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Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 1,279 records · Page 71Linked to original sources

Inhibition of hepatic fibrogenesis: a review of pharmacologic candidates.

Therapeutic attempts with anti-fibrotic drugs are still at an experimental stage. The clinical efficacies of most agents listed in Table II have not been proved. Some potential agents, such as colchicine, analogues of PGE, gamma-interferon, inhibitors of prolyl hydroxylase, malotilate, and PUL, must be further evaluated in controlled clinical trials. In addition, almost all anti-fibrotic agents, except HOE 077, are neither liver-nor fibrosis-specific. Some site-directed (targeted) drug delivery systems, drug-loaded vesicle carrier systems, like liposomes and erythrocyte ghosts, which selectively affect the extracellular matrix-producing cells, may improve efficacy and reduce adverse effects if they can be carriers for anti-fibrotic agents. Developments in biochemistry, immunohistochemistry, and molecular biology have considerably advanced our understanding of pathogenic mechanisms of hepatic fibrosis. With the development of available pathologic and serologic markers for ongoing fibrogenesis, experimental and clinical anti-fibrotic trials have become more active. Some therapeutic strategies have chosen targets for interference in collagen metabolism. In vivo inhibition of Ito cell activation has been a focus for the anti-fibrotic studies (70). In the present review an update of pharmacologic intervention in the process of metabolic pathways of collagen, the main extracellular matrices in both interstitium and basement membrane, has been summarized. Several drugs or biochemical agents that act on different steps of collagen synthesis, crosslinking, and breakdown are listed and discussed briefly. Moreover, agents that inhibit other matrix components are also involved in the review.(ABSTRACT TRUNCATED AT 250 WORDS)

Colchicine↗

Apoptosis defects analyzed in TcR transgenic and fas transgenic lpr mice.

Although autoreactive T cells are thought to play a prominent role in autoimmune disease in MRL-lpr/lpr mice, it has been difficult to directly determine if autoreactive T cells escape from the thymus and react with self-antigens in the periphery. Defective expression of the Fas apoptosis antigen in MRL-lpr/lpr mice results from the insertion of the ETn retrotransposon. The fas defect can be partially corrected in CD2-fas transgenic mice in which the expression of fas is corrected in T cells. To identify a possible defect in clonal deletion or clonal anergy induction of auto-specific T cells, we have studied C57BL/6-lpr/lpr transgenic mice that express TcR genes that recognize a known self-antigen, the male H-Y antigen. In addition, we have analyzed clonal deletion and tolerance induction after neonatal tolerance induction and superantigen-induced arthritis with the class II MHC reactive superantigen staphylococcal enterotoxin B (SEB) in V beta 8 TcR transgenic and non-transgenic MRL-lpr/lpr mice. Neonatal tolerance induction to SEB was normal in lpr/lpr mice. However, over time a loss of tolerance (thymic or peripheral) was observed in lpr/lpr mice but not in +/+ TcR transgenic mice. This defect in lpr/lpr mice was thymic-dependent and was due to increased CD28/CTLA4 signaling. These results suggest that an apoptosis defect involving both thymocytes and peripheral lymphoid cells leads to autoimmune disease in lpr/lpr mice. The challenge in the future will be to determine the role of defective apoptosis in other autoimmune diseases.

Animals↗

[The role of TNF-alpha in the growth and differentiation of U937 cells induced by PMA and IFN-gamma].

The effects of PMA and IFN-gamma on regulation of growth and differentiation of human monoblastic leukemic cell U937 were examined. U937 cells were stimulated by different concentrations of PMA and IFN-gamma respectively and NBT reduction assay was used to detect the differentiation of the cells. The results showed that both PMA and IFN-gamma dose-dependently induced differentiation of U937 cells into mature macrophage-like cells. The data also revealed a time-course response in the differentiation induction. Moreover, the U937 cell growth was significantly inhibited by the treatment of PMA and IFN-gamma. These results suggest that PMA and IFN-gamma coupled the regulation of U937 cell growth and differentiation. It was found that tumor necrosis factor-alpha (TNF-alpha) was expressed by the stimulated U937 cells. The specific monoclonal antibody against TNF-alpha diminished the effects of PMA and IFN-gamma on the growth and differentiation of U937 cells. Thus the endogenous TNF-alpha may involved in the mechanism of the effects of PMA and IFN-gamma on the differentiation of U937 cells. The regulatory action of the endogenous TNF-alpha on U937 cells was not due to its cytotoxic effect.

Cell Transformation, Neoplastic↗

[Studies on a new tumor marker with monoclonal antibody against human colorectal carcinoma antigen].

A hybridoma 1 G 10 clone was derived from fusion between SP 2/0- Ag14 myeloma cells and spleen cells of BALB/C mice immunized with the soluble Noridet P40 extracts from a human colonic adenocarcinoma cell line SW 620. The 1 G 10 clone was identified to be able to produce monoclonal antibody of IgG1 subclass which had sufficient titer for immunoreactivity to both extracts from SW 620 cells and surgical colonic carcinoma tissues, but no immunoreactivity to both extracts from normal adult colorectal tissues, mixed human lymphocytes and normal human serum (NHS) as well as carcinoma embryonic antigen (CEA) by enzyme-linked immunosorbent assay (ELISA). By affinity column on Sepharose 4 B coupled with 1 G 10 IgG, colonic carcinoma-associated antigen (CCA) was purified from SW 620 cell extracts and thoracic ascitic fluid of a patient with lung adenocarcinoma. Western blotting analysis with 1 G 10 IgG demonstrated that one immunoreactive bands corresponding to 55 Kd molecule was observed in the samples of ascitic fluid and SW 620 cell extracts. The 55 Kd band could be stained with Alcian blue. The immunoreactivity of CCA to 1 G 10 antibody could be abolished completely by the treatment of the antigen with NaIO4 and proteinase K. These results indicated that the determinants of CCA reacted with 1 G 10 monoclonal antibody are probably both present in polysaccharide and protein part of the molecule. The specificity of anti-CCA 1 G 10 monoclonal antibody and its possible application for clinical oncology were discussed.

Adenocarcinoma↗

Electrophysiologic effects of total flavones of Hippophae rhamnoides L on guinea pig papillary muscles and cultured rat myocardial cells.

The effects of total flavones of Hippophae rhamnoides L (TFH) were evaluated using conventional microelectrode technic. After administration of TFH 100-200 mg.L-1, the action potential duration of 50% repolarization (APD50) was shortened both in cultured rat myocardial cells and in guinea pig papillary muscles. The slope of phase 4 of depolarization (SP4) in cultured rat myocardial cells was decreased and the contractile force (CF) in guinea pig papillary muscles was weakened. Arrhythmias evoked by strophantin G in guinea pig papillary muscles were suppressed by TFH 100 mg.L-1. These findings suggested that the influence of TFH on myocardial cells may be resulted mainly from its inhibition of Ca2+ influx and its interference with intracellular Ca2+ reservoir.

Action Potentials↗

[Immunohistochemical study on fibrin in brain traumas].

The fibrin formation in brain traumas was studied by immunohistochemical method. Eleven cases of brain trauma were examined. The fibrin was demonstrated not only in the areas of brain contusion and the neuronal cytoplasm of hypothalamus, thalamus, brainstem, and cerebellum, but also on the membrane of endothelial cells and red blood cells within some capillaries. The fibrin was also found around capillaries and the areas far from the brain trauma. It was suggested that injuries to the brain occurred not only in the local areas of the brain subjected to the violence, but also in the areas far from the local injury. It meant that the brain injuries were not local, but diffuse. The fibrin observed in the neuronal cytoplasm, and on the membrane of endothelial cells and red blood cells within some capillaries was a sign of ante mortem brain traumas. The combined HE staining and immunohistochemical staining of the fibrin is useful in the demonstration of simple brainstem traumas.

Brain Chemistry↗

[Resection of the caudate lobe of the liver].

It is difficult and dangerous to remove the caudate lobe of the liver because it not only is deeply embedded between the hilar structures of the liver and inferior vena cava but has its own independent vascular and biliary systems also. Two successful cases of caudate lobe resection are reported with review of literature and discussions on its applied anatomy, image-diagnosis, indications on surgery, technique and method of caudate lobe resection.

Carcinoma, Hepatocellular↗

Population and family planning in China.

As the most populous country of the world, China pursues an integrated programme for socio-economic development with family planning as a vital part of it. The aim is to ensure that population growth does not outpace the economic development, the availability of natural resources and environmental protection efforts. Current policy on family planning includes: the promotion of late marriage and deferred child bearing, advocating the practice of "one couple, one child", to encourage birth spacing for those who want a second child. Technical guidelines are: contraception as the priority; comprehensive use of various contraceptive methods in men and women; induced abortion allowed on request if no contraindications; state provided contraceptives, barrier devices and technical services. The birth rate of 33.34/1000, death rate of 7.6/1000 and natural increase rate of 25.83/1000 in 1970 was brought down to 21.04/1000, 6.7/1000 and 14.26/1000 respectively in 1985. A total fertility for 1950 of 5.87 was gradually brought down to 2.31 in 1990. 260 million births were averted between 1970-1991; the world's "5-billion population day" was postponed for 2 years and Asian "3-billion population day" was postponed for 3 years. The State Family Planning Commission under the State Council was set up in 1981. The China Family Planning Association, the China Population Association and non-governmental organisations promote family planning work in a coordinated way. The current family planning policy is now well accepted in the urban area, and gaining increasing momentum in the rural area. Persistant education is still important to break the millennia old tradition of having more children and more boys.

Aging↗

Plasmid transfer from Escherichia coli to coryneform bacteria by conjugation.

The mobilizable shuttle plasmids pXZ911, pBZ51, pBZ52, carrying the Mob site and replication origin of the Corynebacteria plasmid pXZ10145, were constructed. In E. coli S17-1, they can be transferred to coryneform bacteria C. glutamicum ATCC13032, C. glutamicum ATCC21543, C. pekinense B3, C. pekinense AS1.299, C. herculis B43, B. flavum ATCC14067 by conjugation and the transfer frequencies are 9 x 10(-5), 1 x 10(-4), 8.5 x 10(-5), 2.3 x 10(-4), 6 x 10(-4), 2.9 x 10(-5), respectively. This plasmid transfer system, which is convenient and highly effective, should greatly facilitate the basic research and optimization of amino acid genetic engineering in coryneform bacteria and related species.

Actinomycetales↗

[Enhancing effects of Herpesvirus hominis on sodium glutamate neurotoxicity].

The neurotoxic effects of sodium glutamate (MSG, 2.5 g.kg-1 sc) and the enhancing effects of neurotropic Herpesvirus hominis (HVH, 0.2 ml/mouse ip) on MSG toxicity were studied through histomorphological observations, together with detection of the concentration of both mitochondrial protein bound Ca2+ and intracellular free Ca2+ ([Ca2+]i) by the Tb3+ fluorescent probe and Ca2+ indicator Fura-2/AM, respectively. It was found that in 10-d-old mice the neurons in arcuate hypothalamic nucleus degenerated severely after treatment with HVH+MSG, showing swollen edematous cytoplasm, dark pyknotic nuclei as well as a decrease in the amount of the neurons. The hypothalamic and spinal cord mitochondrial Tb3+ relative fluorescent intensity increased from 20 +/- 3 and 20 +/- 1 to 28 +/- 5 and 34 +/- 6, ie, the mitochondrial protein bound Ca2+ reduced significantly. MSG elevated the [Ca2+]i levels from 0.11 +/- 0.03 to 0.69 +/- 0.19 mumol.L-1 by not only stimulating the Ca2+ influx but also releasing the Ca2+ from intracellular stores. These findings suggested that MSG neurotoxicity was probably related to the overloading of neuroplasmic Ca2+, the destruction of neuronal abilities to deplete or sequester the intracellular Ca2+, as well as the irreversible neuronal injury and death.

Animals↗

Effect of glucocorticoid receptor (GR) blockade on endotoxemia in rats.

To study the clinical significance of the decrease of glucocorticoid receptor (GR) in stress and shock, GR was blocked about 80% by mifepristone (RU38486), and the effects of the blockade on the pathological changes of endotoxemia were studied in rats. The results revealed that GR blockade may exacerbate the pathological and pathophysiological changes of endotoxemia: (1) the more rapid drop in arterial blood pressure, (2) the more severe pathological changes involving multiple organs, especially the lung and small intestine, (3) the increase of leukocyte adherence in venules and more pronounced rheological changes in the mesenteric microcirculation, and (4) the striking elevation of serum acid phosphatase (ACP), phospholipase A2 (PLA2) activity, and lipoperoxide (LPO). The changes of serum ACP, PLA2, and LPO in the rats with 80% GR blockade were more marked than in those with 50% GR blockade. Based on these findings, we propose that the decrease in GR during stress and shock might be a contributing factor in the pathogenesis of shock and multiple organ failure (MOF). The possible mechanisms of the above noted findings are discussed.

Acid Phosphatase↗

Submucous cleft palate.

Submucous cleft palate (SMCP) is a subgroup of cleft palate which is often unawared by general practitioners. The diagnostic triad of (1) bifid uvula, (2) translucent zone in soft palate and (3) bony notch in the posterior edge of the hard palate can be variable in their severity among each patient. Some patients with SMCP will have speech problems with velopharyngeal insufficiency (VPI) and/or articulation errors. Patients will also have middle ear effusion as in an overt cleft palate. Surgical treatment is indicated in the presence of VPI or recurrent otitis media. There are controversies on the timing and type of surgical intervention. This study was the first part of an ongoing study on SMCP. It was a retrospective review of the SMCP patients treated before June 1988 to compare the results among different age groups and surgical procedures. It was found that neither age nor type of surgery was a determinant for a satisfactory correction of VPI. Unless the patient had recurrent otitis media, surgery should not be performed before having a thorough speech evaluation including perceptual assessment and instrumental assessment. The type of surgery should be decided according to the findings from the instrumental assessment.

Adolescent↗

[Transplacental neurotoxic effects of monosodium glutamate on structures and functions of specific brain areas of filial mice].

Monosodium glutamate (MSG) was shown to penetrate placental barrier and distribute almost evenly among embryonic tissues using 3H-Glu as a tracer. When a lower (1.0 mg/g) and a higher (2.5 mg/g) doses of MSG were alternatively injected to Kunming maternal mice in every other days from mating to deliveries, obvious injury occurred in the ability of memory retention and Y-maze discrimination learning of adult filial mice pregnantly treated with higher doses (2.5 mg/g) of MSG. Meanwhile, the neuronal damages were observed in not only arcuate nucleus but also ventromedial nucleus of hypothalamus. Characteristic cytopathological changes induced by MSG showed swollen cytoplasm, dark pyknotic nuclei and loss of neurons. The radioligand-bindings in both hippocampus and hypothalamus altered significantly after the pregnant treatment of MSG. Possible mechanisms underlying MSG excitotoxic phenomena studied in single neuron by use of Ca2+ sensitive indicator Fura-2 with Spex AR-CM-MIC Cation Measurement System, might be due to increases of intracellular free Ca2+ concentration induced by MSG exposure, which was related to both the influx of Ca2+ and the depletion of Ca2+ from the intracellular Ca2+ stores. These experimental findings indicated that MSG performed its transplacental neurotoxicity in a dose-dependent manner. The excessive activation of Glu receptors and the overloading of intracellular Ca2+ induced by MSG ultimately leading to neuronal death may result in the reduction of the capability of learning and memory in adult filial mice pregnantly treated with MSG.

Animals↗

Plasma homocyst(e)ine as a risk factor for early familial coronary artery disease.

We measured plasma homocyst(e)ine [H(e)] and other coronary risk factors in 266 patients with early coronary artery disease from 170 families in which two or more siblings were affected and in 168 unmatched controls. The mean H(e) concentration adjusted for significant correlates (serum creatinine, uric acid, and low-density lipoprotein cholesterol) was 12.0 mumol/L in proband cases compared with 10.1 mumol/L in controls (P = 0.0001). Many (17.6%) of the proband cases had H(e) concentrations exceeding the 95th percentile for the controls (relative odds = 4.9, P < 0.001). H(e) among cases was bimodally distributed even after adjustment for concentrations of plasma vitamins. Concordant high H(e) was seen in at least 10 (12%) of 85 families with two or more affected siblings. We conclude that a substantial proportion of early familial coronary artery disease is probably related to production of high concentrations of H(e) by one or more major genes.

Adult↗

An assessment of corn oil as a vehicle for cyclosporin A (CsA) at varied injection sites in preventing rejection of rat laryngeal allografts.

This study was designed to determine the efficacy of corn oil as an alternative vehicle to olive oil for emulsifying cyclosporin (CsA) in preventing rejection of transplanted rat larynges. The issue of varied site absorption was also addressed. Thirty animals were transplanted to get 5 viable transplants at two weeks for three varied sites of administration; intramuscular (IM), subcutaneous (SQ) and intraperitoneal (IP). Five mg/kg of CsA in corn oil was the dose administered based on earlier data generated in our laboratory. Postulating selective absorption, the indirect measure of laryngeal histopathology, i.e. rejection, was chosen over blood levels for evaluation. In the IM group 2 grafts evidenced mild rejection whereas 3 showed marked cellular and vascular rejection. The SQ group had 1 mild, 1 moderate and 3 with severe rejections. The IP group had one moderate rejection and 4 severe rejections. Qualitatively the IM and SQ groups were similar. The IP group histologically evidenced far greater cellular rejection. CsA 5mg/kg emulsified in corn oil did not differ substantively in histologic scope or pattern of rejection from CsA in olive oil in experimental rat laryngeal transplantation. Further, the data did not support a change in the administration of CsA from an intramuscular site.

Animals↗

Radiolysis of metallothionein in deaerated and oxygen-saturated solutions.

Gamma radiolysis of metallothionein (MT) in phosphate-buffered solutions at pH 8.0 leads to the formation of intra- and intermolecular disulfide bridges as well as the release of chelated metal ions. When MT solutions deaerated with N2 or saturated with N2O were irradiated, G values for RS- loss as determined by Ellman's reagent were 4.2 and 7.0, respectively, whereas those for dimerization were only 0.32 and 0.67. A short chain reaction existed in the decrease in RS- when radiolysis was performed in O2-saturated solutions. The rate constants for reactions of MTs with OH radical and H2O2 were measured to be about 10(12) and 100 M-1 s-1, respectively. A mechanism for the radiolysis of MT-1 is proposed.

Animals↗

[Clinical assessment of 99mTc-MAG3 scintigraphy for impaired renal function].

The renal scintigraphy and clearance of 99mTc-mercaptoacetyltriglycine (MAG3) and 123I-ortho-iodohippuric acid (OIH) were compared in 12 patients with impaired renal function. The patients were first studied with MAG3 and then reinvestigated with OIH two days later. The MAG3 renal scintigraphy gave better quality and functional information in comparison with OIH. The MAG3 and OIH renogram showed identical relative kidney uptake and Tmax, but T1/2 of MAG3 was longer (p < 0.001). The plasma clearance of MAG3 was lower than that of OIH, but they correlated significantly (r = 0.87, p < 0.005). Also, the plasma clearances of MAG3 and para-aminohippuric acid (calculated by the standard clearance technique) showed good correlation (r = 0.77, p < 0.05). The urinary excretion during the first 60 min after injection was the same for the two radiopharmaceuticals. We conclude that 99mTc-MAG3 is a suitable alternative to 123I-OIH in renal scintigraphy.

Adolescent↗

Dose-dependent tolerance to ozone. I. Tracheobronchial epithelial reorganization in rats after 20 months' exposure.

Two salient features of the pulmonary response to reactive oxidant air pollutants such as ozone are the heterogeneity of response by site within the respiratory tract and the development of tolerance to injury with repeated exposure. The purpose of this study was to establish whether the development of tolerance to long-term exposure is associated with changes in the tracheobronchial epithelium. Male F344-N rats were exposed to 0, 0.12, 0.5, or 1.0 ppm ozone 6 hours/day for 5 days/week for 20 months and killed 1 week post-exposure. Samples for light microscopic morphometry were obtained by microdissection from each infusion-fixed trachea and left lung lobe and included: 1) a cranial bronchus with short path length (generation no. 4 to 5) and small diameter; 2) a central bronchus with short path length (generation no. 4 to 5) and large diameter; and 3) a caudal bronchus with long path length (generation no. 10 to 12) and small diameter. In addition, three sites within the central acinus were examined from cranial, central, and caudal regions. These sites included terminal bronchiole, 0.5 to 1 mm proximal to terminal bronchiole and bronchiolarized alveolar duct. Intraepithelial mucin storage (AB/PAS-positive material quantified by image analysis) within the trachea decreased with dose. Mucin storage was unchanged in the central bronchus, increased threefold with dose in the caudal bronchus, and was six times higher in the cranial bronchus at 1.0 ppm ozone. Epithelial composition was unchanged in trachea or any bronchi; however, we noted a significant dose-dependent increase in nonciliated cell mass and volume fraction in terminal bronchioles in all three regions. There was also a significant increase in nonciliated cell mass in the bronchiolarized alveolar ducts. Bronchiolar nonciliated cells were identified greater than fourfold further into alveolar ducts in 1.0 ppm exposed than in 0 ppm animals. Nonciliated cells occurred almost 200 microns deeper into alveolar ducts in cranial regions than in caudal regions. We conclude: 1) that the development of tolerance to injury produced by long-term exposure to ozone involves changes in airway epithelium and 2) that these changes are site specific and involve alterations in both secretory activity and cellular composition.

Animals↗