Effect of 2,4-dichlorophenoxyacetic acid on adsorption and release of copper on montmorillonite.
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Biomedical subjects
Publications and source records attributed to S Li.
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OBJECTIVE: To determine the rates of repeated abortion and contraceptive use among unmarried young women seeking an abortion in China. METHODS: We used an anonymous self-administered questionnaire at abortion clinics in Beijing, Changsha, and Dalian from January to September 2000. RESULTS: Of 4547 unmarried young women seeking an abortion, 33.0% reported having had one previous induced abortion. Of those who had had more than one abortion, only 29.7% used a contraceptive method at their first sexual intercourse after the procedure; and of the 446 women who chose contraception, 41.3% used the traditional methods of withdrawal or rhythm. Although 65.0% of the young women had used condoms at least once, only 9.6% did so consistently and correctly; 47.7% of the current pregnancies were associated with nonuse of any contraceptive, and 52.3% were related to contraceptive failure. CONCLUSION: The rate of unmarried young women seeking repeated abortions was high in China on 2000. The rate of consistent condom use was low, and the rate of contraceptive failure was higher.
It has been reported that several of the effects induced by octadecaneuropeptide (ODN) could be mediated by an activation of a metabotropic receptor. In order to investigate the role and mechanism of action of ODN in gonadotropin-releasing hormone (GnRH) neuron regulation, we studied the effects of the acute i.c.v. administration of ODN and of a new ODN antagonist to metabotropic receptor, cyclo(1-8)[Dleu(5)]OP, on GnRH mRNA expression as evaluated by in situ hybridization in castrated male rats. The administration of ODN produced a decrease in the hybridization signal while the administration of cyclo(1-8)[Dleu(5)]OP alone produced an 18% increase. When administrated concomitantly with ODN, the antagonist both inhibited the depressing effect of ODN and induced a 22% increase over the values detected in ODN-treated rats. The data suggest that the effect of ODN on GnRH mRNA expression might be mediated by interaction with metabotropic receptors.
INTRODUCTION: Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice. METHODS: Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1. RESULTS: I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01). CONCLUSION: These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.
Pigs have been the most likely animal as the source of cells, tissues, and organs for xenotransplantation. But the use of pigs in xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Previous studies have identified that the proviruses are integrated into the genome of normal pigs and that virus particles released from the porcine cells can infect human cells in vitro. As a unique inbred pig, Banna minipig inbred (BMI) has a huge potential value for xenotransplantation and medical research. It has been the focal experimental animal for pig-to-human xenotransplantation in China, due to its clear genetic background and tiny individual differences. To evaluate whether the potential risk of PERV exists in inbred pigs, a series of screening experiments were performed herein. The results of PCR with primers specific for gag, pol, and env showed that proviruses existed in the genome of BMI, and the PERV subtypes were PERV-A and PERV-B. PERV mRNA was expressed functionally in BMI. Positive results of an RT assay identified that PERV in BMI had potential infectivity, but the concentration of PERV reverse transcriptase in BMI was almost 20 times lower than that of HIV. These results suggested that gag, pol and env genes of PERV were not lost during inbreeding, which created favorable conditions to produce viral particles that could possibly infect human cells in xenotransplantation.
PCR amplification was performed on genomic DNA extracted from peripheral blood lymphocytes of three species of Chinese pigs (Banna minipig inbreed [BMI], Wu-Zhi-Shan pig [WZSP], and Nei jiang pig [NJP]), using primers corresponding to the highly conserved regions of polymerase (pol) gene. Extracted PCR products were then cloned in a pGEM-T vector. Phylogenetic analysis of the nucleotide sequences of BMI-PERV, NJJP-PERV, and WZSP-PERV revealed them to be a novel category of PERV. In comparison to other type C retrovirus and lentivirus, their amino acid sequenced show about 30% to 57.7% identities. Our previous research demonstrated that PERV in the three pigs was highly expressed. It appears likely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The novel sequences described in this report will allow such investigations to be actively pursued.
INTRODUCTION: Clinical xenotransplantation is being considered to overcome the shortage of human organ donors. In our previous studies, using human-anti-porcine xenogeneic mixed mononuclear cell-endothelial cell cultures with the suppression subtractive hybridization method, we obtained a subtracted cDNA library that included about 300 clones corresponding to up-regulated genes. One porcine sequence showed 81% identity with the human oxidative-stress responsive 1 (OSR1) molecule. The objective of this study was to confirm the gene up-regulation and obtain the full-length sequences. METHODS: The full-length gene was cloned through the technique of rapid amplification of cDNA ends (RACE). The other methods included bioinformatics analysis and RT-PCR. RESULTS: RT-PCR confirmed that the gene was up-regulated upon the interactions of human peripheral blood mononuclear cells (PBMCs) and porcine endothelial cells. By SMART RACE technique, we obtained the full-length cDNA of porcine OSR1. The gene is 4333 bp. The open-read frame of 1590 bp encodes 529 amino acid residues. GenBank accession number is AY271356. The gene shows 92.8% nucleotide identity and 95.5% amino acid identity with human OSR1. CONCLUSION: We obtained the full-length cDNA of porcine OSR1. It was up-regulated on porcine endothelial cells following activation by human PBMCs. We succeeded in constructing a pcDNA-pOSR1 recombinant eukaryotic cell expression vector, the function of which is the subject as our ongoing work.
Pigs have been thought to be ideal candidates for xenotransplant donors. However besides the immunological barrier, physiological and pharmacokinetic comparabilities of kidney function between donor animals and humans are important factors for successful xenotransplantation. As a unique large inbred animal, Banna Minipig Inbred (BMI) has been reported to be a potential large animal suitable for xenotransplantation. However, its physical and pharmacokinetic compatibilities with humans have not been documented. The purpose of this investigation was to measure renal routine function, glomerular filtration rate (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to humans. The results suggested that the renal function of BMI was similar to that of humans to eliminate nonprotein nitrogenous end products of metabolism. Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used methods to assess ERPF and GFR--showed that BMI showed lower values than humans for GFR, but similar function to humans in ERPF. The pharmacokinetics of cefazolin; a widely used model drug to study kidney drug metabolizing capacity, showed greater overall renal drug elimination of BMI than of humans. These results suggested that BMI did show comparable data to human renal function.
As a unique inbred pig Banna minipig inbred (BMI) is potentially suitable for pig-to-human xenotransplantation due to its clear genetic background and minor interindividual differences. Previous studies of BMI have focused on immunological barriers between BMI and humans. However, a comparison of liver function between donor animals and humans is an essential premise for successful xenotransplantation. In this study, we investigated routine hepatic functions, protein electrophoresis, and drug metabolism to compare capacity of liver synthesis, metabolism, and drainage between BMI and humans. The results showed no significant differences in the concentrations of albumin and globulin synthesized in the liver (alpha1, alpha2, and beta-globulin). Serum enzyme activities in BMI were higher than those in humans, and levels of total bilirubin and direct-reacting bilirubin of BMI were lower than those of humans. In BMI, the clearance of antipyrine, a widely used model drug to study hepatic drug metabolism, was 16 times greater than that by humans, with a mean residual time of antipyrine in BMI, one-tenth of that in human. These findings suggested that BMI livers are similar to humans in albumin and alpha, beta-globulin synthesis, but stronger in bilirubin elimination, enzyme activity, and drug metabolism. BMI livers may have stronger functions compared with those of humans. No incompatibility was identified in hepatic function between BMI and humans.
Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or donor lymphocyte infusions can reduce graft-versus-host disease (GVHD) without compromising graft-versus-leukemia. We explored CD8 depletion in patients undergoing matched related donor (MRD, n=25) and unrelated donor (URD, n=16) peripheral blood stem cell transplantation following myeloablative conditioning with cyclophosphamide (60 mg/kg/day i.v. x 2) and total body irradiation (200 cGy x 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with anti-CD8 antibody coated high-density microparticles removed 99% of CD8+ cells. The median number of CD8+ cells infused was 3.9 x 10(5) cells/kg (2.2 x 10(5) in MRD, and 8.1 x 10(5) in URD patients). Post transplant immune suppression included tacrolimus in the MRD cohort, and tacrolimus plus mini-methotrexate (5 mg/m2 days +1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2-4 acute GVHD incidence was 61% (44% MRD, 88% URD). Chronic GVHD incidence was 50% (48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event-free and overall survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%, respectively, at 2 years. There was no correlation between CD8+ number and GVHD or survival. A 2-log depletion of CD8+ cells from PBSC is insufficient to prevent GVHD.
OBJECTIVE: To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: : Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUC-baseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variance-component-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.
BACKGROUND: The aim of this study was to explore variation in practice patterns and identify factors associated with physicians' treatment decisions for early-stage Hodgkin's disease. METHODS: We conducted a one-time mail survey of oncologists randomly selected from directories of national oncology societies (n = 207) and Hodgkin's disease experts (n = 147). The survey included questions on (i) physician factors, (ii) preferred treatment choices for six case scenarios of early-stage Hodgkin's disease that varied by patient factors, and (iii) thresholds for changing treatment recommendations. RESULTS: The response rate was 50%. For non-bulky Hodgkin's disease, 69% of respondents chose combined modality therapy (CMT). On multivariate analysis, physician factors that independently predicted for choice of CMT included a high Hodgkin's disease case load (P = 0.02) and a high percentage of patients enrolled in clinical trials (P = 0.05). Radiation oncologists had a lower threshold for adding radiation therapy (P = 0.02). More experience with second malignancy cases and longer time in practice were associated with a higher threshold for adding radiation therapy (P = 0.04 and P = 0.008, respectively). In stratified analyses, treatment decisions of non-experts were significantly influenced by physician factors, but not by patient factors. Conversely, choices of Hodgkin's disease experts were insensitive to all physician factors, but experts were significantly more likely to select chemotherapy alone in young women and CMT in older patients. CONCLUSIONS: Our results indicate that physician factors including practice type and experience may in part explain variation in practice pattern for Hodgkin's disease therapy. Hodgkin's disease experts are more likely to tailor therapy according to individual patient factors.
BACKGROUND: The aim of this study was to determine salvage outcome in patients with Hodgkin's disease who relapse after radiation therapy, and to compare the efficacy of mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) versus Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) as salvage treatment. PATIENTS AND METHODS: One hundred patients with Hodgkin's disease (97 with stage I-II disease at presentation) who relapsed after radiation therapy alone were salvaged with either MOPP or ABVD. Freedom from second relapse (FFSR) and overall survival (OS) were determined, and prognostic factors for salvage outcome were evaluated. RESULTS: The median follow-up time since salvage therapy was 12 years. The 10-year FFSR and OS rates were 70% and 89%, respectively. Forty-one patients were salvaged with MOPP and 59 received ABVD. The type of salvage chemotherapy did not significantly influence FFSR or OS. Age >50 years at initial diagnosis was the only significant predictor for an inferior FFSR and OS on both univariate and multivariate analyses. CONCLUSIONS: The two salvage regimens of MOPP and ABVD had similar efficacy in this group of patients with predominantly early-stage disease at initial radiation therapy. The inferior salvage outcome in patients aged >50 years is a contributing factor to the overall poor prognosis of patients presenting with Hodgkin's disease at an older age.
BACKGROUND: Current information on the prognostic importance of body mass index (BMI) for patients with early breast cancer is based on a variety of equivocal reports. Few have data on BMI in relationship to systemic treatment. PATIENTS AND METHODS: Patients (6792) were randomized to International Breast Cancer Study Group trials from 1978 to 1993, studying chemotherapy and endocrine therapy. BMI was evaluated with eight other factors: menopausal status, nodal status, estrogen receptor status, progesterone receptor status, tumor size, vessel invasion, tumor grade and treatment. BMI was categorized as normal (< or =24.9), intermediate (25.0-29.9) or obese (> or =30.0). RESULTS: Patients with normal BMI had significantly longer overall survival (OS) and disease-free survival (DFS) than patients with intermediate or obese BMI in pairwise comparisons adjusted for other factors. Subset analyses showed the same effect in pre- and perimenopausal patients and in those receiving chemotherapy alone. When assessed globally and adjusted for other factors, BMI significantly influenced OS (P = 0.03) but not DFS (P = 0.12). CONCLUSIONS: BMI is an independent prognostic factor for OS in patients with breast cancer, especially among pre-/perimenopausal patients treated with chemotherapy without endocrine therapy.
In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.
Fluorescence in situ hybridization (FISH) analysis can reveal undetected chromosomal rearrangements. We report a patient with cleft palate, hydronephrosis, and minor dysmorphic features, including low-set posteriorly rotated ears, down-slanting palpebral fissures, mandibular micrognathia, and brachymesophalangia. Routine chromosome analysis identified no abnormality of chromosome 22; FISH analysis with the TUPLE1 probe disclosed an interstitial duplication of 22q11.2. FISH analysis did not reveal the duplication on the initial testing of metaphase chromosomes, although, on review, the area was brighter on one chromosome in each metaphase spread. FISH analysis of interphase cells showed three TUPLE1-probe sites with two chromosome-specific identification probes in each cell. Family history showed two older full siblings, a brother with behavior problems, oppositional defiant disorder, and learning problems and a sister with hydronephrosis and mild delays. The father and both siblings had similar facial features, and all three had the same interstitial duplication of the TUPLE1 probe. This family illustrates the novel complementary duplication syndrome of the velocardiofacial syndrome, which adds it to the expanding list of genomic deletion/duplication syndromes. The laboratory results further show the utility and need for careful analysis of interphase cells even in samples where good quality metaphases are available.
The fluroquinolone gemifloxacin was examined for its capacity to modulate secretion of cytokines by human monocytes stimulated with lipopolysaccharide (LPS). Monocytes from six male and two female healthy volunteers were stimulated with LPS, exposed to gemifloxacin and the amounts of secreted IL-1 alpha, IL-1 beta, IL-6, IL-10 and TNF-alpha measured at 3, 6 and 24 h. The results revealed that LPS alone increased secretion of each cytokine significantly. Treatment of the LPS-stimulated monocytes with gemifloxacin resulted in a significant inhibition (p < 0.01) of secretion of each of the cytokines from monocytes of the eight volunteers. Nuclear extracts of the human monocyte cell line, THP-1, were used in the electrophoretic mobility shift assay to determine whether gemifloxacin affects nuclear factor-kappa B (NF-kappa B) activation. In addition, RNA from THP-1 cells was used in Northern blots to determine whether inhibition of secretion of IL-1 beta and TNF-alpha by gemifloxacin occurred at the transcription or translation level. Whereas LPS induced a rapid increase in NF-kappa B activation, gemifloxacin alone did not. Gemifloxacin did not affect the kinetics or decrease the extent of activation. Northern blots indicated that the inhibitory activity of gemifloxacin occurred post-transcription. Thus, gemifloxacin may modulate the immune response by altering secretion of cytokines by human monocytes. Although the concentrations of gemifloxacin used were higher than those observed in the serum of human volunteers treated with the dose under clinical development, it should be taken into consideration that concentrations at tissue and intracellular levels may be considerably higher than serum concentrations.
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