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Biomedical subjects

G Li

Publications and source records attributed to G Li.

At least 505 records · Page 28Linked to original sources

[A study of correlation between essential hypertension and HLA-DQA1 alleles].

OBJECTIVE: To analyse the hereditary susceptibility by genotyping of HLA-DQA1 alleles in essential hypertensives. METHODS: The allelic types of HLA-DQA1 were detected by PCR-SSP technic in 52 cases of essential hypertensives and 86 normal individuals as the control. RESULTS: The frequency of HLA-DQA1*0302 allele in hypertensive group was markedly higher than that in normal control group (17.9572 vs 3.5531), but the frequency of HLA-DQA1*0103 allele in normal group was higher than that in hypertensive group. CONCLUSION: HLA-DQA1*0302 may be a correlative gene of essential hypertension, whereas HLA-DQA1*0103 may be a defence gene of hypertension.

Adult↗

Separation and quantitation of monoclonal antibodies in cell growth medium using capillary zone electrophoresis.

IgG1 is separated from its impurities in cell growth medium under simple CZE conditions without specific sample pretreatment. Linearity, limit of quantitation, limit of detection, precision and accuracy for the method are demonstrated. The quantitation for IgG1 in the cell growth medium is obtained by generating a calibration curve and by using standard additions. This CE method can offer a good alternative to conventional HPLC methods. Attempts are also made to separate the heterogeneous species in monoclonal antibodies using both CZE and MECC.

Antibodies, Monoclonal↗

The C-truncated delta-opioid receptor underwent agonist-dependent activation and desensitization.

The agonist-dependent activation and desensitization of a recombinant analog of delta-opioid receptor lacking the carboxyl-terminal (C-terminal) 31 residue peptide segment were discussed. The cDNA of the C-truncated delta-opioid receptor was created by polymerase chain reaction (PCR), stably expressed in Chinese hamster ovary cells and characterized by binding assay and function assay. Agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) stimulated the specific [35S]GTPgammaS binding to membrane fragments of cells expressing the C-truncated and the wild-type delta-opioid receptors in different levels dose-dependently. EC50 values of DPDPE on truncated and wild-types in stimulation were very similar. Agonist-dependent desensitization, which could be blocked by protein kinase inhibitor staurosporine (Stau), was observed after pretreating truncated receptors with 1 microM DPDPE for 10 min, the same as wild-types. The results reveal that the C-terminal of the delta-opioid receptor is not involved in controlling the G-protein activation and phosphorylation-related functional desensitization.

Animals↗

FTIR study of the thermal denaturation of alpha-actinin in its lipid-free and dioleoylphosphatidylglycerol-bound states and the central and N-terminal domains of alpha-actinin in D2O.

Fourier transform infrared (FTIR) spectroscopy has been carried out to investigate the thermal denaturation of alpha-actinin and its complexes with dioleoylphosphatidylglycerol (DOPG) vesicles. The amide I regions in the deconvolved spectra of alpha-actinin in the lipid-free and DOPG-bound states are both consistent with predominantly alpha-helical secondary structure below the denaturation temperatures. Studies of the temperature dependence of the spectra revealed that for alpha-actinin alone the secondary structure was unaltered up to 40 degrees C. But, in the presence of DOPG vesicles, the thermal stability of the secondary structure of alpha-actinin increased to 55 degrees C. The thermal denaturation mechanisms of the lipid-free and DOPG-bound states of alpha-actinin also vary. The secondary structure of the lipid-free alpha-actinin changed to be predominantly unordered upon heating to 65 degrees C and above. Whereas, the original alpha-helical structure in the DOPG-bound alpha-actinin retained even at 70 degrees C, the highest temperature we examined. Analysis of the reduction in amide II intensities, which is due to peptide H-D exchange upon heating alpha-actinin in D2O, showed that partially unfolded states with increased solvent accessibility but substantial secondary structures could be observed from 35 to 40 degrees C only if DOPG vesicles were present. A so-called "protamine precipitation" method has been developed to purify the N-terminal domain of alpha-actinin by use of the fact that the central domain of alpha-actinin is negatively charged but the N-terminal domain is positively charged. Thermal denaturation of the central and N-terminal domains of alpha-actinin were then investigated with FTIR. The secondary structure of the N-terminal domain of alpha-actinin was found to be thermally sensitive below 35 degrees C, which is characterized as the increase of the alpha-helical structure at the expense of the random coil upon heating the N-terminal domain from 4 to 35 degrees C. The membrane-binding ability of the N-terminal domain of alpha-actinin was proposed in terms of the analysis of the local electrostatic properties of alpha-actinin and the assignment of the amide II bands in the FTIR spctra of alpha-actinin.

Actinin↗

Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA.

Telomerase is the RNA-protein complex which elongates telomeric DNA (TTAGGG)n and appears to play an important role in cellular immortalization. The almost exclusive expression of telomerase in tumor cells, and not in most normal cells, offers an exciting opportunity for therapy by inhibiting its function. Here, we have investigated the effect of inhibition of telomerase on the growth and survival of human malignant glioma cells in vitro and in vivo by using a 19-mer antisense oligonucleotide against human telomerase RNA linked to a 2',5'-oligoadenylate (2-5A). 2-5A antisense functions by activating the endoribonuclease, RNase L, resulting in the degradation of single stranded, targeted RNA. We have shown that the 2-5A antisense treatment effectively suppressed tumor cell growth and survival in vitro. Furthermore, treatment of tumors grown in nude mice with the antisense oligonucleotide inhibited survival of the tumor cells. TUNEL assays suggest that this effect is mediated through the induction of apoptosis. Targeting telomerase RNA with 2-5A antisense, therefore, may represent an effective and novel approach for treatment of a broad range of cancers.

Animals↗

Increased translocations and aneusomy in chromosomes 8 and 21 among workers exposed to benzene.

Chromosome aberrations in peripheral blood lymphocytes have been used for many years to monitor human populations exposed to potential carcinogens. Recent reports have confirmed the validity of this approach by demonstrating that elevated levels of chromosome aberrations in lymphocytes are associated with subsequent increased cancer risk, especially for increased mortality from hematological malignancies including acute myeloid leukemia (AML). We postulated that this approach could be improved in two ways: (a) by detecting oncogenic disease-specific aberrations; and (b) by using chromosome painting so that many more metaphases could be analyzed. Numerical and structural aberrations in chromosomes 8 and 21 are commonly observed in AML. In the present study, we painted chromosomes 8 and 21 in lymphocyte metaphases from 43 healthy workers exposed to benzene, an established cause of AML, and from 44 matched controls. To examine dose-response relationships the workers were divided into two groups at the median exposure level, a lower-exposed group (< or = 31 ppm; n = 21), and a higher-exposed group (> 31 ppm; n = 22). Benzene exposure was associated with significant increases in hyperdiploidy of chromosomes 8 (1.2, 1.5, and 2.4 per 100 metaphases; P < 0.0001) and 21 (0.9, 1.1, and 1.9 per 100 metaphases; P < 0.0001). Translocations between chromosomes 8 and 21 were increased up to 15-fold in highly exposed workers (0.01, 0.04, and 0.16 per 100 metaphases; P < 0.0001). In one highly exposed individual, these translocations were reciprocal and were detectable by reverse transcriptase-PCR. These data indicate a potential role for t(8;21) in benzene-induced leukemogenesis and are consistent with the hypothesis that detection of specific chromosome aberrations may be a powerful approach to identify populations at increased risk of leukemia.

Acute Disease↗

Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age.

BACKGROUND: Change in body weight is a potentially modifiable risk factor for hip fracture in older women but, to our knowledge, its relationship to risk in older men has not been reported previously. OBJECTIVE: To investigate the effects of weight loss and weight gain from age 50 years to old age on the risk of hip fracture among elderly men. METHODS: The association between weight change and risk of hip fracture was studied in a cohort of 2413 community-dwelling white men aged 67 years or older from 3 sites of the Established Populations for Epidemiologic Study of the Elderly. RESULTS: The older men in this study, observed for a total of 13620 person-years during the 8 years of follow-up, experienced 72 hip fractures, yielding an overall incidence rate of 5.3 per 1000 person-years. Extreme weight loss (> or =10%) beginning at age 50 years was associated in a proportional hazards model with increased risk of hip fracture (relative risk, 1.8; 95% confidence interval, 1.04-3.3). Weight loss of 10% or more was associated with several indicators of poor health, including physical disability, low mental status score, and low physical activity (P<.05). Weight gain of 10% or more beginning at age 50 years provided borderline protection against the risk of hip fracture (relative risk, 0.4; 95% confidence interval, 0.1-1.00). CONCLUSIONS: Despite differences between older men and women in the incidence of and risk factors for hip fracture, weight history is also an important determinant of the risk of hip fracture among older men. Weight loss of 10% or more beginning at age 50 years increases the risk of hip fracture in older white men; weight gain of 10% or more decreases the risk of hip fracture. The relationship between extreme weight loss and poor health suggests that weight loss is a marker of frailty that may increase the risk of hip fracture in older men. Physicians should include weight history in their assessment of the risk of hip fracture among older men.

Aged↗

Catalytic domain of the p120 Ras GAP binds to RAb5 and stimulates its GTPase activity.

Ras is a master GTPase switch controlling multiple signal transduction cascades in the regulation of cell proliferation and differentiation. Rab5 is a local GTPase switch that is localized on early endosomes and controls early endosome fusion. This study demonstrates that the catalytic domain of p120 GTPase-activating protein (GAP), a well known Ras GAP, is able to interact physically with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5, however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6, indicating that it is not a generic GAP for the Rab family of GTPases that regulate intracellular membrane fusion during endocytosis and exocytosis. The findings indicate a level of structural similarity between Ras and Rab5 unexpected from their primary sequences. They also suggest a possible signal transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.

Catalysis↗

Nuclease-resistant composite 2',5'-oligoadenylate-3', 5'-oligonucleotides for the targeted destruction of RNA: 2-5A-iso-antisense.

A new modification of 2-5A-antisense, 2-5A-iso-antisense, has been developed based on a reversal of the direction of the polarity of the antisense domain of a 2-5A-antisense composite nucleic acid. This modification was able to anneal with its target RNA as well as the parental 2-5A-antisense chimera. The 2-5A-iso-antisense oligonucleotide displayed enhanced resistance to degradation by 3'-exonuclease enzyme activity such as that represented by snake venom phosphodiesterase and by that found in human serum. 2-5A-Iso-antisense was able to effect the degradation of a synthetic nontargeted substrate, [5'-32P]pC11U2C7, and two targeted RNAs, PKR and BCR mRNAs, in a cell-free system containing purified recombinant human 2-5A-dependent RNase L. These results demonstrated that the novel structural modification represented by 2-5A-iso-antisense provided a stabilized biologically active formulation of the 2-5A-antisense strategy.

DNA, Complementary↗

Architectural specificity in chromatin structure at the TATA box in vivo: nucleosome displacement upon beta-phaseolin gene activation.

Extensive studies of the beta-phaseolin (phas) gene in transgenic tobacco have shown that it is highly active during seed embryogenesis but is completely silent in leaf and other vegetative tissues. In vivo footprinting revealed that the lack of even basal transcriptional activity in vegetative tissues is associated with the presence of a nucleosome that is rotationally positioned with base pair precision over three phased TATA boxes present in the phas promoter. Positioning is sequence-dependent because an identical rotational setting is obtained upon nucleosome reconstitution in vitro. A comparison of DNase I and dimethyl sulfate footprints in vivo and in vitro strongly suggests that this repressive chromatin architecture is remodeled concomitant with gene activation in the developing seed. This leads to the disruption of histone-mediated DNA wrapping and the assembly of the TATA boxes into a transcriptionally competent nucleoprotein complex.

Journal Article↗

Interphase cell cycle dynamics of a late-replicating, heterochromatic homogeneously staining region: precise choreography of condensation/decondensation and nuclear positioning.

Recently we described a new method for in situ localization of specific DNA sequences, based on lac operator/repressor recognition (Robinett, C.C., A. Straight, G. Li, C. Willhelm, G. Sudlow, A. Murray, and A.S. Belmont. 1996. J. Cell Biol. 135:1685-1700). We have applied this methodology to visualize the cell cycle dynamics of an approximately 90 Mbp, late-replicating, heterochromatic homogeneously staining region (HSR) in CHO cells, combining immunostaining with direct in vivo observations. Between anaphase and early G1, the HSR extends approximately twofold to a linear, approximately 0.3-mum-diam chromatid, and then recondenses to a compact mass adjacent to the nuclear envelope. No further changes in HSR conformation or position are seen through mid-S phase. However, HSR DNA replication is preceded by a decondensation and movement of the HSR into the nuclear interior 4-6 h into S phase. During DNA replication the HSR resolves into linear chromatids and then recondenses into a compact mass; this is followed by a third extension of the HSR during G2/ prophase. Surprisingly, compaction of the HSR is extremely high at all stages of interphase. Preliminary ultrastructural analysis of the HSR suggests at least three levels of large-scale chromatin organization above the 30-nm fiber.

Animals↗

Skateboarding: more dangerous than roller skating or in-line skating.

OBJECTIVE: To describe the circumstances, severity, and outcomes of skating-related injuries among children admitted to trauma centers. DESIGN: A cross-sectional comparison of roller skaters (n = 154), in-line skaters (n = 190), and skateboarders (n = 254) aged 5 to 19 years who were hospitalized with injuries. SETTING: Seventy-nine hospitals and pediatric trauma centers participating in the National Pediatric Trauma Registry between October 1988 and April 1997. RESULTS: Three quarters (75.8%) of the study sample were male, nearly half (47.8%) were injured on roads, and more than one third (37.1%) had head injuries. Among skateboarders, 50.8% had head injuries compared with 33.7% of in-line skaters and 18.8% of roller skaters (P<.001). According to the Injury Severity Score, injuries to skateboarders were 8 times more likely to be severe or critical compared with roller skaters' injuries and more than 2 times as likely to be severe or critical compared with in-line skaters' injuries. Mean hospital length of stay was 6.0 days for skateboarders, 3.4 days for in-line skaters, and 2.4 days for roller skaters (P<.001). Skateboarders were more likely to be male and to be injured on roads than were in-line skaters or roller skaters. CONCLUSIONS: Skateboarding-related injuries are more severe and have more serious consequences than roller skating or in-line skating injuries. Research is needed to identify ergonomic and behavioral factors responsible for higher head injury risk to skateboarders, and interventions are needed to reduce the risk.

Accidental Falls↗

Acute traumatic injuries in automotive manufacturing.

Motor vehicle manufacturing, with its varied tasks, challenging work environment, and diverse worker populations, presents many hazards to employees. This study examined routinely collected surveillance data from a major motor vehicle manufacturer to identify injury types, high-risk workers, causes of injury, and factors associated with work loss. Injury and personnel data were used to calculate injury rates. Injury data were from the routinely collected medical and safety surveillance system on occupational injuries. The number of persons working in the plants was estimated using year-end personnel reports. Key word searches supplementing the analyses provided insight into the specific circumstances of injury. The most common injuries were sprains/strains (39% of the total), lacerations (22%), and contusions (15%). Forty-nine percent of the injuries resulted in one or more lost or restricted workdays; 25% resulted in 7 or more lost or restricted workdays. The injuries most likely to result in work loss were amputations, hernias and fractures. Sprains/strains accounted for 65% of all lost workdays. Injury rates ranged from 13.8 per 100 person-years at stamping plants to 28.7 at parts depots. Even within similar types of plants, injury rates varied widely, with a twofold difference among the individual assembly plants in overall injury rates. Injury surveillance systems with descriptive data on injury events shed light on the circumstances under which certain types of injuries occur and can provide the basis for preventive interventions. Sources of variation and potential biases are discussed, providing guidance for those interested in designing and using surveillance systems for occupational injuries.

Accidents, Occupational↗

A common region of allelic loss on chromosome region 3p25.3-26.3 in nasopharyngeal carcinoma.

Loss of heterozygosity (LOH) of chromosome arm 3p has been commonly observed in carcinomas of various tissues, including those of nasopharyngeal carcinoma (NPC). To determine the frequency and extent of allelic loss in NPC, we investigated 16 loci on chromosome bands 3p21-26 in 24 tumor tissues by microsatellite analysis. LOH on 3p21-26 was found in 16 of 24 (66.7%) tumors. The highest frequency of allelic loss was found in two adjacent loci, D3S1620 (11/22, 50%) and D3S1560 (9/18, 50%). Eight cases showed LOH in one contiguous region and 5 cases in more than one region. Samples 1, 3, 4, 7, 8, 10, 16, 17, 18, 19, and 22 had a contiguous stretch of allelic loss between D3S1297 and D3S1597. The smallest common LOH/deletion region seems likely to lie between D3S1297 (3p26.3-26.2) and D3S1560 (3p25.3). The allelic loss map defined here will facilitate finer mapping of putative tumor suppressor gene loci and positional cloning of such genes, which may play a role in carcinogenesis of NPC.

Adult↗

Effect of combined axial compressive and anterior tibial loads on in situ forces in the anterior cruciate ligament: a porcine study.

This study investigated the impact of a combination of axial compressive and anterior-posterior tibial loads on the in situ forces in the anterior cruciate ligament. An axial compressive load is believed to contribute to increased stability of the knee joint; however, its effect on in situ forces in the anterior cruciate ligament has not been clearly defined, to our knowledge. It was hypothesized that the application of an axial compressive load, when combined with an anterior tibial load, would result in larger in situ forces in the anterior cruciate ligament than those caused by an isolated anterior tibial load. With use of a porcine knee model, the results confirmed this hypothesis; the addition of a 200 N axial compressive load to a 100 N anterior tibial load increased knee stability by reducing anterior-posterior tibial translation and internal-external tibial rotation and also caused a significant increase in in situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was a 34% increase in the in situ force at 30 degrees of flexion, a 68% increase at 60 degrees of flexion, and an 84% increase at 90 degrees of flexion compared with those for an isolated anterior tibial load of 100 N. Additionally, there was a statistically significant increase of the in situ forces in the anterior cruciate ligament at 60 and 90 degrees as compared with those at 30 degrees. These results suggest that axial compressive loads on the knee may play a role in injury of the anterior cruciate ligament when the knee is flexed.

Animals↗

Tumor necrosis factor alpha, interleukin-6, interleukin-8, and interferon alpha in children with viral hepatitis.

To investigate the cellular immunological changes in children with viral hepatitis, interleukin 6 (IL-6), interleukin 8 (IL-8), interferon alpha (IFN alpha), and tumor necrosis factor alpha (TNF alpha) in supernatant of cultured peripheral blood mononuclear cells (PBMCs) of 49 children with hepatitis A, B or C were measured. The levels of IL-6, IL-8, TNF alpha in PBMCs of the 3 viral hepatitis groups were increased and the level of IFN alpha decreased as compared with those of normal control group. But there were no significant differences among the 3 viral hepatitis groups. It was concluded that cellular immunological disorders were related to the onset and the induced damage of the viral hepatitis in children.

Adolescent↗

Extraction of Phytolacca acinosa and its mulloscacidal effects.

The total saponins extracted from the plant root of Phytolacca Esculenta Van Houtte were studied for its mulloscacidal effect. The results showed the death rate of oncomelania was 95.6% under the concentration of 125 mg/L of saponins, at 28 degrees C with action time being 24 h.

Animals↗