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Biomedical subjects

B Zhang

Publications and source records attributed to B Zhang.

At least 109 records · Page 6Linked to original sources

[The expression and clinical significance of pRB and E(2)F(1) in human neuroendocrine lung tumor].

OBJECTIVE: To investigate the role pRB and E(2)F(1) play in the cell cycle and the oncogenesis of human nemoendocrine lung fumor and the correlation between their expression and the invasiveness and prognosis of human neuroendocrine lung tumor. METHODS: Immunohistochemistry and in situ hybridization were used to detect the expression of pRB and E(2)F(1) mRNA in the paraffin embedded tissues of 78 cases of human neuroendocrine lung tumor. Statistics was used to analyze the data. RESULTS: The positive expression rate of pRB in both typical and atypical carcinoid was 87.5% (14/16). However, pRB was not expressed in large cell neuroendocrine carcinoma and small cell lung cancer (P < 0.001). The positive rate of E(2)F(1) mRNA expression in human neuroendocrine lung tumor was 87.2% (68/78). The strength of expression of pRB and E(2)F(1) was obviously correlated with the tumor stage, lymph node metastasis and prognosis (P < 0.05). CONCLUSION: The loss of pRB and E(2)F(1) overexpression may play a key role in the development of human neuroendocrine lung tumors.

Adult↗

Determination of alcohols by high-performance liquid chromatography with fluorimetric detection after pre-column derivatisation with carbazole-9-N-acetic acid and chromatographic behaviour of alcoholic derivatives.

Alcohols were derivatised to their carbazole-9-N-acetic acid (CRA) esters with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl) as the dehydrating agent. Studies on derivatisation conditions indicated that the coupling reaction proceeded rapidly and smoothly in the presence of a base catalyst in acetonitrile to give the corresponding sensitively fluorescent derivatives. The retention behaviour of alcohol derivatives was investigated by varying mobile phase compositions (ACN-water and MeOH-water). The parameters from the equation log k'=A-BX were evaluated by retention data of derivatives using an isocratic elution with different mobile phases. The results indicated that the parameters derived allowed computation of retention factors in good agreement with experiments. At the same time, a general equation was derived that makes possible predictions of partition coefficient in binary mobile phases with different proportions of organic solvent to water based on some simple regression analysis. The LC separation for the derivatised alcohols containing higher carbon alcohols showed good reproducibility on a reversed-phase C18 column with gradient elution. The detection limits (excitation at 335 nm, emission at 360 nm) for derivatised alcohols (signal-to-noise ratio=3:1) were in the range of 0.1-0.4 pg per injection.

Alcohols↗

A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.

Clathrin-mediated endocytosis plays a major role in retrieving synaptic vesicles from the plasma membrane following exocytosis. This endocytic process requires AP180 (or a homolog), which promotes the assembly and restricts the size of clathrin-coated vesicles. The highly conserved 33 kDa amino-terminal domain of AP180 plays a critical role in binding to phosphoinositides and in regulating the clathrin assembly activity of AP180. The crystal structure of the amino-terminal domain reported herein reveals a novel fold consisting of a large double layer of sheets of ten alpha helices and a unique site for binding phosphoinositides. The finding that the clathrin-box motif is mostly buried and lies in a helix indicates a different site and mechanism for binding of the domain to clathrins than previously assumed.

Adaptor Proteins, Vesicular Transport↗

Synthesis of 5'-deoxy-5'-thioguanosine-5'-monophosphorothioate and its incorporation into RNA 5'-termini.

[figure: see text] 5'-Deoxy-5'-thioguanosine-5'-monophosphorothioate (GSMP) was synthesized in four steps with 35% overall yield. GSMP serves as a good substrate for in vitro transcription with T7 RNA polymerase to yield 5'-GSMP-RNA, which was converted to 5'-HS-RNA by dephosphorylation with alkaline phosphatase. The thiol-reactive agents can be efficiently introduced into the 5'-terminus of RNA.

DNA-Directed RNA Polymerases↗

Age-related cancer detection rate and costs for one cancer detected in one screening by immunochemical fecal occult blood test.

PURPOSE: This study was performed to assess, from the aspects of screening efficiency and cost-effectiveness, the optimal lower limit of age in immunochemical occult blood screening for colorectal cancer. METHODS: Seven thousand four hundred asymptomatic individuals were the subjects of this study. They gave samples for an immunochemical fecal occult blood test (OC-Hemodia), and colonoscopy was performed during a medical checkup. They were divided into three groups according to their ages: younger (40-49), middle (50-59), and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: The detection rate for colorectal cancer and the average costs to detect one cancer patient were calculated as 0.3 percent and $6024 for the younger group, 1.6 percent and $1425 for the middle group, and 1.7 percent and $1410 for the older group, respectively. The cancer detection rate was significantly different between the younger and middle groups (P < 0.05) and between the younger and older groups (P < 0.05). CONCLUSIONS: This analysis suggests that the subjects aged less than 50 have some disadvantage when carrying out the immunochemical fecal occult blood test, OC-Hemodia for colorectal cancer screening, from the aspects of screening efficiency and cost-effectiveness.

Adult↗

Does stool collection method affect outcomes in immunochemical fecal occult blood testing?

PURPOSE: This paper compares the positive predictive value of an immunochemical fecal occult blood test for colorectal neoplasms between the stool specimens obtained during the digital rectal examination and those obtained during the routine screening. METHODS: In a medical check-up, 1,688 subjects received both an immunochemical fecal occult blood test and a colonoscopy. Fecal occult blood was tested by two methods: digital rectal examination and routine screening. The positivity rate of an immunochemical fecal occult blood test and the positive predictive value for colorectal cancer and large adenomatous polyp were determined by these two methods. RESULTS: The positivity rate and the positive predictive value were 5.4 percent and 19.8 percent (4.4 percent for cancer and 15.4 percent for adenomatous polyp) in the digital rectal examination method and 3.5 percent and 27.1 percent (6.8 percent for cancer and 20.3 percent for adenomatous polyp) in the routine screening method, respectively. These figures indicate a significant difference in the positivity rate (P < 0.01) and the positive predictive value (P < 0.05) between these two methods. CONCLUSIONS: These findings indicate that the stool obtained by routine screening has a better positive predictive value than stool collected during the digital rectal examination.

Adult↗

Comparisons of cancer detection rate and costs of one cancer detected among different age-cohorts in immunochemical occult blood screening.

PURPOSE: This study was carried out to compare the detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer among three different age-cohorts in immunochemical occult blood screening by OC-Hemodia. METHODS: In a population-screening program, 17,432 subjects received an immunochemical fecal occult blood test. In a medical checkup for colorectal cancer 7,232 subjects received colonoscopy. They were divided into three groups according to their ages: younger (4,049 years); middle (50-59); and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: In the screening program-based study, the cancer detection rate and the average costs for one colorectal cancer detected were calculated as 0.09% and $13,352, 0.28% and $4,555, 0.29% and $4,461 for the younger, middle, and older groups, respectively. In addition, in the medical checkup-based study, the detection rate and the average costs were calculated as 0.3% and $6,851, 1.5% and $1,517, 1.7% and $1,391 for the younger, middle, and older groups, respectively. In these two studies, the cancer detection rates were significantly different between the younger and middle groups (P < 0.05), and between the younger and older groups (P < 0.05). CONCLUSIONS: These findings indicate that the subjects aged under 50 have some disadvantage when carrying out the immunochemical fecal occult blood test--OC-Hemodia for colorectal cancer screening--from the viewpoint of screening efficiency as well as cost-effectiveness.

Adult↗

Isolation and characterization of a novel cDNA, UBAP1, derived from the tumor suppressor locus in human chromosome 9p21-22.

PURPOSE: To clone the putative tumor suppressor gene(s) in a refined region at 9p21-22 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). METHODS: We systematically screened the expression patterns of 25 novel ESTs (expressed sequence tags) in a minimal common deleted region of 9p21-22 in NPC. One of these ESTs was found down-regulated in NPC. Subsequently, the corresponding gene sequence of this EST was established by cDNA cloning and RACE (rapid amplification of cDNA end) procedures. Furthermore, a mouse homologue of this gene was identified. The expression of this gene was examined using Northern blot or reverse transcription-polymerase chain reaction (RT-PCR) in various human and mouse tissues. A limited screen for mutation of coding sequence of this novel human gene was undertaken using RT-PCR and direct sequencing analysis. RESULTS: A novel gene was cloned. This gene is a new member of the UBA domain family, so we named it UBAPI for ubiquitin-associated protein 1 (HUGO Gene Nomenclature Committee-approved symbol). Northern blot and RT-PCR analysis demonstrate a ubiquitous pattern of gene expression in human and mouse tissues. The direct sequencing analysis of the coding region of hUBAP1 following RT-PCR failed to reveal any mutations in a preliminary screen of NPC cell line HNE1 and primary nasopharyngeal carcinoma samples. CONCLUSIONS: We cloned a novel gene UBAPI, which is highly conserved between human and mouse. Clearly, as a novel member of UBA domain protein family and taking its map location into account, a more extensive analysis is essential to establish whether subtle mutations are present in nasopharyngeal carcinomas.

Amino Acid Sequence↗

Age-dependent induction of congophilic neurofibrillary tau inclusions in tau transgenic mice.

Intraneuronal filamentous tau inclusions such as neurofibrillary tangles (NFTs) are neuropathological hallmarks of Alzheimer's disease (AD) and related sporadic and familial tauopathies. NFTs identical to those found in AD brains have also been detected in the hippocampus and entorhinal cortex of cognitively normal individuals as they age. To recapitulate age-induced NFT formation in a mouse model, we examined 12- to 24-month-old transgenic (Tg) mice overexpressing the smallest human brain tau isoform. These Tg mice develop congophilic tau inclusions in several brain regions including the hippocampus, amygdala, and entorhinal cortex. NFT-like inclusions were first detected in Tg mice at 18 to 20 months of age and they were detected by histochemical dyes that bind specifically to crossed beta-pleated sheet structures (eg, Congo red, Thioflavin S). Moreover, ultrastructurally these lesions contained straight tau filaments comprised of both mouse and human tau proteins but not other cytoskeletal proteins (eg, neurofilaments, microtubules). Isolated tau filaments were also recovered from detergent-insoluble tau fractions and insoluble tau proteins accumulated in brain in an age-dependent manner. Thus, overexpression of the smallest human brain tau isoform resulted in late onset and age-dependent formation of congophilic tau inclusions with properties similar to those in the tangles of human tauopathies, thereby implicating aging in the pathogenesis of fibrous tau inclusions.

Aging↗

Modeling AFM-induced PEVK extension and the reversible unfolding of Ig/FNIII domains in single and multiple titin molecules.

Molecular elasticity is associated with a select number of polypeptides and proteins, such as titin, Lustrin A, silk fibroin, and spider silk dragline protein. In the case of titin, the globular (Ig) and non-globular (PEVK) regions act as extensible springs under stretch; however, their unfolding behavior and force extension characteristics are different. Using our time-dependent macroscopic method for simulating AFM-induced titin Ig domain unfolding and refolding, we simulate the extension and relaxation of hypothetical titin chains containing Ig domains and a PEVK region. Two different models are explored: 1) a series-linked WLC expression that treats the PEVK region as a distinct entropic spring, and 2) a summation of N single WLC expressions that simulates the extension and release of a discrete number of parallel titin chains containing constant or variable amounts of PEVK. In addition to these simulations, we also modeled the extension of a hypothetical PEVK domain using a linear Hooke's spring model to account for "enthalpic" contributions to PEVK elasticity. We find that the modified WLC simulations feature chain length compensation, Ig domain unfolding/refolding, and force-extension behavior that more closely approximate AFM, laser tweezer, and immunolocalization experimental data. In addition, our simulations reveal the following: 1) PEVK extension overlaps with the onset of Ig domain unfolding, and 2) variations in PEVK content within a titin chain ensemble lead to elastic diversity within that ensemble.

Amino Acid Sequence↗

The associations among thoracic aortic atherosclerosis, coronary atherosclerosis and the function of high density lipoprotein.

We sought to determine the associations among thoracic aortic atherosclerosis, coronary atherosclerosis and the function of high density lipoprotein (HDL) in a case-control study. The function of HDL can be assessed by the fractional esterification rate of cholesterol in low density lipoprotein (LDL)- and very low density lipoprotein (VLDL)-depleted plasma (FER(HDL)), which reflects a balance of cholesterol uptake by HDL and cholesterol ester (CE) transport in the reverse cholesterol transport (RCT) system in humans. Cases (n=51, age: 64.3+/-8.0 years) and controls (n=51, age: 58.7+/-13.1 years) were defined as subjects with/without angiographically proven coronary artery disease (CAD), respectively and examined for thoracic aortic atherosclerosis (TAA) by transesophageal echocardiography. The severity of TAA was determined by the ratio of average sclerotic areas (ASA) and average sclerotic lengths (ASL). The cases had significantly (P<0.05) higher values of ASA (0.22+/-0.18 vs. 0.10+/-0.11), ASL (0.82+/-0.56 vs. 0.48+/-0.45), ASA/ASL ratio (0.23+/-0.08 vs. 0.17+/-0.09) and FER(HDL) (10.3+/-3.8 vs. 8.3+/-3.5% per hour) and lower HDL-C and apolipoprotein A-I levels than the controls. A receiver operating characteristic (ROC) curve analysis showed that ASA/ASL and FER(HDL) had moderate discriminating ability for CAD and the diagnostic accuracy of ASA/ASL was better than that of FER(HDL) (area under ROC curve: 0.703 and 0.656, respectively). Multivariate logistic regression analysis indicated that ASA/ASL and FER(HDL) were independent indicators for CAD [odds ratio (95% CI): 7.5 (2.4-27), P<0.01 and 4.0 (1.2-15), P<0.05] after adjusting for age, gender and other conventional risk factors, and that a high FER(HDL) value greatly increased the relative risk of CAD associated with a high ASA/ASL. The function of HDL, as assessed by FER(HDL), enhances the ability of TAA to predict CAD.

Aged↗

PTHrP increases pancreatic beta-cell-specific functions in well-differentiated cells.

Parathyroid hormone-related protein (PTHrP) is reportedly produced in normal islets and insulinomas. PTHrP induces differentiation in some cell-types and growth in others. We examined whether PTHrP production is greater in well-differentiated or growing beta cells and whether PTHrP induces differentiation or growth in beta cells. We used four groups of the well-differentiated mouse beta cell line MIN6 with 17, 25, 31 and 41 passages, and mouse pancreatic islets. With passage, insulin content diminished, whereas the expression of PTHrP, its activating enzyme furin and cell growth gradually increased. PTHrP increased insulin content and mRNA levels more in MIN6-17 cells than in MIN6-41 cells. In contrast, PTHrP increased DNA synthesis more extensively in MIN6-41 cells than in MIN6-17 cells. Dibutyryl cAMP reproduced PTHrP's effect on insulin content and DNA synthesis. We conclude that PTHrP increases insulin expression in well-differentiated beta cells through the cAMP pathway and stimulates growth in growing beta cells.

Animals↗

Evaluation of the optimum cut-off point in immunochemical occult blood testing in screening for colorectal cancer.

This study was carried out to assess, from the aspects of cost-effectiveness and diagnostic validity, the optimum cut-off point for immunochemical occult blood testing using a 2-day method as a means of screening for colorectal cancer. Four thousand, two hundred and sixty asymptomatic individuals were subjects of this study. They gave samples for an immunochemical fecal occult blood test, and colonoscopy was carried out during a medical check-up. For evaluation of the optimum cut-off point, three cut-off levels of fecal haemoglobin, 50, 150 and 300 ng/ml, were used. A total of 27 patients with colorectal cancer were diagnosed. The average costs to detect one patient with colorectal cancer and the sensitivity and specificity of these three cut-off points of fecal haemoglobin were evaluated. The average costs for the detection of one cancer case were calculated as $2870.45 for cut-off level of 50 ng/ml, $2492.98 for that of 150 ng/ml and $3329.09 for that of 300 ng/ml, respectively. The sensitivity and specificity were calculated as 89 and 94% for the 50 ng/ml cut-off level, 81% and 96% for the 150 ng/ml cut-off level and 56 and 97% for the 300 ng/ml cut-off level, respectively, indicating a significant difference in the sensitivity between the 50 and 300 ng/ml levels (P<0.05), as well as between the 150 and 300 ng/ml levels (P<0.05), and a significant difference in the specificity between the 50 and 300 ng/ml levels (P<0.05). However, no significant difference was observed in the specificity between the 50 and 150 ng/ml levels. The findings show that 150 ng/ml of fecal haemoglobin is the optimal cut-off point when carrying out the OC-Hemodia test as a means of screening for colorectal cancer.

Adult↗

Mass resolved MPI spectra of methyl iodide in the 430-490 nm region.

The mass resolved multiphoton ionization (MPI) spectra of methyl iodide were obtained in the 430-490 nm region using a time-of-flight (TOF) mass spectrometer. They have the same vibrational structure, which testifies that the fragment species, in the wavelength region under study, are from the photodissociation of multiphoton ionized molecular parent ions. Some features in the spectra are identified as three-photon excitations to 6p and 7s Rydberg states of methyl iodide. Two new vibrational structures of some Rydberg states are observed. The mechanism of ionization and dissociation is also discussed.

Hydrocarbons, Iodinated↗

Solvent effects on the absorption and fluorescence characteristics of tin(IV) mesoporphyrin.

The absorption and fluorescence characteristics of tin(IV) mesoporphyrin (SnMP) and its analog tin(IV) protoporphyrin (SnPP) were studied in a series of organic solvents. Fluorescence quantum yields were calculated using the Strickler-Berg equation. Good correlation was found between calculated values and measured relative values. Fluorescence lifetime, radiative lifetime and non-radiative lifetime were also calculated. The parameters showed variation depending on ligation as well as H-bonding. Unusual long lifetime and high quantum yields were found in alcohol solvents. This finding might contribute to elucidation of the nature of tin porphyrins to inhibit heme oxygenase.

Enzyme Inhibitors↗