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Biomedical subjects

Jiang Zhu

Publications and source records attributed to Jiang Zhu.

46 records · Page 3Linked to original sources

Molecular dynamics simulation of the unfolding of the human prion protein domain under low pH and high temperature conditions.

Four 10-ns molecular dynamics (MD) simulations of the human prion protein domain (HuPrP 125-228) in explicit water solution have been performed. Each of the simulations mimicked a different environment of the protein: the neutral pH environment was simulated with all histidine residues neutral and bearing a ND proton and with other titratable side chains charged, the weakly acidic environment was simulated with all titratable side chains charged, the strongly acidic environment was simulated with all titratable side chains protonated. The protein in neutral pH environment was simulated at both ambient (298 K) and higher (350 K) temperatures. The native fold is stable in the neutral pH/ambient temperature simulation. Through out all other simulations, a quite stable core consisted of 10-20 residues around the disulfide bond retain their initial conformations. However, the secondary structures of the protein show changes of various degrees compared to the native fold, parts of the helices unfolded and the beta-sheets extended. Our simulations indicated that the heat-induced unfolding and acid-induced unfolding of HuPrP might follow different pathways: the initial stage of the acid-induced unfolding may include not only changes in secondary structures, but also changes in the tertiary structures. Under the strongly acidic condition, obvious tertiary structure changes take place after 10-ns simulation, the secondary structure elements and the loops becoming more parallel to each other, resulting in a compact state, which was stabilized by a large number of new, non-native side chain-side chain contacts. Such tertiary structure changes were not observed in the higher temperature simulation, and intuitively, they may favor the further extension of the beta-sheets and eventually the agglomeration of multiple protein molecules. The driving forces for this tertiary structure changes are discussed. Two additional 10-ns MD simulations, one with Asp202 protonated and the other with Glu196 protonated compared to the neutral pH simulation, were carried out. The results showed that the stability of the native fold is very subtle and can be strongly disturbed by eliminating a single negative charge at one of such key sites. Correlations of our results with previous experimental and theoretical studies are discussed.

Computer Simulation↗

Midlatitude cirrus cloud climatology from the Facility for Atmospheric Remote Sensing. IV. Optical displays.

In this fourth of a series of papers that describe long-term cloud research at the Facility for Atmospheric Remote Sensing at Salt Lake City, Utah, an approximately 10-year record of polarization lidar and photographic observations is analyzed to characterize the occurrence of optical displays in our local varieties of midlatitude cirrus clouds. The frequencies of occurrence of various types of halo, arc, and corona displays are evaluated according to their appearance and longevity over nominal 1-h observation periods and to the meteorological source of the cirrus. We find that complex halo-arc displays are rare at our locale and that even the so-called common 22 degree halo occurs infrequently as a complete long-lived ring. For example, only approximately 6% of the 1561-h daytime cirrus periods have bright and prolonged 22 degree halos, although a total of 37.3% have some indications of this halo, even if they are brief and fragmentary. Other fairly frequent features are the 22 degree upper tangent arc (8.6%), 22 degree parhelia (8.5%), and solar corona (7.2%). Of the optical displays observed, 83.6% are refraction based, only 1.9% are due to reflection phenomena, and a surprising 15.4% are caused by diffraction. Complex halo-arc displays are disproportionally associated with cirrus formed in tropical or subtropical airflow and also contain more horizontally oriented planar ice crystals. Lidar linear depolarization ratios from a subset of vivid displays show significant differences between halo- and the corona-producing cirrus, reflecting the effects of particle shape. Halos are associated with relatively warm cirrus that contain randomly and horizontally oriented planar ice crystals, whereas the colder corona cirrus produce much stronger depolarization from crystals too small to be uniformly oriented. Comparisons are made with available information from other locales, and we attempt to explain the geographical differences in terms of basic cirrus cloud processes.

Journal Article↗

[Experimental and clinical study on the chemosensitivity assay in vitro for head and neck tumor by AgNOR methods].

OBJECTIVE: To evaluate in vitro chemosensitivity of head and neck tumor to eight kinds of antineoplastic drugs by AgNOR technique. METHOD: Fifty-nine cases' fresh specimens were obtained from head and neck tumors. We severed tumor tissue with simple mechanical separation method. After the acting of drugs, cell smear and argyophilie staining, mean Inhibiting rate was calculated. 12 cases were treated with chemotherapy at the same time. RESULT: 54 cases' specimens succeeded in the experiments, the rate of success was 91.5%. The changes of mean Inhibiting rate were from 0 to 63.0%. The chemosensitivity to DDP was the highest in eight kinds of antineoplastic drugs. VCR, 5-Fu, PYM were higher sensitive drugs respectively. The sensitivity to drugs in NPC was significantly higher than laryngeal cancer. The coincidence between the experiment and clinic was 75.0%. CONCLUSION: AgNOR method is simple and convenient. In addition, it has clear correlation with the results of therapy. The method is useful for chemotherapy.

Aged↗

[The treatment of benign prostatic hyperplasia by means of transurethral holmium laser enucleation].

OBJECTIVES: To evaluate the clinical effect of the holmium laser enucleation and morcellation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia(BPH). METHODS: In the treatment of 35 BPH patients, 100 watt high-powered holmium laser set was used transurethrally and a reciprocating blade tissue morcellator was introduced via a nephroscope to enucleate and morcellate the prostatic tissue. RESULTS: Operations in all 35 cases were successful. The average operation time was 60 +/- 23.2 (range 30-180) min. The removed prostatic tissue weighed 31 +/- 9 (range 10-56) g on average. The average catheter time was 1.5 d (from 20 h to 4 d). No blood transfusion was performed in all cases. Histopathological analysis confirmed the diagnosis of BPH in all cases. In the 3-month follow up of 32 cases, IPSS dropped from 24 +/- 6.2 to 5.6 +/- 3.6; the peak urinary flow rate(Qmax) went up from 8.5 +/- 3.9 ml/s to 22.0 +/- 7.2 ml/s; the residual volume of urine dropped from 138 +/- 125 ml to 21 +/- 15 ml. No serious complications were found. CONCLUSIONS: HoLEP is effective in treating BPH. It can completely enucleate the hyperplastic tissue with little bleeding in operation. The treatment has the advantages of short catheter time and significant clinical improvements.

Aged↗

[A study on the application of Nickle-Titanium alloys stent for prevention and treatment tracheostomal stenosis after total laryngectomy].

OBJECTIVE: To evaluate the effect of Nickle-Titanium alloys annular stent to prevent and treatment tracheostomal stenosis after total laryngectomy. METHOD: The stent was used following total laryngectomy and after total laryngectomy. RESULT: Long stent was implanted in 2 cases following total laryngectomy and in 1 cases after total laryngectomy, Which resulted in widening stenosis and relieving obstruction of airway. The tracheostomal diameter is 2 cm afterwards, but the patients have crusts, granuloma and stretch feeling in tracheostoma. Tracheostomaplasty was performed using short stent in 18 cases during laryngectomy. All the cases have no tracheostomal stenosis following over 6 months. The tracheostoma is smooth, enough larger and stable. CONCLUSION: Nickle-Titanium alloys annular short stent is fixed outside the wall of trachea, its complication is less. It may prevent from tracheostomal stenosis. Nickle-Titanium alloys annular long stent is a better method to resolve dyspnea.

Adult↗

APCs in the liver and spleen recruit activated allogeneic CD8+ T cells to elicit hepatic graft-versus-host disease.

Host APCs are required for initiating T cell-dependent acute graft-vs-host disease (GVHD), but the role of APCs in the effector phase of acute GVHD is not known. To measure the effect of tissue-resident APCs on the local development of acute GVHD, we selectively depleted host macrophages and DCs from the livers and spleens, but not from the skin, peripheral lymph nodes (PLN), or mesenteric lymph nodes (MLN), of C57BL/6 (B6) mice by i.v. administration of liposomal clodronate before allogeneic bone marrow transplantation. Depletion of host hepatic and splenic macrophages and DCs significantly inhibited the proliferation of donor C3H.SW CD8(+) T cells in the spleen, but not in the PLN or MLN, of B6 mice. Such organ-selective depletion of host tissue APCs also markedly reduced the trafficking of allogeneic CD8(+) T cells into the livers and spleens, but not PLN and MLN, of B6 recipients compared with that of the control mice. Acute hepatic, but not cutaneous, GVHD was inhibited as well, resulting in improved survival of liposomal clodronate-treated B6 recipients. When C3H.SW CD8(+) T cells were activated in normal B6 recipients, recovered, and adoptively transferred into secondary B6 recipients, activated donor CD8(+) T cells rapidly migrated into the livers and spleens of control B6 recipients but were markedly decreased in B6 mice that were depleted of hepatic and splenic macrophages and DCs. Thus, tissue-resident APCs control the local recruitment of allo-reactive donor T cells and the subsequent development of acute GVHD.

Acute Disease↗

Hematopoietic cytokines, transcription factors and lineage commitment.

The past two decades have witnessed significant advances in our understanding of the cellular physiology and molecular regulation of hematopoiesis. At the heart of stem cell self-renewal and lineage commitment decisions lies the relative expression levels of lineage-specific transcription factors. The expression of these transcription factors in early stem cells may be promiscuous and fluctuate, but ultimately comes under the influence of extracellular regulatory signals in the form of hematopoietic cytokines. In this review, we first summarize our current understanding of the phenotypic characterization of hematopoietic stem cells. Next, we describe key known transcription factors which govern stem cell self-renewal and lineage commitment decisions. Finally, we review data concerning the role of specific cytokines in influencing these decisions. From this review, a picture emerges in which stem cell fate decisions are governed by the integrated effects of intrinsic transcription factors and external signaling pathways initiated by regulatory cytokines.

Apoptosis↗

Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease.

To understand the relationship between host antigen-presenting cells (APCs) and donor T cells in initiating graft-versus-host disease (GVHD), we followed the fate of host dendritic cells (DCs) in irradiated C57BL/6 (B6) recipient mice and the interaction of these cells with minor histocompatibility antigen- (miHA-) mismatched CD8+ T cells from C3H.SW donors. Host CD11c+ DCs were rapidly activated and aggregated in the T cell areas of the spleen within 6 hours of lethal irradiation. By 5 days after irradiation, <1% of host DCs were detectable, but the activated donor CD8+ T cells had already undergone as many as seven divisions. Thus, proliferation of donor CD8+ T cells preceded the disappearance of host DCs. When C3H.SW donor CD8+ T cells were primed in vivo in irradiated B6 mice or ex vivo by host CD11c+ DCs for 24-36 hours, they were able to proliferate and differentiate into IFN-gamma-producing cells in beta(2)-microglobulin-deficient (beta(2)m(-/-)) B6 recipients and to mediate acute GVHD in beta(2)m(-/-) --> B6 chimeric mice. These results indicate that, although host DCs disappear rapidly after allogeneic bone marrow transplantation, they prime donor T cells before their disappearance and play a critical role in triggering donor CD8+ T cell-mediated GVHD.

Animals↗

[Genescan analysis of non-small cell lung cancer in the long arm of chromosome 6].

OBJECTIVE: To investigate if there are microsatellite loci in the long arm of chromosome 6 that have close relationship with non-small cell lung cancer. METHODS: Multiple PCR approach was used to analyze the 18 loci in the long arm of chromosome 6. The PCR products were analyzed in PAGE, and then the electrophoresis maps were analyzed with Gene Scan(TM) and Genotyper(TM). RESULTS: There were different frequencies of loss of heterozygosity (LOH) in different loci (varying from 3.85% to 38.45%). The total frequency of LOH in 41 gastric cancers was 58.5%(24/41). Eight loci with the LOH frequency higher than 20% were mainly located in 2 regions: 6q24 and 6q27. The accurate location is 6q24-6q25.3 [D6S1699(35%), D6S409(23.33%), D6S441(33.33%)] and 6q26-27 [D6S1550(38.45%), D6S264(20%), D6S1585(25%), D6S446(33.33%), D6S281(30.77%)]. CONCLUSION: There may be tumor suppressor genes located in the region of 6q24 and 6q27, which have close relationship with non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

[Development of Acute Promyelocytic Leukemia in PML-RARalpha Transgenic Mice]

To investigate the leukemogenic potential of PML-RARalpha fusion protein in vivo, hCG-PML-RARalpha transgene was constructed using molecular cloning technique and hCG-PML-RARalpha transgenic mice were generated. The genotype and phenotype of hCG-PML-RARalpha transgenic mice were analyzed by PCR, RT-PCR, morphology of peripheral blood and bone marrow cells, and pathological examination of spleen, liver and bone marrow. As a result, acute promyelocytic leukemia was developed in 3 hCG-PML-RARalpha transgenic mice in 1 - 5 months. The results demonstrated that PML-RARalpha fusion protein plays a crucial role in leukemogenesis.

Journal Article↗