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Biomedical subjects

A Lu

Publications and source records attributed to A Lu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Down syndrome critical region gene 2: expression during mouse development and in human cell lines indicates a function related to cell proliferation.

The isolation of the genes located in chromosome 21 and the characterisation of their function are essential steps towards the understanding of the physiopathological mechanisms involved in Down syndrome. We have used two complementary approaches to characterise the function of the novel gene DSCR2 (Down Syndrome Critical Region gene 2): the isolation and characterisation of the mouse gene homologue to the human DSCR2 gene, and the analysis of the expression of the gene in different human cell lines. We have isolated and characterised a 1012 bp of a mouse cDNA having a high homology to the human DSCR2 gene. The predicted mouse dscr2 protein has an identity of 85.4% as compared to the human protein, indicating that the DSCR2 protein has been conserved during the evolution. However, the amino acid sequence is not homologous to other known proteins, or to known protein domains. The dscr2 gene is expressed throughout all the stages of the mouse embryo development. In the adult mouse the gene is expressed in testis, kidney, liver, brain, heart, skeletal muscle, and pancreas. The expression analysis of the DSCR2 gene in different human tumour derived cell lines indicates that the gene is expressed in all proliferating cell lines tested. The levels of the DSCR2 mRNA correlate with cellular growth of T98G and Jurkat cells in response to different treatments. The expression pattern throughout the foetal development together with the correlation observed with the cell cycle indicates a possible function for the DSCR2 gene related to cell proliferation.

Amino Acid Sequence↗
PubMed2000

Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.

Animals↗
PubMed2000

Cellubrevin is present in the basolateral endocytic compartment of hepatocytes and follows the transcytotic pathway after IgA internalization.

The endocytic compartment of polarized cells is organized in basolateral and apical endosomes plus those endocytic structures specialized in recycling and transcytosis, which are still poorly characterized. The complexity of the various populations of endosomes has been demonstrated by the exquisite repertoire of endogenous proteins. In this study we examined the distribution of cellubrevin in the endocytic compartment of hepatocytes, since its intracellular location and function in polarized cells are largely unknown. Highly purified rat liver endosomes were isolated from estradiol-treated rats, and the early/sorting endosomal fraction was further subfractionated in a multistep sucrose density gradient, and studied. Analysis of dissected endosomal fractions showed that cellubrevin was located in early/sorting endosomes, with Rab4, annexins II and VI, and transferrin receptor, but in a specific subpopulation of these early endosomes with the same density range as pIgA and Raf-1. Interestingly, only in those isolated endosomal fractions, endosomes enriched in transcytotic structures (of livers loaded with IgA), the polymeric immunoglobulin receptor specifically co-immunoprecipitated with cellubrevin. In addition, confocal and immuno-electron microscopy identification of cellubrevin in tubular structures underneath the sinusoidal plasma membrane together with the re-organization of cellubrevin, in the endocytic compartment, after the IgA loading, strongly suggest the involvement of cellubrevin in the transcytosis of pIgA.

Animals↗
PubMed2000

EGF triggers caveolin redistribution from the plasma membrane to the early/sorting endocytic compartment of hepatocytes.

In this study, we demonstrate that, in rat liver, epidermal growth factor (EGF) is responsible for the partial redistribution of caveolin-1 from the plasma membrane into the early/sorting endocytic compartment. Highly purified endosomes and plasma membrane fractions were isolated from control rat liver and from rats injected with EGF or pIgA for different times. Whereas in subcellular fractions from control hepatocytes most of caveolin was concentrated in the plasma membrane and the receptor-recycling fractions, after EGF injection there was a significant redistribution of caveolin toward the early/sorting (CURL) endocytic fractions. The recruitment of caveolin into the endocytic compartment was not induced by pIgA.

Animals↗
PubMed2000

Multiple molecular penumbras after focal cerebral ischemia.

Though the ischemic penumbra has been classically described on the basis of blood flow and physiologic parameters, a variety of ischemic penumbras can be described in molecular terms. Apoptosis-related genes induced after focal ischemia may contribute to cell death in the core and the selective cell death adjacent to an infarct. The HSP70 heat shock protein is induced in glia at the edges of an infarct and in neurons often at some distance from the infarct. HSP70 proteins are induced in cells in response to denatured proteins that occur as a result of temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after focal ischemia in regions that can extend beyond the HSP70 induction. The region of HIF induction is proposed to represent the areas of decreased cerebral blood flow and decreased oxygen delivery. Immediate early genes are induced in cortex, hippocampus, thalamus, and other brain regions. These distant changes in gene expression occur because of ischemia-induced spreading depression or depolarization and could contribute to plastic changes in brain after stroke.

Apoptosis↗
PubMed2000

Sex differences in inferior parietal lobule volume in schizophrenia.

OBJECTIVE: The inferior parietal lobule is a heteromodal association cortical region that has been implicated in the pathophysiology of schizophrenia. Inferior parietal lobule gray matter volumes have been shown to differ between healthy male and female subjects, with male subjects having larger left volumes. The authors sought to determine whether these volumetric sex differences also exist in patients with schizophrenia. METHOD: The authors used magnetic resonance imaging to measure inferior parietal lobule volumes of 15 pairs of male and female schizophrenic subjects who were individually matched to each other and to 15 pairs of healthy male and female subjects. RESULTS: Male schizophrenic patients exhibited a reversal of the normal left-greater-than-right male asymmetry in this region and had left inferior parietal lobule gray matter volumes that were significantly smaller than those of healthy male subjects. Female schizophrenic patients did not differ significantly from healthy female subjects in left or right inferior parietal lobule volume or in asymmetry. CONCLUSIONS: This study provides further evidence of brain morphology sex differences in schizophrenia that possibly contribute to the differential clinical disease expression in men and women.

Age Factors↗
PubMed2000

[The early biochemical changes of cataractous lenses of rats cultured in vitro].

OBJECTIVE: To study the mechanism of cataractogenesis. METHODS: Tissue culture was used to study the cataractous lenses of rats induced by sodium selenite or galactose. At the early stage, the content of nonprotein sulfhydryl (NP-SH), protein sulfhydryl (P-SH), non-soluble disulfide bond, malonaldehyde (MDA) and the activities of glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R) and glutathione-S-transferase (GSH-S) were measured in the cataractous lenses, and they were compared with that of the normal lenses. RESULTS: The two kinds of material could all induce cataract in rats, sodium selenite being more potent. In the early period of culture (lenses were transparent), NP-SH and P-SH were decreased, while disulfide and MDA were increased, the activity of GSH-PX rose obviously, that of GSH-S also had a tendency of rise, however, the activity of GSSG-R had no obvious changes. CONCLUSIONS: Rat lens opacity may occur after the lens is cultured in vitro with the addition of sodium selenite or galactose, and biochemical changes may develop in the lens at the early period of culture (lenses are transparent).

Animals↗
PubMed2000

[The influence of external stimulation on content and quality of volatile oil in Lignun Santali albi].

The authors analyzed the quality of Ligmum Santali Albi formed by the external stimulation of hormone and windburn by GC-MS-DS. The results showed that the content of volatile oil is 2.34% in the heart wood formed in 10 years tree age of Santalum album (SA) after 2 years stimulation continuously with a definite concentration of hormone, which is near to the 25 years tree age of SA in the same place. The GC-MS analysis showed that the content of santalol and other chemical components in volatile oil are similar to the 25 years tree age of SA. It is indicated that a definite concentration of hormone stimulated the SA may shorten the formation of the heart wood. The heart wood can be also formed by the broken branches after 2 years windburn, but its content of volatile oil is only 1/2 of the heart wood formed by hormone stimulation.

Age Factors↗
PubMed1999

Enhanced growth of animal and human endothelial cells on biodegradable polymers.

Biodegradable polymers such as poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA) and PGA coated with PLLA are being employed for cell transplantation and for in vivo regeneration of vascular tissue. Ingrowth and organization of fibrovascular tissue inside polymer scaffolds lead to the occlusion of the regenerated blood vessel. In order to provide regulatory mechanisms to control the development of an inner capsule, endothelialization of these materials is necessary. To achieve this, we employed a novel ammonia plasma technique to surface modified PLLA substrates. Human endothelial cell (HUVEC) and rabbit microvascular endothelial cell (RbMVEC) growth was studied on modified PLLA and control PLLA. Our studies show that modified PLLA and fibronectin (Fn)-coated modified PLLA exhibited statistically significant improvement in HUVEC and RbMVEC growth (P<0.001) when compared to PLLA and Fn-coated PLLA. Therefore, ammonia plasma treatment gives us the unique capability of modifying prosthetic biomaterials of various constructs with the eventual transplantation of mammalian cells to be used in tissue engineering or as biological implants.

Animals↗
PubMed1999

A new, unique and simple method for ureteral implantation in kidney recipients with small, defunctionalized bladders.

BACKGROUND: Major, almost insurmountable, deterrents exist to the use of the small capacity, defunctionalized, nonneurogenic urinary bladder in renal transplantation, namely, the technical difficulty in performing a satisfactory ureteral implantation with conventional methods and the potential secondary problems with high grade ureteral reflux and obstruction. Alternatives are less than ideal and include transplantation into a bowel-augmented urinary bladder with intermittent self-catheterization, ileal conduit urinary diversion, or avoidance of transplantation and relegating the patient to life-long dialysis. METHODS: Eight consecutive patients (ages 13 months to 29 years) with small, defunctionalized urinary bladders underwent a new method of intravesical implantation of the transplant ureter. The mean capacity of these bladders was 18.5+/-13.1 ml (range 6 to 45 ml), with the bladders defunctionalized for a mean 81.6+/-24.3% of the patients' total lifetime. The technique involved placement of the transplant ureter into a shallow, mucosa-denuded, rectangular trough extending from a superiorly placed ureteral hiatus distally to the trigone. We hypothesized that the mucosal margins on the two lateral aspects of the rectangular trough would grow over the anterior surface of the ureter until they met the advancing mucosal edges from the contralateral side to form a natural neosubmucosal tunnel. RESULTS: Posttransplantation cystoscopic examination demonstrated bladder mucosal regeneration and growth over the ureter, confirming the spontaneous development of a good length neosubmucosal tunnel. All patients demonstrated no evidence of ureteral reflux or ureteral obstruction, whereas an immediate prior cohort of four consecutive patients with bladder capacities < or =30 ml showed that three of four had ureteral reflux (P=0.02) and four of four developed hydronephrosis (P=0.002). All urinary bladders in the present cohort enlarged to expected normal or nearnormal capacities. Serum creatinines were stable throughout the entire follow-up period, with the exception of one patient who had rejection episodes. Two patients had urinary tract infections posttransplantation, but there were no episodes of acute pyelonephritis. CONCLUSIONS: This novel technique for ureteral implantation successfully capitalizes on the regenerative potential of the bladder mucosa, resulting in a physiological, anatomically natural, and very effective neosubmucosal tunnel. It appears to guarantee success against both ureteral reflux and obstruction, no matter how small the urinary bladder, and offers no hindrance to enlarging the bladder to near normal capacity posttransplantation. The implantation technique is simple and safe, and its use should eliminate the reluctance to use these bladders. Moreover, this procedure offers a major incentive for the successful rehabilitation of small, defunctionalized, nonneurogenic bladders after kidney transplantation.

Adult↗
PubMed1999

The "early-sorting" endocytic compartment of rat hepatocytes is involved in the intracellular pathway of caveolin-1 (VIP-21).

The sinusoidal plasma membrane of the hepatocyte is organized into functional and structural microdomains whose origin, maintenance, and functioning are closely related with the endocytic compartment. Three different subcellular fractions, from rat liver, containing caveolin-1, the structural protein of caveolae, were morphologically and biochemically characterized. A caveolae-enriched plasma membrane fraction (CEF), contains large membrane structures surrounding attached internal plasmalemmal vesicles; the receptor-recycling compartment (RRC), contains tubules and vesicles with similar morphology to the internal vesicles observed by electron microscopy in CEF; and finally, caveolin-1 was also detected in early-sorting endosomes (CURL, compartment of uncoupling receptors and ligands). In this study, we show that following an intravenous administration of retinol-binding protein (RBP), there was a redistribution of caveolin-1 from the plasma membrane (CEF) to intracellular endocytic compartments (RRC and early-sorting endosomes). Thus, these results indicate that, in the hepatocyte, caveolae are dynamic structures actively interacting with the endocytic compartment.

Animals↗
PubMed1999

Alteration in brain proteins following occlusion of the middle cerebral artery in rat.

The effects of permanent focal ischemia on specific proteins of the cerebral hemisphere were studied by unilateral occlusion of the middle cerebral artery (MCAO) in rat. Brain proteins were prepared 72 h after the occlusion and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The proteins were identified by their interaction with rabbit antibodies against rat serum proteins and anti-transferrin antibodies. SDS-PAGE analysis of the proteins prepared from ischemic tissue showed significant increase in the 66 and 80 kDa components; where a marked decrease in the 260 kDa protein occurred in the ischemic and para-ischemic tissues. The 66 kDa and 80 kDa proteins stained intensely with anti-serum protein antibodies, indicating that they are related to plasma components. Moreover, the 66 kDa band had the same electrophoretic mobility as bovine serum albumin used as a standard molecular size marker. The 80 kDa band was identified as transferrin by staining with the specific antibody. Transferrin was immunolocalized in the penumbra of cerebral cortex, hippocampal CA1 region and dentate gyrus of the ischemic cerebral hemisphere. The present results suggest that alteration in the brain content of 66 kDa (albumin), 80 kDa (transferrin) and 260 kDa (unidentified) proteins may reflect early effects of focal ischemia.

Albumins↗
PubMed1999

Sex differences in the inferior parietal lobule.

The inferior parietal lobule (IPL) - a neocortical region and part of the heteromodal association cortex (HASC) - has been hypothesized to exhibit sexual dimorphism, as do other HASC regions, particularly with regard to asymmetry. Using a reliable method for measuring IPL gray matter volume based upon individual sulcal-gyral landmarks, we measured this region on magnetic resonance imaging scans from a sample of 15 individually matched pairs of normal male and female subjects. Male subjects showed significantly larger left, but not right, IPL volumes when compared to females. Males also showed a leftward (left > right) asymmetry for the IPL, with a less marked opposite asymmetry in females. Such sexual dimorphisms may possibly underlie the subtle cognitive differences observed between the sexes.

Adult↗
PubMed1999

In vivo and in vitro analysis of baculovirus ie-2 mutants.

Upon transient expression in cell culture, the ie-2 gene of Autographa californica nuclear polyhedrosis virus (AcMNPV) displays three functions: trans activation of viral promoters, direct or indirect stimulation of virus origin-specific DNA replication, and arrest of the cell cycle. The ability of IE2 to trans stimulate DNA replication and coupled late gene expression is observed in a cell line derived from Spodoptera frugiperda but not in a cell line derived from Trichoplusia ni. This finding suggested that IE-2 may exert cell line-specific or host-specific effects. To examine the role of ie-2 in the context of infection and its possible influence on the host range, we constructed recombinants of AcMNPV containing deletions of different functional regions within ie-2 and characterized them in cell lines and larvae of S. frugiperda and T. ni. The ie-2 mutant viruses exhibited delays in viral DNA synthesis, late gene expression, budded virus production, and occlusion body formation in SF-21 cells but not in TN-5B1-4 cells. In TN-5B1-4 cells, the ie-2 mutants produced more budded virus and fewer occlusion bodies but the infection proceeded without delay. Examination of the effects of ie-2 and the respective mutants on immediate-early viral promoters in transient expression assays revealed striking differences in the relative levels of expression and differences in responses to ie-2 and its mutant forms in different cell lines. In T. ni and S. frugiperda larvae, the infectivities of the occluded form of ie-2 mutant viruses by the normal oral route of infection was 100- and 1,000-fold lower, respectively, than that of wild-type AcMNPV. The reduction in oral infectivity was traced to the absence of virions within the occlusion bodies. The infectivity of the budded form of ie-2 mutants by hemocoelic injection was similar to that of wild-type virus in both species. Thus, ie-2 mutants are viable but exhibit cell line-specific effects on temporal regulation of the infection process. Due to its effect on virion occlusion, mutants of IE-2 were essentially noninfectious by the normal route of infection in both species tested. However, since budded viruses exhibited normal infectivity upon hemocoelic injection, we conclude that ie-2 does not affect host range per se. The possibility that IE-2 exerts tissue-specific effects has not been ruled out.

Animals↗
PubMed1999

Application of recombinant human granulocyte colony stimulating factor in children with acute myeloid leukemia.

OBJECTIVE: To evaluate the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on accelerating neutrophil recovery and decrease fatal infections for childhood acute myeloid leukemia (AML). METHODS: From November 1992 to March 1997, 45 patients were enrolled into our study and 15 were newly diagnosed. All were treated with high dose chemotherapy combined with rhG-CSF. RESULTS: Of 15 newly diagnosed patients, 13 achieved complete remission (CR) after one course of therapy and 2 achieved CR after two courses of therapy. For newly diagnosed patients, the durations of absolute neutrophil counts (ANC) < 0.5 x 10(9)/L were 5 days and 10 days in rhG-CSF group and control group respectively (P < 0.05). The incidences of infection of these two groups were 40% and 60% respectively (P < 0.05). As for patients who received intensive therapy, the durations of ANC < 0.5 x 10(9)/L were 5 days and 8 days in rhG-CSF group and control group, respectively (P < 0.05), and the incidences of infection were 25% and 44.4% respectively (P < 0.05). CONCLUSIONS: The application of rhG-CSF in children with AML after chemotherapy may hasten the hematopoietic recovery. The duration of neutropenia was shortened by 3-4 days, and the incidence of fatal infection was reduced. rhG-CSF does not stimulate AML growth in vivo.

Antineoplastic Agents↗
PubMed1999

[Effect of kidney deficiency caused by ovariectomy on serum osteocalcin level and tumor necrosis factor in mice with collagen induced arthritis].

OBJECTIVE: To explore the effect of ovariectomy caused Kidney Deficiency on the metabolism of bone in mice with collagen induced arthritis. METHODS: The mice for experiment were immunized with subcutaneous injection of type II collagen to induce arthritis after ovariectomy. Severity of joint swelling, radioimmunoassay of serum estradiol (E2), osteocalcin (OC) and tumor necrosis factor (TNF), and pathological changes of joint, including changes on synovia, articular cartilage and bone, were observed once weekly. RESULTS: The E2 level of ovariectomized mice dropped down obviously, while the contents of OC and TNF increased significantly. Severe pathological changes can be seen in synovial tissues, cartilage and bone. CONCLUSION: Kidney Deficiency caused by ovariectomy exacerbated the pathological changes of collagen-induced arthritis in mice.

Animals↗
PubMed1999

[Research on petroleum ether extract of rhizoma Drynariae].

OBJECTIVE: To study the petroleum ether extract of Rhizoma Drynariae. METHOD: Solvent extraction silica gel column isolation, and structure elucidation by physico-chemical evidence and spectral analysis. RESULT: Three compounds were isolated and elucidated as fern-9(11)-ene, hop-22(29)-ene and cyclolaudenol. CONCLUSION: All the three compounds are triterpenoids.

Drugs, Chinese Herbal↗