Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

At least 145 records · Page 8Linked to original sources

PubMed2001

Additive effect of alfacalcidol on bone mineral density of the lumbar spine in Taiwanese postmenopausal women treated with hormone replacement therapy and calcium supplementation: a randomized 2-year study.

OBJECTIVE: To evaluate the effect of 1alpha-hydroxyvitamin D3 on bone mineral density of the lumbar spine in postmenopausal women receiving hormone replacement therapy and calcium supplement. DESIGN: A randomized, prospective 2-year clinical trial. PATIENTS AND MEASUREMENTS: A total of 240 postmenopausal women were enrolled with randomized assignment of 120 patients to each treatment group (the D + E group of 1alpha-hydroxyvitamin D3 + sequential combined HRT + calcium supplement; the E group: sequential combined HRT + calcium supplement). None of the patients had received HRT for menopausal syndrome or osteoporosis before being enrolled in our study. Serum biochemical assays, electrolytes and calcitonin were performed at baseline and after 6 and 12 months of treatment. Bone mineral density (BMD) of L2-L4 was measured by dual energy X-ray absorptiometry (DXA) at the initial assessment and after 12 and 24 months of treatment. RESULTS: One hundred and five patients (87.5%) in the D + E group and 92 patients (76.7%) in the E group completed the first 1-year study. Ninety-six patients (80%) in the D + E group and 80 patients (66.7%) in the E group completed the 2-year trial. Renal function, liver function, electrolytes and calcitonin showed no significant changes during the first year of follow-up. In the D + E group, the BMD of L2-4 increased 3.24 +/- 0.32% from baseline after 1 year (P < 0.05) and 5.32 +/- 0.23% after 2 years of treatment (P < 0.05). On the other hand, the changes of BMD in the E group were 1.12 +/- 0.34% after 1 year (P < 0.05) and 2.42 +/- 0.26% after 2 years of treatment (P < 0.05). The changes of BMD of L2-L4 of the D + E group were higher than the changes of the E group after both 1 and 2 years of treatment (P < 0.05). CONCLUSIONS: Our study demonstrated that combination of 1alpha-hydroxyvitamin D3 with HRT is superior to HRT alone for the preservation of bone mineral density in postmenopausal women under calcium supplementation.

Absorptiometry, Photon↗

PubMed2001

Factitious disease of the breast of a male due to injection of liquid plastic.

BACKGROUND: Factitious disease involving the breast is unusual. The rarely reported cases of this entity have been encountered in middle-aged women. In general, factitious disease can be distinguished on clinical and/or psychological grounds from self-induced disorders seen in malingerers and among those demonstrating Munchausen's syndrome. METHODS: We report herein a male patient displaying factitious disease of the breast due to injection of a high viscosity liquid plastic material. RESULTS: Establishment of the proper diagnosis was greatly delayed due to a lack of suspicion of this entity. Only direct confrontation of the patient with the biopsy results (lipogranulomatosis) led to a reluctant and then only partial admission of the self-induced nature of this patient's illness. CONCLUSION: The clinician should remain vigilant for factitious disease when confronted with chronic or recurrent lesions of a bizarre or atypical morphology. Any body site can be involved, including the breast. Management is difficult and is best accomplished in conjunction with an appropriate mental health professional. Continued dramatic surgical interventions are contraindicated.

Adult↗

PubMed2001

Antenatal glucocorticoids and renal function after birth.

Antenatal glucocorticoid treatment is widely used in cases of threatening preterm delivery. Both human and animal studies have confirmed that glucocorticoids promote pulmonary maturation in fetuses. Several studies indicate that prenatal glucocorticoids also stimulate renal maturation. Although the current knowledge about the effects of glucocorticoids on kidney function is mainly concentrated on short-term effects, there are animal studies suggesting that antenatal glucocorticoid treatment may also cause permanent changes in kidney morphology and renal function. It still remains to be investigated if antenatal glucocorticoid treatment induces long-term effects in humans.

Female↗

PubMed2001

The smooth muscle cell membrane during atherogenesis: a potential target for amlodipine in atheroprotection.

BACKGROUND: Atherosclerotic disease has been present in the human population apparently from the beginning of time. However, it has only been in the 20th century that improvements in the control of infectious diseases have allowed the average life span to increase to the point where atherosclerosis has been able to affect the general population. By the middle of the 20th century, atherosclerosis had reached epidemic levels, and it is currently pandemic and increasing worldwide. Despite its growing significance to health care, we still know relatively little about the cellular basis for plaque genesis in the vessel wall. Current thinking holds that atherosclerosis is caused by an unchecked chronic inflammatory process involving the cells of the arterial wall and their interaction with LDL and various inflammatory cells. Considerable evidence suggests that the principal insults underlying atherogenesis are serum dyslipidemias and oxidative stress mediated primarily by oxidized LDL. However, just how these insults alter the cell biology of vascular cells and lead to the atherosclerotic phenotype is still under intense investigation. Moreover, recent clinical trials have provided evidence that certain classes of drugs, including newer calcium channel blockers (CCBs), can remodel the arterial smooth muscle cell (SMC) membrane and inhibit the progression of atherosclerotic disease. METHODS: This review summarizes our current thinking on atherogenesis in the arterial SMC and considers recent developments regarding alterations in the SMC membrane during the very early period of atherogenesis. We also discuss how certain CCBs might operate to produce atheroprotection. RESULTS: The SMC membrane becomes enriched in unesterified cholesterol soon after the development of serum hypercholesterolemia. With excess membrane cholesterol, the membrane becomes thicker and develops distinct cholesterol domains. These alterations in the membrane increase the permeability of SMC to calcium and induce a variety of alterations in SMC function that contribute to cellular atherogenic processes during plaque genesis. Amlodipine, a third-generation CCB, markedly inhibits the progression of lesions. The explanation of this novel action may lie in the effects of this drug on various potential cellular targets. CONCLUSIONS: Evidence is accumulating that excess membrane cholesterol may contribute to the cellular defects responsible for the transformation of the SMC to the atherosclerotic phenotype. Amlodipine, which has membrane-remodeling properties, is emerging as an important atheroprotective drug.

Amlodipine↗

PubMed2001

Detection of single- and double-strand DNA breaks after traumatic brain injury in rats: comparison of in situ labeling techniques using DNA polymerase I, the Klenow fragment of DNA polymerase I, and terminal deoxynucleotidyl transferase.

DNA damage is a common sequela of traumatic brain injury (TBI). Available techniques for the in situ identification of DNA damage include DNA polymerase I-mediated biotin-dATP nick-translation (PANT), the Klenow fragment of DNA polymerase I-mediated biotin-dATP nick-end labeling (Klenow), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). While TUNEL has been widely utilized to detect primarily double-strand DNA breaks, the use of PANT to detect primarily single-strand DNA breaks and Klenow to detect both single- and double-strand DNA breaks has not been reported after TBI. Accordingly, coronal brain sections from naive rats and rats at 0, 0.5, 1, 2, 6, 24, and 72 h (n = 3-5/group) after controlled cortical impact with imposed secondary insult were processed using the PANT, Klenow, and TUNEL methods. Cells with DNA breaks were detected by PANT in the ipsilateral hemisphere as early as 0.5 h after injury and were maximal at 6 h (cortex = 66.3+/-15.8, dentate gyrus 58.6+/-12.8, CA1 = 15.8+/-5.9, CA3 = 12.8+/-4.2 cells/x 400 field, mean +/- SEM, all p < 0.05 versus naive). Cells with DNA breaks were detected by Klenow as early as 30 min and were maximal at 24 h (cortex = 56.3+/-14.3, dentate gyrus 78.0+/-16.7, CA1 = 25.8+/-4.7, CA3 = 29.3+/-15.1 cells/x 400 field, all p < 0.05 versus naive). Cells with DNA breaks were not detected by TUNEL until 2 h and were maximal at 24 h (cortex = 47.7+/-21.4, dentate gyrus 63.0+/-11.9, CA1 = 5.6+/-5.4, CA3 = 6.9+/-3.7 cells/x 400 field, cortex and dentate gyrus p < 0.05 versus naive). Dual-label immunofluorescence revealed that PANT-positive cells were predominately neurons. These data demonstrate that TBI results in extensive DNA damage, which includes both single- and double-strand breaks in injured cortex and hippocampus. The presence of multiple types of DNA breaks implicate several pathways in the evolution of DNA damage after TBI.

Animals↗

PubMed2001

Prevalence of serotypes and molecular epidemiology of Streptococcus pneumoniae strains isolated from children in Beijing, China: identification of two novel multiply-resistant clones.

Three-hundred and seventy-six strains of Streptococcus pneumoniae isolated from clinical specimens and nasopharyngeal swabs from children at daycare centers and hospitals in Beijing China, between January 1997 and March 1998, were serotyped. Twenty-seven different serotypes were identified. The most prevalent serotypes in the carriage isolates were 6A, 19F, 23F, and 15 and were found in 66.8% of cases. Serotype data indicate that 51.8% of carrier strains would be included in the 11-valent conjugate vaccine formulation, while inclusion of vaccine-related serotypes, increased the potential vaccine coverage to 79.4%. Serotypes 7, 6B, 23F, 19F, 15, and 3 accounted for 62% of clinical strains, with 70% vaccine-related serotypes. DNA fingerprinting of 47 penicillin resistant and 71 penicillin-susceptible/macrolide-resistant strains by BOX polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and penicillin binding protein (PBP)-fingerprinting identified two novel clones: one a serotype 23F multiresistant clone resistant to penicillin, tetracycline, erythromycin, clindamycin, and variably resistant to chloramphenicol and trimethoprim-sulphamethoxazole; and the second a multiresistant penicillin-susceptible, macrolide-resistant serotype 6A clone, highly resistant also to tetracycline, clindamycin, and trimethoprim-sulphamethoxazole. The macrolide resistance determinant in 89% of erythromycin-resistant strains tested (penicillin-susceptible and penicillin-resistant) was the erm gene, both the erm and mef genes were simultaneously found in 6%, and mef alone in 3.4%. The data demonstrates that macrolide resistant strains in China include clonal strains and strains with dual mef and erm resistance determinants.

Anti-Bacterial Agents↗

PubMed2001

Mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine in lacZ upper aerodigestive tissue and liver and inhibition by green tea.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nitrosonornicotine (NNN) were administered to lacZ mice (MutaMouse) at equal concentrations in drinking water (2 weeks at 0.1 followed by 2 weeks at 0.2 mg/ml) over a 4 week period, for a total estimated dose of 615 mg/kg) and mutagenesis in a number of organs was measured. For mutagenesis induced by NNK the potency order was: liver > lung> pooled oral tissues kidney > esophagus > tongue. The mutant fraction varied from approximately 6 to 40 mutants per 10(-5) plaque forming units This corresponds to approximately 2-13 times the background levels. A somewhat different pattern was observed with NNN, where the order was liver > esophagus oral tissue approximately tongue > lung > kidney. The potency of NNK was about twice that of NNN in liver and lung, but somewhat less in aerodigestive tract tissue. When compared with results previously obtained for a similar administered dose of benzo[a]pyrene, NNK was approximately 10-100% as mutagenic in the corresponding organs. Reported target organs for carcinogenesis by NNN and NNK in rodents were targets for mutagenesis, but mutagenesis was also observed at other sites, suggesting that these sites are initiated. The effect of green tea consumption on mutagenesis by NNK was also investigated. Green tea reduced mutagenesis by approximately 15-50% in liver, lung, pooled oral tissue and esophagus.

Animals↗

PubMed2001

Multivariate prognostic analysis of stage I(E) primary non-Hodgkin's lymphomas of the nasal cavity.

From January 1968 to December 1997, a total of 71 patients with stage I(E) (Ann Arbor staging system, 1971) primary non-Hodgkin's lymphomas of the nasal cavity received treatment in the Cancer Center of Sun Yat-Sen University of Medical Sciences. Thirty-seven lesions were limited to the nasal cavity (limited I(E)), whereas the other 34 were extended to the structure out of the nasal cavity (extended I(E)). Forty-four patients were treated with radiochemotherapy and 27 with radiotherapy alone. Kaplan-Meier methods were used in the survival analysis. Multivariate analysis was carried out using the Cox proportional hazard model. The 5- and 10-year survival rates were 71.85% and 59.67% for the patients with a complete response to irradiation, and both were 13.89% for the patients with residue lesions (p = 0.0004). The 5- and 10-year survival rates were 69.81% and 56.72% for limited I(E), and 40.65% and 35.57% for extended I(E) (p = 0.0047). The prognosis was better for those younger than 44 years (p = 0.0003). The 10-year survival rates for radiotherapy alone and combined radiochemotherapy are 52% and 75% for limited I(E) versus 37.58% and 45% for extended I(E) (p = 0.0644). B symptoms did not significantly affect clinical outcome (p = 0.729). Multivariate analysis showed that complete response of local lesion after radiotherapy, invasion of the primary tumor to adjacent structures, and patients' age were independent prognostic factors. Our study showed that radiotherapy is the main treatment method for the primary non-Hodgkin's lymphomas of the nasal cavity; the addition of chemotherapy may improve long-term survival. The local tumor response to radiotherapy, whether the extranasal structures were invaded, and patients' age were independent prognostic factors.

Adolescent↗

PubMed2001

Calcitonin gene-related peptide-enhanced nitric oxide release and inducible NOS activity and mRNA expression in LPS-stimulated mouse peritoneal macrophages.

Previously we have shown that calcitonin gene-related peptide (CGRP), a neuropeptide increases lipopolysaccharide- (LPS) induced nitric oxide (NO) production in mouse peritoneal macrophages by using the Griess method. In this study we further examined whether CGRP could modulate inducible NO synthase (iNOS) protein and mRNA expression from mouse peritoneal macrophages. Macrophages were obtained from the peritoneal exude of male Balb/c mouse. The cells were plated on culture dishes at a density of 5 x 10(5) cells per well and were allowed to adhere for 2 h. After incubation for 24 h, the macrophages were cultured with 0.01 to 1 microg/mL LPS with or without CGRP (1-1,000 nM) for 24 h. The results showed that CGRP markedly enhanced 0.5 microg/mL LPS-induced NO release as compared with that of lower doses of LPS, such as 0.01 and 0.1 microg/mL LPS. NO was increased from 19.8 +/- 2.6 to the highest level of 31.5 +/- 4.2 microM in 5 x 10(5) cells by 10 nM CGRP in 0.5 microg/mL LPS-stimulated macrophages. The cGMP level in macrophages was augmented when CGRP was added with LPS. However, when using higher dose (1.0 microg/mL) of LPS to stimulate the macrophages, CGRP had no effect at all on NO release. CGRP had no direct effect on NO and cGMP production. CGRP increased the expression of inducible NOS protein in LPS-stimulated macrophages shown by immunocytochemistry method. The activity of iNOS was also enhanced by CGRP as compared with LPS-stimulation alone by detecting the 3H-L-citruline formation from 3H-L-arginine. We found that CGRP also increased the LPS-induced iNOS mRNA levels by using reverse transcriptase-PCR method. These data suggest that CGRP enhances LPS-induced NO release, iNOS activity, and iNOS mRNA in mouse peritoneal macrophages.

Animals↗

PubMed2001

The Arabidopsis dual-affinity nitrate transporter gene AtNRT1.1 (CHL1) is activated and functions in nascent organ development during vegetative and reproductive growth.

The AtNRT1.1 (CHL1) transporter provides a primary mechanism for nitrate uptake in Arabidopsis and is expected to localize to the epidermis and cortex of the mature root, where the bulk of nitrate uptake occurs. Using fusions to GFP/GUS marker genes, we found CHL1 expression concentrated in the tips of primary and lateral roots, with very low signals in the epidermis and cortex. A time-course study showed that CHL1 is activated in the primary root tip early in seedling development and at the earliest stages of lateral root formation. Strong CHL1 expression also was found in shoots, concentrated in young leaves and developing flower buds but not in the shoot meristem. These expression patterns were confirmed by immunolocalization and led us to examine CHL1 function specifically in the growth of developing organs. chl1 mutants showed a reduction in the growth of nascent roots, stems, leaves, and flower buds. The growth of nascent primary roots was inhibited in the mutants even in the absence of added nitrate, whereas elongation of lateral root primordia was inhibited specifically at low nitrate and acidic pH. Interestingly, chl1 mutants also displayed a late-flowering phenotype. These results indicate that CHL1 is activated and functions in the growth of nascent organs in both shoots and roots during vegetative and reproductive growth.

Anion Transport Proteins↗

PubMed2001

Transcatheter closure of secundum atrial septal defect with a new self-expanding nitinol double disk device (Amplatzer device): experience in Nanjing.

PURPOSE: Various devices have been developed for the transcatheter closure of secundum atrial septal defect (ASD II) to avoid the morbidity, discomfort, and thoracotomy scar associated with surgical closure. The purpose of this study was to evaluate the safety and efficacy of the Amplatzer septal occluder for transcatheter closure of ASD II. PATIENTS AND METHODS: Only patients who were clinically diagnosed with ASD II were selected. The anatomy of ASD had to meet certain echocardiographic criteria. Under the guidance of echocardiography and fluoroscopy, the implantation of the device was accomplished as recommended by the manufacturer. RESULTS: Thirty patients (median age 18.4 years) with an ASD II underwent transcatheter closure. Procedure time ranged from 30-200 minutes and fluoroscopy time from 10-50 minutes. The diameter of the ASD measured by echocardiography ranged from 13-25 mm, while both the stretched diameters of the ASDs and the sizes of the devices ranged from 18-34 mm. The successful placement rate was 100%. The residual shunt rate was 100% immediately after device implantation and 10% after 24 hours. After 3 months, 3.3% of the patients had a (trivial) residual shunt. The device did not affect the surrounding structures of ASD. No embolization of the device occurred. CONCLUSION: The Amplatzer device designed for the closure of ASD II can be implanted easily and also is retrievable. Due to a low ratio of residual shunt and few complications, this device is a good choice for transcatheter closure of ASD II. Long-term follow-up will be required for widespread clinical use.

Adolescent↗

PubMed2001

Different respiratory syncytial virus and Quillaja saponin formulations induce murine peritoneal cells to express different proinflammatory cytokine profiles.

The recognition of a pathogen or a vaccine antigen formulation by cells in the innate immune system leads to production of proinflammatory cytokines, which will determine the ensuing acquired immune response quantitatively and qualitatively. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are the first set of cytokines produced upon such an encounter, which have roles both in protective immunity and immunopathogenesis evident with respiratory syncytial virus (RSV). RSV antigens in different physical adjuvant-vaccine formulations were analysed for their capacity to provoke cultured murine peritoneal cells to produce these three proinflammatory cytokines. RSV immunostimulating complex (ISCOM), i.e. both antigen and adjuvant are incorporated in the same particle, induced high levels of IL-1alpha being of the same magnitude or higher than those of live RSV and lipopolysaccharide (LPS). Live virus and LPS induced higher levels of IL-6 and TNF-alpha than ISCOM and so did non-adjuvanted UV-inactivated RSV but only at high doses. ISCOM-Matrix, i.e. ISCOM without antigens, admixed as a separate entity to inactivated RSV, downregulated or blocked the cytokine response to the inactivated RSV in contrast to ISCOM. Kinetic studies showed that ISCOM induced cytokine production first detected at hours 1, 2, 4 for TNF-alpha, IL-6 and IL-1alpha respectively, which was earlier than for the other antigen formulations containing corresponding doses of antigen and/or Quillaja adjuvant. Peak values for production of TNF-alpha and IL-6 were at 8 h and for IL-1alpha at 72 h following stimulation with ISCOM. The delayed appearance of IL-1alpha may reflect the cell-bound nature of this cytokine.

Adjuvants, Immunologic↗

PubMed2001

Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations.

The genetic basis for fluoroquinolone resistance was examined in 30 high-level fluoroquinolone-resistant Escherichia coli clinical isolates from Beijing, China. Each strain also demonstrated resistance to a variety of other antibiotics. PCR sequence analysis of the quinolone resistance-determining region of the topoisomerase genes (gyrA/B, parC) revealed three to five mutations known to be associated with fluoroquinolone resistance. Western blot analysis failed to demonstrate overexpression of MarA, and Northern blot analysis did not detect overexpression of soxS RNA in any of the clinical strains. The AcrA protein of the AcrAB multidrug efflux pump was overexpressed in 19 of 30 strains of E. coli tested, and all 19 strains were tolerant to organic solvents. PCR amplification of the complete acrR (regulator/repressor) gene of eight isolates revealed amino acid changes in four isolates, a 9-bp deletion in another, and a 22-bp duplication in a sixth strain. Complementation with a plasmid-borne wild-type acrR gene reduced the level of AcrA in the mutants and partially restored antibiotic susceptibility 1.5- to 6-fold. This study shows that mutations in acrR are an additional genetic basis for fluoroquinolone resistance.

Anti-Infective Agents↗

PubMed2001

Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones.

Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4'-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4'-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major promastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC(50)) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC(50) of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmania parasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs.

Animals↗

PubMed2001

Induction of potent immune responses by cationic microparticles with adsorbed human immunodeficiency virus DNA vaccines.

The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8(+) T-cell and antibody responses by approximately 100- and approximately 1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. Further enhancement of antibody responses was observed in animals vaccinated with PLG/DNA microparticles formulated with aluminum phosphate. The magnitude of anti-Env antibody responses induced by PLG/DNA particles was equivalent to that induced by recombinant gp120 protein formulated with a strong adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing HIV env and HIV gag DNA plasmids on PLG microparticles, substantially superior antibody responses were induced against both components, as measured by onset, duration, and titer. Furthermore, PLG formulation overcame an apparent hyporesponsiveness of the env DNA component in the combination vaccine. Finally, preliminary data in rhesus macaques demonstrated a substantial enhancement of immune responses afforded by PLG/DNA. Therefore, formulation of DNA vaccines by adsorption onto PLG microparticles is a powerful means of increasing vaccine potency.

AIDS Vaccines↗

PubMed2001

Gut expression and regulation of FAT/CD36: possible role in fatty acid transport in rat enterocytes.

Fatty acid translocase (FAT)/CD36 is one of several putative plasma membrane long-chain fatty acid (LCFA) transport proteins; however, its role in intestinal absorption of LCFA is unknown. We hypothesized that FAT/CD36 would be differentially expressed along the longitudinal axis of the gut and during intestinal development, suggesting specificity of function. We found that intestinal mucosal FAT/CD36 mRNA levels varied by anatomic location along the longitudinal gut axis: stomach 45 +/- 7, duodenum 173 +/- 29, jejunum 238 +/- 17, ileum 117 +/- 14, and colon 9 +/- 1% (means +/- SE with 18S mRNA as control). FAT/CD36 protein levels were also higher in proximal compared with distal intestinal mucosa. Mucosal FAT/CD36 mRNA was also regulated during intestinal maturation, with a fourfold increase from neonatal to adult animals. In addition, FAT/CD36 mRNA levels and enterocyte LCFA uptake were rapidly downregulated by intraduodenal oleate infusion. These findings suggest that FAT/CD36 plays a role in the uptake of LCFA by small intestinal enterocytes. This may have important implications in understanding fatty acid absorption in human physiological and pathophysiological conditions.

Animals↗

PubMed2001

Autocrine signaling by IL-10 mediates altered responsiveness of atopic sensitized airway smooth muscle.

To elucidate the role and mechanism of action of interleukin (IL)-10 in regulating airway smooth muscle (ASM) responsiveness in the atopic asthmatic state, isolated rabbit tracheal ASM segments were passively sensitized with serum from atopic asthmatic patients or nonatopic nonasthmatic (control) subjects in both the absence and presence of an anti-IL-10 receptor blocking antibody (Ab). Relative to control ASM, atopic asthmatic serum-sensitized tissues exhibited enhanced isometric constrictor responses to administered acetylcholine and attenuated the relaxation responses to isoproterenol. These proasthmatic effects were prevented in atopic asthmatic serum-sensitized ASM that was pretreated with anti-IL-10 receptor Ab. In complementary experiments, exposure of cultured human ASM cells to atopic asthmatic serum induced upregulated expression of IL-10 mRNA. Moreover, extended studies demonstrated that 1) exogenous IL-10 administration to naive ASM elicited augmented contractility to acetylcholine and impaired relaxation to isoproterenol, 2) these effects of IL-10 were prevented by pretreating the tissues with an IL-5 receptor Ab, and 3) IL-10 administration induced upregulated mRNA expression and release of IL-5 protein from cultured ASM cells. Collectively, these findings provide new evidence demonstrating that the altered responsiveness of atopic asthmatic serum-sensitized ASM is largely attributed to activation of an intrinsic T helper type 2-type autocrine mechanism involving IL-10-mediated release and the action of IL-5 in the sensitized ASM itself.

Acetylcholine↗

PubMed2001

A major role for VCAM-1, but not ICAM-1, in early atherosclerosis.

VCAM-1 and ICAM-1 are endothelial adhesion molecules of the Ig gene superfamily that may participate in atherogenesis by promoting monocyte accumulation in the arterial intima. Both are expressed in regions predisposed to atherosclerosis and at the periphery of established lesions, while ICAM-1 is also expressed more broadly. To evaluate functions of VCAM-1 in chronic disease, we disrupted its fourth Ig domain, producing the murine Vcam1(D4D) allele. VCAM-1(D4D) mRNA and protein were reduced to 2-8% of wild-type allele (Vcam1(+)) levels but were sufficient to partially rescue the lethal phenotype of VCAM-1-null embryos. After crossing into the LDL receptor-null background, Vcam1(+/+) and Vcam1(D4D/D4D) paired littermates were generated from heterozygous intercrosses and fed a cholesterol-enriched diet for 8 weeks. The area of early atherosclerotic lesions in the aorta, quantified by en face oil red O staining, was reduced significantly in Vcam1(D4D/D4D) mice, although cholesterol levels, lipoprotein profiles, and numbers of circulating leukocytes were comparable to wild-type. In contrast, deficiency of ICAM-1 either alone or in combination with VCAM-1 deficiency did not alter nascent lesion formation. Therefore, although expression of both VCAM-1 and ICAM-1 is upregulated in atherosclerotic lesions, our data indicate that VCAM-1 plays a dominant role in the initiation of atherosclerosis.

Animals↗