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Biomedical subjects

Q Zhang

Publications and source records attributed to Q Zhang.

At least 505 records · Page 28Linked to original sources

Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals.

Nickel and cobalt, which belong to the same elemental group, are known to cause interstitial lung disease and bronchial asthma. The ability of these metals to injure lung cells and cause inflammation is likely to be important in their pathogenicity but comparative studies are rare. Additionally, ultrafine (uf) forms of these metals are used increasingly and there is little available information on their toxicity. Thus the inflammatory response following intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz as a positive control. Male Wistar rats were intratracheally instilled with the 3 particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7, 15, and 30 d after the injection, lung weight and the cellular and biochemical changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and sustained inflammation, cytotoxicity and increased epithelial permeability. The next most toxic material was DQ12 quartz, with Uf-Co being closely similar in ability to cause inflammation. Uf-TiO2 was more active than the saline control in all of the indices, but was the least toxic of the particles studied. The present study reveals that three ultrafine particles of the same diameter are dramatically different in their ability to cause inflammation. The three ultrafines were compared as to their ability to cause free-radical damage to supercoiled plasmid DNA, and the result of free-radical activity was found to be Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity therefore could underlie the difference in inflammation of these three ultrafine particle types.

Animals↗

Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms.

Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of approximately 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.

Bacterial Typing Techniques↗

Developmental regulation of mossy fiber afferent interactions with target granule cells.

In an in vitro model system based on purified target cerebellar granule neurons and explants of afferents, pontine mossy fiber afferents stop growing through contact-mediated mechanisms when they encounter granule neurons. Here we studied the developmental regulation of the stop signal posed by granule cells and the response of mossy fibers to the stop signal in two culture systems. Granule neurons presented in slices or as dissociated cells from postnatal day (P) 4 and P7 cerebellum were more potent in the arrest of P0 pontine neurites than younger (P0-P2) or older (up to P14) granule neurons. In contrast, pontine neurites at embryonic day (E) 18, during their period of normal growth toward the cerebellum, grew extensively on both cerebellar slices of all ages from P0 to P10 and dissociated P4 granule neurons. When E18 explants were maintained for 2 days before plating in medium conditioned by neonatal cerebellar cells, E18 pontine explants were rendered more responsive to the stop signal from P4 granule cells. These results indicate that the stop signal, and the response of afferents to it, are developmentally regulated. Moreover, factors within the target region may initiate these interactions.

Animals↗

Insulin-like growth factor II inhibits glucose-induced insulin exocytosis.

We have investigated the effect of IGF-II on glucose-induced insulin release in the pancreatic beta-cell. Introduction of IGF-II during perifusion of the cells with 20 mM glucose abolished glucose-induced insulin release. Concomitant addition of IGF-II with 20 mM glucose caused a complete inhibition of insulin release. In addition, IGF-II inhibited Ca(2+)-induced insulin release from electropermeabilized pancreatic beta-cells. IGF-II had no effect on K(+)-or tolbutamide-induced insulin release. However, IGF-II could suppress K(+)-stimulated insulin release when cells were pretreated with the protein phosphatase inhibitor okadaic acid. The inhibitory effect of IGF-II on insulin release was not associated with significant changes in membrane potential, activity of the voltage-gated L-type Ca(2+)-channel or cytoplasmic free Ca2+ concentration. Pretreatment of the cells with pertussis toxin or the phorbol ester TPA abolished the inhibitory action of IGF-II on insulin release. Hence, the molecular mechanism whereby activation of the IGF-II/M6P receptor by IGF-II inhibits glucose-stimulated insulin exocytosis in the pancreatic beta-cell involves pertussis toxin-sensitive G proteins and is dependent on PKC activity.

Animals↗

Uncoupling protein-3: a muscle-specific gene upregulated by leptin in ob/ob mice.

We identified and partially characterized another member of the uncoupling protein termed UCP3. Human and mouse UCP3 protein sequences are 86% identical to each other, and 73% and 59% identical to UCP2 and UCP1, respectively. Expression of human UCP3 in yeast resulted in a drastic decrease of mitochondria membrane potential. Northern analysis showed that UCP3 was highly expressed in skeletal muscle in human, rat, and mouse. Mapping of UCP3 placed it to the same chromosomal region of UCP2 in both human and mouse, a region that is linked to obesity and hyperinsulinemia. Furthermore, adenovirus-mediated leptin expression in obese ob/ob mice led to increased expression of UCP3 in skeletal muscle. The data indicate that UCP3 encodes a muscle-specific uncoupling protein that may play an important role in the regulation of energy expenditure and development of obesity.

Adenoviridae↗

Distinct patterns of folding and interactions with calnexin and calreticulin in human class I MHC proteins with altered N-glycosylation.

Calnexin is a lectin-like chaperone that binds to class I MHC molecules soon after their synthesis, retaining unassembled heavy chains and also assisting their folding. Following association with beta2-microglobulin (beta2m) in the endoplasmic reticulum, a large proportion of human class I molecules release from calnexin, whereas mouse class I molecules do not. We asked whether addition of a second N-glycan to the human class I molecule A*0201 at position 176, a site present in mouse, would affect its binding to calnexin. The 176dg mutant with N-glycans at positions 86 and 176, when transfected into CIR cells, demonstrated increased binding to calnexin, detectable both before and after association with beta2m, and reduced interaction with calreticulin and TAP relative to wild-type protein bearing a single N-glycan at position 86. Cell surface levels of the mutant were decreased only slightly relative to the wild type, suggesting that the protein is not misfolded or grossly altered structurally. A subpopulation of mutant molecules was retained in the endoplasmic reticulum, and surprisingly, these molecules reacted with w6/32, which recognizes an epitope present on transport-competent class I HLA complexes. Transfection into Daudi cells demonstrated that 176dg reacts with w6/32 in the absence of beta2m, suggesting that the Ab epitope can be induced by binding of calnexin. These data may explain previously noted differences between mouse and human class I MHC proteins and demonstrate that the location of N-oligosaccharides within proteins can influence their folding and interactions with chaperones such as calnexin and calreticulin.

Alleles↗

Angelman syndrome: correlations between epilepsy phenotypes and genotypes.

We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11-13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed-circuit television videotaping and digitized electroencephalogrpahic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched class II, III, and IV patients had either no epilepsy or drug-responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as GABRB3, may explain severe epilepsy in AS.

Adolescent↗

Single- and multiple-dose pharmacokinetic comparison of a sustained-release tablet and conventional tablets of naproxen in healthy volunteers.

The pharmacokinetics of a new sustained-release tablet of naproxen (500 mg once daily) were compared with a conventional tablet (250 mg twice daily) after single- or multiple-dose oral administration in healthy volunteers using an open, randomized two-way crossover experimental design. Naproxen was well absorbed from the sustained-release tablet (approximately 97%) compared with the conventional tablet. Pharmacokinetic data showed that the sustained-release formulation reached significantly delayed mean peak plasma levels (Cmax) in both single- and multiple-dose studies and lower Cmax in a single-dose study than the conventional formulation. However, there were no statistically significant differences in other pharmacokinetic parameters, including area under the concentration-time curve (AUC), elimination half-life (t1/2), and elimination rate constant (Ke), in either single- or multiple-dose studies between the two treatments. In addition, there were no significant differences between formulations in Cmax, minimum plasma concentration (Cmin), and fluctuation index in the multiple-dose study.

Adult↗

Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects.

The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.

Alleles↗

The diagnosis of diffuse goitre by ultrasound imaging in children.

In order to find an easy and accurate procedure for diagnosis of diffuse goitre in children, we examined 50 patients with diffuse goitre using fine needle aspiration biopsy cytology, thyroid antibody detection, thyroid hormone analysis and ultrasound imaging. In the meantime, 109 healthy children (control) were examined by ultrasound imaging. The results showed that thyroid imaging in health children was a smooth echo pattern with stronger homogenous echogram than surrounding muscle tissues. The patients with diffuse goitre showed an abnormally enlarged thyroid volume. In 22 (84.6%) of 26 children with chronic lymphocytic thyroiditis, a varied patch hypoechogenicity was found, of whom 18 (81.8%) had positive results of antibody testing. On the contrary, echo-pattern was normal in 17 (70.8%) of 24 patients with diffuse thyroid proliferation and only the remainder (7/24, 29.1%) had abnormal echo-pattern as well as elevated auto-antibody titers, of whom 2 were confirmed as chronic lymphocytic thyroiditis by a repeat fine needle aspiration biopsy 1 year later. By using combined ultrasound imaging and antibody determination, 92% of the cases with chronic lymphocytic thyroiditis could be diagnosed. Our study suggests that ultrasonic imaging is an easy, non-invasive, reproducible and effective procedure in the differential diagnosis of chronic lymphocytic thyroiditis in children.

Adolescent↗

Binding properties and stoichiometries of a palladium(II) complex to metallothioneins in vivo and in vitro.

This paper will be the first to discuss the in vivo and in vitro properties of a Pd(II) complex, K2PdCl4, interacting with metallothioneins (MTs). In vivo experiments revealed that intraperitoneal injections of K2PdCl4 into rabbits led to the simultaneous synthesis of Pd-MT in the kidney and Zn7MT in the liver. The renal Pd-MT complex contains 3.6 +/- 0.3 Pd, 2.1 +/- 0.2 Zn, and 1.0 +/- 0.1 Cu per mole protein. It was found that pre-treatment with Zn(NO3)2 before K2PdCl4 injections significantly enhanced renal Pd-MT level. The same pre-treatment also increases hepatic Zn-MT levels. These results strongly suggest that Pd(II) ions can be bound in vivo by MT existing in the rabbit kidneys to form Pd-MT. Gel-filtration chromatographic studies after the incubation of either native Cd5Zn2MT2 or Zn7MT2 with K2PdCl4 in vitro demonstrate that Pd(II) ions promote the non-oxidative oligomerization of native MTs. Increasing the level of Pd(II) relative to MT led to a concomitant increase in the apparent yield of MT oligomers. At relatively low Pd-MT ratio, Pd(II) is found predominantly in the oligomers while the monomeric products are chiefly composed of the reactants, Cd5Zn2MT2 or Zn7MT2. Based on our experimental data, the mechanisms of the reactions between Pd(II) and MTs in vivo and in vitro are discussed.

Animals↗

Purification of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) and analyses of the structural proteins.

The Kaposis's sarcoma-associated herpesvirus (KSHV) infected BCBL-1 cell line, adapted to and grown in medium containing 10% horse serum, was induced to lytic replication with 12-O-tetradecanoylphorbol-13-acetate (TPA) for virus production. Supernatants from induced cells were filtered through a 0.45-microm filter and virions were concentrated by polyethylene glycol extraction and high speed centrifugation. The virus was purified by a glycerol gradient zonal centrifugation step followed by isopycnic separation using positive density negative viscosity gradients. Two visible bands were detected after the final centrifugation step: an upper band that contained a homogenous population of purified virions and a lower band that contained aggregates of purified virus and other cellular debris. Fractionation of purified virion preparations by SDS-PAGE revealed 32 bands with estimated molecular weights between 19 and 280 K in silver stained gels. The glycoprotein bands in purified virus were identified with biotinylated lectins and horseradish peroxidase-labeled streptavidin. Two lectins were used to identify the KSHV glycoproteins: concanavalin A and Ricinus communis agglutinin I. Eight distinct glycoproteins were detected with these lectins. In addition, antisera from KS patients were used to detect immunoreactive proteins in purified virions. An apparent immunodominant band of Mr 94,000 (94 K) was recognized by patients' antisera. Other proteins detected with some of the KS antisera tested corresponded to molecular weights of 57 K, 70 K, 180 K, 200 K and 240 K. The 94 K band was identified as gp94 by Endo F digestion.

Cell Line↗

Use of serum soluble interleukin-2 receptor levels to monitor the progression of cutaneous T-cell lymphoma.

BACKGROUND: The serum concentration of soluble alpha chain of the interleukin-2 receptor (sIL-2R) correlates with tumor burden in cutaneous T-cell lymphoma (CTCL). Therefore the sIL-2R level may be useful to monitor the condition of patients treated with extracorporeal photopheresis or other treatments. OBJECTIVE: Our goal was to determine the utility of serum sIL-2R as a test in monitoring of patients with advanced CTCL. METHODS: Serum sIL-2R was measured serially in 36 patients with advanced CTCL treated with extracorporeal photopheresis and other modalities (interferon alfa, methotrexate, topical nitrogen mustard, electron beam). RESULTS: Serum concentrations of sIL-2R as well as lactate dehydrogenase (LDH) correlated strongly with lymph node size, but only sIL-2R correlated significantly with the severity of skin manifestations in erythrodermic patients. In addition, serum sIL-2R, but not LDH, was significantly higher in patients with nodal involvement. The level of sIL-2R also was significantly higher in patients with large-cell transformation in the skin or lymph nodes compared with patients without transformed disease. During treatment, serum concentrations of both serum sIL-2R and LDH correlated with changes in clinical status, but only sIL-2R showed statistically significant differences in mean levels for different relative global response scores. Pretreatment levels of both sIL-2R and LDH correlated significantly with survival, but only sIL-2R retained significance when both were entered into the Cox proportionate hazards model. CONCLUSION: The concentration of serum sIL-2R correlates well with disease status and is more useful than LDH or Sézary cell counts to monitor clinical change in patients with advanced CTCL. Moreover, our data suggest that sIL-2R is produced at a relatively low rate by tissue-based lymphoma cells, and that large-cell transformation in CTCL results in marked increase in sIL-2R production in some patients.

Adult↗

Local excision of the parotid gland in the treatment of Warthin's tumour.

The results of local excision of Warthin's tumour in the parotid gland (n = 61) (resection of the tumour together with surrounding normal gland and associated lymph nodes) were compared with those of superficial parotidectomy (n = 88) for incidence of recurrence, duration of operation, and degree of facial deformity. A subgroup of patients in each group were tested for gustatory sweating (iodine starch test) and parotid function (quantitative scintigraphy). Local excision had the following advantages over superficial parotidectomy: shorter operating time, less risk of facial nerve damage, less facial deformity, lower incidence of Frey's syndrome, and better preservation of the function of the parotid gland.

Adenolymphoma↗

Morphological and molecular changes of maize plants after seeds been flown on recoverable satellite.

Dry seeds of Zea mays, heterozygous for Lw1/lw1 alleles, sandwiched between nuclear track detectors aboard Chinese satellite for 15 days, were recovered and mutations in morphological characters on plants developed from these seeds, as well as their selected progenies, were investigated. The dosimetric results indicated that 85% of the seeds received at least 1 hit with Z > or = 20. About 10% of plants developed from flown seeds and 40% of observed selfed lines from the first generation plants showed some morphological changes, such as yellow stripes displayed on leaves, dwarf, anomogensis of floral organs and yellow-green seedlings, when compared with those from ground control. Using yellow stripes on leaves as the main endpoint for evaluating mutation induced in space environment, the frequency of stripe occurrence was 4.6% in the first generation plants, comparable with the results obtained from Long Duration Exposure Facility (LDEF) mission (Mei et al., 1994), but much lower than those from ground based 60 Co-gamma treatment at a dose of 100 Gy, which reached 35.5% in the selfed lines of the second generation. One hundred and ten random primers were screened in RAPD analysis to detect the variation on genomic DNA of plants with stripes on leaves. Of these primers, 10.9% were able to generate polymorphic bands between mutated plants and control, also, common band patterns in several progenies with the same mutation phenotype were observed. These results demonstrated that space radiation environment could induce inheritable mutagenic effects on plant seeds, and verified the change in genetic material in the mutants. Further study will be needed for a better understand of the nature and mechanism of this induction of mutation.

Cobalt Radioisotopes↗

Modified bilateral cleft lip repair with orbicularis reconstruction and prolabial self-elongation.

PURPOSE: This article describes the details of a modified method for bilateral cleft lip repair and presents some examples of patients whose condition was repaired by this technique. PATIENTS AND METHODS: Sixty-five patients ranging in age from 2 to 5 years were treated with this modified procedure. The method was characterized by prolabial lengthening and reconstruction of the orbicularis oris muscle in one stage. RESULTS: Satisfactory results were achieved with this method. The Cupid's bow and the central tubercle appeared more natural. None of the patients developed dehiscence of the wound. CONCLUSIONS: This modified procedure is of special value for complete bilateral cleft lip patients with a short prolabium. The long-term effect of muscle reconstruction on maxillary growth remains to be evaluated.

Child, Preschool↗

Effects of neurotoxins and hindpaw inflammation on opioid receptor immunoreactivities in dorsal root ganglia.

Three types of opioid receptors mediate peripheral opioid antinociception in inflammation. Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid receptors have been developed. Using these antisera we examined the regulation of opioid receptors in rat dorsal root ganglia after hindpaw inflammation and the influence of neurotoxins for primary afferent neurons and sympathetic neurons thereon. Peripheral tissue inflammation was produced by injection of complete Freund's adjuvant into the right hindpaw. Capsaicin was injected subcutaneously once a day for three days using a total dose of 150 mg/kg. 6-hydroxydopamine was injected intraperitoneally 75 mg/kg/day for three days. Freund's adjuvant induced a marked increase in the percentage of mu-, but a decrease in delta- and kappa-opioid receptor-positive neurons. Capsaicin significantly decreased mu-, delta- and kappa-opioid receptor immunoreactivity in both Freund's adjuvant treated and non-treated rats. No significant changes on the mu-, delta- and kappa-opioid receptor immunoreactivities were observed after 6-hydroxydopamine treatment in either Freund's adjuvant-treated or non-treated rats. Our studies indicate: (1) Peripheral inflammation can differentially regulate the expression of the three opioid receptors in dorsal root ganglia neurons with an up-regulation of mu- and down-regulation of delta- and kappa-opioid receptors. 2) A significant portion of mu-, delta- and kappa-opioid receptors are located on capsaicin-sensitive neurons in dorsal root ganglia of both non-inflamed and inflamed hindlimbs. 3) The expression of opioid receptors in dorsal root ganglia of either inflamed or non-inflamed hindlimbs is not influenced by sympathetic postganglionic neurons.

Animals↗