dimensional localization map is obtained through reflectance probe geometry and goniometric reconstruction. In vivo measurements with a tumor-bearing mouse model by use of the novel Cypate-mono-2-deoxy-glucose fluorescent contrast agent, which targets the enhanced tumor glycolysis, demonstrate the feasibility of detection of a 2-cm-deep subsurface tumor in the tissuelike medium, with a localization accuracy within 2-3 mm.

Animals↗
PubMed2003

The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase.

The breast cancer-associated T2A10 clone was originally isolated from a cDNA library enriched for tumour messenger ribonucleic acids. Our survey of 125 microarrayed primary tumour tissues using affinity purified polyclonal antibodies has revealed that corresponding protein is overexpressed in invasive breast cancer and is weakly expressed in kidney and prostate tumours. Now known as RNF11, the gene encodes a RING-H2 domain and a PY motif, both of which mediate protein-protein interactions. In particular, the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFbeta receptor complex. Using various mutants of RNF11 in GST pulldown and immunoprecipitation assays, we found that RNF11 interacts with Smurf2 through the PY motif, leading to ubiquitination of both proteins. Smurf2 plays an active role in the repression of TGFbeta signalling, and our data indicate that overexpression of RNF11, through its interaction with Smurf2, can restore TGFbeta responsiveness in transfected cells.

Breast Neoplasms↗
PubMed2003

Suppressor of cytokine signalling gene expression is elevated in breast carcinoma.

Cytokines are important for breast cell function, both as trophic hormones and as mediators of host defense mechanisms against breast cancer. Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines. We examined the expression of SOCS genes in 17 breast carcinomas and 10 breast cancer lines, in comparison with normal tissue and breast lines. We report elevated expression of SOCS-1-3 and CIS immunoreactive proteins within in situ ductal carcinomas and infiltrating ductal carcinomas relative to normal breast tissue. Significantly increased expression of SOCS-1-3 and CIS transcripts was also shown by quantitative in situ hybridisation within both tumour tissue and reactive stroma. CIS transcript expression was elevated in all 10 cancer lines, but not in control lines. However, there was no consistent elevation of other SOCS transcripts. CIS protein was shown by immunoblot to be present in all cancer lines at increased levels, mainly as the 47 kDa ubiquitinylated form. A potential proliferative role for CIS overexpression is supported by reports that CIS activates ERK kinases, and by strong induction in transient reporter assays with an ERK-responsive promoter. The in vivo elevation of SOCS gene expression may be part of the host/tumour response or a response to autocrine/paracrine GH and prolactin. However, increased CIS expression in breast cancer lines appears to be a specific lesion, and could simultaneously shut down STAT 5 signalling by trophic hormones, confer resistance to host cytokines and increase proliferation through ERK kinases.

Breast Neoplasms↗