Search PubMed⌕ Search

Biomedical subjects

D Zhong

Publications and source records attributed to D Zhong.

At least 37 records · Page 2Linked to original sources

[Multivariate analysis of the parameters related to prognosis of astrocytoma].

OBJECTIVE: To investigate the clinical and pathological characteristics of astrocytoma and the factors related to pathologic gradings as well as prognosis in astrocytoma. METHODS: 120 cases of the astrocytoma with complete clinical data were selected as the study group, of which 94 cases had follow-up data. 20 cases of normal brain tissue and demyelinating plaques with astrocyte hyperplasia were used as the control group. The expression of Ki-67, VEGF, collagen IV and TRT by immunohistochemical staining and detection of TRTmRNA and telomerase RNA by in situ hybridization were studied. RESULTS: (1) Both astrocytoma and demyelinating lesions showed various positivity for Ki-67. The difference between different gradings of the astrocytoma and non-neoplastic lesions were significant(P < 0.01). Taking 8.5% of Ki-67 expression as threshold, there was significant difference between two survival curves indicating favorable and unfavorable prognosis in the tumor group respectively (P < 0.01). (2) Microvascular changes, such as the density of blood vessels, did not demonstrate any difference between grade I, II astrocytoma and normal tissue, but was significantly increased in grade III and IV astrocytoma and even more in the necrotic area (P < 0.01). The expression of VEGF correlated closely to the density of the blood vessel (P < 0.01). (3) The expression of TRT protein was negative in normal astrocytes but positive in proliferative disease and astrocytoma. The intensity of the positivity was enhanced by the grading of the tumor and correlated with the prognosis (P < 0.01). The expression of hTR, TRTmRNA was less than that of TRT but was well correlated to TRT expression. CONCLUSIONS: Use of the cox-regression model in multivariate analysis shows that there are six parameters closely related to the prognosis of astrocytoma, of which the pathological grade being the most critical factor. Ratio of Ki-67 positivity, age of patient, duration of symptoms are also important factors, while microcystic changes in the tumor and expression of VEGF are independent favorable factors for astrocytoma.

Adult↗

[Difference of T helper cell subsets and B7 co-stimulatory molecule expressions by alveolar macrophages in bronchoalveolar lavage fluid between patients with allergic asthma and chronic obstructive pulmonary disease].

OBJECTIVE: To elucidate the differences of T helper cell subsets and expressions of B7 co-stimulatory molecules by alveolar macrophages (AM) between patients with allergic asthma and chronic obstructive pulmonary disease (COPD). METHODS: Bronchoalveolar lavage fluid (BALF) cells were obtained from 16 normal control volunteers, 16 patients with allergic asthma and 16 patients with COPD. IFN-gamma and IL-4 levels in the supernatant of BLAF lymphocytes cultured with PHA were determined using sandwich ELISA and the CD80 (B7-1) and CD86 (B7-2) expressed by AM stimulated with LPS were determined using avdin-biotin complex technique. RESULTS: In COPD group, IFN-gamma level was significantly higher than those of the control group and asthma group (P < 0.01). IFN-gamma in asthma group was lower than that of the control group (P < 0.01). IL-4 level and the ratio of AM expressing CD86 in asthma group were higher than those of the control group and COPD group (P < 0.01). The IL-4 level and ratio of AM expressing CD86 showed no significantly difference between COPD and control group (P > 0.05). The IL-4 levels in 3 groups were significantly positively correlated with the ratio of AM expressing CD86 (r = 0.61, P < 0.05). No difference of the ratio of AM expressing CD80 was found among three groups (P < 0.05). CONCLUSION: Asthma is characterized by a predominance of Th2-type response in BALF T cells, and COPD of Th1-type response in BALF T cells. The increased expression of co-stimulation of CD86 in AM is probably involved in Th2-type response in the airway inflammation in allergic asthmatics.

Adult↗

[Expression of cytokeratin 7 and 20 in ovarian metastatic carcinomas].

OBJECTIVE: To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas. METHODS: The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods. RESULTS: On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer. CONCLUSIONS: CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results.

Adenocarcinoma↗

[Spectral emissivity of thin films].

In this paper, the contribution of multiple reflections in thin film to the spectral emissivity of thin films of low absorption is discussed. The expression of emissivity of thin films derived here is related to the thin film thickness d and the optical constants n(lambda) and k(lambda). It is shown that in the special case d-->infinity the emissivity of thin films is equivalent to that of the bulk material. Realistic numerical and more precise general numerical results for the dependence of the emissivity on d, n(lambda) and k(lambda) are given.

Absorption↗

Femtosecond studies of protein-ligand hydrophobic binding and dynamics: human serum albumin.

In this contribution, we report studies of the nature of the dynamics and hydrophobic binding in protein-ligand complexes of human serum albumin with 2-(2'-hydroxyphenyl)-4-methyloxazole. With femtosecond time resolution, we examined the orientational motion of the ligand, its intrinsic nuclear motions, and the lifetime changes in the hydrophobic phase. For comparisons, with similar but chemical nanocavities, we also studied the same ligand in micelles and cyclodextrins. The hydrophobic interactions in the binding crevice are much stronger than those observed in cyclodextrins and micelles. The confined geometry restrains the nonradiative decay and significantly lengthens the excited-state lifetime. The observed dynamics over the femtosecond-to-nanosecond time scale indicate that the binding structure is rigid and the local motions of the ligand are nearly "frozen" in the protein. Another major finding is the elucidation of the directed dynamics by the protein. Proton transfer and intramolecular twisting of 2-(2'-hydroxyphenyl)-4-methyloxazole were observed to evolve along two routes: one involves the direct stretching motion in the molecular plane (approximately 200 fs) and is not sensitive to the environment; the second, less dominant, is related to the twisting motion (approximately 3 ps) of the two heterocyclic rings and drastically slows down in the protein hydrophobic pocket.

Biological Transport↗

Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human coagulation factor xa. Studies on catalytic efficiency and inhibitor binding.

The serine protease domain of factor Xa (FXa) contains a sodium as well as a calcium-binding site. Here, we investigated the functional significance of these two cation-binding sites and their thermodynamic links to the S1 site. Kinetic data reveal that Na(+) binds to the substrate bound FXa with K(d) approximately 39 mm in the absence and approximately 9.5 mm in the presence of Ca(2+). Sodium-bound FXa (sodium-Xa) has approximately 18-fold increased catalytic efficiency ( approximately 4.5-fold decrease in K(m) and approximately 4-fold increase in k(cat)) in hydrolyzing S-2222 (benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide), and Ca(2+) further increases this k(cat) approximately 1.4-fold. Ca(2+) binds to the protease domain of substrate bound FXa with K(d) approximately 705 microm in the absence and approximately 175 microm in the presence of Na(+). Ca(2+) binding to the protease domain of FXa (Xa-calcium) has no effect on the K(m) but increases the k(cat) approximately 4-fold in hydrolyzing S-2222, and Na(+) further increases this k(cat) approximately 1.4-fold. In agreement with the K(m) data, sodium-Xa has approximately 5-fold increased affinity in its interaction with p-aminobenzamidine (S1 site probe) and approximately 4-fold increased rate in binding to the two-domain tissue factor pathway inhibitor; Ca(2+) (+/-Na(+)) has no effect on these interactions. Antithrombin binds to Xa-calcium with a approximately 4-fold faster rate, to sodium-Xa with a approximately 24-fold faster rate and to sodium-Xa-calcium with a approximately 28-fold faster rate. Thus, Ca(2+) and Na(+) together increase the catalytic efficiency of FXa approximately 28-fold. Na(+) enhances Ca(2+) binding, and Ca(2+) enhances Na(+) binding. Further, Na(+) enhances S1 site occupancy, and S1 site occupancy enhances Na(+) binding. Therefore, Na(+) site is thermodynamically linked to the S1 site as well as to the protease domain Ca(2+) site, whereas Ca(2+) site is only linked to the Na(+) site. The significance of these findings is that during physiologic coagulation, most of the FXa formed will exist as sodium-Xa-calcium, which has maximum biologic activity.

4-Aminobenzoic Acid↗

Stereoselective pharmacokinetics of propafenone and its major metabolites in healthy Chinese volunteers.

The stereoselective pharmacokinetics of propafenone (PPF) and its active metabolite 5-hydroxypropafenone (5-OHP) as well as their glucuronide and sulfate conjugates have been investigated, in order to clarify the relationship between metabolism and stereoselective disposition of PPF in humans. After oral administration of 300 mg racemic PPF hydrochloride to 10 healthy Chinese subjects, the areas under the plasma concentration-time curves (AUCs) for (S)-PPF were significantly higher (S/R ratio, 1.50+/-0.17) and the apparent oral clearance significantly lower (S/R ratio, 0.68+/-0.07) than those parameters for (R)-PPF. In contrast, the AUCs of PPF glucuronide (PPF-G) were lower for (S)-PPF-G than for the (R)-enantiomer (S/R ratio, 0.83+/-0.12). The partial clearance of (S)-PPF by glucuronidation pathway was lower than that of (R)-PPF and the enantiomeric ratio was 0.62+/-0.04. The t(max) values of PPF glucuronide diastereoisomers showed no statistically significant differences between each other, but were much shorter than the corresponding values of the parent drug, implying that glucuronidation may be the 'first-choice' pathway in presystemic metabolism of PPF. Glucuronidation of 5-OHP favored the (S)-enantiomer, whereas the sulfation showed a large preference for the (R)-enantiomer. After beta-glucuronidase hydrolysis, no significant differences were observed in AUCs between 5-OHP enantiomers (including unconjugated and conjugated 5-OHP). The results suggest that the significant difference in disposition between PPF enantiomers may be, at least in part attributed to stereoselective metabolism in the glucuronidation pathway.

Adult↗

Identification of the metabolites of roxithromycin in humans.

The semisynthetic antibiotic roxithromycin (RXM) exists in an (E)-configuration. Metabolites of RXM in the bile of four cholecystectomy patients with T-tube drainage and in the urine and plasma of four healthy volunteers after single oral doses of 150 mg of RXM were investigated. A total of 15 metabolites were found in bile, urine, and plasma by HPLC with ion trap mass spectrometric and electrochemical detection. These metabolites were identified as descladinose derivative of RXM (M1), erythromycin-oxime (M2), N-, O-, and N,O-di-demethylated derivatives of RXM (M3, M4, and M6), and N-mono- and N-di-demethylated derivatives of erythromycin-oxime (M5 and M7), as well as the (Z)-isomers (M8-M15) of RXM and metabolites M1 to M7, respectively. Structures of six major metabolites (M1-M4, M8, and M10) were established by chromatographic and mass spectrometric determination and comparison with synthesized standards. The stability of RXM and the six synthesized substances was investigated to exclude artifact products. These results, together with previous findings, suggest that biotransformation pathways elucidated for RXM include: 1) isomerization of RXM derivatives, from E-isomer to Z-isomer; 2) O-demethylation; 3) N-demethylation; 4) hydrolysis of the cladinose moiety; and 5) dealkylation of the oxime ether side chain. Secondary metabolism via these pathways was also evidenced. The O-demethylation and isomerization of RXM derivatives represent two novel biotransformation pathways recovered for RXM.

Adolescent↗

[Alteration of interferon-gamma and interleukin-12 released by bronchoalveolar lavage cells from pulmonary tuberculosis].

OBJECTIVE: To explore the change of cytokine released in bronchoalveolar lavage fluid (BALF) cells from pulmonary tuberculosis (TB) patients. METHODS: BALF cells were obtained from group A: 10 normal control volunteers (normal control group); group B: 10 radiographically uninvolved sites of pulmonary TB patients (uninvolved sites group); group C: radiographically involved two lobes of lung and smear-positive of 10 pulmonary TB patients with an onset less than one year; and group D: radiographically involved more than three lobes and smear-positive of 10 pulmonary TB patients with an onset longer than two years. The IFN-gamma and IL-4 production in the culture supermate of BALF lymphocytes stimulated with PHA and IL-12 production in the culture supermate of BALF macrophage (AM) stimulated with lipopolysaccharide were determined using sandwich ELISA. RESULTS: In group C, the IFN-gamma and IL-12 levels [(834 +/- 101) and (294 +/- 73) ng/L, respectively] were not only significantly higher than those of the group B[(197 +/- 59) and (67 +/- 23) ng/L, respectively, all P < 0.01] and normal control group[(179 +/- 51) and (57 +/- 24) ng/L, respectively, all P < 0.01], but also significantly higher than those of group D[(431 +/- 169) and (121 +/- 63) ng/L, respectively, all P < 0.01]; in group D, the IFN-gamma and IL-12 levels were significantly higher than those of the group B and normal control group (all P < 0.01); there were no significant differences between the group C and normal control group (P > 0.05); no differences were seen in IL-4 level among the 4 study groups. CONCLUSIONS: A TH1 type response occurs in involved sites of pulmonary TB patients and that may result from AM which as a regulator through production of IL-12, and the TH1 type response may affect presentation and outcome in pulmonary TB.

Adult↗

[Morphologic analysis of 14 cases of hepatic angiomyolipoma].

OBJECTIVE: To study the morphology of hepatic angiomyolipoma (HAML). METHODS: HE staining, PAS staining, immunohistochemistry and electronic microscopy were used to study 10 cases from our department and 4 cases from consultation. RESULTS: All 14 HAML cases showed perivascular epithelioid cells (PEC) with 4 different types of morphology. They presented characteristic PAS positivity premelanosome like structures and dense body under electronic microscopy. Immunohistochemistry demonstrated positive reaction for both actin and HMB45. CONCLUSION: Light and electronmicroscopic features and immunophenotype of HAML are characteristic of PEC related lesion.

Actins↗

[Giant cell reparative granuloma of the skull].

OBJECTIVE: To investigate the clinical course, histologic feature, diagnosis, differential diagnosis and treatment of giant cell reparative granuloma (GCRG). METHODS: Three cases of GCRG, which arose in the skull, were collected from 1987 to 1999 and analyzed clinicopathologically. RESULTS: Two patients had the lesion in the temporal bone and one in the orbit. One patient with GCRG had a recurrence after incomplete surgical resection. Histologically, all of three cases were characterized by fibroblastic proliferation with osteoclast-like giant cell rich areas, hemorrage, and newly formed bone or osteoid trabeculae. GCRG appeared as a typical bony lytic lesion on computed tomography (CT) and as low signal intensity on both T1 and T2 weighted images on magnetic resonance imaging (MRI). CONCLUSION: GCRG is an uncommon nonneoplastic lesion that typically arises in mandible and maxilla and its involvement in skull is rare. Although behaves benignly, GCRG may be locally aggresive. It is usually misdiagnosed for a giant cell tumor (GCT). Diagnosis of GCRG is based on typical histologic features as well as clinical information. Complete surgical resection is believed to be the most suitable treatment for GCRG and long-term follow-up by CT scanning is essential.

Adult↗

Femtosecond dynamics of dative bonding: concepts of reversible and dissociative electron transfer reactions.

With fs time, speed, and angular resolution of the elementary steps in electron transfer reactions, we report direct observation of reversible and dissociative processes for dative bonding involving covalent and ionic characters. For bimolecular reactions of various donors and acceptors we find strong correlation between the structure and the dynamics. The dynamics from the transition state to final products involve two elementary processes, with different reaction times, speed, and angular distributions. For example, for the R2S.I2 (R = C2H5) system, it is shown that after charge separation, the reversible electron transfer occurs in less than 150 fs (fastest trajectory) and is followed by the rupture of the I-I bond with the release of the first I-atom in 510 fs. However, the second process of the remaining and trapped I-atom takes 1.15 ps with its speed (500 m/s) being much smaller than the first one (1,030 m/s). The S-I-I average angle is 130 degrees. These findings, on this and the other systems reported here, elucidate the mechanism and address some concepts of nonconcertedness, caging, and restricted energy redistribution.

Journal Article↗

Enantioselective determination of propafenone and its metabolites in human plasma by liquid chromatography-mass spectrometry.

A sensitive and stereospecific method was developed to determine propafenone (PPF), 5-hydroxypropafenone (5-OHP) as well as their glucuronide and sulfate conjugates in human plasma. Quantitative analyses and preparative isolations of PPF and 5-OHP were performed on a Nucleosil C18 column after liquid-liquid extraction. Afterwards the enantiomeric ratios of PPF and 5-OHP were determined on a Chiral-AGP column with ion trap mass spectrometric detection in the selected reaction monitoring (SRM) mode via electrospray ionization (ESI). The enantiomers of PPF and 5-OHP were separated with different mobile phases. For PPF enantiomers, the mobile phase consisted of 10 mM ammonium acetate buffer (pH 5.96)-1-propanol (100:9, v/v), at a flow-rate of 0.5 ml/min; And for 5-OHP enantiomers, the mobile phase was 10 mM ammonium acetate buffer (pH 4.1)-2-propanol (100:0.9, v/v), at a flow-rate of 0.6 ml/min. The SRM transitions m/z 342 to m/z 324 and m/z 358 to m/z 340 were monitored for detection of enantiomers of PPF and 5-OHP, respectively. Linear calibration curves were obtained in the concentration range of 20-1600 ng/ml for each enantiomer of PPF and 20-500 ng/ml for the 5-OHP enantiomer. The limits of quantification for each enantiomer of PPF and 5-OHP were found to be 20 ng/ml. Precision and accuracy were within 11% over the calibration range for each of the analytes. Incubation of the plasma samples with beta-glucuronidase/arylsulfatase and the use of the specific beta-glucuronidase inhibitor saccharo-1,4-lactone allows the quantitation of both the glucuronide and sulfate conjugates of the enantiomers. The method was applied to human plasma samples from ten Chinese male volunteers after oral administration of 300 mg racemic propafenone.

Anti-Arrhythmia Agents↗

Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene.

Late infantile neuronal ceroid lipofuscinosis, LINCL, is one of the most common pediatric neurodegenerative disorders. It is caused by mutations in the CLN2 gene, which encodes a lysosomal pepstatin-insensitive peptidase (LPIP). We have identified a novel mutation, T523-1G --> A, by molecular analyses of three unrelated LINCL cases. The mutation was found to affect a 3' intronic splicing acceptor site, resulting in an aberrant mRNA with an insertion of 146 bp of intronic sequence. This causes a frame shift, produces a nonfunctional truncated protein, and results in LINCL.

Adenine↗

Some human inhibitor antibodies interfere with factor VIII binding to factor IX.

Factor VIII (fVIII) functions as a cofactor of factor IXa in the intrinsic pathway of blood coagulation. Its absence or abnormality causes the bleeding disorder hemophilia A. About 23% of hemophiliacs who receive therapeutic fVIII infusions develop antibodies that inhibit its activity. We previously showed by inhibitor neutralization assays that the fVIII A2 and C2 domain polypeptides contain common inhibitor epitopes. Often hemophilic inhibitor plasmas were partially neutralized by C2 and more completely neutralized by fVIII light chain (A3-C1-C2), suggesting the presence of an additional major inhibitor epitope(s) within the A3-C1 domains. In immunoprecipitation assays, 17 of 18 inhibitor IgGs bound to recombinant 35S-A3-C1. Amino acids 1811-1818 of the A3 domain comprise a binding site for factors IX and IXa. Three inhibitor IgGs prevented binding of factor IXa to fVIII light chain, and the binding of each IgG to light chain was competed by A3 peptide 1804-1819. The generation of factor Xa by the fVIIIa/fIXa complex in a chromogenic assay was prevented by these inhibitors. Therefore, we propose that another important mechanism of fVIII inactivation by human inhibitors is the prevention of fVIIIa/fIXa association.

Antibodies, Blocking↗

Effect of inhaled interleukin-5 on airway hyperreactivity and eosinophilia in asthmatics.

In order to investigate the role of interleukin-5 (IL-5) in airway hyperreactivity and eosinophilia, we observed the effect of inhaled recombinant human IL-5 on airway responsiveness to methacholine and cell populations in induced sputum in eight patients with allergic bronchial asthma using a placebo-controlled study design. Our results demonstrated that the inhalation of IL-5 did not alter lung function in allergic asthmatics. In the control experiments receiving either vehicle or 0.4 ng of endotoxin, methacholine PC20 values did not change nor did the numbers of eosinophils or eosinophil cationic protein (ECP) sputum values change from baseline. In contrast, after IL-5 inhalation, methacholine PC20 fell from baseline (0.90 +/- 166 mg/ml) to 0.32 +/- 1.63 mg/ml (p < 0.01) at 24 h, and to 0.55 +/- 1.49 mg/ml (p < 0.05) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia and elevated concentrations of ECP in induced sputum. Our data provided direct evidence that IL-5 increases airway responsiveness and infiltration of activated eosinophils into the airway in patients with allergic bronchial asthma. It also could be concluded that the observed airway hyperreactivity and eosinophilia were not endotoxin related.

Administration, Inhalation↗

[Diagnosis and treatment of periampullary diverticulum].

OBJECTIVE: To provide a better surgical method for periampullary diverticulum, its teraninology and typing, and some experience in its diagnosis. METHOD: In 11 cases of recurrent cholangitis or (and) pancreatitis resulting from periampullary diverticula juxta-ampullary diverticula was observed in 9, intra-ampullary diverticulum in 1, and ampullocele in 1. All patients underwent elective operation including combined diverticulo-sphincteroplasty (7 cases), diverticulectomy with sphincteroplasty (2), diverticulectomy (1), and papilloplasty (1). RESULT: The perioperative and long-term results were excellent. There were no recurrence and morbidity. CONCLUSION: The combined diverticulo-sphincteroplasty is simpl, safe, effective for the treatment of juxta-ampullary diverticula.

Adult↗