Biomedical subjects

S Qi

Publications and source records attributed to S Qi.

At least 37 records · Page 2Linked to original sources

PubMed2000

Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus.

BACKGROUND: In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates. METHODS: Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. RESULTS: The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection. CONCLUSIONS: The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.

Animals↗

PubMed2000

Effect of tacrolimus (FK506) and sirolimus (rapamycin) mono- and combination therapy in prolongation of renal allograft survival in the monkey.

BACKGROUND: Our previous studies confirmed that tacrolimus (FK506) and sirolimus [rapamycin (RAPA)], in combination, are not antagonistic but are synergistic in the prolongation of heart and small bowel grafts in the rodent. The aim of this study was to confirm further the synergistic effect of combined FK506 and RAPA in the more clinically relevant model, kidney transplantation in monkeys. METHODS: A total of 60 male Vervet monkeys were randomly assigned to 10 groups (n> or =5). Monkeys with renal allografts were treated with different doses of FK506 and/or RAPA orally for 60 days. Graft survival, body weight, clinical biochemistry determinations, oral glucose tolerance test, trough levels of the two drugs, and histopathology were investigated. RESULTS: Low doses of FK506 (1 or 4 mg/kg) combined with RAPA (0.5 mg/kg) produced synergistic effect in the prolongation of renal graft survival [combination index (CI) = 0.292, 0.565]. There were no additive or synergistic drug-associated toxicities such as hyperglycemia, nephrotoxicity, and hyperlipidemia. There also was no pharmacological antagonism. CONCLUSION: Concomitant therapy of low-dose (drug-optimal) FK506 and RAPA produced a synergistic effect in the prolongation of kidney allograft survival in Vervet monkeys without additive drug-associated toxicities.

Animals↗

PubMed2000

Blocking of CD44-hyaluronic acid interaction prolongs rat allograft survival.

BACKGROUND: Lymphocyte activation and infiltration into a transplanted organ is an integral component of the rejection process. Graft infiltration of lymphocytes requires adhesion of leukocytes to the endothelium, diapedesis, and transmigration. One of several proteins involved in this process is CD44, which is known to interact with endothelial hyaluronan (HA). Blockade of cell-matrix and cell-cell interactions have been used extensively for modulation of immune responses and graft rejection. Based on these observations, we evaluated the effects of blocking CD44-HA interactions in a transplantation model. METHODS: We used a low molecular weight hyaluronic acid formulation (LMWHA) for the treatment of rat renal and cardiac allograft recipients. LMWHA was administered intraperitoneally at 0.5-5 mg/kg for 5-10 days after transplantation with or without a subtherapeutic dose of cyclosporine. RESULTS: LMWHA monotherapy prolonged allograft survival significantly, but only for a few days. In combination with low-dose cyclosporine, long-term survival of allografts was observed in some of recipients. CONCLUSION: Further definition of the underlying mechanism of LMWHA therapy may provide a rationale for the development of novel, nontoxic, nonimmunogenic immunotherapies.

Animals↗

PubMed2000

Expression and regulation of the messenger ribonucleic acid encoding the prostaglandin F(2alpha) receptor in the rat myometrium during pregnancy and labor.

OBJECTIVE: We examined expression of messenger ribonucleic acid encoding the prostaglandin F(2alpha) receptor in the rat myometrium throughout late gestation and its regulation by progesterone and mechanical stretch. STUDY DESIGN: Normal pregnant rats were killed on gestational day 15, 22, or 23 (during labor) or 1 day post partum. The effects of progesterone on prostaglandin F(2alpha) receptor messenger ribonucleic acid levels were investigated by daily injections of progesterone (4 mg) from day 20 of normal gestation or from day 17 in rats bilaterally ovariectomized on day 17. To investigate the effects of myometrial stretch, unilaterally pregnant rats underwent either sham surgery or placement of a polyvinyl tube 3 mm in diameter in the nongravid uterine horn on day 15 or 18 and were killed 5 days later. Prostaglandin F(2alpha) receptor messenger ribonucleic acid levels in the myometrium were determined by a semiquantitative reverse transcription-polymerase chain reaction method. RESULTS: Myometrial prostaglandin F(2alpha) receptor messenger ribonucleic acid levels significantly increased during both term and ovariectomy-induced preterm labor. This increase was blocked by progesterone. In rats with unilateral pregnancies prostaglandin F(2alpha) receptor messenger ribonucleic acid levels in the nongravid horns were similar to those in the contralateral gravid horns on day 20 and during labor regardless of whether they were stretched by a 3-mm tube. CONCLUSION: Increased myometrial expression of prostaglandin F(2alpha) receptor messenger ribonucleic acid during term and preterm labor is temporally associated with progesterone withdrawal but is not dependent on mechanical stretch of the myometrium.

Animals↗

PubMed2000

Liarozole fumarate (R85246): in the treatment of ER negative, tamoxifen refractory or chemotherapy resistant postmenopausal metastatic breast cancer.

Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1: 1n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150-300mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0-52.3%: median duration (MD) 20 months; range 2-36.5); 25% in group 2 (95% CI 11.0-52.3%; MD 6.5 months: range 3.5-38): 11% in group 3 (95% CI 4.2-29.2%; MD 7 months; range 3-8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre-treatment levels of 72.7 pM (9.1-1,839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer.

Administration, Oral↗

PubMed2000

Rotating Gamma System radiosurgery for cerebral arteriovenous malformations.

One hundred and thirty-two patients with cerebral arteriovenous malformations (AVMs) were treated using the Rotating Gamma System, a new radiosurgical system between November 1996 and May 2000. The average size of the AVMs was 23 mm in diameter (range 6 to 69 mm). The mean dose delivered to the AVM margin was 19.2 Gy (range 13 to 25 Gy), and that delivered to the center of the AVMs was 37.6 Gy (range 32.5 to 50 Gy). One hundred and six patients were followed up for an average of 18.4 months (range 5 to 44 months). Five patients (4.7%) experienced rebleeding which took place between 5 and 13 months after treatment, but none of them died from hemorrhage. No bleeding took place after complete angiographic obliteration. Neuroimaging studies showed radiation-induced edema in 19 (22%) of the 87 patients, none of whom had severe permanent neurological deficits. Of the 68 patients followed up for more than one year, 57 underwent angiography at 1 year after treatment. The complete obliteration was demonstrated in 24 patients (42%) at 1 year. Of the 27 patients followed for more than 2 years, 23 patients underwent angiography 2 years after treatment, and complete obliteration was demonstrated in 18 patients (78%). These results are comparable to the results of treatment with other radiosurgical systems.

Adolescent↗

PubMed2000

Coordinate expression of novel genes during osteoblast differentiation.

To achieve new insights into the coordinate regulation of gene expression during osteoblast differentiation we utilized an approach involving global analysis of gene expression to obtain the identities of messenger RNAs (mRNAs) expressed using an established in vitro model of bone development. MC3T3-E1 osteoblast-like cells were induced to differentiate by the addition of beta-glycerophosphate (beta-GP) and ascorbic acid. RNA samples derived from induced and uninduced control MC3T3-E1 cells were used to prepare complementary DNA (cDNA) for serial analysis of gene expression (SAGE). A preliminary SAGE database was produced and used to prepare a hybridization array to further facilitate the characterization of changes in the expression levels of 92 of the SAGE-mRNA assignments after induction of osteoblast differentiation, specifically after 6 days and 14 days of ascorbate treatment. SAGE-array hybridization analysis revealed coordinate induction of a number of mRNAs including Rab24, calponin, and calcyclin. Levels of MSY-1, SH3P2, fibronectin, alpha-collagen, procollagen, and LAMPI mRNAs, present at day 6 postinduction, were markedly reduced by day 14 postinduction. A number of unanticipated and potentially important developmental genes were identified including the transforming growth factor beta (TGF-beta) superfamily member Lefty-1. Lefty-1 transcript and translation product were found to be induced during the course of MC3T3-E1 cell differentiation. We present evidence, using transient transfection and antibody neutralization approaches, that Lefty-1 modulates the induction of alkaline phosphatase (ALP) after treatment of MC3T3-E1 cells with ascorbate and beta-GP. These data should provide useful new information for future analysis of transcriptional events in osteoblast differentiation and mineralization.

Alkaline Phosphatase↗

PubMed2000

[Inhibiting effect of antisense oligodeoxynucleotide of alpha 1(I) Precollagen gene on hypertrophic scar in an animal model].

OBJECTIVE: To study the effect of antisense oligodeoxynucleotide (ODN) of alpha 1(I) precollagen gene on hypertrophic scar in an animal model. METHOD: Hypertrophic scar was explanted in athymic mice. The effect of antisense oligodeoxynucleotide 1 and 2 on the animal model and the inhibition of ODN1 and ODN2 were observed. RESULT: It was showed that antisense oligo (ODN1, 21 bp) located 5'end from the translation start region and antisense oligo (ODN2, 22 bp) between the first exon and the first intron could effectively inhibit scar hypertrophy. However the control groups showed no inhibition. CONCLUSION: Antisense oligodeoxynucleotide could effectively inhibit scar hypertrophy by inhibiting the synthesis of type I collagen protein.

Animals↗

PubMed2000

[Effects of Asiaticoside on hypertrophic scars in a nude mice model].

OBJECTIVE: To study the effect of Asiaticoside on the fibroblast collagen biosynthesis in vitro culture and on the hypertrophic scar in a nude mice model, and its mechanism. METHODS: Light microscope (LM) and electron microscope (EM) were employed to study the morphological changes in fibroblast before and after the application of Asiaticoside. The fibroblast collagen synthesis was assayed by (3)H-proline incorporation. A nude mice model with hypertrophic scar was established for observing the effect of Asiaticoside given by local injection. RESULTS: It was found that Asiaticoside could significantly affect the ultrastructure of fibroblast and inhibit its collagen synthesis in vitro culture (P < 0.01) in a manner of dose-effect relationship. Local injection of Asiaticoside into the nude mouse body could inhibit the proliferation of scar without any toxic effect. CONCLUSION: The possible mechanism of the effect of Asiaticoside on hypertrophic scars is related to its inhibitory action on the fibroblast proliferation and collagen synthesis.

Animals↗

PubMed1999

Chromosomal localization of phospholipase A2 activating protein, an Ets2 target gene, to 9p21.

A murine Ets2 target gene isolated by differential display cloning was identified as the phospholipase A2 activating protein (PLAA) gene. A 2.7-kb human cDNA demonstrating high homology to mouse and rat Plaa genes was then isolated and characterized. Human PLAA contains six WD-40 repeat motifs and three different protein kinase consensus domains. Fluorescence in situ hybridization (FISH) mapping placed PLAA on chromosome 9p21, a region frequently deleted in various cancers. A comprehensive mapping strategy was employed to define further the chromosomal localization of PLAA relative to CDKN2A within the 9p21 locus. Radiation hybrid mapping placed the gene 7.69 cR from WI-5735 (LOD >3.0), a marker in close proximity to CDKN2A and CDKN2B. Yeast artificial chromosome (YAC) mapping localized PLAA proximal to the CDKN2A/CDKN2B genes and to a region flanked by D9S171 and INFA commonly deleted in many neoplasms. Two YACs contained both PLAA and D9S259, a marker present in a second more proximal minimal deleted region observed in cutaneous melanoma and squamous cell lung carcinoma. Double-color fiber FISH mapping confirmed the location of PLAA centromeric to D9S171 and CDKN2A/CDKN2B. The mapping data suggest a possible tumor suppressor role for this gene.

Animals↗

PubMed1999

Nanoliter-scale sample preparation methods directly coupled to polymethylmethacrylate-based microchips and gel-filled capillaries for the analysis of oligonucleotides.

We are currently developing miniaturized, chip-based electrophoresis devices fabricated in plastics for the high-speed separation of oligonucleotides. One of the principal advantages associated with these devices is their small sample requirements, typically in the nanoliter to sub-nanoliter range. Unfortunately, most standard sample preparation protocols, especially for oligonucleotides, are done off-chip on a microliter-scale. Our work has focused on the development of capillary nanoreactors coupled to micro-separation platforms, such as micro-electrophoresis chips, for the preparation of sequencing ladders and also polymerase chain reactions (PCRs). These nanoreactors consist of fused-silica capillary tubes (10-20 cm x 20-50 microns I.D.) with fluid pumping accomplished using the electroosmotic flow generated by the tubes. These reactors were situated in fast thermal cyclers to perform cycle sequencing or PCR amplification of the DNAs. The reactors could be interfaced to either a micro-electrophoresis chips via capillary connectors micromachined in polymethylmethacrylate (PMMA) using deep X-ray etching (width 50 microns; depth 50 microns) or conventional capillary gel tubes using zero-dead volume glass unions. For our chips, they also contained an injector, separation channel (length 6 cm; width 30 microns; depth 50 microns) and a dual fiber optic, near-infrared fluorescence detector. The sequencing nanoreactor used surface immobilized templates attached to the wall via a biotin-streptavidin-biotin linkage. Sequencing tracks could be directly injected into gel-filled capillary tubes with minimal degradation in the efficiency of the separation process. The nanoreactor could also be configured to perform PCR reactions by filling the capillary tube with the PCR reagents and template. After thermal cycling, the PCR cocktail could be pooled from multiple reactors and loaded onto a slab gel or injected into a capillary tube or microchip device for fractionation.

Electrophoresis, Capillary↗

PubMed1999

Examination of POU homeobox gene expression in human breast cancer cells.

Abnormal expression of homeobox genes may lead to the development of leukemias, lymphomas, and solid tumors. Expression of homeobox genes in mammary glands, however, has not been studied actively until recently. We have examined the expression of POU homeobox genes in human breast cancer cell lines and human breast tissue samples. Using a pair of degenerate primers for reverse transcription-polymerase chain reaction (RT-PCR) followed by DNA sequencing, we found that the human breast cancer cell line, MCF7, expresses at least 4 POU gene products: OCT1, OCT2, OCT3 and OCT11 (Skn-1a/i, Epoc-1). The expression of OCT1 and OCT2 in other human breast epithelial cell lines was further determined by Western blot analyses and electrophoretic mobility shift assay. We were unable to detect OCT11 in human breast cancer cell lines using the anti rat Skn-1a/i antibody, although the expression of this gene in both human breast cancer cell lines and human primary breast tumors was detected by RT-PCR. OCT3 is an embryonic transcription factor. We found that this gene is also expressed in human breast cancer cell lines and all human primary breast carcinomas examined, but not in normal human breast tissue. Taken together, we have shown that several POU genes are expressed in human breast epithelial cells. As OCT3 expression was detected only in the breast cancerous cells, this embryonic transcription factor could play an important role in mammary gland carcinogenesis.

Amino Acid Sequence↗

PubMed1999

Prolongation of rat heart allograft survival with K(+)ATP-dependent channel modulators.

Controversies exist regarding the immunoregulatory properties of K(+) ATP channel modulators. We investigated the effects of aprikalim, a K(+) ATP-dependent channels activator, and glibenclamide and gliclazide, two inhibitors of K(+) ATP-dependent channels, on the prolongation of heart allograft survival in the rat. Nine groups (n >/= 5) were involved in this study with the Brown-Norway to Lewis rat combination treated with aprikalim, glibenclamide, gliclazide, and/or cyclosporine. The results indicate that modulators of K(+) ATP-dependent channels can improve the survival of rat heart allograft without interfering with the immunosuppressive properties of cyclosporine.

Animals↗

PubMed1999

Improved techniques for kidney transplantation in the monkey.

Improved microsurgical techniques for kidney transplantation in the monkey are described. The left graft kidney is transplanted to the lower part of abdomen with end-to-side anastomoses of renal artery to aorta without a patch of aorta, renal vein to inferior vena cava, and end-to-end anastomosis of donor and recipient ureter with 8-0 nylon sutures in a bilateral nephrectomized recipient monkey. We recently performed 60 kidney transplantations in Vervet monkeys. None died of surgery or surgical complications. This reproducible model provides a useful tool to test new immunosuppressants and to investigate the mechanism of drug-induced tolerance and xenotransplantation in primates as a support to clinical trial.

Animals↗

PubMed1999

Synergistic effect of rapamycin and cyclosporine in prevention of acute kidney allograft rejection in the mouse.

The effect of rapamycin (RAPA) and cyclosporine A (CsA) monotherapy and combination therapy was examined in prevention of kidney allograft rejection in the mouse. Both drugs were administered orally for up to 14 days in BALB/c (H-2(d)) to C57BL/6 (H-2(b)) mice strong combination. Six groups were treated with RAPA and/or CsA. This study shows that concomitant therapy of RAPA and CsA produces strong synergistic interaction in prolonging renal allograft survival in mice when compared with monotherapy of RAPA or CsA.

Animals↗

PubMed1999

Effects of the 21-aminosteroid U74389G in a model of chronic myocardial infarction in the rat.

21-Aminosteroids are a group of new synthetic compounds developed as antiperoxidants. Although several studies have demonstrated their cardioprotective properties in acute ischemic models, none has assessed their long-term benefits after chronic myocardial infarction. In this investigation, we examined the cardioprotective effects of U74389G, a novel 21-aminosteroid, in a model of chronic myocardial infarction in the rat. After permanent ligation of the proximal branch of the left coronary artery, the experimental animals were treated daily by gavage with U74389G (10 mg/kg) for 21 days. After the study period, harvested hearts were perfused ex vivo and submitted to cold cardioplegia with 90-min global ischemia and 30-min reperfusion (surgical stress). Myocardial function and coronary endothelial (bradykinin, 1 microM) and smooth muscle (sodium nitroprusside, 1 microM) reactivity were assessed before and after exposure to the surgical stress. Percentage infarct size of the left ventricle was computed as the ratio of infarct area (mg)/total left ventricle (mg) x 100. During or immediately after surgery, there were eight deaths, which were considered technical failures. No further deaths occurred during the follow-up period (21 days). Compared with vehicle-treated rats, long-term administration of U74389G elicited a significant reduction of infarct size (percentage of left ventricle, 9 +/- 5% in the U74389G-treated group vs. 32 +/- 5% in the vehicle-treated group; p < 0.01). Ex vivo heart-perfusion studies showed no significant difference in baseline coronary flow, left ventricular developed pressure, and heart rate between normal and chronic infarcted hearts treated with the vehicle or with U74389G. However, a reduced endothelium-dependent coronary dilator response was observed in infarcted hearts from vehicle-treated controls but not in those from U74389G-treated rats. When cardioplegia and global myocardial ischemia/reperfusion were added, most of the benefits from U74389G were lost. These results indicate that 21-aminosteroids can reverse oxygen-derived free radicals and lipid peroxidation-induced myocardial and coronary dysfunction associated with chronic myocardial infarction. However, additive protective measures are required when an acute ischemic stress is superimposed.

Animals↗

PubMed1999

Immunomodulating effects of second-generation calcium channel blockers on experimental heart transplantation.

The administration of second-generation calcium channel blockers (CCBs) to counteract the adverse effects of conventional immunosuppression gains more and more acceptance. Since these newly developed molecules differ in their chemical structure and possess specific pharmacokinetic profiles, we hypothesized that exposure to clinically relevant concentrations may have a significant immunomodulatory potential. The effects of various second-generation CCBs, felodipine, amlodipine, mibefradil and clentiazem, on cardiac allograft survival were therefore evaluated. Inbred male Lewis rats were used as recipients and Brown-Norway rats as donors. After abdominal implantation of the donor heart, allograft recipients were exposed to felodipine (31 microg/kg/day), amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). Other allograft recipients were treated with low-dose cyclosporine (CsA) alone (2 mg/kg/day) or with low-dose CsA combined with amlodipine (25 microg/kg/day), mibefradil (3 mg/kg/day) or clentiazem (2.5 mg/kg/day). All drugs were given daily by gavage. Median survival time of untreated cardiac allografts was 6.5 days. When given alone, not all the second-generation CCBs elicited a positive effect: the dihydropyridines felodipine and amlodipine were ineffective (median survival time was 6.5 and 7.0 days, respectively), the T- and L-type CCB mibefradil had a significant but minor impact (median survival time = 9.0 days, p <0.0015) while the benzothiazepine clentiazem produced the most significant result (median survival time = 16.0 days, p <0.0033). Neither amlodipine nor mibefradil modified the extent of survival provided by low-dose CsA (median survival time = 9.0 days), while clentiazem had a significant positive effect. These data indicate that second-generation CCBs differ in their immunomodulatory potential. These observations of pharmacodynamic specificity appear to be related to differences in their chemical structure as well as their interaction with other sites than the calcium channel.

Adjuvants, Immunologic↗

PubMed1999

[Experiences of early management of mass burn casualties].

OBJECTIVE: Inquire into the effective method of treatment to mass burn casualties. METHODS: The experiences of 22 batches of mass burns (403 cases) were reviewed. RESULTS: 1. The receiving hospital should take effective measures for initial care, and report to the higher health department. 2. Health department should send additional specialists to the hospital if necessary, and a leader should be appointed. 3. Ambulances with special pass or helicopter should be deployed to ensure dispatch of the helpers. 4. Emphasis on local hospital's initial treatments, including fluid resuscitation, establishment of an adequate airway, early wound management to prevent and premature dissolution of eschar. 5. Proper triage of patients, and severe burn patients should be hospitalized to burn units with adequate facilities. 6. Transportation: Patients can be transferred along where there are good transportation facilities, with fluid resuscitation, on the other hand, when transportation if poorly developed, transfer the patients after fluid resuscitation until the general condition becomes stable. CONCLUSION: 1. Mass burn casualties can be handled with satisfactory results if emergency care and professional treatment are well organized. 2. Mass burn casualties are usually caused by human errors, therefore they can be prevented.

Accidents, Occupational↗