Biomedical subjects

M Yin

Publications and source records attributed to M Yin.

At least 19 recordsLinked to original sources

PubMed2006

Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years.

OBJECTIVES: To evaluate the long-term impact on physical function of a single course of rituximab in rheumatoid factor, seropositive patients with active rheumatoid arthritis (RA) despite ongoing methotrexate treatment. METHODS: A randomized, controlled trial comparing rituximab alone [1,000 mg intravenously (iv) on days 1 and 15, n= 40], or in combination with cyclophosphamide (750 mg iv on days 3 and 7, n= 41) or oral methotrexate (> or =10 mg/week, n= 40) with placebo + methotrexate (> or =10 mg/week, n= 40), resulted in significant reductions in disease activity at weeks 24 and 48. Sustained improvements in physical function and standard effect sizes (SES) for changes in components of ACR and EULAR criteria were evaluated over 2 yrs. RESULTS: More patients receiving rituximab + methotrexate completed a 2-yr follow-up without further treatment than those receiving placebo + methotrexate (45% vs 15%, respectively), rituximab alone (10%) or rituximab + cyclophosphamide (22%). This reflected a higher percentage of patients receiving rituximab + methotrexate reporting improvements in Health Assessment Questionnaire Disability Index > or = minimum clinically important difference at 1 and 2 yrs (68% and 30%, respectively) compared with placebo + methotrexate (28% and 15%), rituximab monotherapy (43% and 10%) or rituximab + cyclophosphamide (39% and 12%). SES were high in all rituximab groups and revealed differing patterns of response over time. CONCLUSION: A single course of rituximab with continuing methotrexate in patients with active RA provided clinically meaningful improvements in physical function over 2 yrs, with lower discontinuation rates and larger SES for improvements in ACR and EULAR criteria components.

Adult↗

PubMed2006

Switch to an invasive growth phase in melanoma is associated with tenascin-C, fibronectin, and procollagen-I forming specific channel structures for invasion.

Malignant melanomas are characterized by their high propensity to invade and metastasize, but the molecular mechanisms of these traits have remained elusive. Our DNA microarray analyses of benign nevi and melanoma tissue specimens revealed that the genes encoding extracellular matrix proteins tenascin-C (TN-C), fibronectin (FN), and procollagen-I (PCOL-I) are highly upregulated in invasive and metastatic melanomas. The expression and distribution of these proteins were further studied by immunohistochemistry in benign nevi, radially and vertically growing melanomas, sentinel node micrometastases, and macrometastases. TN-C was increased in all invasive tumours and metastases, especially at invasion fronts, but not in benign nevi or non-invasive melanomas. Significantly, the intensity of TN-C staining correlated with metastasis to sentinel lymph nodes, better than tumour thickness (Breslow). Moreover, TN-C, FN, and PCOL-I appeared to co-localize in the tumours and form tubular meshworks and channels ensheathing the melanoma cells. Our data suggest that melanoma invasion is associated with the formation of special channel-like structures, providing a new concept, structured tumour cell spreading. Altogether, these data provide potential new prognostic markers and therapeutic targets/strategies for preventing melanoma dissemination.

Biomarkers, Tumor↗

PubMed2006

Varied presentations of pseudoxanthoma elasticum in a family.

Pseudoxanthoma elasticum (PXE) is a hereditary disorder of elastic tissue. The characteristic skin changes are asymptomatic yellow papules around the neck and in body folds giving the skin a characteristic cobblestone appearance. The eyes, cardiovascular and gastrointestinal systems are also commonly involved. In this case-series, we present a family of four children, three of whom demonstrated diverse manifestations of PXE. The first child presented with sudden death at age 3 and showed marked coronary and renal arterial intimal fibrosis with prominent fragmentation of the internal elastic lamina, initially attributed to idiopathic arterial calcification. The second child presented with clinical features and histology of the skin typical of PXE at age 11 and the third child, with abnormal, but non-specific cardiological findings at age 8, which raised the possibility of an early stage of PXE. This report emphasizes the importance of considering pseudoxanthoma elasticum in diverse clinical settings, early diagnosis and appropriate screening for asymptomatic family members.

Child↗

PubMed2005

Urethral polyps in prepubertal girls.

PURPOSE: Urethral polyps in girls are included in the differential diagnosis of interlabial masses. Only 6 cases have been described in the English literature to date and etiology is uncertain. We present 5 more cases and review the literature. We also propose an etiology for urethral polyps in young girls and compare polyps between girls and boys as well as older females. MATERIALS AND METHODS: The medical records of prepubertal girls with urethral polyps seen at our hospital between 1980 and 2003, including operative reports and followup, were reviewed. A senior pathologist re-inspected the specimens to confirm the diagnosis. A MEDLINE search of urethral polyps was performed. RESULTS: We identified 5 girls 2 to 10 years old with urethral polyps. All girls presented with "vaginal" bleeding, 1 had recurrent urinary tract infections and vulvitis, 1 had urinary frequency, and 1 had painful voiding. The polyps were not site specific and were located in the distal, mid and proximal urethra. All polyps were excised and were found benign. Four girls were cured after 1 procedure, while in one girl the polyp reappeared. The patients were followed for 1 to 17 years and eventually became asymptomatic. CONCLUSIONS: Urethral polyps in prepubertal girls are probably benign. We suggest that the etiology of most of polyps in girls is similar to those in older females, that is a prolapsing urothelium that has evolved into a polyp.

Child↗

PubMed2005

Severe colonic diverticulitis in an adolescent with Williams syndrome.

Williams Syndrome (WS) is a condition with multisystemic involvement caused by a genetic deletion in chromosome 7. Colonic diverticulosis has been described in adults with WS; however, it has not previously been reported in adolescents with WS. We report an adolescent boy with WS who developed complicated colonic diverticulitis and briefly review the possible aetiology of diverticular disease.

Adolescent↗

PubMed2004

Off-line separation and determination of rare earth elements associated with chloroplast pigments of hyperaccumulator Dicranopteris dichotoma by normal-phase liquid chromatography and ICP-MS.

An off-line normal-phase liquid chromatography-ICP-MS method has been used for separation and determination of the rare earth elements (REE) associated with chloroplast pigments of Dicranopteris dichotoma. The stability of REE-bound pigments was tested, and almost no destruction of REE-bound pigments occurred during the so-called normal-phase liquid chromatography. The accumulated free REE ions on the microcrystalline cellulose column were cleaned by elution with 5 mmol L(-1) 2-ethylhexyl hydrogen 2-ethylhexylphosphonate (P507), to avoid exchange of these free ions with metals from the pigments. When these precautions were taken, the method was applied to the study of REE-bound pigments in D. dichotoma. ICP-MS results showed REE were present in chlorophylls and lutein, although REE concentrations in carotene and pheophytin were both below procedural blank levels. By careful analysis of the eluate fractions containing chlorophyll a it was found that REE-bound chlorophyll a in D. dichotoma was slightly enriched in the fractions with relatively short retention time. Results indicated that the retention time of REE-bound chlorophyll a might be slightly less than that of magnesium chlorophyll a, and REE-bound chlorophylls might be of relatively low polarity in comparison with magnesium bound chlorophylls. This phenomenon could be explained by the special double-decker sandwich-structure of REE-bound chlorophylls, as was reported by us and other authors. On the basis of these results we preferred to consider that REE can replace magnesium in chlorophyll a of D. dichotoma, and that the role of REE-bound chlorophylls in photosynthesis cannot be neglected. These data might be useful for understanding of both the properties of REE-bound pigments and the effect of REE on plant photosynthesis.

Chlorophyll↗

PubMed2004

Epitope DNA vaccines against tuberculosis: spacers and ubiquitin modulates cellular immune responses elicited by epitope DNA vaccine.

Cell-mediated immune responses are crucial in the protection against tuberculosis. In this study, we constructed epitope DNA vaccines (p3-M-38) encoding cytotoxic T lymphocyte (CTL) epitopes of MPT64 and 38 kDa proteins of Mycobacterium tuberculosis. In order to observe the influence of spacer sequence (Ala-Ala-Tyr) or ubiquitin (UbGR) on the efficacy of the two CTL epitopes, we also constructed DNA vaccines, p3-M-S(spacer)-38, p3-Ub (UbGR)-M-S-38 and p3-Ub-M-38. The immune responses elicited by the four DNA vaccines were tested in C57BL/6 (H-2b) mice. The cytotoxicity of T cells was detected by LDH-release method and by enzyme-linked immunospot assay for epitope-specific cells secreting interferon-gamma. The results showed that DNA immunization with p3-M-38 vaccine could induce epitope-specific CD8+ CTL response and that the spacer sequence (AAY) only enhanced M epitope presentation. The protein-targeting sequence (UbGR) enhanced the immunogenicity of the two epitopes. The finding that defined spacer sequences at C-terminus and protein-targeting degradation modulated the immune response of epitope string DNA vaccines will be of importance for the further development of multi-epitope DNA vaccines against tuberculosis.

Animals↗

PubMed2001

The role of Kupffer cell oxidant production in early ethanol-induced liver disease.

Considerable evidence for a role of Kupffer cells in alcoholic liver disease has accumulated and they have recently been shown to be a predominant source of free radicals. Several approaches including pharmacological agents, knockout mice, and viral gene transfer have been used to fill critical gaps in understanding key mechanisms by which Kupffer cell activation, oxidant formation, and cytokine production lead to liver damage and subsequent pathogenesis. This review highlights new data in support of the hypothesis that Kupffer cells play a pivotal role in hepatotoxicity due to ethanol by producing oxidants via NADPH oxidase.

Adenoviridae↗

PubMed2001

The Chk1-Cdc25C regulation is involved in sensitizing A253 cells to a novel topoisomerase I inhibitor BNP1350 by bax gene transfer.

Promotion of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the efficacy of cancer treatment. The transfection of the proapoptotic bax gene, which results in the overexpression of bax protein, augments the growth inhibition of A253 cells by BNP1350. Increased drug response was associated with the induction of DNA fragmentation in the size of 30-200 Kb, generating a cleaved fragment of 18 kDa from full-length 21 kDa bax and the cleavage of PARP. A253/vec cells treated with 0.07 microM(IC50) of BNP1350 accumulated in G2 phase at 24 h after drug removal. In contrast, A253/Bax cells treated with an equimolar concentration of BNP1350 primarily displayed a G1 phase accumulation with a concurrent decrease in G2 phase. Certain cell cycle regulatory protein expression and activities were altered following drug exposure in both cell lines under similar conditions. Cdk2- and cdc2-associated H1 kinase activities were markedly increased in the A253/Bax cell line with marginal increased activity in the A253/vec cell line. A chk1 activity assay was performed with GST-cdc25C (200-256) or GST-cdc25C(S216A) (200-256) fusion proteins as the substrate. Increased chk1 activity was observed in the A253/vec cell line, with little change in the A253/Bax cell line, when exposed to equimolar concentrations of BNP1350 (0.07 microM). A Western blot of immunoprecipitated chk1 indicated that increased chk1 phosphorylation following DNA damage induced by BNP1350 was accompanied by the observed G2 accumulation in the A253/vec cell line, while only a slight increase in chk1 phosphorylation was seen in the A253/Bax cell line. A decreased expression of cdc25C was observed in the BNP1350-treated A253/Bax cells, but not in the A253/vec cell line. Following exposure to BNP1350, increased binding of 14-3-3 proteins to chk1 occurred in both cell lines, with more being observed in the A253/vec cell line. The data have shown that inhibition of the chk1 pathway accompanied by the abrogation of G2 arrest is involved in sensitizing A253 cells to BNP1350 by bax gene transfer. These findings suggest that bax gene transfer sensitizes A253 cells to BNP1350 through apoptosis promoting and G2/M DNA damage checkpoint regulatory pathways.

Apoptosis↗

PubMed2001

Reduced early alcohol-induced liver injury in CD14-deficient mice.

Activation of Kupffer cells by gut-derived endotoxin is associated with alcohol-induced liver injury. Recently, it was shown that CD14-deficient mice are more resistant to endotoxin-induced shock than wild-type controls. Therefore, this study was designed to investigate the role of CD14 receptors in early alcohol-induced liver injury using CD14 knockout and wild-type BALB/c mice in a model of enteral ethanol delivery. Animals were given a high-fat liquid diet continuously with ethanol or isocaloric maltose-dextrin as control for 4 wk. The liver to body weight ratio in wild-type mice (5.8 +/- 0.3%) was increased significantly by ethanol (7.3 +/- 0.2%) but was not altered by ethanol in CD14-deficient mice. Ethanol elevated serum alanine aminotransferase levels nearly 3-fold in wild-type mice, but not in CD14-deficient mice. Wild-type and knockout mice given the control high-fat diet had normal liver histology, whereas ethanol caused severe liver injury (steatosis, inflammation, and necrosis; pathology score = 3.8 +/- 0.4). In contrast, CD14-deficient mice given ethanol showed minimal hepatic changes (score = 1.6 +/- 0.3, p < 0.05). Additionally, NF-kappa B, TGF-beta, and TNF-alpha were increased significantly in wild-type mice fed ethanol but not in the CD14 knockout. Thus, chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury.

Acute-Phase Proteins↗

PubMed2001

Vascular regression is required for mesenchymal condensation and chondrogenesis in the developing limb.

Vascular regression occurs during limb mesenchymal cell condensation and chondrogenesis, but it is unclear whether it is required for these processes or is a secondary phenomenon without major regulatory roles. To address this issue, beads presoaked with the potent angiogenic factor vascular endothelial growth factor (VEGF) were implanted in the vicinity of the prospective digit 2 in early chick embryo wing buds and the effects on angiogenesis and digit development were determined over time. We found that VEGF treatment caused a marked local increase in blood vessel number and density. Strikingly, this was accompanied by inhibition of digit 2 development as revealed by lack of expression of chondrogenic transcription factor Sox9 and absence of Alcian blue staining. Vascular distribution and skeletal development in adjacent areas remained largely unaffected. Inhibition of digit formation and excess vascularization were both reversible upon further embryonic growth and dissipation of VEGF activity. When supernumerary digits were induced at the anterior limb margin by retinoic acid treatment, their development was also preceded by vascular regression; interestingly, cotreatment with VEGF inhibited supernumerary digit development as well. Direct exposure of limb mesenchymal cells in micromass cultures to VEGF caused no obvious effects on condensation and chondrogenesis, indicating that VEGF effects are not due to direct action on skeletal cells. Our results are the first to provide evidence that vascular regression is required for mesenchymal condensation and chondrogenesis. A model of how patterning mechanisms and vascular regression may intersect and orchestrate limb skeletogenesis is proposed.

Animals↗

PubMed2001

A mechanism for the partial insertion of protein kinase C into membranes.

We propose that the principle driving force allowing protein kinase C (PKC) to insert partway into membranes is the transient creation of an interior hydrophilic phase within the membrane. We further suggest that this phase is composed of non-bilayer-forming elements, such as diacylglycerol or phorbol esters. We used the combination of fluorescence resonance energy transfer (using fluorescently labeled phospholipid molecules and the endogenous tryptophan residues of PKC) and fluorescence quenching by the water-soluble reagent potassium iodide. The experimental system used micelles and purified PKC. Our model accounts for both the established kinetic data on PKC as well as the physical requirements of protein-membrane interaction. Moreover, it establishes PKC as the first example of a partially embedded membrane protein, and provides a mechanism to account for its activation.

Animals↗

PubMed2001

Rare earth elements in naturally grown fern Dicranopteris linearis in relation to their variation in soils in south-Jiangxi region (southern China).

Ferns (Dicranopteris linearis) and soils, sampled from four rare earth mining areas and one non-mining area locating in South-Jiangxi region, were chosen for analysis of 15 rare earth elements (REEs) by inductively coupled plasma-mass spectrometry (ICP-MS). The fern samples were divided into 4 parts: root, stem, petiole, and lamina. The soils of the same sites were also sampled, and 4 soil layers were observed at the profile: A (0-20 cm depth), B (20-150 cm depth), C (150-400 cm depth), and D (rock). The distribution patterns and transportation characteristics of REEs of different soil layers and of different parts of D. linearis were studied. The results showed that in the soil layers, the sigma REE (the sum of the concentrations of 15 REEs) of A layer, as well as B layer were lower than that of C layer, but Ce was relatively concentrated in A layer. The sigma REE of different parts of D. linearis were lamina, root > stem > petiole. The REE distribution patterns of D. linearis root were similar to the total REE distribution patterns of the A layer of their host soils, especially to the soluble REE distribution patterns of the A layer of their host soils. The REEs were fractionated in their transportation in D. linearis. The abundances of heavy rare earth elements (HREEs, Gd to Lu and Y) in the stem, petiole, lamina are lower than those in the root.

Environmental Monitoring↗

PubMed2001

Viral delivery of superoxide dismutase gene reduces cyclosporine A-induced nephrotoxicity.

BACKGROUND: Cyclosporine A (CsA) increases free radical formation in the kidney. Accordingly, this study investigated whether gene delivery of superoxide dismutase (SOD) reduced radical production and nephrotoxicity caused by CsA. METHODS: Rats were given adenovirus (Ad) carrying lacZ or Cu/Zn-SOD genes three days prior to CsA treatment. Histology, glomerular filtration rates (GFRs) and free radical adducts in urine were assessed. RESULTS: SOD activity was increased 2.5-fold three days after viral infection and remained at 2- and 1.6-fold higher 10 and 17 days later. Treatment with CsA for seven days decreased GFR by 70% in rats infected with Ad-lacZ as expected; however, the decrease was diminished significantly in rats receiving Ad-SOD. CsA treatment for two weeks caused a loss of brush border and dilation of proximal tubules, necrosis, and increased leukocyte infiltration into the kidney; these effects were minimized by SOD. Dimethyl sulfoxide (DMSO) was attacked by the hydroxyl radical to produce a methyl radical. Indeed, administration of CsA with 12C-DMSO in rats infected with Ad-lacZ produced a radical adduct with hyperfine coupling constants similar to 4-POBN/methyl radical adduct and another unknown radical adduct. CsA given with 13C-DMSO produced a 12-line spectrum, confirming the involvement of hydroxyl radicals. Free radical adducts detected in urine were increased approximately fivefold by CsA, an effect blocked completely by SOD. CONCLUSIONS: CsA increases free radical formation. Gene delivery of SOD blocks formation of free radicals, thereby minimizing nephrotoxicity caused by CsA.

Adenoviridae↗

PubMed2001

Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats.

BACKGROUND AND AIMS: Alcohol-induced liver injury is associated with an increase in oxidants from a variety of possible sources. Therefore, it was hypothesized that increased and stable expression of the antioxidant enzyme Cu/Zn-superoxide dismutase (SOD1) would diminish oxygen free radicals and reduce alcohol-induced liver injury. METHODS: To test this hypothesis, rats were given recombinant adenovirus containing Cu/Zn-superoxide dismutase (Ad.SOD1) or beta-galactosidase (Ad.lacZ) and fed ethanol enterally for 3 weeks. RESULTS: SOD was increased significantly 3-5-fold over endogenous levels in both hepatocytes as well as Kupffer cells 3 weeks after infection. Serum transaminase levels and pathology were elevated significantly in Ad.lacZ-treated animals by using an intragastric feeding model. This effect was blunted significantly in Ad.SOD1-infected animals. Importantly, electron spin resonance-detectable free-radical adducts caused by ethanol were also decreased by SOD1 overexpression. Moreover, the increase in nuclear factor kappaB (NFkappaB), tumor necrosis factor alpha (TNF-alpha), and interleukin 1 messenger RNA (mRNA) caused by ethanol was blunted in animals treated with Ad.SOD1. CONCLUSIONS: These data support the hypothesis that oxidant production is critical in early alcohol-induced liver injury and that gene delivery of antioxidant enzymes may be useful in prevention and treatment.

Adenoviridae↗

PubMed2001

Alcohol-induced free radicals in mice: direct toxicants or signaling molecules?

Tumor necrosis factor alpha (TNF-alpha) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor alpha receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-alpha production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-alpha production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-alpha production and do not directly damage cells in early alcohol-induced hepatic injury.

Animals↗

PubMed2001

In vitro activity of garlic oil and four diallyl sulphides against antibiotic-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.

The in vitro antibacterial activities of garlic oil and four diallyl sulphides naturally occurring in this oil were studied against Pseudomonas aeruginosa and Klebsiella pneumoniae (total 237 clinical isolates). Garlic oil at 4 x MIC could reduce original inoculum to diallyl disulphide > diallyl trisulphide (DAT) > diallyl tetrasulphide (DATS) (P < 0.05). Most interactions of ceftazidime, gentamicin, imipenem and meropenem with DAT or DATS, determined according to the fractional inhibitory concentration index, showed synergic or additive effects. These results suggest that garlic oil, DAT and DATS may have potential for the prevention or treatment of nosocomial, antibiotic-resistant bacterial infections.

Allyl Compounds↗

PubMed2001

Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells.

The role of oxidants in the mechanism of tumor promotion by peroxisome proliferators remains controversial. The idea that induction of acyl-coenzyme A oxidase leads to increased production of H(2)O(2), which damages DNA, seems unlikely; still, free radicals might be important in signaling in specialized cell types such as Kupffer cells, which produce mitogens. Because hard evidence for increased oxidant production in vivo after treatment with peroxisome proliferators is lacking, the spin-trapping technique and electron spin resonance spectroscopy were used. Rats were given di(2-ethylhexyl) phthalate (DEHP) acutely. The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was also given and bile samples were collected for 4 h. Under these conditions, the intensity of the six-line radical adduct signal increased to a maximum value of 2.5-fold 2 h after administration of DEHP, before peroxisomal oxidases were induced. Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo. Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals. Moreover, similar treatments were performed in knockout mice deficient in NADPH oxidase (p47(phox) subunit). Importantly, DEHP increased oxidant production in wild-type but not in NADPH oxidase-deficient mice. These data provide evidence for the hypothesis that the molecular source of free radicals induced by peroxisome proliferators is NADPH oxidase in Kupffer cells. On the contrary, radical adduct formation was not affected in peroxisome proliferator-activated receptor alpha knockout mice. These observations represent the first direct, in vivo evidence that phthalates increase free radicals in liver before peroxisomal oxidases are induced.

Animals↗