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Biomedical subjects

K Zhang

Publications and source records attributed to K Zhang.

At least 181 records · Page 10Linked to original sources

Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides.

We have investigated whether antisense oligonucleotides delivered intravitreally could reduce gene expression specifically in the retina. In this study, phosphorothioate antisense oligonucleotides targeted to fibronectin transcripts were coupled to a novel carrier and used to specifically reduce fibronectin (FN) expression in retinal vascular cells. Using confocal microscopy, fluorescence from fluorescein isothio-cyanate-labeled FN-oligonucleotides was detected in retinal vascular cells at 24 h postinjection and persisted until day 6 (the end point of this study). The fibronectin mRNA level was consistently decreased to 86.7% +/- 7.9% of control (p<0.05) at day 2, and 46.7% +/- 4.9% of control (p<0.01) at day 6. In contrast, the beta-actin mRNA level, an internal control, was unaltered in rat retinas that received FN-oligonucleotides. Fibronectin protein level at day 6 was also significantly reduced to 61.4% +/- 16% of control (p<0.01). No toxic effect resulting from the carrier was detected histologically. Thus, intravitreal delivery of antisense oligonucleotides to modulate abnormal gene expression in retinal diseases may be an effective approach for ocular gene therapy.

Animals↗

A comparison of the impact of hospital reform on medical subcultures in some Australian and New Zealand hospitals.

This article examines similarities and differences in the way that hospital staff in Australia and New Zealand are evaluating efforts to improve quality, clinical effectiveness and service integration, and to strengthen clinical accountability. We draw on data from a cross-national study of hospital staff in Australia and New Zealand. The results highlight the way in which respondents' views about reform are influenced by the interplay of two factors: the impact of respondents' occupational backgrounds (our findings point to differences in the profession-based subcultures of medicine, nursing and general management and the way that these are reflected in respondents' assessments of particular aspects of reform); and the way that the impact of professional subcultures may be mitigated by differences between the systems in which respondents were located, including differences between the programs of reform that have been pursued in each country. The implications of these findings are discussed.

Australia↗

Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease.

Cone-rod dystrophy (CORD) and Stargardt disease (STGD) are two hereditary retinal dystrophies with similarities to age-related macular degeneration. Cone-rod dystrophies are a group of degenerative disorders resulting in decreased visual acuity and color vision, attenuated electroretinographic (ERG) responses, and atrophic macular lesions. Autosomal dominant, autosomal recessive, and X-linked forms of cone-rod dystrophy have been reported. Stargardt disease is characterized by reduced visual acuity, atrophic macular changes, prominent 'flavimaculatus flecks' in the pigment epithelium of the posterior retina, and a virtually pathognomic 'dark choroid' pattern on fluorescein angiography. Stargardt disease is classically inherited as an autosomal recessive trait, although numerous families have been described in which features of Stargardt disease are transmitted in an autosomal dominant manner. We have identified a new kindred with autosomal dominant cone-rod dystrophy with features of Stargardt-like disease. Detailed clinical evaluation, genotype analysis, and linkage analysis were performed. Fluorescein angiography revealed a 'dark choroid' pattern in three affected subjects. Electroretinography disclosed markedly reduced scotopic and photopic responses in three affected individuals. Genetic analysis revealed linkage to known loci for cone-rod dystrophy (CORD7) and Stargardt-like disease (STGD3) on chromosome 6q14. A peak lod score of 3.3 was obtained with the marker D6S280 at straight theta =0.010. A physical map was constructed by screening a YAC library with short tandem repeat markers in the region. Screening of a candidate gene, the rho1 subunit of the GABA receptor, failed to reveal any mutations.

Adult↗

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↗

A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

Chromosome Mapping↗

Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase.

Bruton's tyrosine kinase (Btk) is required for normal B-cell development, as defects in Btk lead to X-linked immunodeficiency (xid) in mice and X-linked agammaglobulinemia (XLA) in humans. Here we demonstrate a functional interaction between the multifunctional transcription factor TFII-I and Btk. Ectopic expression of wild-type Btk enhances TFII-I-mediated transcriptional activation and its tyrosine phosphorylation in transient-transfection assays. Mutation of Btk in either the PH domain (R28C, as in the murine xid mutation) or the kinase domain (K430E) compromises its ability to enhance both the tyrosine phosphorylation and the transcriptional activity of TFII-I. TFII-I associates constitutively in vivo with wild-type Btk and kinase-inactive Btk but not xid Btk. However, membrane immunoglobulin M cross-linking in B cells leads to dissociation of TFII-I from Btk. We further show that while TFII-I is found in both the nucleus and cytoplasm of wild-type and xid primary resting B cells, nuclear TFII-I is greater in xid B cells. Most strikingly, receptor cross-linking of wild-type (but not xid) B cells results in increased nuclear import of TFII-I. Taken together, these data suggest that although the PH domain of Btk is primarily responsible for its physical interaction with TFII-I, an intact kinase domain of Btk is required to enhance transcriptional activity of TFII-I in the nucleus. Thus, mutations impairing the physical and/or functional association between TFII-I and Btk may result in diminished TFII-I-dependent transcription and contribute to defective B-cell development and/or function.

Agammaglobulinaemia Tyrosine Kinase↗

Suppressed impact of nitric oxide on renal arteriolar function in rats with chronic heart failure.

We performed experiments to test the hypothesis that experimental heart failure (HF) is associated with altered nitric oxide (NO)-dependent influences on the renal microvasculature, including diminished modulation of constrictor responses to ANG II. Eight to ten weeks after inducing HF in rats by coronary artery ligation, we administered enalaprilat to suppress ANG II synthesis and studied renal arteriolar function using the in vitro blood-perfused juxtamedullary nephron technique. In kidneys from sham-operated rats, NO synthase inhibition [100 microM Nomega-nitro-L-arginine (L-NNA)] reduced afferent arteriolar diameter by 4.1 +/- 0.6 microm and enhanced ANG II responsiveness (10 nM ANG II decreased afferent diameter by 10.1 +/- 1.4 micrometer before and 12.8 +/- 1.6 micrometer during L-NNA treatment; P < 0.05). In kidneys from HF rats, L-NNA did not alter afferent arteriolar baseline diameter or ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 +/- 1.5 micrometer before and 12.5 +/- 2.3 micrometer during L-NNA). The effects of L-NNA on efferent arteriolar function were also abated in HF rats. In renal cortex of HF rats, NO synthase activity was decreased by 63% and superoxide dismutase activity was diminished by 39% relative to tissue from sham-operated rats. Urinary nitrate/nitrite excretion was also reduced in HF rats. Thus both diminished synthesis and augmented degradation are likely to contribute to a decreased renal microvascular impact of endogenous NO during chronic HF, the consequences of which include loss of NO-dependent modulation of ANG II-induced vasoconstriction.

Animals↗

Repeat cDNA synthesis and RT-PCR with the same source of RNA.

A simple method has been developed that enables reextraction of RNA from an RNA-cDNA mixture. The reextracted RNA was converted to cDNA followed by polymerase chain reaction (PCR). Thus, cDNA synthesis (followed by PCR) was carried out two times on the same source of RNA. The method has been applied to 40 RNA samples of diverse tissue origin with a success rate of 100%. Thus, the method offers more versatile use of small but valuable RNA sources than currently possible.

DNA, Complementary↗

High temperature cDNA synthesis by AMV reverse transcriptase improves the specificity of PCR.

The enzyme avian myeloblastosis virus reverse transcriptase (AMV-RT) is routinely used for cDNA synthesis, which is generally carried out at temperatures between 37 degrees C and 42 degrees C. We show that this enzyme can support cDNA synthesis, at temperatures as high as 70 degrees C. We have utilized this property of the AMV-RT to improve the specificity of polymerase chain reaction (PCR). Furthermore, this apparently thermophilic property of the enzyme, which is an important constituent of a mesophilic organism, raises intriguing questions regarding evolution of the enzyme structure.

Avian Myeloblastosis Virus↗

GSH, GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.

Glutathione (GSH) contents and activities of glutathione S-transferase (GST), glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione conjugate export pump (GS-X pump) were determined in eight human tumor cell lines with different sensitivities to adriamycin and chlorambucil. Correlations between sensitivities of the human tumor cells to adriamycin and chlorambucil and the glutathione related factors were analyzed statistically. Sensitivities of the human tumor cells to chlorambucil were found to be correlated to all the glutathione related factors tested (r=0.68-0.88). IC50 values of adriamycin were also positively correlated to GSH contents and activities of GSH-RD, GSHpx and GS-X pump with r values ranging from 0.66 to 0.77 but not to GST activity (r=0.25). Chang liver cells with highest GSH content and highest activities of GST, GSH-RD, GSHpx and GS-X pump were most resistant to both adriamycin and chlorambucil. These data suggested that glutathione related factors may work as an overall detoxification system participating in the detoxification of anticancer drugs such as adriamycin and chlorambucil, and to be involved in cellular resistance to these drugs.

Antineoplastic Agents↗

[Susceptibility gene location of simple congenital heart defect by transmission disequilibrium test].

OBJECTIVE: To locate the susceptibility gene of human simple congenital heart defect(CHD) and provide a sound basis for further gene cloning. METHODS: Three short tandem repeats(STRs) in regions of chromosome 7p14-15, 17q21 where exist Hox gene family's A, B clusters which regulate the embryonic heart development were chosen. Genotypes of 112 members in 39 CHD families were analyzed by amplifying the STR fragments using fluorescence-PCR technique. Then transmission disequilibrium test(TDT) was used to test the data of genotypes. RESULTS: Statistical chi(2) values of D7S1808, D7S673 and D17S791 were 31.3(P<0.005), 11.12(P<0.05) and 6.65 (P>0.05) respectively. These suggest that the former two are associated with CHD, while the latter is not. CONCLUSION: Human simple CHD is associated with Hox gene A cluster. Hox A gene may be a candidate CHD's susceptive genes. The location of the CHD's susceptive genes is in chromosome 7p14-15.

Chromosomes, Human, Pair 7↗

In vitro and in vivo studies of the effect of a Chinese herb medicine on osteoclastic bone resorption.

OBJECTIVE: To study the effect of a Chinese herb on osteoclastic bone resorption and osteoporosis. MATERIALS AND METHODS: Osteoclasts were isolated and cultured for in vitro study of the effect of the Chinese herb Guizhou epimedium (Epimedium Leptorrhizum Stearn). The in vivo effect of this Chinese herb was also investigated in rats in whom osteoporosis was induced by ovariectomy; these results were then compared with the effects of estradiol in the same group of rats. RESULTS: The in vitro study showed that the epimedium inhibited the osteoclastic resorption of bone. The in vivo investigation demonstrated that both the epimedium and estradiol were able to increase mineral content and promote bone formation. CONCLUSION: The Chinese herb Guizhou epimedium is of potential use in the treatment of osteoporosis.

Animals↗

[Comparison between copper needle insertion and stainless steel needle insertion into rabbit ear central veins].

OBJECTIVE: The clinical application of copper needle insertion has been proceeded satisfactorily for peripheral vascular disorders. This work was to study the mechanism of the copper needle insertion on a pathological basis. METHODS: Sixty rabbits were used in the experiments. The copper needle or the stainless steel needle was inserted into the ear central vein of the animal. Then the specimens of the central vein including its surrounding tissue were taken for light and electron microscopic examinations. RESULTS: At 7 days after copper needle insertion, acute inflammation reaction of the venous wall and vascular thrombosis were revealed in the specimens. At 14 days, giant cells granuloma and destruction of the venous wall were seen. After 28 days to 2 months, granuloma and the residual destroyed venous wall were gradually absorbed and fibrosis resulted. The vascular inflammation and thrombosis caused by stainless steel needle insertion was slight and slow. CONCLUSION: Copper needle treatment for vascular disorders is superior to the stainless steel needle.

Animals↗

Corneal topographic analysis after excimer photorefractive keratectomy.

OBJECTIVE: To evaluate the corneal surface changes and visual quality after excimer photorefractive keratectomy (PRK) for myopia. METHODS: Corneal topographic analysis was performed on 23 patients (38 eyes) with myopia after PRK at the 1-, 3-, 6- month postoperative follow-up visits. RESULTS: The corneal sphericity was changed after excimer PRK. As time went on, the mean surface regularity index (SRI) and the surface asymmetry index (SAI) decreased gradually, and the corneal surface became more smooth; mean simulated keratoscope readings (SimK) showed a gradual restoration. At the 6-month postoperative examination, corneal topography showed four main patterns of ablation: round or oblong (50%), collar-button (23.68%), semicircular (18.42%) and central island (7.9%). Patterns of ablation were correlated with visual acuity. CONCLUSION: The quantitative analysis of corneal topography is essential for evaluating corneal surface changes after PRK and helpful in the surgical design of PRK and in predicting the refractive outcome with greater precision.

Adolescent↗

[The isolation and drug susceptibility of penicillin resistant Streptococcus pneumoniae in Guangzhou].

OBJECTIVE: To investigate the isolation rate and drug susceptibility of PRSP in Guangzhou and in vitro antimicrobial activities of 8 antimicrobial agents against PRSP. METHODS: MICs were tested by E-test. RESULTS: Of 102 strains of Streptococcus pneumoniae, 12 strains were low-level resistant against penicillin (isolation rate 11.8%) and the antimicrobial activites of 5 drugs (augmentin, cefaclor, ceftriaxone, cefuraxime, ofloxaxin) against them were within their MICs, augmentin and ceftriaxone being the most powerful. They were resistant to azithromicin, oxacillin and penicillin. CONCLUSIONS: The isolation rate of Penicillin resistant Streptococcus pneumoniae was not high in Guangzhou, but it may increase with the extensive use of antimicrobial agents, which deserves much attention.

Anti-Bacterial Agents↗

[Mechanical ventilation of advanced chronic obstructive pulmonary disease patients with recurrent severe respiratory failure].

OBJECTIVE: To summarize the results of patients of severe respiratory failure using multiple times mechanical ventilation (MV) via tracheal intubation (or via tracheotomy). METHODS: We retrospectively analysed clinical information and follow-up results of 15 acute exacerbation of COPD patients using MV more than 3 times. RESULTS: MV was used 77 times in 15 patients. The highest number of MV was 20.86% were weaned successfully. The mean duration of MV via intubation was 13 days and via tracheotomy was 37 days, mean 649 days via the latest brocheotomy after using MV multiple times. The survival duration after the first MV varied from 196 to 4 420 days in 15 patients, mean 1 093 days, medium survival duration of the patients was 1 673 days, survival rates after 1, 2, 3 and 5 years were 73%, 64%, 33% and 25% respectively. The causes of death were failure of multiple organs or disfunction of other vital organs. CONCLUSIONS: Repeated application of MV may prolong the survival rates of COPD with severe respiratory failure. It's important to take strictly the indication of MV, correctly to select the methods of artificial airway, combining invasive and noninvasive ventilation, properly to apply the strategies of MV.

Aged↗

[Association of body size at birth with impaired glucose tolerance during their adulthood for men and women aged 41 to 47 years in Beijing of China].

OBJECTIVE: To explore if there was relationship between small body size at birth and type 2 diabetes and impaired glucose tolerance (IGT) during adulthood in China. METHODS: Six hundred and twenty-eight singletons born in the Peking Union Medical College Hospital in Beijing during July 1948 to the end of 1954 were followed-up and their medical records at birth were abstracted. Anthropometry and standard oral glucose tolerance test were carried out for all of them. Plasma insulin level was measured with radioimmunoassay for them. RESULTS: Prevalence of type 2 diabetes and IGT decreased with the increase in their birth weight, Ponderal index (PI) and head circumference at birth (for trend test, chi(2) = 6.7, P = 0.01; chi(2) = 4.8, P = 0.03; and chi(2) = 5.8, P = 0.02; respectively), with the highest of 43.8% in those with thin body size (PI < 24 kg/m(3)) at birth and obesity (BMI < 75 percentile) during adulthood, and the lowest of 8.3% in those with more fat at birth (PI >or= 28 kg/m(3)) and keeping relatively thin (BMI < 25th percentile) during adulthood. BMI of mothers in their early and late pregnancy correlated reversely with blood glucose levels two hours after sugar load for their children in adulthood. In addition, body weight, PI and head circumference at birth correlated reversely with their plasma insulin levels fasting and two hours after sugar load and levels of 32 -- 33 split pro-insulin during their adulthood. After adjustment for current BMI, lifestyle and economic status, body size at birth mentioned above still associated with their glucose tolerance and level of plasma insulin during adulthood. CONCLUSION: There was relationship between small body size at birth and prevalence of type 2 diabetes and IGT during adulthood. Prevalence of type 2 diabetes and IGT depended on the synergic effect of thin body size at birth and obesity during adulthood.

Adult↗