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Biomedical subjects

Y Jin

Publications and source records attributed to Y Jin.

At least 235 records · Page 13Linked to original sources

A novel depot preparation of desferrioxamine-B: development of formulation principles.

This report describes the feasibility of simple oil-based depot formulations of a novel n-decanesulfonate salt of the iron chelator desferrioxamine-B. After subcutaneous administration in rodents, desferrioxamine-B n-decanesulfonate depot induces both (a) prolonged release of drug and (b) an increase of at least threefold to fourfold in iron excretion efficiency compared with the parent compound Desferal (desferrioxamine-B mesylate). Optimization experiments probing vehicle composition, surfactant loading, drug loading, and particle size distribution of the depot preparation are described, and the physiochemical stability of an identified pilot formulation is assessed.

Animals↗

Structured Interview for Assessing Perceptual Anomalies (SIAPA).

Clinical descriptions of perceptual and attentional anomalies in schizophrenia emphasize phenomena such as flooding, or inundation, by sensory stimuli. A failure of sensory "gating" mechanisms in the brain is hypothesized to account for these symptoms, and this hypothesis has led to a marked interest in their putative psychophysiological substrates. However, there are no systematic analyses of the phenomenology of these perceptual experiences, nor has the hypothesized connection between the clinical phenomena and their reported psychophysiological substrates been tested. In this investigation, a structured interview instrument was developed to measure perceptual anomalies as distinct from hallucinations and to determine their prevalence across sensory modalities in schizophrenia in 67 schizophrenia subjects and 98 normal controls. The instrument includes Likert ratings of hypersensitivity, inundation, and selective attention to external sensory stimuli. Good interrater agreement, determined from interviews, was obtained. Schizophrenia subjects had significantly higher auditory, visual, and combined scores (i.e., across all modalities) than normal controls did, indicating significantly more perceptual anomalies. For the schizophrenia group, the prevalence of auditory and visual anomalies was significantly greater than the other sensory modalities. The data indicate that the putative phenomenological correlates of sensory gating may be reliably measured and tested with the Structured Interview for Assessing Perceptual Anomalies.

Adult↗

The yeast a1 and alpha2 homeodomain proteins do not contribute equally to heterodimeric DNA binding.

In diploid cells of the yeast Saccharomyces cerevisiae, the alpha2 and a1 homeodomain proteins bind cooperatively to sites in the promoters of haploid cell-type-specific genes (hsg) to repress their expression. Although both proteins bind to the DNA, in the alpha2 homeodomain substitutions of residues that are involved in contacting the DNA have little or no effect on repression in vivo or cooperative DNA binding with a1 protein in vitro. This result brings up the question of the contribution of each protein in the heterodimer complex to the DNA-binding affinity and specificity. To determine the requirements for the a1-alpha2 homeodomain DNA recognition, we systematically introduced single base-pair substitutions in an a1-alpha2 DNA-binding site and examined their effects on repression in vivo and DNA binding in vitro. Our results show that nearly all substitutions that significantly decrease repression and DNA-binding affinity are at positions which are specifically contacted by either the alpha2 or a1 protein. Interestingly, an alpha2 mutant lacking side chains that make base-specific contacts in the major groove is able to discriminate between the wild-type and mutant DNA sites with the same sequence specificity as the wild-type protein. These results suggest that the specificity of alpha2 DNA binding in complex with a1 does not rely solely on the residues that make base-specific contacts. We have also examined the contribution of the a1 homeodomain to the binding affinity and specificity of the complex. In contrast to the lack of a defective phenotype produced by mutations in the alpha2 homeodomain, many of the alanine substitutions of residues in the a1 homeodomain have large effects on a1-alpha2-mediated repression and DNA binding. This result shows that the two proteins do not make equal contributions to the DNA-binding affinity of the complex.

Consensus Sequence↗

EMAP II: a modulator of neovascularization in the developing lung.

Neovascularization is a key regulatory process in fetal growth and development. Although factors promoting growth and development of the pulmonary vasculature have been investigated, nothing is known regarding the molecular mechanisms that may counteract these stimuli. Endothelial monocyte-activating polypeptide (EMAP) II has recently been identified as an antiangiogenic factor in tumor vascular development. We postulated that EMAP II is a putative negative modulator of lung vascular growth. EMAP II mRNA and protein decrease fivefold (P < 0.01) as the developing lungs in the fetal mouse progress from having poor vascularization (day 14) to having complete vascular development at term (day 18.5). EMAP II protein expression continues to remain low throughout postnatal life and into adulthood, with the exception of a surge that correlates with microvascular maturation. Furthermore, through the use of in situ hybridization and immunohistochemistry, EMAP II is localized throughout the lung, with significant expression in the submyoepithelial area during the early stages of lung development when there is minimal vascular development. In contrast, EMAP II is distributed around the large vessels during the end of vascular development, suggesting that EMAP II modulates the neovascularization process. We speculate that EMAP II is a director of neovascularization in the developing lung.

Animals↗

Hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji).

We report five cases of hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). After having worked for 5 to 20 years, they began to notice symptoms of cough, sputum, and dyspnea. They were diagnosed as having a hypersensitivity pneumonitis based on clinical features, bronchoalveolar lavage and transbronchial lung biopsy. By the double immunodiffusion test, precipitating lines between shimeji spore antigen and sera were observed in all of the patients. By enzyme-linked immunosorbent assay, the antibody activities against shimeji and three species of fungi (Cladosporium sphaerospermum, Penicillium frequentans, and Scopulariopsis species) were significantly higher in the sera of the patients than in those of normal subjects who were cultivating shimeji. Although it is not clear what causes this disease, these findings may be helpful in determining the specific antigen.

Adult↗

Familial aggregation of pulmonary function in a rural Chinese community.

We investigated familial aggregation of pulmonary function among asthma index families and randomly selected nuclear families in a rural community in China. Measurements of pulmonary function and related risk factors were obtained from each family member. A generalized estimation equation model was used to explore the independent relation of pulmonary function among family members, with adjustment for sex, age, height, weight, education, smoking, and asthma status. There was a significant parent-child and sib-sib correlation of pulmonary function. The parent-child correlation of pulmonary function was similar for the first and second children. The correlation was greatest between sib-sibs, followed by mother-child, and less pronounced between father-child among asthma families. The rate of reduced pulmonary function in a subsequent sibling was lowest (4.0%) when both of the parents and the first sibling were in the high-pulmonary-function tertile (high-high group) and was highest (18.4%) when both the parents and the first sibling were in the low-pulmonary-function tertile (low-low group). The rates were intermediate if only the parents (7.0%, low-high group) or only the first sibling (11.5%, high-low group) was in the reduced-pulmonary-function tertile. Our data indicate a strong familial aggregation of pulmonary function in both asthma and random families in this population.

Adolescent↗

Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.

OBJECTIVE: The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia. METHOD: In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly. RESULTS: The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms. CONCLUSIONS: These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.

Adult↗

Nasal administration of transforming growth factor-beta1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis.

Cytokines have a crucial role in initiation and perturbation of EAE that represents an animal model of multiple sclerosis (MS). Administration of transforming growth factor-beta1 (TGF-beta1) to EAE mice improves clinical EAE and prevents relapses by unknown mechanisms. Administering low doses of TGF-beta1 nasally, we confirmed that TGF-beta1 inhibited development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. Infiltration of CD4+ T-cells and macrophages within the central nervous system was clearly reduced, while proliferation and IFN-gamma secretion of mononuclear cells (MNC) was augmented in TGF-beta1-treated EAE rats compared to PBS-treated control EAE rats. TGF-beta1 administered nasally also increased nitric oxide production and CD4+ T cell apoptosis. TGF-beta1 treated rats showed augmented proliferation of dendritic cells (DC) compared to MNC. These data imply that low doses of TGF-beta1 given by the nasal route prevent PR-EAE and upregulate DC functions that may be involved for disease prevention.

Administration, Intranasal↗

A role for A/T-rich sequences and Pit-1/GHF-1 in a distal enhancer located in the human growth hormone locus control region with preferential pituitary activity in culture and transgenic mice.

A region located remotely upstream of the human pituitary GH (GH-N) gene and required for efficient GH-N gene expression in the pituitary of transgenic mice was cloned as a 1.6-kb Bg/II (1.6G) fragment. The 1.6G fragment in the forward or reverse orientation increased -496GH-N promoter activity significantly in pituitary GC and GH3 cells after gene transfer. The 1.6G fragment was also able to stimulate activity from a minimal thymidine kinase (TK) promoter which, unlike -496GH-N, lacked any Pit-1/GHF-1 element. Enhancer activity was localized by deletion analysis to a 203-bp region in the 3'-end of the 1.6G fragment and was characterized by the presence of a diffuse 136-bp nuclease-protected site, observed with pituitary (GC) but not nonpituitary (HeLa) cell nuclear protein. A major low-mobility complex was observed by electrophoretic mobility shift assay (EMSA) with GC cell nuclear protein, and the pattern was distinct from that seen with a HeLa cell extract. The nuclease-protected region contains three A/T-rich Pit-1/ GHF-1-like elements, and their disruption, in the context of the 203-bp region fused to the TK promoter, reduced enhancer activity significantly in pituitary cells in culture. A mutation in this region was also shown to decrease enhancer activity in transgenic mice and correlated with a decrease in the 203-bp enhancer region complex observed by EMSA. The participation of Pit-1/GHF-1 in this complex is indicated by competition studies with Pit-1/GHF-1 elements and antibodies, and direct binding of Pit-1/GHF-1 to the A/T-rich sequences was shown by EMSA using recombinant protein. These studies link the A/T-rich sequences to the distal enhancer activity associated with the GH locus control region in vitro and in vivo.

Animals↗

Chromatin structure and nuclear remodeling.

Nuclear architecture is remodeled during interphase in response to changes in gene activity as well as to changing structural and functional requirements during cell division. Using the monoclonal antibody mAb2A, we have identified two proteins that appear to play important roles in these processes: JIL-1 is a tandem serine-threonine kinase implicated in the regulation of chromatin structure, whereas Skeletor is a novel protein participating in structural nuclear remodeling during the cell cycle. Antibody staining and live imaging of JIL-1-GFP transgenic flies show that JIL-1 localizes to the gene-rich interband regions of larval polytene chromosomes and is upregulated almost twofold on the hypertranscribed male X chromosome compared with autosomes. We propose that JIL-1 may play a role in transcriptional control potentially by regulating chromatin structure. The other mAb2A antigen, Skeletor, is distributed in a nuclear meshwork pattern that can be observed in stereo pair images to reorganize during the cell cycle to form a spindle-like structure at prometaphase that is distinct from the microtubule spindle apparatus. Taking advantage of the powerful molecular and genetic approaches offered in Drosophila, the study of these two proteins promises to yield new insight into what defines nuclear architecture at the molecular level and how its remodeling is regulated.

Amino Acid Sequence↗

[Pneumonitis induced by the drug ougon].

We report a case of drug-induced pneumonitis associated with the herbal medications Sho-saiko-to and Ouren-gedoku-to. A 62-year-old man experienced fever and dry cough after using Ouren-gedoku-to for 2 months. He was admitted to our hospital because a subsequent 5-day course of Sho-saiko-to for suspected bronchitis aggravated these symptoms and caused exertional dyspnea. Chest X-ray films revealed a ground-glass appearance in both lower lung fields. Cessation of these medications improved the patient's clinical and X-ray findings. Bronchoalveolar lavage showed an increase in lymphocytes with a decreased CD 4/CD 8 ratio. While drug-induced lymphocyte stimulation tests gave negative results, challenge tests for Ouren-gedoku-to and Sho-saiko-to were both positive. A diagnosis of drug-induced pneumonitis was made. Our findings suggested the involvement of Ougon, the only common ingredient in the two medications.

CD4-CD8 Ratio↗

[Hypereosinophilic syndrome associated with antineutrophil cytoplasmic antibody].

A 68-year-old man was admitted to our hospital with complaints of fever, cough, and shortness of breath. He had several erythematous maculae on the trunk and experienced hypesthesia in his lower extremities. Laboratory data showed marked eosinophilia (20,235/mm3) and enhanced hepatobiliary enzymes. Chest X-ray films and computed tomographic scans revealed diffuse patchy infiltrative changes in the lungs. Histologic findings confirmed eosinophilic infiltration of the skin, liver, and lungs. A diagnosis of hypereosinophilic syndrome (HES) was made in accordance with clinical criteria proposed by Chusid et al. The patient was positive for antineutrophil cytoplasmic antibodies (a marker for vasculitis). This suggested a clinical picture resembling Churg-Strauss syndrome (CSS) despite the lack of bronchial asthma. The findings in this report could contribute to a better understanding of the diversity of HES cases, several of which are considered to represent a continuum of pathologies sharing an etiology similar to that of CSS.

Aged↗

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers.

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.

Adult↗

Ectomesenchymal stem cells and all-trans-retinoic acid induced apoptosis.

OBJECTIVE: This study aimed to establish and characterize ectomesenchymal stem cells and further reveal the effects of all trans-retinoic acid (RA) on the biologic behaviors of these cells. METHODS: Ectomesenchymal stem (EMS) cells of developing palatal processes were explanted from the palatal shelves of embryonic BALB/c mice. The characterization of EMS cells was accomplished by immunohistochemical analysis and growth curves. The action of RA on EMS cells was evaluated according to population doubling time and the terminal deoxyribonucleotidyl transferase dUTP nick end-labeling assay. RESULTS: Primary culturing of EMS cells proceeded successfully. The results of immunohistochemistry showed that EMS cells stained neuron-specific enolase (+), S-100 (+), vimentin (+3), keratin (-), myoglobin (-) and factor VIII (-). The population doubling time of RA-treated EMS cells was much longer compared with nontreated EMS cells. RA also dramatically increased the number of apoptotic cells. CONCLUSION: Ectomesenchymal stem cells may be undifferentiated. RA inhibited their proliferation and induced apoptosis. The inhibition of growth and excess apoptosis may contribute to the formation of cleft lip/palate and other orofacial congenital malformations.

Animals↗

Non-invasive assessment of myocardial risk and infarct area in canine model of myocardial reperfusion by intravenous contrast echocardiography.

OBJECTIVE: To evaluate the newly developed perfluoropropene-filled echo-contrast agent (FCT-188) in non-invasive assessment of risk areas (RA) and infarct areas (IA) with intravenous myocardial contrast echocardiography (MCE) in canine model of ischemia followed by reperfusion. METHODS: Eight chest-opened Beagle dogs with a 90-minute ischemia followed by a 240-minute reperfusion were studied. MCE was performed after a bolus injection of FCT-188 (0.025 ml/kg, i.v.) into a superficial vein of the forelimb at baseline, 20 minutes after occlusion, and 4 h after reperfusion to non-invasively assess the left ventricular myocardium area (LVMA), myocardial ischemic risk area (RA), and infarct area (IA) in a short-axis view of left ventricle. The accuracy of detecting myocardial perfusion with intravenous MCE was further assessed by in vitro myocardial staining of the matched cross-sections. Both RA and IA were expressed as percent of LVMA. RESULTS: LVMA, RA, IA, and IA/RA ratio were accurately assessed by MCE (LVMA: 6.60 cm2 +/- 0.76 cm2; RA: 35.7% +/- 6.68%; IA: 21.0% +/- 13.2%; IA/RA: 60.3% +/- 31.4%; n = 7) as compared with those of the matched cross-section (LVMA: 6.81 cm2 +/- 0.73 cm2, P = 0.062; RA: 35.3% +/- 9.9%, P = 0.84; IA: 25.10% +/- 14.5%, P = 0.07; IA/RA: 68.0% +/- 22.2%, P = 0.28, respectively). There was a significant correlation of MCE-assessed IA/RA ratio and its corresponding pathologically determined finding in vitro (Y = 1.21 x -21.6, r = 0.73, P = 0.015). No significant changes of electrocardiogram (ECG), mean artery pressures (MAP), pulmonary artery pressures (PAP), and pulmonary artery wedge pressures (PAWP) were found between pre- and post-intravenous injection of FCT-188 at each time point. CONCLUSION: These indicate that FCT-188 can be used to assess risk areas and infarct areas accurately and non-invasively with intravenous MCE in the canine model of a 90-minute ischemia followed by a 240-minute reperfusion and might have potential significance for non-invasive assessment of myocardial reperfusion clinically.

Animals↗

[Killing of leukemic cells by anti-CD3McAb plus rIL-2 activated cord blood].

OBJECTIVE: To investigate the killing efficacy of cord blood monocyte activated by Anti-CD3 monoclonal antibody(McAb) in K562 and HL-60 cell lines. METHODS: By using indirect rosette forming test, antigen expression rate of monocyte was detected. The levels of interleukin-8 (IL-8), IL-6 and tumor necrosis factor alpha (TNF-alpha) were measured by ELISA. The killing efficacy in 3H-thymidine target cells was detected by beta-liquid scintillator. RESULTS: After being activated by Anti-CD3McAb and rIL-2, the antigen expression of monocyte was changed markedly. The levels of IL-8, IL-6 and TNF-alpha were increased; The Anti-CD3 McAb activated killer cells produced significant lysis in K562 and HL-60 cell lines and the optimum conditions were as follows: concentration of cells, 1 x 10(6)/ml; Anti-CD3McAb, 1 microgram/ml; rIL-2 1,000 U/ml; time of culture, 72 hrs; ratio of effector/target: 100:1. CONCLUSION: Anti-CD3 McAb activated killer cells exhibited a strong cytotoxicity to leukemic cells. Our study provides a theoretical basis for the adoptive immunotherapy of leukemia by activated cord blood.

Antibodies, Monoclonal↗

[Effects of human BMP2 gene transfection on NIH3T3 cells in vitro].

OBJECTIVE: To elucidate the mechanism of bone morphogenetic protein (BMP) on cell differentiation and to provide basis for BMP gene therapy. METHODS: A phagemid expression vector for human BMP2 (pBK-B2) was constructed and transfected into the NIH3T3 cells by using Lipofect AMINE. Positive cell clones were selected with G-418. The stable transfection, expression and secretion of hBMP2 were determined by in situ hybridization, immunohistochemistry and sandwich-in ELISA methods. The proliferativity of the transfected cells were assayed by methabenzthiazuron (MTT) method. Alkaline phosphatase (ALP) and osteocalcin (OC) production were also measured in the transfected cells. RESULTS: The results showed that cell proliferation was inhibited after the transfection with hBMP2 gene. But the transfected cells showed increased ALP activity and OC production. CONCLUSION: These results indicate that BMP2 is expressed stably and efficiently in the NIH3T3 cells and is involved in inducing differentiation of NIH3T3 cells into osteoblast-like cells.

3T3 Cells↗