Exclusion of chromosome 11q13 region as a genetic locus responsible for autosomal dominant Stargardt's disease.
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Chromosome Mapping↗
Biomedical subjects
K Zhang
Publications and source records attributed to K Zhang.
Switch circles from IL-4-directed epsilon class switching from human B lymphocytes. Evidence for direct, sequential, and multiple step sequential switch from mu to epsilon Ig heavy chain gene.
Ig isotype switch via deletional recombination is accompanied by excision of the intervening DNA between the two switch regions. The excised DNA is looped out as extrachromosomal circular DNA or switch circle. Such switch circles have been isolated and characterized in mice. We investigated deletional recombination in human B cells undergoing Ig isotype switching to demonstrate whether switch circles are also excised, and to thereby gain insight into the processes involved in human isotype switching. We characterized the deleted switch circular DNA from IL-4 directed mu to epsilon switching in polyclonal human B lymphocytes. By using two sets of specially designed PCR primers, we amplified switch circle fragments representing switch circles resulting from mu to epsilon direct switching and mu-gamma-epsilon sequential switching. The PCR-amplified products were subcloned by a TA cloning strategy and resulting clones were screened by hybridization with a 5'S epsilon probe. Sequence analysis of the positive clones revealed that all clones representing mu to epsilon direct switching indeed had 5'S epsilon directly joined to 3' S mu. Most clones representing mu-gamma-epsilon sequential switching showed 5'S epsilon joined to 3' S gamma as expected. However, two clones contained S mu and S alpha 1 sequences interposed between 5'S epsilon and 3'S gamma, respectively. These data demonstrate that switch circles are excised during human B cell isotype switching, and that IL-4 directed epsilon class switching is accomplished by 1) direct mu to epsilon switching, 2) sequential mu-gamma-epsilon switching, and 3) double sequential mu-alpha-gamma-epsilon switching.
B-Lymphocytes↗
Direct measurements of room-temperature oxygen diffusion in YBa2Cu3Ox.
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Journal Article↗
Normal-state resistance fluctuations in high-Tc cuprate films.
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Journal Article↗
Complex alternative RNA splicing of epsilon-immunoglobulin transcripts produces mRNAs encoding four potential secreted protein isoforms.
In RNA from human IgE-producing lymphocytes, we previously discovered two alternatively spliced epsilon-immunoglobulin mRNA isoforms that encode a novel secreted form of IgE and a membrane-bound species. Further analysis using epsilon-specific reverse transcriptase polymerase chain reactions has elucidated several additional alternatively spliced species of epsilon mRNA. One RNA isoform is generated by splicing the CH4 exon to a novel distal splice acceptor site, forming an epsilon RNA species (designated CH4-M2") that encodes a secreted epsilon protein 6 amino acids larger than the classic secreted epsilon protein. The other three novel epsilon RNAs are generated by splicing from within CH4 to a new exon structure (designated CH5) that is located between CH4 and the membrane exons. Since the three new mRNAs using CH5 share the same stop codon in CH5, they all encode the same novel protein, which is 10 amino acids shorter than the classic secreted epsilon heavy chain. The new alternatively spliced epsilon mRNAs reported here, in addition to the previously reported forms encoding membrane and larger secreted IgE, appear to reflect the normal splicing pattern in humans, as we have detected all these epsilon RNAs in all the human IgE-secreting cells and cell lines tested.
Alternative Splicing↗
A dominant Stargardt's macular dystrophy locus maps to chromosome 13q34.
OBJECTIVE: To identify the chromosomal location of a mutated gene that causes an autosomal dominant Stargardt's macular dystrophy. METHODS: Ocular examinations were performed on 67 members of a large kindred to identify those with macular dystrophy. DNA analyses defined the genotype of all family members at 49 polymorphic loci. Linkage between the gene defect responsible for this macular dystrophy and each polymorphic locus was assessed by lodscore calculations. RESULTS: Diminished visual acuity and funduscopic abnormalities were found in 29 family members, which was diagnostic of macular dystrophy. Genetic analyses demonstrated that polymorphic loci from chromosome 13 band q34 were linked to the gene defect in this family. Haplotype analyses localized the disease locus to an 8-centimorgan interval between loci D13S159 and D13S158/D13S174. CONCLUSION: A disease locus responsible for an autosomal dominant Stargardt's macular dystrophy is located on chromosome 13 band q34. Identification of the mutated gene at this locus will lead to a better understanding of macular degeneration.
Adolescent↗
Influence of polysaccharides on neutrophil function: specific antagonists suggest a model for cooperative saccharide-associated inhibition of immune complex-triggered superoxide production.
We have previously shown that certain monosaccharides (N-acetyl-D-glucosamine and mannose) could cooperatively inhibit the ability of neutrophils to release superoxide anions in response to immune complexes. To test the possible origins of the cooperative inhibition of superoxide release, we have examined the effect of a panel of polysaccharides on superoxide release in the presence or absence of immune complexes. Although exposure to particulate beta-glucan and hyaluronan triggered superoxide release from neutrophils, other polysaccharides including chitin and mannan were without effect. Both chitin and mannan, but not other polysaccharides, inhibited the immune complex-mediated stimulation of superoxide release in a dose-dependent fashion. In sharp contrast to the cooperative inhibition mediated by monosaccharides, chitin and mannan exhibited Hill coefficients of 1. This inhibition of superoxide production was not due to simple blockage of Fc receptors since fluorescent immune complexes bound equally well to neutrophils in the presence or absence of mannan or chitin as shown by epifluorescence microscopy and quantitative fluorometry. Furthermore, this inhibition of superoxide release was not observed when neutrophils were stimulated with phorbol myristate acetate and ionophore A23187 or hyaluronan. Therefore, the specific inhibition of superoxide production by mannan and chitin could not be explained by either receptor blockage or by some nonspecific effect on cells. We suggest that these molecules interfere with a step in transmembrane signaling, presumably involving the integrin CR3. The observed Hill coefficients suggest the possibility that one polysaccharide may simultaneously bind to two monosaccharide binding sites yielding a Hill coefficient of 1, whereas individual monosaccharides separately bind yielding a Hill coefficient of 2.
Adult↗
Body mass, fat distribution and cardiovascular risk factors in a lean population of south China.
The associations of body mass index and abdominal adiposity, represented by an elevated waist/hip circumference ratio, with cardiovascular risk factors were examined in men and women, aged 28-69 years, from urban and rural areas of Guangzhou, China. Mean body mass index ranged from 20.1 to 21.9 kg/m2 across the four sex- and area-groups. Mean waist/hip ratio was 0.84 in men and 0.80 in women. After accounting for age and body mass index, waist/hip ratio was associated negatively (p < 0.05) with fasting serum HDL cholesterol (both sexes), and positively with serum triglycerides (both sexes), total and LDL cholesterol (men only), uric acid (both sexes), glucose (women only), and mean systolic blood pressure (women only). Body mass index was associated in a similar direction with most of these risk factors. These data confirm that abdominal adiposity is independently associated with cardiovascular disease risk factors, even in a lean Asian population.
Abdomen↗
Stereoselective pharmacokinetics of stiripentol: an explanation for the development of tolerance to anticonvulsant effect.
An earlier pharmacodynamic study of the chiral antiepileptic drug stiripentol in an intravenous pentylenetetrazol-induced seizure model in the rat showed the development of a significant degree of tolerance to the anticonvulsant and neurotoxic effects following subacute treatment with the racemic compound. A more recent study with the pure enantiomers of stiripentol indicated that the (+)-enantiomer is 2.4 times more potent than the (-)-enantiomer, based on a comparison of brain EC50 values for the anticonvulsant effect. Moreover, (-)-stiripentol has a much longer elimination half-life than (+)-stiripentol. We have re-analyzed the brain and blood samples from the first pharmacodynamic study using a newly developed chiral HPLC assay to investigate whether the tolerance phenomenon with racemic stiripentol was due to a shift in the enantiomeric composition of stiripentol in brain tissue during repetitive administration of racemic drug. A large increase, as much as 5-6-fold, in the (-)/(+) ratio in brain concentration of stiripentol was observed after subacute administration, as compared with that after a single dose of the racemic drug. The enrichment in the less potent enantiomers during repetitive drug administration explains the previous observation of an apparent development of tolerance when the pharmacologic effects were related to total [(-)+(+)] brain concentrations of stiripentol as measured by a non-stereoselective assay. The results of this study highlight the importance of stereoselective pharmacokinetics in investigating the pharmacodynamics of the racemic mixture of a chiral anticonvulsant.
Animals↗
Formation of a disulfide bond in the immunoglobulin domain of the myelin P0 protein is essential for its adhesion.
It is widely accepted, although never demonstrated, that the formation of a disulfide bond in the majority of immunoglobulin (Ig)-like domains stabilizes their final conformation and thus is essential to their functioning as adhesion/recognition molecules. The myelin P0 protein, which has been shown directly to behave as a homophilic adhesion molecule, contains a single Ig-like domain, stabilized by a putative Cys21-Cys98 disulfide bond. To test if this bond is indeed necessary to the adhesive function of P0, the nucleotides in the P0 cDNA coding for Cys21 were altered to code for an alanine. The mutated P0 cDNA was transfected into Chinese hamster ovary cells, expression of the mutated P0 protein was characterized, and the adhesiveness of Cys21-mutated P0-expressing cells and that of cells expressing equivalent surface amounts of the unmutated protein were compared. It was found, as we previously reported, that incubation of a single cell suspension of the unmutated P0-expressing cells resulted in the rapid formation of large aggregates. In contrast, after a similar incubation the cells expressing the Cys21-mutated P0 were still mostly single cells, a result indistinguishable from that observed with the control transfected cells. This suggests that the P0 protein, when mutated at Cys21, does not behave as a homophilic adhesion molecule, which in turn implies that the formation of an Ig domain disulfide bond is essential to the functioning of this molecule.
Animals↗
Protein kinase-dependent Cl- currents in feline ventricular myocytes.
A Cl- current (ICl) induced by isoproterenol (ISO) has been identified in isolated guinea pig ventricular myocytes. This ISO-induced ICl can be inhibited by propranolol and mimicked by forskolin (FSK), suggesting that beta-receptors, cAMP, and protein kinase A (PKA) are involved in regulating the involved Cl- channel. Because activation of protein kinase C (PKC) mediated via alpha-adrenergic receptor stimulation is also known to regulate several ion channels, the idea that activation of PKC also can induce ICl was investigated by using isolated feline ventricular myocytes and the whole-cell patch-clamp technique. We found that extracellularly applied phorbol 12-myristate 13-acetate (PMA) could activate ICl in feline ventricular cells. Control experiments indicated that in the absence of PMA or other interventions, the steady-state current-voltage relation of patches maintained for more than 40 minutes was unchanged over a voltage range from -100 to +80 mV. This suggests that the present findings are not complicated by the development over time after patching of a steady-state ICl, similar to the findings reported for canine atrial myocytes. When induced by PMA, ICl was noninactivating and outwardly rectifying; it reversed polarity at approximately the equilibrium potential for Cl- and was sensitive to the Cl- channel blocker 9-anthracene carboxylic acid. In contrast, PMA failed to induce ICl when either staurosporine or calphostin C was added to the patch pipette solution used to internally dialyze the myocytes. The kinetic properties of PMA- and FSK-induced ICl were similar. When supramaximal concentrations of both ISO (1 mumol/L) and PMA (6 mumol/L) were applied simultaneously, the size of the induced ICl was the same as that induced by the same concentrations of either agonist applied alone. In addition, maximal induction of ICl with PMA (6 mumol/L) prevented the effects of FSK (1 mumol/L, the concentration causing approximately 40% of the maximal response [approximately EC40]), yet the effects of simultaneously applied submaximal concentrations (eg, approximately EC25 to approximately EC40) of both 0.5 mumol/L PMA and 1 mumol/L FSK were roughly additive. The results suggest that (1) both PMA and ISO or FSK can induce ICl with approximately equal efficacy, (2) the PMA- and ISO- or FSK-induced ICls are similar, and (3) they all flow through the same set of Cl- channels, implying that channel phosphorylation via either PKA or PKC can activate this feline cardiac ICl.
Animals↗
Characteristics of acupuncture meridians and acupoints in animals.
In recent years, an increasing number of studies has been conducted on the biophysical characteristics of the meridians and acupoints in humans and animals. The authors aim to further illustrate the objective existence and superficial locations of the meridians in various species of animals. Twelve sheep, ten goats, thirteen pigs, eleven cats, eight rabbits and seven donkeys were used to measure low impedance lines (LILs) and high percussion sound lines (HPSLs) on the skin surface of the animals, along the vertical planes of the dorsal line, using electrical impulses and high percussion sound. The results of these studies are given.
Acupuncture Points↗
In situ hybridization analysis of rat lung alpha 1(I) and alpha 2(I) collagen gene expression in pulmonary fibrosis induced by endotracheal bleomycin injection.
BACKGROUND: Endotracheal bleomycin administration in rats and other animal species causes rapid development of pulmonary fibrosis, characterized by a transiently increased number of contractile, filament-laden parenchymal cells and increased lung collagen synthesis and deposition. However, the identity and source of the cells that actively synthesize collagen and other extracellular matrix and their relationship to the altered lung structure and function remain uncertain. EXPERIMENTAL DESIGN: In this study, the cells expressing alpha 1(I) and alpha 2(I) procollagen genes were identified and their localization analyzed in control and bleomycin-treated rat lungs at different time points, by in situ and Northern hybridization analyses. RESULTS: In control lungs, only a few scattered fibroblasts with weak expression of the alpha 1(I) procollagen gene were localized exclusively in the adventitia of the primary and tertiary bronchi, as well as major blood vessels. At day 3 after bleomycin treatment, scattered interstitial cells with significantly increased alpha 1(I) and alpha 2(I) procollagen gene expression were observed in the adventitia of bronchioles, terminal bronchioles, and adjacent small blood vessels. At days 7 and 14, there was a dramatic increase in the number of interstitial cells expressing large amounts of alpha 1(I) procollagen messenger RNA in these areas and extending to the lung parenchyma. This was followed on days 21 and 28 by significant decreases in procollagen gene expression and the number of cells with increased collagen gene expression. Most of the cells with enhanced collagen gene expression were arrayed in a disorganized fashion and were localized mainly around bronchioles, terminal bronchioles, and adjacent small blood vessels as well as in the irregularly distributed fibrotic foci, some submesothelial areas, and injured parenchyma. Northern blot analysis was consistent with the above in situ hybridization observation of the kinetics of collagen gene expression. CONCLUSIONS: The results indicate that in this rat fibrosis model, increased numbers of the interstitial cells with high expression of type I procollagen genes are derived primarily from the fibroblasts in the adventitia of bronchioles, terminal bronchioles, and adjacent blood vessels, as well as the submesothelial region. This then can result in further expansion to adjacent parenchyma and alveolar areas.
Animals↗
Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.
Appearance of contractile filament-laden stromal cells or myofibroblasts is a characteristic of lung fibrotic lesions. The role of these cells in fibrosis and their cytoskeletal phenotype are not fully delineated. This study was undertaken to further investigate these issues using a model of lung fibrosis. Rats were treated endotracheally with bleomycin on day 0, and their lungs examined at various time points by in situ hybridization for alpha 1(I) procollagen mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin expression. The results show an increase in the number of cells resembling fibroblasts and strongly positive for alpha-smooth muscle actin, desmin and procollagen mRNA expression in lungs of animals treated with bleomycin, with the increase being maximal between days 7 and 14 after bleomycin treatment. Two types of newly positive cells could be discerned. The first expressing alpha-smooth muscle actin, desmin, and procollagen mRNA was localized in active fibrotic lesions. The second expressing only alpha-smooth muscle actin and procollagen mRNA was localized in fibrotic submesothelial areas. Almost all of the newly reactive alpha-smooth muscle actin-positive cells strongly express procollagen mRNA, and they constituted most of the cells actively expressing procollagen. These findings suggest that the newly appearing myofibroblast characterized by alpha-smooth muscle actin and/or desmin expression may be responsible for most if not all of the increased lung collagen gene expression in pulmonary fibrosis.
Actins↗
[Direct determination of tin in water by oscillopolarography].
Sn(IV) has a sensitive polarographic wave in the system of H2SO4-KI-VitC-V (IV). We examined the factors influencing the polarographic wave and found that the concentration of sulfuric acid and temperature were critical factors for the determination. The sensitivity of the method was increased nearly 50-fold by decreasing the concentration of sulfuric acid from 0.8 mol/L to 0.1 mol/L. The coefficient of variation (CV) percentages of the method were less than 5% and 8% for 6-7 determinations of Sn (IV) standard and sample respectively. The recovery ranged from 97.3% to 101%. The proposed method is suitable for direct determination of trace Sn (IV) in most natural water samples.
Polarography↗
[The study of mechanisms and effects of prophylaxis and cure of electroacupuncture against ischemia injury in brain].
In order to observe the influence of electroacupuncturing (EA) "Ren Zhong" point on acute ischemia injury in brain, an experimental model of acute ischemia injury in brain was produced by antidromically blocking double common carotid arteries in 18 rabbits. The basic arteries' pressure will be increased by EA, RA and the contents of AI, A II increased and the content of LA reduced obviously in brain. An experimental evidence was given for the safety of EA anesthesia and the curative effect of EA on ischemia in brain.
Angiotensin II↗
[A KABP (knowledge, attitude, belief and behavior) study about AIDS among taxi drivers and hotel attendants in Beijing].
This article reports the KABP study on 448 taxi drivers and 556 hotel attendants in Beijing for the first time in China. A self-administered questionnaire was used to investigate knowledge, attitude, belief and practice (KABP) about AIDS. In terms of knowledge, 23.8% of hotel attendants and 36.8% of taxi drivers did not know that contact with blood could transmit HIV. Thirtyfive percent of hotel attendants and 42.2% of taxi drivers did not believe that intravenous drug users were at high risk. Some drivers (13.6%) and hotel attendants (3.4%) reported having multiple sexual partners. Forty-one point nine percent of taxi drivers and 16.6% of hotel attendants preferred the idea of multiple sexual partners. Among hotel attendants, a negative association was found between knowledge about AIDS and multiple sexual behavior (P < 0.01). Regarding attitude toward condom use, 56.2% of taxi drivers and 47.8% of hotel attendants who have had a sexual experience thought that condom use interfered with sexual pleasure. Seventy-six point eight percent of taxi drivers and 79.8% of hotel attendants believed that they could change their behaviors in order to minimize the chances of getting HIV. This study indicates that HIV education is important in reducing the number of sexual partners and promoting the use of safe sex practices like condom use. Furthermore, as reported by the study population, education can change behavior.
Acquired Immunodeficiency Syndrome↗