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Biomedical subjects

J Hu

Publications and source records attributed to J Hu.

At least 253 records · Page 14Linked to original sources
PubMed2000

Increased expression of insulin-like growth factor I in skin in amyotrophic lateral sclerosis.

OBJECTIVES: Insulin-like growth factor I (IGF-I) has potent effects on motor neuron survival and is being studied as a possible therapeutic agent for ALS. However, little is known concerning IGF-I in the skin of patients with amyotrophic lateral sclerosis (ALS). The aim was to evaluate IGF-I immunoreactivity of skin in patients with ALS. METHODS: IGF-I immunoreactivity of skin from 18 patients with ALS and 16 controls was examined. RESULTS: IGF-I immunoreactivity was markedly positive in the epidermis and dermal blood vessels and glands and was moderately positive in the reticular dermis in all patients with ALS. On the other hand, the epidermis and dermal blood vessels and glands and the reticular dermis showed a weak IGF-I immunoreactivity in controls. The optical density for IGF-I immunoreactivity of the epidermis and dermal blood vessels and glands, and the reticular dermis in patients with ALS was significantly higher than in diseased controls, and was significantly increased with duration of illness. CONCLUSIONS: These data suggest that a metabolic alteration of IGF-I may take place in the skin of patients with ALS.

Aged↗
PubMed2000

Characteristic expression of thrombomodulin in the muscle sarcoplasm in patients with the acute phase of rhabdomyolysis.

The expression of thrombomodulin and neural cell adhesion molecule (NCAM) was studied immunocytochemically in biopsied muscle specimens from 10 patients with rhabdomyolysis with different etiologic factors, including 5 with malignant hyperthermia. We have already reported that thrombomodulin was expressed on regenerating muscle cell membranes as well as on vessel walls in patients with various neuromuscular diseases, including Duchenne muscular dystrophy, Becker muscular dystrophy and inflammatory myopathy. We found increased expression of thrombomodulin not only on the sarcolemma, but also in the sarcoplasm of a fair number of muscle fibers in the acute phase of rhabdomyolysis. The granular pattern of thrombomodulin expression in the sarcoplasm seems to be a characteristic finding in the acute phase of rhabdomyolysis. Most muscle fibers which expressed NCAM on the sarcolemma also expressed thrombomodulin. However, the muscle fibers which expressed thrombomodulin in the sarcoplasm did not express NCAM, and showed a degenerative appearance on electron microscopic examination. These results suggest that thrombomodulin is expressed in the sarcoplasm during the acute degeneration phase of rhabdomyolysis in addition to the expression on the sarcolemma during the muscle fiber regeneration as shown in our previous study, and the former process, which is characterized by the granular expression of thrombomodulin in the sarcoplasm, may be a characteristic finding in rhabdomyolysis.

Adolescent↗
PubMed2000

Production and interaction of oxygen and nitric oxide free radicals in PMA stimulated macrophages during the respiratory burst.

The activity of nitric oxide synthase (NOS) during the respiratory burst in phorbol-1,2-myristate-1,3-acetate (PMA) stimulated macrophages has been the topic of much debate in the literature. To help clarify the role of NOS, we have examined the chemiluminescence arising from peroxynitrite production, nitrite/nitrate and nitric oxide production, and oxygen consumption during the respiratory burst in PMA-stimulated macrophages. The Griess reaction was used to measure nitrite/nitrate, spin trapping with N-methyl D-glucamine dithiocarbamate (MGD)2-Fe2+ was used to quantify nitric oxide, and the spin probe 2,2,6,6-tetramethylpiperidine-N-oxyl-4-ol (TEMPOL) was used to measure oxygen consumption. Oxygen free radical production (hydroxyl and superoxide free radicals) was also investigated using the spin trap 5,5-dimethyl-1-pyroline-1-oxide (DMPO). The chemiluminescence emitted by the PMA-stimulated macrophages and nitrite/nitrate in the culture system were both found to increase. However, the rate of nitric oxide release remained constant, indicating that the activity of NOS is not enhanced during the respiratory burst in PMA stimulated macrophages.

Animals↗
PubMed2000

A human epithelium-specific vector optimized in rat pneumocytes for lung gene therapy.

Gene therapy vectors based on mammalian promoters offer the potential for increased cell specificity and may be less susceptible than viral promoters to transcription attenuation by host cytokines. The human cytokeratin 18 (K18) gene is naturally expressed in the lung epithelia, a target site for gene therapies to treat certain genetic pediatric lung diseases. Our original vector based on the promoter and 5' control elements of K18 offered excellent epithelial cell specificity but relatively low expression levels compared with viral promoters. In the present study, we found that adding a stronger SV40 poly(A) signal boosted primary rat lung epithelial cell expression but greatly reduced cell specificity. Addition of a 3' portion of the K18 gene to our vector as a 3' untranslated region (UTR) improved epithelial cell-specific expression by reducing expression in lung fibroblasts. The effect of the 3' UTR was not related to gross differences in cell-specific splicing. A deletion variant of this UTR further increased lung epithelial cell expression while retaining some cell specificity. These data illustrate the possibilities for using 3' UTR to regulate cell-specific transgene expression. Our improved K18 vector should prove useful for pediatric lung gene therapy applications.

Animals↗
PubMed2000

Effects of a calcimimetic compound and naturally activating mutations on the human Ca2+ receptor and on Ca2+ receptor/metabotropic glutamate chimeric receptors.

Naturally occurring mutations identified in subjects with autosomal dominant hypocalcemia (ADH) and the calcimimetic compound, R-568, have both been reported to increase Ca2+ sensitivity of the Ca2+ receptor (CaR). To gain insight into their mechanism of action, we studied interactions between four different ADH mutations located in the amino-terminal extracellular domain (ECD) and R-568. We found that R-568 increased the sensitivity of three of the ADH mutant receptors, but the Leu125Pro mutant appeared to be maximally left-shifted in that neither R-568 addition nor combining other ADH mutations with Leu125Pro gave increases in sensitivity comparable to those seen with the three other ADH mutations studied. We also made use of truncation and deletion mutants of the CaR and CaR/metabotropic glutamate receptor type 1 (mGluR1) chimeras to study both the site of action of R-568 and the effect of the Leu125Pro activating mutation. R-568 was effective in receptor constructs containing the seven transmembrane domain (7TM) of the CaR, but not in those containing the mGluR1 7TM. R-568, moreover, imparted Ca2+ responsiveness to CaR constructs lacking all or part of the CaR ECD. The Leu125Pro mutation in contrast conferred no or minimal increase in Ca2+ responsiveness to CaR constructs lacking part of the CaR ECD but showed a striking increase in basal activity in the context of chimeras containing an mGluR1 7TM. Our results localize the site of action of NPS-568 specifically to the CaR 7TM. Our results with the Leu125Pro mutant, furthermore, suggest that the mGluR1 7TM domain may be more permissive for activation than the 7TM domain of the CaR.

Amino Acid Sequence↗
PubMed2000

Functional interactions between the extracellular domain and the seven-transmembrane domain in Ca2+ receptor activation.

We studied the activity of mutants involving the aminoterminal extracellular, seven-transmembrane (7TM) and carboxy-terminal tail domains of the human Ca2+ receptor to gain insight into the functional interactions between these domains during receptor activation. Missense mutations of highly conserved residues, D190 and E297, in the extracellular domain (ECD), and a mutation within part of the proximal carboxyterminal tail, A877-880E, resulted in receptors with severely reduced response to Ca2+ despite adequate cell surface expression. Coexpression of either D190A or E297K mutants with A877-880E led to significant reconstitution of function. No such reconstitution occurred when D190A or E297K mutants were coexpressed with a truncation mutant possessing an intact amino-terminal extracellular and first transmembrane domain, despite evidence for heterodimerization and cell surface expression of the respective mutant receptors. In addition, no reconstitution of function was observed when D190A was coexpressed with a deletion Ca2+ receptor mutant lacking only a cysteine-rich region located in the ECD of the Ca2+ receptor (Ca-//-Ca). Moreover, coexpression of this Ca-//-Ca with A877-880E did not recover function. The results show that Ca2+ receptor extracellular and 7TM domains are discrete entities that can communicate within the context of a heterodimer composed of complementary mutant receptors. Two intact 7TM domains and two intact cysteine-rich regions appear to be required for such communication to occur. The results are discussed in the context of a speculative model of receptor structure and function.

Amino Acid Sequence↗
PubMed2000

Image-processing algorithms for behavior analysis of group-housed pigs.

Computational algorithms of image processing were developed and evaluated to select, by motion detection, images of resting artificial pigs and to segment the pigs (mixture of black and white pigs) from their background. Motion detection of the pigs was implemented by detecting interframe differences of postural behavioral images. This algorithm combines the advantages of likelihood ratio method and shading model method and shows a stable performance under noisy and dynamic illumination conditions. Segmentation of the pigs from their background was implemented by employing multilevel thresholding and background reference techniques. The algorithm automatically determines the number of thresholds needed and produces satisfactory segmentation when both black and white pigs with different image intensities are present at the same time (the most complicated situation). The reference background image is updated so that temporal changes in illumination and/or spatial changes of the pen condition have little effect on the performance of image segmentation. The algorithm employs statistical models of the pigs and background and Bayes hypothesis testing to obtain and update the exposed portion of the reference background. Linear filters were used in this process for updating the parameters. These algorithms will serve as essential components for a novel, behavior-based, interactive approach to assess and control thermal comfort of group-housed pigs, which is expected to result in enhanced animal health and well-being.

Algorithms↗
PubMed2000

Design, expression, and renaturation of a lesion-targeted recombinant epidermal growth factor-von Willebrand factor fusion protein: efficacy in an animal model of experimental colitis.

In the present study, the mature epidermal growth factor (EGF) protein was engineered to incorporate a high affinity collagen-binding domain (CBD) derived from co-agulation von Willebrand factor, to specifically target EGF to colonic lesions. The fusion protein was expressed in an E. coli bacterial expression system, purified by metal chelate chromatography, and renatured by oxidative refolding into a soluble biologically active growth factor. The EGF-CBD fusion protein bound tightly to collagen matrices under conditions in which native non-targeted EGF was washed away. In biologic assays, the EGF-CBD fusion protein stimulated NIH3T3 cell proliferation with near wild-type biological activity. In vivo binding studies showed that the collagen-targeted EGF, but not the non-targeted EGF, accumulated at areas of exposed collagen on the luminal surface of the inflamed colon. Finally, a single colonic instillation of the collagen-targeted EGF-induced a more rapid regeneration of intestinal crypts 24 h after treatment (no. of crypts = 89.2+/-8.1) compared to the non-targeted EGF (no. of crypts = 52.2+/-29.8; p=0.027), and the PBS control (no. of crypts = 24. 0+/-22.9; p=0.001). Taken together, these findings indicate that intracolonic delivery of collagen-targeted EGF represents a potentially effective therapeutic strategy for acute or chronic inflammatory bowel disease.

3T3 Cells↗
PubMed2000

Long-term survey of outcome in acute promyelocytic leukemia.

OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event-free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post-remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL.

Adolescent↗
PubMed2000

Non-Hodgkin's lymphoma and occupational exposure to chemicals in Canada. Canadian Cancer Registries Epidemiology Research Group.

BACKGROUND: The incidence of non-Hodgkin's lymphoma (NHL) has been increasing in Canada. This study assessed the effect of occupational exposure to specific chemicals on the risk of NHL. PATIENTS AND METHODS: Mailed questionnaires were used to obtain data on 1469 newly diagnosed, histologically confirmed NHL cases and 5073 population controls between 1994 and 1997 in eight Canadian provinces. Data was collected on socioeconomic status, life-style, diet, occupation, and years of exposure to any of 17 chemicals. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. RESULTS: The study found an increased risk of NHL among males exposed to benzidine, mineral, cutting, or lubricating oil, pesticides, and herbicides. Compared with non-exposure to each specific chemical, the adjusted ORs were 1.9 (95% CI: 1.1-3.4) for benzidine, 1.3 (95% CI: 1.0-1.5) for mineral, cutting, or lubricating oil, 1.3 (95% CI: 1.0-1.6) for herbicides, and 1.3 (95% CI: 1.0-1.6) for pesticides. Excess risk of NHL among females was associated with exposure to pesticides and wood dust. ORs increased with increasing exposure in years to benzidine and herbicides for males and with increasing exposure years to wood dust for females. These trends were statistically significant (P < 0.05). CONCLUSIONS: The findings in this study suggest that occupational exposure to specific chemicals plays an important role in the development of NHL in Canada.

Adult↗
PubMed2000

Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains.

Iron regulatory proteins (IRPs) are cytoplasmic mRNA binding proteins involved in intracellular regulation of iron homeostasis. IRPs regulate expression of ferritin and transferrin receptor at the mRNA level by interacting with a conserved RNA structure termed the iron-responsive element (IRE). This concordant regulation of transferrin receptors and ferritin is designed so a cell can obtain iron when it is needed, and sequester iron when it is in excess. However, we have reported that iron accumulates in the brain in Alzheimer's disease without a concomitant increase in ferritin. An increase in iron without proper sequestration can increase the vulnerability of cells to oxidative stress. Oxidative stress is a component of many neurological diseases including Alzheimer's. We hypothesized that alterations in the IRP/IRE interaction could be the site at which iron mismanagement occurs in the Alzheimer's brains. In this report we demonstrate that in normal human brain extracts, the IRP is detected as a double IRE/IRP complex by RNA band shift assay, but in 2 of 6 Alzheimer's brain (AD) extracts examined a single IRE/IRP complex was obtained. Furthermore, the mobility of the single IRE/IRP complex in Alzheimer's brain extracts is decreased relative to the double IRE/IRP complex. Western blot and RNA band super shift assay demonstrate that IRP1 is involved in the formation of the single IRE/IRP complex. In vitro analyses suggest that the stability of the doublet complex and single AD complex are different. The single complex from the AD brain are more stable. A more stable IRE/IRP complex in the AD brain could increase stability of the transferrin receptor mRNA and inhibit ferritin synthesis. At the cellular level, the outcome of this alteration in the molecular regulatory mechanism would be increased iron accumulation without an increase in ferritin; identical to the observation we reported in AD brains. The appearance of the single IRE/IRP complex in Alzheimer's brain extracts is associated with relatively high endogenous ribonuclease activity. We propose that elevated RNase activity is one mechanism by which the iron regulatory system becomes dysfunctional.

Alzheimer Disease↗
PubMed2000

[Progress in the field of tissue engineering].

Tissue engineering is a new field in biomedical engineering. In this review, progress in the field of tissue engineering is presented in detail, including a general introduction, design and fabrication principles, key technologies, various applications, new directions, as well as related market and R&D issues.

Animals↗
PubMed2000

Metabolic fate of chemical mixtures. I. "Shuttle Oxidant" effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics.

Many carcinogens, mutagens, teratogens, and other toxicants are known to be oxidized by lipoxygenases to potentially deleterious free radical intermediates. In this study, we tested for the first time the possibility that certain efficient substrates for lipoxygenase produce shuttle oxidants that stimulate the generation of reactive species from other chemicals. To evaluate the hypothesis, we investigated the metabolic interaction of two well-known substrates, chlorpromazine and benzidine, which have been shown to be oxidized by soybean lipoxygenase in the presence of hydrogen peroxide. The evidence presented here clearly indicates that the chlorpromazine cation radical generated by the lipoxygenase triggers a rapid oxidation of benzidine to benzidine diimine. Under the experimental conditions employed, the metabolic interaction resulted in a 42-fold stimulation in the rate of benzidine oxidation. The magnitude of stimulation of benzidine oxidation exhibited a dependence on the pH of the reaction medium, amount of the enzyme, and concentration of chlorpromazine, benzidine, and hydrogen peroxide. A number of other phenothiazines were also found to stimulate benzidine oxidation, albeit to a lesser degree. The chlorpromazine cation radical stimulated the oxidation of all six other xenobiotics tested. The highest stimulation (94-fold) was noted with tetramethyl phenylenediamine oxidation to the Wursters blue radical, while the lowest stimulatory response (2-fold) was observed with guaiacol. Preliminary data suggest that purified human term placental lipoxygenase also displays a similar stimulatory response in the benzidine oxidation in the presence of chlorpromazine. Although the toxicological significance of these in vitro findings remains to be established, it is worth pondering whether such a synergistic interaction occurs in humans in vivo. Teratogenesis Carcinog. Mutagen. 20:195-208, 2000.

Benzidines↗
PubMed2000

[TBX5 mutation in Chinese patients with Holt-Oram syndrome].

OBJECTIVE: To analyse TBX5 mutation in Chinese patients with Holt-Oram syndrome(HOS). METHODS: Seven HOS families were analysed with single strand conformation polymorphism(SSCP) and sequencing. RESULTS: Three SSCP changes were detected and identified as the TBX5 gene mutation at three new sites. One of the changes is a frameshift mutation caused by a base cytidine deletion at the cDNA sequence of 416, which altered all the codons after the point, thus it can not encode the protein of normal amino acid sequence; another is a missense mutation induced by a base substitution(C-->A) at the cDNA sequence of 145, which made the codon of that point change from CAG-->AAG, and encoded amino acid changed from glutamine(Gln) to lysine(Lys), consequently the change weakened the function of TBX5 protein; the third is also a missense mutation which resulted from a base substitution (T-->C) at the cDNA sequence of 161, this change made the codon of that point change from ATC-->ACC, it changed the encoded amino acid from isoleucine(Ile) to threonine(Thr), which reduced the function of TBX5 protein. CONCLUSION: HOS in Chinese is caused by mutation in TBX5.

Abnormalities, Multiple↗
PubMed2000

[Effects of a novel KATP channel opener JTV-506 on myocardial infarct size of isolated rat heart].

AIM: To study the influence of a novel KATP channel opener JTV-506(JTV) on cardiac function and myocardial infarct size of isolated rat heart. METHODS: The Langendorff apparatus was used to study the effect of JTV at different concentrations on the flow of coronary artery and the pressure of left ventricle. The effect of JTV on infarction size was observed on the isolated rat double coronary arteries perfusion model. RESULTS: JTV 1 mumol.L-1 increased the flow of coronary artery obviously. When the concentration reached 10 mumol.L-1, JTV decreased the systolic pressure of the left ventricle. JTV 1 mumol.L-1 reduced the myocardial infarct size whether it was administrated during both preischemic and ischemic period or only during ischemic period. This effect was completely blocked by glibenclamide, but when glibenclamide was administrated alone, it showed no obvious effect on infarct size. CONCLUSION: The KATP channel opener JTV can obviously dilate coronary artery and decrease cardiac systolic function when administrated at high doses. JTV was found to decrease the infarct size when administrated in doses that did not affect cardiac function. These effects were related to the opening of KATP channel.

Animals↗