Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

At least 127 records · Page 7Linked to original sources

PubMed2001

Establishment of gene-vaccinated skin grafting against Toxoplasma gondii infection in mice.

Vaccine effects of in vivo gene-vaccinated skin graft were evaluated against Toxoplasma gondii (T. gondii) infection. By using a gene gun, cDNA coding T. gondii SAG1 molecule was intracutaneously vaccinated into C57BL/6 (B6; a susceptible strain), BALB/c (a resistant strain) and (C57BL/6 x BALB/c) F1 (CBF1) mice, and the gene-vaccinated skin of these strains was transplanted to CBF1 mice. Regarding the antibody production against SAG1, CBF1-recipient mice transplanted with the SAG1 gene-vaccinated B6 skin were high responders, whereas CBF1 mice skin grafted with vaccinated skin of both BALB/c and CBF1 mice were low responders. The donor-derived LC/DC migrated to the draining lymph nodes of the recipients from the skin graft within 3 days. The vaccine effect against T. gondii challenge infection was obtained in CBF1 mice which received the skin graft of the SAG1 gene-vaccinated BALB/c mice.

Animals↗

PubMed2001

Determination of naphthenic acids in crude oils using nonaqueous ion exchange solid-phase extraction.

A method is presented for the routine, rapid, and quantitative analysis of aliphatic and naphthenic acids in crude oils, based on their isolation using nonaqueous ion exchange solid-phase extraction cartridges. The isolated acid fractions are methylated and analyzed by gas chromatography and gas chromatography/mass spectrometry. The method is effective on both light and heavy oils and is capable of providing mechanistic information of geochemical significance on the origin of the acids in the oils. Analysis of oils that were solvent extracted from laboratory and field mesocosm marine sediment oil degradation studies indicate that this new method of analyzing the products of hydrocarbon biodegradation may be a useful tool for monitoring the progress of bioremediation of oil spills in the environment.

Journal Article↗

PubMed2001

Evaluation of the HUD lead hazard control grant program: early overall findings.

This study evaluates the effectiveness of lead hazard control methods used in the Lead Hazard Control (LHC) grant program of U.S. Department of Housing and Urban Development. The LHC Program awards funds to local jurisdictions to address lead hazards in privately owned, low-income dwellings. Grantees in 14 cities, states, or counties collected environmental data in over 2600-treated dwellings making this the largest study of residential lead hazard control ever undertaken. Grantees employed a range of treatments, the most common being replacement of windows and repair of deteriorated lead-based paint. In this paper, dust lead loading levels and blood lead levels of children (6 months-6 years, if present) were observed at four periods of time (preintervention, immediate, and 6- and 12-months postintervention) in 1212 dwellings. Dust lead loading levels were also observed in a subset of these dwellings at 24- and 36-months postintervention. The geometric mean floor and window dust lead loadings declined at least 50 and 88% (P<0.0001), respectively, immediately postintervention. Three years later, floor dust lead loadings remained at or below the immediate postintervention levels. Window dust lead loadings had moderate increases, but remained substantially reduced from preintervention levels and below clearance standards. At 1 year after intervention, geometric mean age-adjusted blood lead levels had declined from 11.0 to 8.2 microg/dL, a 26% decline (P<0.0001). The LHC Program interventions produced blood lead declines similar to or greater than the percentage changes reported in earlier 1-year lead intervention studies.

Child↗

PubMed2001

Widespread expression of the nonclassical class I Qa-2 antigens in hemopoietic and nonhemopoietic cells.

We reexamined expression patterns of one of the best characterized mouse class Ib MHC molecules, Qa-2. Transcripts encoding glycosylphosphatidylinositol-linked and soluble forms of Qa-2 are expressed in all organs except brain. The membrane-bound Qa-2 proteins are detectable, to varying degrees, in many cell types of immunological interest: on professional antigen-presenting cells capable of inducing anti-Qa-2 allogeneic responses, on thymic epithelial cells essential for T-cell positive selection, on mature as well as immature thymocytes, in immunologically privileged sites (testis/spermatazoa), and on cells implicated in mucosal immunity (lymphoid-derived and epithelial gut cells and hepatocytes). Although Qa-2 has a nearly ubiquitous tissue distribution similar to H2-Kb and Db molecules, the relative levels of Qa-2 and class Ia displayed on cell surfaces vary in a cell-specific fashion. Analyses of primary cell lines derived from normal mouse tissues also support the conclusion that Qa-2 is present in all cells that can express class Ia antigens. In contrast, tumor lines from Qa-2-positive mice are frequently Qa-2 deficient, suggesting that the Qa-2-negative phenotype of malignant cells is selected in vivo.

Animals↗

PubMed2001

Adrenocortical carcinoma in two female children.

Adrenocortical carcinoma is a rare tumor in children. This tumor is more likely to be hormonally active in children than in adults and tends to cause a variety of symptoms, which may mimic other benign endocrinopathies. These tumors are usually diagnosed at advanced stages and portend a dismal prognosis. We describe two cases of adrenocortical carcinoma. One child presented with Cushingoid symptoms secondary to hypercortisolism, including amenorrhea, hirsutism and weight gain. The other child presented with precocious puberty. Both children underwent resection of the tumors. We describe their presenting symptoms, postoperative course, adjuvant therapy and clinical course. Pertinent literature regarding the anatomy of the adrenal gland, pathology of adrenocortical carcinoma, factors influencing outcome, diagnostic modalities and treatment, are discussed.

Adolescent↗

PubMed2001

Effect of low fat diet on lipid absorption and fatty-acid transport following bowel resection.

Low-fat diets (LFD) are used extensively in many different clinical conditions. However, the effect of this diet on lipid absorption and cellular long-chain fatty-acid (LCFA) transport is unknown. Fatty-acid translocase (FAT), the rat homologue of human CD36, is one of several LCFA plasma-membrane transport proteins that may play an important role in intestinal lipid uptake. The purpose of this study was to investigate the effects of a LFD on intestinal expression of FAT/CD36, enterocyte fatty-acid transport, and in-vivo lipid absorption in rats following bowel resection. Adult male Sprague-Dawley rats were divided into five experimental groups: normal rats fed normal chow(NR-NC) (10 kcal% fat), normal rats fed a LFD (NR-LFD) (3 kcal% fat), sham rats fed normal chow (Sham-NC), short-bowel syndrome rats fed normal chow (SBS-NC), and SBS rats fed a LFD (SBS-LFD). SBS rats underwent 75% small-bowel resection, while sham animals underwent bowel transection and reanastomosis. Food intake, fecal mass, and fecal fat were measured over the last 3 days before death on day 14. Final body weight, plasma lipids and protein, and tissue total lipids in liver, adipose tissue, and intestine were determined at death. Total RNA from the mucosa of the duodenum, jejunum, and ileum was extracted for Northern blot analysis to determine fatty-acid translocase (FAT)/CD36 mRNA levels. An established cellular LCFA transport assay was used to determine isolated enterocyte [3H]-oleate uptake. Students t-test was used to determine statistical significance (P < 0.05). NR-LFD rats demonstrated a small increase in overall food absorption and no change in fat absorption compared to NR-NC animals. A significant decrease in FAT/CD36 mRNA levels was seen in the duodenum and jejunum in NF-LFD rats (vs NR-NC) and was accompanied by reduced LCFA transport by isolated enterocytes from the jejunum and ileum. SBS-LFD rats demonstrated decreased FAT/CD36 mRNA levels in all three segments and a concomitant decrease in LCFA uptake enterocytes compared to the SBS-NC group. In addition, SBS-LFD rats showed significantly lower final body weight and plasma lipids compared to SBS-NC animals.

Animals↗

PubMed2001

A complex flow pattern of low shear stress and flow reversal promotes monocyte binding to endothelial cells.

Predilection sites for atherosclerosis within the vasculature are characterized by low shear stress and flow reversal. In this study, endothelial cells were exposed to a complex flow pattern that was characterized by particle velocity determination. Bovine aortic endothelial cells exposed to low shear stress and flow reversal demonstrated higher levels of monocyte binding compared to endothelial cells exposed to one-directional flow. In addition, endothelial cells exposed to low shear stress and flow reversal responded to inflammatory stimuli with substantial increases in monocyte binding, similar to that seen in cells exposed to one-directional flow. These findings suggest a mechanism by which areas of low shear stress and flow reversal are predisposed to the development of atherosclerotic lesions.

Animals↗

PubMed2001

Modeling the T-helper cell response in acute and chronic hepatitis B virus infection using T-cell receptor transgenic mice.

Chronicity following hepatitis B virus (HBV) infection may be maintained by high levels of viral proteins circulating in the serum. To examine the characteristics of T cells capable of co-existing with the secreted hepatitis B e-antigen (HBeAg), T-cell receptor (TCR) transgenic (Tg) mice were produced. To insure that HBeAg-specific T cells would not be deleted in the presence of serum HBeAg, the TCR alpha and beta-chain genes used to produce the TCR-Tg mice were derived from T-cell hybridomas from HBeAg-Tg mice. A TCR-Tg lineage (11/4-12) was produced that possessed a high frequency (approximately 67%) of CD4(+) T cells that expressed a TCR-Tg specific for the HBeAg. As predicted, when 11/4-12 TCR-Tg mice were bred with HBeAg-Tg mice no deletion of the HBeAg-specific CD4(+) T cells occurred in the thymus or the spleen. Functional analysis of the TCR-Tg T cells revealed that the HBeAg-specific CD4(+) T cells escaped deletion in the thymus and periphery by virtue of low avidity. Regardless of their low avidity, HBeAg-specific TCR-Tg T cells could be activated by exogenous HBeAg as measured by cytokine production in vitro and T-helper cell function for anti-HBe antibody production in vitro and in vivo. Furthermore, activated TCR-Tg HBeAg-specific T cells polarized to the Th(1) subset were able to elicit liver injury when transferred into HBeAg or HBcAg-Tg recipients. Therefore, HBeAg-specific CD4(+) T cells that can survive deletion or anergy in the presence of circulating HBeAg nonetheless are capable of being activated and of mediating liver injury in vivo.

Adoptive Transfer↗

PubMed2001

Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases.

Janus kinases comprise carboxyterminal kinase, pseudokinase, SH2-like, and N-terminal FERM domains. We identified three patient-derived mutations in the FERM domain of Jak3 and investigated the functional consequences of these mutations. These mutations inhibited receptor binding and also abrogated kinase activity, suggesting interactions between the FERM and kinase domains. In fact, the domains were found to physically associate, and coexpression of the FERM domain enhanced activity of the isolated kinase domain. Conversely, staurosporine, which alters kinase domain structure, disrupted receptor binding, even though the catalytic activity of Jak3 is dispensable for receptor binding. Thus, the Jak FERM domain appears to have two critical functions: receptor interaction and maintenance of kinase integrity.

Adenosine Triphosphate↗

PubMed2001

Improved neuromagnetic detection of fetal and neonatal auditory evoked responses.

OBJECTIVE: To assess the quality of fetal and neonatal auditory evoked responses (fAERs and nAERs) obtainable with a low-noise, high-channel count SQUID gradiometer in a well-shielded environment. METHODS: Measurement of long-latency fAERs was attempted in 19 normal fetuses in 28 sessions at 29-40 weeks' gestation, using a 37-channel SQUID gradiometer. Postnatal measurement was attempted in 16 neonates in 25 sessions at age 2-6 weeks. RESULTS: Signals of amplitude 8 fT or greater were detected in 15 of 28 fetal measurement sessions, yielding a higher success rate (54%) than in a previous study of ours. Signals of amplitude greater than 25 fT were detected in 23 of 25 (92%) of neonatal measurement sessions. The spatial and temporal characteristics of the signals were studied in greater detail. Dipole patterns consistent with a source in the auditory cortex were observable in nearly all neonates and in many fetuses. The dominant component of the nAER was compatible with the P250 seen in neonatal EEG recordings; however, the largest component of the fAERs had longer latency and in many subjects had opposite polarity. CONCLUSION: A higher success rate, earlier detection, and improved characterization of signal morphology and topography were demonstrated for fAER recordings.

Acoustic Stimulation↗

PubMed2001

Torsion of the previously normal uterine adnexa. Evaluation of the correlation between the pathological changes and the clinical characteristics.

BACKGROUND: Treatment of adnexal torsion remains a clinical dilemma when future fertility is wanted. The purpose of this study was to evaluate the correlation between the pathological changes and the clinical characteristics on patients having torsion of the previously normal uterine adnexa which may help us decide whether detorsion is worthwhile. METHODS: A retrospective study of 69 patients undergoing surgical intervention for adnexal torsion was performed. Among them, 13 patients diagnosed with torsion of the previously normal adnexa were identified. Their clinical and pathological features were compared. RESULTS: Extensive hemorrhagic necrosis of the twisted ovary was observed in five patients, and each of them had their duration of torsion last 48 hours or longer. Three of 13 cases (23.1%) with torsion of the previously normal adnexa had local thrombus formation within the twisted adnexa. Their duration of torsion varied from 18 hours to 288 hours. CONCLUSIONS: The likelihood of preserving viable ovarian tissue is significantly decreased if the duration of torsion lasts 48 hours or longer. Local thrombus formation in the twisted adnexa cannot be predicted simply from the duration of torsion.

Adnexa Uteri↗

PubMed2001

Purification and enzymatic activity of an NADH-fumarate reductase and other mitochondrial activities of Leishmania parasites.

A 65 kD membrane-associated NADH-fumarate reductase subunit, which has a molecular weight similar to that of one of the enzyme subunits from bacteria, was purified from Leishmania donovani promastigotes. NADH-fumarate reductase and other mitochondrial enzymatic activities of L. major and L. donovani promastigotes and amastigotes were investigated. The presence of NADH-fumarate reductase was demonstrated in digitonin-permeabilized L. major promastigotes and mitochondria of L. major and L. donovani promastigotes and amastigotes. The activity of solubilized NADH-fumarate reductase was measured in L. major and L. donovani promastigotes. Succinate exhibited a clear concentration-dependent inhibitory effect on fumarate reductase, whereas fumarate also exhibited a clear concentration-dependent inhibitory effect on succinate dehydrogenase. The data indicate that fumarate reductase is an obligatory component of the respiratory chain of the parasite. Since the enzyme is an important component in the intermediate metabolism in the Leishmania parasite and is absent in mammalian cells, it could be a potential target for antileishmanial drugs.

Animals↗

PubMed2001

The importance of impermeant support in small bowel preservation: a morphologic, metabolic and functional study.

BACKGROUND: Ambiguity exists as to which preservation solution is the most effective for small bowel (SB); studies have shown equivalent results with normal saline and University of Wisconsin (UW) solution. This study was designed to investigate the requirement of SB for oncotic and osmotic support, thereby reassessing one of the key principles of static organ storage. METHODS: Rodent SB was vascularly flushed with the following solutions: group 1, 0.9% saline (154 mM NaCl); group 2, 154 mM NaCl +5% dextran; group 3, 104 mM NaCl +100 mM lactobionate + 5% dextran; and group 4, UW solution. Analysis of cellular energetics, permeability and histology (by electron microscopy) was performed over a 10-h time course of cold storage. RESULTS: The addition of dextran and lactobionate to a simple saline solution (group 3) resulted in superior maintenance of several key parameters of energy metabolism throughout prolonged storage. At all times, ATP/ADP and EC ratios in group 3 remained unchanged from those of freshly isolated tissue; storage in normal saline and UW solution resulted in a progressive decline between 1 and 10 h of storage. ATP was also notably greater in group 3 than in group 1 or UW after 10 h of storage. Functional parameters demonstrated significant improvements in maintaining barrier function and membrane ion/electrical activity in group 3. Of particular note, after 10 h of storage, permeability for groups 1, 3 and UW was 215, 76 and 400 nmol/cm2/h, respectively, compared with a fresh tissue value of 22 nmol/cm2/h. Scanning electron micrographs revealed complete epithelial denudation of bowel stored in simple saline and UW solutions at 10 h. The incorporation of 100 mM lactobionate plus 5% dextran in group 3 prevented extensive villus denudation; the presence of intact microvilli indicated normal epithelial cell morphology. CONCLUSION: The order of solution effectiveness was group 3 > group 2 > group 1 > group 4. Vascular supplied impermeants, when supplied in simple solution, provide markedly improved preservation of metabolism, barrier function, and morphology of SB compared with UW.

Adenosine↗

PubMed2001

The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM.

Amino Acid Sequence↗

PubMed2001

The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis.

The hybrid peptide-polyketide backbone of bleomycin (BLM) is assembled by the BLM megasynthetase that consists of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. BlmIX/BlmVIII/BlmVII constitute a natural hybrid NRPS/PKS/NRPS system, serving as a model for both hybrid NRPS/PKS and PKS/NRPS systems. Sequence analysis and functional comparison of domains and modules of BlmIX/BlmVIII/BlmVII with those of nonhybrid NRPS and PKS systems suggest that (1) the same catalytic sites appear to be conserved in both hybrid NRPS-PKS and nonhybrid NRPS or PKS systems, with the exception of the KS domains in the hybrid NRPS/PKS systems that are unique; (2) specific interpolypeptide linkers may play a critical role in intermodular communication to facilitate transfer of the growing intermediates between the interacting NRPS and/or PKS modules; and (3) posttranslational modification of the BLM megasynthetase has been accomplished by a single PPTase with a broad substrate specificity toward the apo forms of both acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs).

Antibiotics, Antineoplastic↗

PubMed2001

The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen.

Human keratinocyte motility plays an important role in the re-epithelialization of human skin wounds. The wound bed over which human keratinocytes migrate is rich in extracellular matrices, such as fibrin, fibronectin, and collagen, and serum factors, such as platelet-derived growth factor and transforming growth factor beta 1. Extracellular matrices and the serum factors bind to cell surface receptors and initiate a cascade of intracellular signaling events that regulate cell migration. In this study, we identified an intracellular signaling pathway that mediates collagen- driven motility of human keratinocytes. Pharmaco logic inhibition of the activation of p38-alpha and p38-beta mitogen-activated protein kinase activation potently blocked collagen-driven human keratinocyte migration. Transfection of the same keratinocytes with the kinase-negative mutants of p38-alpha or p38-beta mitogen-activated protein kinase markedly inhibited keratinocyte migration on collagen. Attachment of keratinocytes to collagen activated p38 mitogen- activated protein kinase, as well as p44/p42 ERKs. Interestingly, activation of the p38 mitogen-activated protein kinase cascade by overexpressing the constitutively active MKK3 and MKK6, MKK3b(E) and MKK6b(E), could neither initiate migration in the absence of collagen nor enhance collagen-driven migration. This study provides evidence that the p38-MAPK/SAPK pathway is necessary, but insufficient, for mediating human keratinocyte migration on collagen.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed2001

Regulation of K+ transport in the rat distal colon via angiotensin II subtype receptors and K+ -pathways.

The role of angiotensin subtype-1 (AT1) and -2 (AT2) receptors in mediating the effects of angiotensin II (ANG II) on several K+ transporters was studied in rat distal colon using an Ussing chamber. Angiotensin II induced K+ secretion at two different doses. Secretion occurred at 10-(8) and 10-(4) M, as a result of an increase in serosal-to-mucosal flux (Js-m). The ANG II-induced stimulation of Js-m at a low dose (10-(8) M) was abolished by PD123319 while losartan did not alter the low-dose ANG II-dependent increase in Js-m. In contrast, the increase in Js-m induced by a high-dose of ANG II (10-(4) M) was blocked by losartan, whereas PD123319 partially reduced the stimulatory effect. In the presence of both blockers, high-dose ANG II induced an inhibition of basal Js-m. Low-dose ANG II activated the barium-sensitive K+ channels, whereas the Na+, K+, 2Cl- cotransporter and the Na+, K+ -ATPase pump were unchanged. At the high dose, ANG II activated the barium-sensitive K+ channels and the Na+, K+, 2Cl- cotransporter and inhibited the Na+, K+ -ATPase pump. These data indicate that ANG II stimulates serosal-to-mucosal K+ flux in the rat distal colon at high and low doses via different receptors and K+ transporters.

Angiotensin II↗

PubMed2001

Effectiveness and safety of nizatidine, 75 mg, for the relief of episodic heartburn.

BACKGROUND: The most frequent cause of episodic heartburn is food and beverage ingestion. Nizatidine, an H2-receptor antagonist, is currently approved for non-prescription use in the prevention and relief of heartburn at a dose of 75 mg up to twice a day. METHODS: Two identical studies were carried out to evaluate the efficacy of nizatidine, 75 mg, compared with placebo in treating heartburn in an "at-home" setting. The studies were multicentre, multiple-dose, placebo-controlled, randomized, parallel group design. A total of 994 subjects were randomized to treatment. Adequate relief of heartburn was assessed at 15, 30 and 45 min and 1, 2 and 3 h following a treatment dose. A subject's responses with respect to time to relief and attainment of adequate relief were combined into a derived response profile, the sustained adequate relief score. Adverse experiences were noted throughout the study period. RESULTS: The individual and combined study results showed that nizatidine, 75 mg, relieved heartburn faster and/or more consistently than placebo. The mean sustained adequate relief score, calculated over a subject's first four episodes, was 2.43 in the nizatidine-treated group compared with 2.14 in the placebo group (P < 0.001). Nizatidine-treated subjects attained sustained adequate relief in a significantly (P < 0.001) larger percentage (75%) of their heartburn episodes than did subjects treated with placebo (66%). No serious adverse experiences were associated with nizatidine treatment. CONCLUSION: Nizatidine, 75 mg, is a safe and effective treatment for episodic heartburn. The results showed that subjects taking nizatidine had heartburn relief that was achieved faster and/or more reliably than did subjects taking placebo.

Adolescent↗