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Biomedical subjects

Hua Yang

Publications and source records attributed to Hua Yang.

At least 145 records · Page 8Linked to original sources

Gene alteration of intestinal intraepithelial lymphocytes with administration of total parenteral nutrition.

BACKGROUND: Total parenteral nutrition (TPN) is associated with sepsis and loss of immune reactivity. The authors previously have shown that changes in the intestinal mucosal immune system--ie, intraepithelial lymphocytes (IEL)--lead to a loss of epithelial barrier function. This may be a mechanism by which bacteria and toxins endanger individuals receiving TPN. To identify altered IEL gene expression during TPN administration, microarray assays were used. METHODS: Mice received oral feeding (control) or TPN for 7 days. Small bowel IEL were separated and retained, RNA purified, and microarray assays performed (Affymetrix system, 12,491 genes). Results were expressed as quantile-normalized trimmed-means. Significance equals a greater than 2-fold change (TPN v control), P <.01 (t test) or greater than 3-fold, P <.05. RESULTS: In the TPN group 88, IEL genes were significantly up regulated and 114 downregulated (v control). Of these genes, 4 were identified to have highest degree of upregulation (FK506-binding protein 5; mannose-binding lectin, metallothionein 1 and 2), 2 were highly downregulated (microsomal epoxide hydrolase 1 and cytochrome P450 1a1). These genes were found to have high potential for immune-modulatory effects. CONCLUSIONS: The observed alterations in IEL gene expression may have an important role in the altered immune response with TPN and may relate to the increase in sepsis with TPN administration.

Animals↗

Alteration of intestinal intraepithelial lymphocytes after massive small bowel resection.

BACKGROUND: Intraepithelial lymphocytes (IEL) comprise the inner most layer of the gut immune system, and play a critical role in protecting the host from enteric organisms. Massive small bowel resection (MSBR) is one such clinical condition where patients are at particularly high risk for the development of such enteric infectious complications. Because of this, we hypothesized that the IEL may change significantly after the formation of a MSBR. To address this, a mouse model of MSBR was created and the acute phenotypic and functional characteristics of the IEL were studied. MATERIALS AND METHODS: Mice underwent a 70% mid-small bowel resection. After 7 days, IEL were isolated and analyzed for phenotypic changes by flow cytometry. IEL cytokine expression was performed with semiquantitative polymerase chain reaction techniques. To assess the functional significance of these changes, IEL proliferative response was assessed in vitro.Results. MSBR led to significant decreases in specific IEL subpopulations: CD 44+ (used as a marker of cell maturity); CD 8alphabeta+ (marker of thymic derivation), and CD 69+ (marker of T cell activation). Compared with controls, IEL TNF-alpha mRNA expression increased 84%, while IL-2 and IL-10 mRNA expression decreased by 69 and 72%, respectively. Spontaneous proliferation of IEL in the MSBR group was significantly higher than controls, however, proliferation failed to increase with T cell stimulation.Conclusion. These changes suggest a shift to a more immature and possibly less activated cell population. It is possible that such alterations may play an important role in the increase in enterically derived infections in patients with MSBR.

Animals↗

Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) block copolymers: characterization and their use as drug carriers for a controlled delivery system.

Poly(epsilon-caprolactone)-poly(ethylene glycol) (PECL) copolymers were synthesized from polyethylene glycol (PEG) and epsilon-caprolactone (epsilon-CL) using stannous octoate as catalyst at 160 degrees C by bulk polymerization. The effect of the molecular weight of PEG and the copolymer ratio on the properties of the copolymers was investigated by (1)H-NMR, IR, DSC and GPC. PCL and PECL microspheres containing human serum albumin were elaborated by solvent extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of morphology, size, loading efficiency, and the efficiency of microspheres formation. The results show that the microspheres prepared from PECL-10 and PECL-15 copolymers achieved the highest loading efficiency (about 50%) among all copolymers. These results indicate that the properties of copolymers could be tailored by adjusting polymer composition. It is suggested that these matrix polymers may be optimized as carriers in the protein (antigen) delivery system for different purposes.

Calorimetry, Differential Scanning↗

Xenogeneic milieu markedly remodels endocrine cell populations after transplantation of fish islets into streptozotocin-diabetic nude mice.

It is unknown whether irrelevant foreign endocrine products secreted by xenografts would be biologically active and potentially harmful to recipients; even if entirely inert, continuous production might result in harmful circulating antigen-antibody complexes. We examined the fate of such a product using a fish (tilapia)-to-mouse islet xenograft model. Teleost fish islets, like mammalian islets, are composed primarily of cells producing insulin, glucagon or somatostatin; however, teleost fish have two different populations of somatostatin (SST) producing delta cells, one producing SST-14, a 14 amino acid SST identical to mammalian SST, which is derived from the pre-proSST-I gene which is present in all vertebrates, and the other a "large" (i.e. 22 to 28 amino acid) SST derived from a pre-proSST-II gene, which is not found in mammals. In contrast to 'large' SST, which has no mammalian homolog, teleost fish insulins, glucagons and SST-14 exhibit significant biological activity in mammals. Tilapia islets were transplanted under the kidney capsules of streptozotocin-diabetic nude mice, and mice with functioning grafts were killed at various times after transplantation. Serial sections of graft-bearing kidneys were stained by immunoperoxidase for insulin, SST-14, SST-25 and glucagon positive cells, and the areas of each cell type in the graft were measured using image analysis. Sections of untransplanted tilapia islets (both in situ and after harvest/culture) were also immunostained and measured as controls. Xenotransplantation of fish islets into diabetic nude mice resulted in the rapid degeneration and near total loss of SST-25+ cells, as well as a marked redistribution of the proportions of the remaining endocrine cell types. The proportions of cell types in the grafts gradually changed from a piscine pattern to that of mammalian islets.

Animals↗

Regional left ventricle mechanical asynchrony in patients with heart disease and normal QRS duration: implication for biventricular pacing therapy.

LV electromechanical delay results in asynchronized contraction. However, it is not known if the presence of cardiac diseases without QRS prolongation may result in inter- or intraventricular asynchrony. This study investigated the occurrence of systolic mechanical delay in different regions of the LV in patients with underlying heart diseases and normal QRS duration. Tissue Doppler imaging (TDI) was performed in 141 patients (age 63.7 +/- 11.5 years) with underlying heart diseases (82% had ischemic heart disease) and 92 normal healthy volunteers (age 63.9 +/- 9.8 years) based on the four-basal and four-mid-segment model by apical views. Of these, 124 patients had normal QRS duration (< or = 120 ms) while 17 were prolonged due to LBBB or intraventricular conduction defect. Patients with normal QRS duration had significantly lower peak myocardial isovolumic contraction velocity (IVCM), sustained systolic velocity (SM), and prolonged time to peak IVCM and SM in almost all myocardial segments when compared to controls. The time to peak IVCM (basal lateral vs basal septal segment: 61.0 +/- 29.4 vs 53.3 +/- 24.1 ms, P < 0.005) and SM (basal lateral vs basal septal segment: 174 +/- 44 vs 154 +/- 36 ms, P < 0.001) was further delayed in the LV free-wall segments. Mechanical delay was also evident in the LV free-wall segments in patients with preserved or impaired systolic function, in patients with or without previous myocardial infarction, and in patients with prolonged QRS duration. Patients with prolonged QRS had a higher prevalence of LV free-wall delay of > 50 ms (47 vs 24%, chi-square = 4.6, P < 0.05). In conclusion, the presence of cardiac diseases was characterized by LV global mechanical delay; and, intraventricular asynchronized contraction characterized mostly by further mechanical delay in the free-wall region. These changes occur even in those with normal QRS duration.

Cardiac Pacing, Artificial↗

Assessment of left and right ventricular systolic and diastolic synchronicity in normal subjects by tissue Doppler echocardiography and the effects of age and heart rate.

OBJECTIVES: This study examined inter- and intraventricular synchronicity in systole and diastole by tissue Doppler imaging (TDI), and investigated if these parameters and the regional velocities were affected by age and heart rate. METHODS: TDI was performed in 106 normal subjects (64.3 +/- 9.5 years, 60% male) using three apical views and a six-basal, six mid-segmental model. The regional parameters measured off line in both ventricles included peak isovolumic contraction velocity IVC(M), peak sustained systolic velocity (SM), peak early diastolic velocity (EM), peak late diastolic velocity (AM), and the E/AM ratio, as well as their time to these peak velocities: T(IVC), T(S), T(E), and T(A). RESULTS: The systole and diastole within the left ventricle (LV) was highly synchronized without difference in T (IVC), TS, TE, and TA. However, the right ventricle (RV) was about 20 msec later than the LV for T(IVC) and TS. For regional velocities, IVC(M), S(M), E(M), and A(M) were significantly higher in basal than mid-segments (all P < 0.001). In the base of the LV, SM, and EM were the highest at the lateral segment and the lowest at the anterolateral segment. Age and heart rate did not affect systolic velocities or the timing of events. In diastole, age correlated negatively with EM(r =-0.36 to -0.48, P <or= 0.001)and E/AM ratio(r =-0.37 to -0.51, P <or= 0.01), while increasing heart rate affected AM (r = 0.17 to 0.43) positively and TE(r =-0.49 to -0.66, P < 0.001)and TA(r =-0.85 to -0.93, P < 0.001)negatively. CONCLUSION: (1). Systolic and diastolic functions of the normal hearts are highly synchronized, though LV contraction slightly preceded that of RV. (2). Age and heart rate predominantly affect the diastolic, but not systolic, parameters that need to be taken into account.

Age Factors↗

Keratinocyte growth factor decreases total parenteral nutrition-induced apoptosis in mouse intestinal epithelium via Bcl-2.

BACKGROUND/PURPOSE: Total parenteral nutrition (TPN) induces epithelial cell (EC) apoptosis. Keratinocyte Growth Factor (KGF) increases EC-growth; however, little is known of its effect on apoptosis. This study aims to determine if mRNA expression of Bcl-2 proteins (major mediators of epithelial cell apoptosis) is altered with TPN, and if KGF-administration influences Bcl-2 family expression. METHODS: C57BL/6J mice (n = 6 per group) received oral feeding (control), TPN (TPN), or TPN plus intravenous KGF daily (TPN + KGF). After 7 days, intestine was harvested and EC isolated. Apoptosis was identified using flow cytometry. EC mRNA expression of Bcl-2 family members was measured by reverse transcriptase polymerase chain reaction; Bcl-2 protein level was measured by immunoblot analysis. RESULTS: EC apoptotic rates were: control, 14.4% +/- 5.1%; TPN, 29.4% +/- 11.3%; KGF, 17.2% +/- 5.6%. Pro-apoptotic Bcl-2 proteins changed minimally with TPN or KGF; however, the antiapoptotic protein Bcl-2 changed significantly: control, 0.78 +/- 0.24; TPN, 0.10 +/- 0.13; KGF, 0.76 +/- 0.36. EC Bcl-2 protein levels were: control, 0.16 +/- 0.13; TPN 0.18 +/- 0.16; and TPN + KGF 0.47 +/- 0.19. CONCLUSIONS: TPN-induced apoptosis decreased Bcl-2 mRNA expression. KGF decreased EC apoptosis and increased Bcl-2 expression. Modalities to increase endogenous KGF, or KGF-administration may have benefit in patients on TPN.

Animals↗

Use of strain imaging in detecting segmental dysfunction in patients with hypertrophic cardiomyopathy.

BACKGROUND: The distribution and magnitude of left ventricular hypertrophy are not uniform in patients with hypertrophic cardiomyopathy (HCM). Previous echocardiographic studies have focused on global left ventricular function. Recently, myocardial Doppler strain (epsilon) imaging, a newly developed technique, has allowed the quantification of regional myocardial motion. The aim of this study was to characterize regional left ventricular systolic function by myocardial Doppler epsilon imaging in patients with HCM. METHODS: Included in this study were 31 patients with asymmetric septal hypertrophy and HCM, and 41 age-matched healthy patients. Regional longitudinal axial systolic epsilon was assessed at the basal, mid, and apical segments of the septal and lateral walls and compared between both groups. RESULTS: Patients with HCM had reduced epsilon at the ventricular septum (-10.3 +/- 5.7%) compared with control patients (-19.4 +/- 3.3%, P <.001). In the HCM group, epsilon in the midseptum (-1.3 +/- 8.2%) was significantly less than at the basal (-12.2 +/- 8.7%, P <.01) and apical septum (-17.3 +/- 10.4%, P <.01), and was also less than at the midlateral wall (-9.4 +/- 5.3%, P <.05). There was a significant correlation between midseptal epsilon and intraventricular septum to posterior wall thickness ratio (r = 0.81, P <.001). CONCLUSION: Midseptal longitudinal epsilon was markedly decreased, even reversed in patients with HCM (paradoxic longitudinal systolic expansion), which was directly related to the degree of septal hypertrophy. Myocardial Doppler epsilon imaging could offer a unique approach to quantify regional systolic dysfunction in these patients.

Adult↗

Alteration in epithelial permeability and ion transport in a mouse model of total parenteral nutrition.

OBJECTIVE: To investigate the effects of total parenteral nutrition administration on intestinal ion transport and intestinal epithelial permeability. Additionally, to assess the role of interferon-gamma on the total parenteral nutrition-induced loss of epithelial barrier function. DESIGN: Randomized, controlled study. SETTING: Experimental laboratory, University of Michigan Medical School, Ann Arbor. SUBJECTS: Adult wild-type and interferon-gamma knockout mice. INTERVENTIONS: Wild-type mice received total parenteral nutrition or enteral diet (control group) for 7 days. Segments of small bowel from the mice were mounted in Ussing chambers. Short circuit current, as an indictor of active ion transport, was constantly monitored. Epithelial barrier function was assessed by measuring transepithelial resistance and transmural passage of 51Cr-EDTA and 3H-mannitol. Intestinal intraepithelial lymphocyte-derived interferon-gamma protein expression was detected with enzyme-linked immunosorbent assay and confirmed by using intracellular staining and flow cytometry. To investigate the effect of total parenteral nutrition on intestinal ion transport, we used a secretory agonist, carbachol, and an absorptive agent, glucose. MEASUREMENTS AND MAIN RESULTS: Total parenteral nutrition significantly increased small-bowel permeability. Ion transport in the total parenteral nutrition group was significantly increased. To stimulate ion transport, we found that increases in short circuit current induced by carbachol and glucose were higher in the total parenteral nutrition group compared with the control group. Intestinal intraepithelial lymphocyte interferon-gamma protein expression significantly increased with the administration of total parenteral nutrition. Intestinal permeability in interferon-gamma knockout total parenteral nutrition mice was significantly lower than in wild-type mice receiving total parenteral nutrition. CONCLUSION: Total parenteral nutrition has significant effects on intestinal epithelial physiology, stimulating ion secretion and reducing epithelial barrier function. Interferon-gamma appears to play an important role in the loss of the epithelial barrier function that is associated with total parenteral nutrition.

Animals↗

Establishment of transgenic mice carrying the gene of human nuclear receptor NR5A2 (hB1F).

AIM: Human hepatitis B virus enhancer II B1 binding factor (hB1F) was cloned and characterized as a novel member of the Ftz-F1 (NR5A) nuclear receptor subfamily. Although progresses have recently been made, its biological function remains largely unidentified. The aim of this study was to establish an hB1F transgenic mouse model to promote the functional study of hB1F. METHODS: Transgene fragments were microinjected into fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offsprings were identified by PCR and Southern blot analysis. Transgene expression was analyzed with RT-PCR and Western blot analysis. Transgenic founder mice were used to establish transgenic mouse lineages. The F1 and F2 mice were identified by PCR analysis. RESULTS: Seven mice were identified as carrying copies of transgene. RT-PCR and Western blotting results showed that the transgene was expressed in heart, liver, lung, kidney and stomach in one of the transgenic mouse lineages. Genetic analysis of the transgenic mice demonstrated that the transgene was integrated into the chromosome at a single site, and was transmitted stably. CONCLUSION: In this study we established an hB1F transgenic mouse model, which will facilitate the investigation of the biological function of hB1F in vivo.

Animals↗

[Detection of human/goat xenogeneic models by interphase fluorescence in situ hybridization].

OBJECTIVE: To establish a high sensitive and specific method of interphase fluorescence in situ hybridization (IFISH) to detect the low-frequency human cells in human/goat xenogeneic models. METHODS: Human-specific Y-chromosome satellite DNA CEPY and 17-chromosome satellite DNA p17H8 were used as probes for IFISH. The peripheral blood samples from 2 goats transplanted with human male hematopoietic stem cells (HSC), 1 normal negative goat and 1 normal man were analyzed. The actual FISH efficiency was confirmed by serial dilutions (1/100, 1/500 and 1/1000) of the cell mixture of normal man and normal negative goat. A set of signal scoring criteria was determined to guarantee the stability and reliability of the method. RESULTS: Positive cell (human cell) frequencies were consistent with the established frequencies for the human/goat cell mixture. The average frequencies of positive cells were 98.60% (CEPY) and 100% (p17H8) for normal man, 0 for normal negative goat, 0.23% (CEPY) and 0.11% (p17H8) for human/goat xenogeneic models. The results demonstrated that low-frequency human cells (male cells confirmed by Y-chromosome probe) existed in human/goat xenogeneic models. CONCLUSION: The IFISH developed in this study is of high sensitivity and specificity and can identify the actual frequency of human cells, which offers a direct, sensitive and specific approach to the detection of low-frequency human cells in human/goat xenogeneic models.

Animals↗

[Characteristics of bacteriology and drug sensitivity in patients with COPD combined with pneumonia].

OBJECTIVE: To investigate the characteristics of bacteriology and the drug resistance in the patients with chronic obstructive disease (COPD) combined with pneumonia at our respiratory intensive care unit(RICU) in 2001. METHODS: The sputum of 543 patients with COPD combined with pneumonia was collected with a regular method, the bacteria were cultured, and then the drug sensitivity was analyzed with K-B method. RESULTS: There were 181 positive samples in the 543 patients with the positive rate 33.9%. The main bacteria in the G- bacillus were Pseudomonas (21.55%), Haemophilus influenza (14.36%), Enteric bacilli (13.26%), and Klebsiella (11.60%) which were sensitive to impipenem, amikacin, and ceftazidime. The main bacteria in G+ bacteria were Staphylococcus aureus (7.18%) and Staphylococcus epidermindis (4.42%) which were sensitive to vancomycin, imipenem, ceftazidime, and amikacin. CONCLUSION: The bacteria in the patients with COPD combined with pneumonia at RICU of the hospital in 2001 are mainly made up of G- bacillus and secondarily of G+ bacteria which are sensitive to imipenem, amikacin, and ceftazidime. The G+ bacteria are highly sensitive to vancomycin.

Adult↗

[90-day subchronic toxicity study of aloe whole-leaf powder].

90-day subchronic toxicity study of aloe whole-leaf powder was conducted to observe the effect of aloe whole-leaf powder on health. 88 SD rats were divided randomly into 4 groups, and each group consisted of 11 males and 11 females. The animals in group 2-4 received aloe whole-leaf powder mixed in regular rodent diet at doses of 2, 4 and 8 g/kg BW (by rate of 2.5, 5 and 10 percent in diet) for 90 days. The animals in group 1 received the regular rodent diet. The results showed that aloe whole-leaf powder promoted defecation of rats. Food efficiency and body weight males exposed to 8 g/kg BW were significantly less than those of the controls. Food efficiency males exposed to 4 g/kg BW was significantly decreased, but body weight was not affected. No adverse effect were observed on food efficiency and body weight by males exposed to 2 g/kg BW and all exposed groups of females. Relative kidney weight was significnatly increased in males exposed to 8 g/kg BW and females exposed to 2 g/kg BW or greater. Relative testis weight of rats exposed to 4 and 8 g/kg BW were significantly increased compared to the control groups. Aloe whole-leaf powder at the dose of 2, 4 and 8 g/kg BW did not have adverse effect on hematology, serum AST, ALT, TC, TG, Cr as well as NAG activity of urine, serum BUN was significantly increased at the dose of 8 g/kg BW. Pathology findings: the incidences of pigmentation in renal tubular, mesenteric lymph nodes and lamina propria of the colonic mucosa, and proliferation in mesenteric lymph nodes were significantly increased at all of the exposed groups, but no pigmentation in colonic mucosa was observed at the dose of 2 g/kg BW. No pathological changes were observed in livers, spleens, testes (or ovaries). It was concluded that observed adverse effect level of aloe whole-leaf powder was 2 g/kg BW (LOAEL of aloin was 11.8 g/kg BW).

Aloe↗

[Study on the preserving techniques of squeezed juice of fresh ginger and Glutinous rehannia].

OBJECTIVE: To study the preserve techniques of squeezed juice of Chinese medicinal materials. METHOD: The techniques of refrigeration, rapid freezing, 60Cogamma-ray sterilization, freeze-drying and spray-drying were used for preservation of squeezed juice of Ginger and Glutinous Rehannia. Different results were compared. RESULT: The period of preservation was half or one year. CONCLUSION: The rapid freezing, freeze-drying and spray-drying are suitable for preservation of squeezed juice of Chinese medicinal materials.

Cobalt Radioisotopes↗

Proapoptotic Bax is hyperexpressed in isolated human islets compared with antiapoptotic Bcl-2.

BACKGROUND: Apoptosis is a well-documented pathway for islet cell death. One potential mechanism is overexpression of death-promoting Bax compared with antiapoptotic Bcl-2 in islets. METHODS: We isolated islets from 10 human pancreata and measured the expression of Bax mRNA and Bcl-2 mRNA by real-time quantitative polymerase chain reaction; islet and pancreas expression of Bax, Bcl-2, activated caspase-3, and cleaved poly (ADP-ribose) polymerase were also assessed by immunohistochemistry. Islet cell apoptosis was evaluated by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay and by flow cytometry. RESULTS: The mean (+/-SE) level of Bax mRNA was 336+/-79 copies per nanogram of total RNA, and the level of Bcl-2 mRNA was 36+/-10 (P=0.001). A positive correlation existed between islet expression of Bax mRNA and Bcl-2 mRNA (P=0.001). The islet Bax to Bcl-2 ratio was 10.8+/-1.3 and 1.71+/-0.3 for the spleens (P=0.0001). Bax mRNA (P=0.04), but not Bcl-2 mRNA, was expressed at a higher level in islets compared with spleens. Human islets contained large numbers of cells expressing Bax protein, whereas only infrequent islet cells expressed Bcl-2 protein, activated caspase-3, and poly (ADP-ribose) polymerase. The apoptotic index was 5% by TUNEL assay, and the percentage of apoptotic islet cells was 9.7+/-2.5% by flow cytometry. Sections of human pancreas before islet isolation showed islet staining for Bax but not Bcl-2. CONCLUSIONS: Our finding that isolated human islets express Bax at a higher level compared with Bcl-2 suggests a molecular mechanism for islet cell death by apoptosis. We hypothesize that reducing islet expression of Bax, or regulating its activation, will help preserve islet cell mass after islet transplantation.

Adult↗

Observation of an anomalous discontinuous liquid-structure change with temperature.

The nature of liquid structures with their changing behaviors remains an unsolved fundamental problem in many fields of science and technology. It has been widely accepted that liquid structures change gradually with temperature and/or pressure. With x-ray diffraction in the melt In-Sn80, however, we have confirmed that a temperature-dependent discontinuous structural change could occur in some binary liquids, which does not fall into any other up-to-date recognized liquid-liquid changes. This finding, together with the recently recognized pressure-induced liquid change, suggests that the conventional view on liquids should be revised.

Journal Article↗