Biomedical subjects

S Nishida

Publications and source records attributed to S Nishida.

At least 73 records · Page 4Linked to original sources

PubMed2004

Immunoenzymatic and morphological detection of epithelial cell apoptotic stages in gastrointestinal allografts from multivisceral transplant patients.

Acute allograft rejection (AR) is a major contributor to morbidity and mortality among patients who undergo multivisceral transplantation. Critical to the assessment of AR is detection of apoptosis in the glandular epithelium of the gastrointestinal allograft. We utilized the TUNEL stain (TdT-mediated biotin 16-dUTP nick-end labeling) to test whether this method improved detection of apoptosis compared to standard slide evaluation. TUNEL and H&E stains were performed on paraffin-embedded tissue sections to estimate the number of apoptotic bodies per 10 high power fields, as determined by independent pathologists in blinded fashion. Both methodologies showed similar numbers and distributions of apoptotic foci present among the epithelial cells. There was a correlation between the number of apoptosis and the grade of rejection (P <.001). This is the first use of the TUNEL stain in gastrointestinal allograft biopsies to our knowledge. The similarity in pattern and sensitivity of TUNEL with standard morphology confirms that biopsy assessment with routine H&E staining allows an accurate appraisal of epithelial cell apoptosis. Therefore, current staining protocols for endoscopically derived mucosal biopsies of gastrointestinal allografts are sufficiently accurate to enumerate the critical feature of epithelial apoptosis as a determinant of the grade of acute rejection.

Apoptosis↗

PubMed2004

Lymphoplasmacytic hyperplasia (possibly pre-PTLD) has varied expression and appearance in intestinal transplant recipients receiving Campath immunosuppression.

Posttransplant lymphoproliferative disorders (PTLD) are a frequent complication in bowel transplant recipients. Histological changes in PTLD range from expansile lymphoplasmacytic (LP) hyperplasia to frank lymphoma. Small bowel allograft biopsies obtained in the first 250 days posttransplant were retrospectively graded after patients had received induction immunosuppression with either anti-CD52 (Campath) or anti-CD25 (Zenapax) monoclonal antibodies. The biopsies were analyzed with respect to the onset intensity of lymphoplasmacytic infiltrates and presence of in situ EBV hybridization (EBER) positivity. We observed that lymphoplasmacytic infiltrates were a frequent change in all bowel transplant patients over the examined period. Campath-treated patients developed earlier LP infiltrates of mild to moderate intensity between day 1 and 100 posttransplant, thereafter decreasing to mild. No EBER positivity was detected in this group. Zenapax-treated patients presented with LP infiltrates later of mild to moderate intensity through day 100 posttransplant. However, more persistent and intense LP infiltrates was observed after day 101 in this group, including a case of lymphoma and two cases of EBER positivity. We conclude that Campath immunosuppression results in an earlier appearance of LP lesions that are generally less intense than those evident with Zenapax. We attribute these findings to the more profound immunodeficiency and cell targeting following Campath treatment.

Alemtuzumab↗

PubMed2004

Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation.

Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression.

Alemtuzumab↗

PubMed2004

Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation.

Surgical principles and techniques derived from organ transplantation surgery can provide novel applications in general surgery. We present an update on our 5-year experience with intestinal autotransplantation and abdominal wall transplantation. Nine patients underwent intestinal or multivisceral transplantation with the addition of 10 abdominal wall grafts to cover the large open areas from previous surgeries. Seven patients underwent near-total abdominal evisceration, ex vivo resection of masses at the base of the mesentery, followed by intestinal autotransplantation; 44% of the abdominal wall graft recipients are alive, but none of the fatalities were related to the graft itself. In two cases the graft had to be removed due to venous thrombosis. Of patients with intestinal autotransplants, 71% are alive with two mortalities due to recurrent metastatic malignancy. In only one case, the intestinal autograft had to be removed because of venous thrombosis. All surviving patients but one are on a regular diet; two are on supplemental enteral feeds. These results show that anastomotic and resection techniques derived from the experience in solid organ transplant can be utilized in complex wound closure, as is the case of abdominal wall transplantation, or resection of large retroperitoneal tumors with intestinal autotransplantation.

Abdominal Wall↗

PubMed2004

The long-term effects of immune suppression on liver transplant recipients with recurrent hepatitis C viral infection.

INTRODUCTION: Adequate immune suppression following liver transplantation in recipients with recurrence of hepatitis C virus (HCV) is not standardized. The aim of this study was to evaluate the association between immune suppression protocol and the clinical/histological parameters in HCV transplant recipients with an HCV recurrence. METHODS: A retrospective analysis was performed on recipients of liver transplants from June 1998 to October 2003 who experienced HCV recurrence. Only patients with liver biopsies at 3 to 5 years following liver transplantation were included in the analysis. The data set included: patient demographics, immune suppression, antiviral therapies, as well as histology to evaluate ductopenia and chronic rejection. Patients divided into groups of high, medium, and low immune suppression were subdivided by treatment with versus without interferon. A control group with similar demographics suffering from cryptogenic cirrhosis was used for comparison. RESULTS: During this period 45 patients had liver biopsies at 3 to 5 years posttransplantation. Their mean age was 56.5 years and mean time from transplant to biopsy was 1543 days. Their average posttransplant survival was 1964 days. There was no difference among the three groups with respect to HCV RNA levels (log(10) IU/mL), age, gender, time from transplant, donor age, and UNOS status. Median HCV RNA levels within the three groups were comparable at various time periods pre- and posttransplant. CONCLUSION: The development of chronic allograft damage following transplantation in recipients with recurrent HCV tended to be worse among patients with low levels of immune suppression, suggesting the importance of therapy to maintain allograft function.

Antiviral Agents↗

PubMed2004

Identification of a gene element essential for leukemia-specific expression of transgenes.

Leukemia-specific promoters and enhancers for gene therapy had never been reported. Since the Wilms' tumor gene WT1 is overexpressed in almost all types of leukemia, WT1 is an ideal target of leukemia-specific therapy. To explore the possibility of gene therapy for leukemia using WT1 promoter and enhancer, their activities in several kinds of cells were analyzed by using the enhanced green fluorescent protein (EGFP) gene as a reporter. First, we identified the best combination (654P/EGFP/int3- enh/3'-enh vector) of the 654-bp WT1 promoter and the two WT1 enhancers located in intron 3 and at the 3' end of the WT1 gene for inducing EGFP expression in K562 cells, which endogenously expressed WT1. When this was transfected into WT1-expressing leukemia cells (K562, HEL), WT1-nonexpressing hematopoietic cells (Daudi, U937), and WT1-expressing nonhematopoietic cells (TYK-nu-CPr, SW480, 293 T), 19.8, 22.9, 1.47, 1.43, 4.50, 4.16, and 1.09 times EGFP expression was induced, respectively, compared to that by the promoter-less EGFP vector. These results showed that the 654P/EGFP/int3-enh/3'-enh vector specifically induced high levels of EGFP expression in WT1-expressing leukemia cells. 654P/int3- enh/3'-enh vector containing transgenes such as suicide genes might become useful tools for leukemia-specific gene therapy.

Enhancer Elements, Genetic↗

PubMed2004

Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells.

Primitive hematopoietic progenitor cells such as severe combined immunodeficiency- repopulating cells and long-term culture-initiating cells are enriched in CD34+CD38- cells derived from various stem cell sources. In this study, to elucidate the features of such primitive cells at the molecular level, we tried to isolate genes that were preferentially expressed in umbilical cord blood (CB)-derived CD34+CD38- cells by subtractive hybridization. The gene for VPAC1 receptor, a receptor for the neuropeptide vasoactive intestinal peptide (VIP), was thereby isolated and it was shown that this gene was expressed in both CD34+CD38- and CD34+CD38+ CB cells and that the expression levels were higher in CD34+CD38- CB cells. Next, we assessed the effects of VIP on the proliferation of CD34+ CB cells using in vitro culture systems. In serum-free single-cell suspension culture, VIP enhanced clonal growth of CD34+ CB cells in synergy with FLT3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO). In serum-free clonogenic assays, VIP promoted myeloid (colony-forming unit-granulocyte/macrophage (CFU-GM)) and mixed (CFU-Mix) colony formations. Furthermore, in Dexter-type long-term cultures, VIP increased colony-forming cells at week 5 of culture. These results suggest that VIP functions as a growth-promoting factor of CB-derived hematopoetic progenitor cells.

ADP-ribosyl Cyclase↗

PubMed2003

Observation of the D(sJ)(2317) and D(sJ)(2457) in B decays.

We report the first observation of the B-->Dmacr;D(sJ)(2317) and B-->Dmacr;D(sJ)(2457) decays based on 123.8x10(6) BBmacr; events collected with the Belle detector at KEKB. We observe the D(sJ)(2317) decay to D(s)pi(0) and the D(sJ)(2457) decay to the D(*)(s)pi(0) and D(s)gamma final states. We also set 90% C.L. upper limits for the decays D(sJ)(2317)-->D(*)(s)gamma, D(sJ)(2457)-->D(*)(s)gamma, D(sJ)(2457)-->D(s)pi(0), and D(sJ)(2457)-->D(s)pi(+)pi(-).

Journal Article↗

PubMed2003

Tandem duplication of alkaline phosphatase genes and polymorphism in the intergenic sequence in Bombyx mori.

Alkaline phosphatases are ubiquitous in organisms from bacteria to human. Two alkaline phosphatase genes, Alp-m and Alp-s, were independently cloned from the silkworm Bombyx mori. They were mapped to a small DNA region and shown to be organized in tandem. Exon-intron structures of the two genes were highly conserved, with the exception of the second intron in Alp-m, which has no counterpart in Alp-s. The similarity between the nucleotide sequences of the exons of the two genes was strikingly high (60-79%), suggesting that Alp-m and Alp-s originated from a duplication of their common ancestor gene. The intergenic sequence between the two Alp genes shows length polymorphism in different B. mori strains, which can be explained by presence/absence of two putative insertion sequences. This structural variation suggests a possible scenario for the divergence of the two Alp genes after the duplication event.

Alkaline Phosphatase↗

PubMed2003

Observation of B0-->pLambda(pi)(-).

We report the first observation of the charmless hyperonic B decay, B0-->pLambda(pi)(-), using a 78 fb(-1) data sample recorded on the Upsilon(4S) resonance with the Belle detector at KEKB. The measured branching fraction is B(B0-->pLambda(pi)(-))=(3.97(+1.00)(-0.80)+/-0.56)x10(-6). Searches for B0-->pLambda(K)- and pSigma(0)pi(-) yield no significant signals and we set 90% confidence-level upper limits of B(B0-->pLambda(K)-)<8.2x10(-7) and B(B0-->pSigma(0)pi(-))<3.8x10(-6).

Journal Article↗

PubMed2003

Observation of B0 -->D0K0 and B0 -->D0K*0 decays.

We report on a search for B(0)-->D(*0)K(*0) decays based on 85 x 10(6) BB events collected with the Belle detector at KEKB. The B(0)-->D0K(0) and B(0)-->D0K(*0) decays have been observed for the first time with the branching fractions B(B(0)-->D0K(0))=(5.0(+1.3)(-1.2)+/-0.6)x10(-5) and B(B(0)-->D0K(*0))=(4.8(+1.1)(-1.0)+/-0.5)x10(-5). No significant signal has been found for the B(0)-->D(*0)K*0) and B(0)-->D(*0)K(*0) decay modes, and upper limits at 90% C.L. are presented.

Journal Article↗

PubMed2003

Sclerosing mesenteritis in small bowel transplantation: possible manifestation of acute vascular rejection.

BACKGROUND: Acute rejection of human small bowel allografts is characterized by clinical symptoms combined with characteristic morphologic alterations. The typical geographic distribution of acute rejection in the bowel is involvement of the intestinal parenchyma, which can be transmural, particularly when the rejection is more severe. However, little is known concerning the potential for donor-derived soft tissue adjacent to the bowel to become involved by the host alloimmune response. METHODS: We describe a male patient who, several weeks after combined small bowel and liver transplantation, demonstrated sclerosing mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The vascular lesions in the mesentery demonstrated increased IgG deposition and the patient developed an alloantibody to the donor. CONCLUSIONS: The changes described herein may represent a novel presentation of acute vascular rejection.

Acute Disease↗

PubMed2003

Bacterial infections after intestine and multivisceral transplantation.

BACKGROUND: The frequency of bacterial infections (BI) in intestinal transplant (IT) patients is high with sepsis being the leading cause of death after this procedure. We herein report our experience with major BI to ascertain the incidence, microbiological and clinical factors, risk factors and outcome. MATERIALS AND METHODS: 124 patients (72 children and 52 adults) received 135 grafts: namely, 39 isolated intestine, 33 liver-intestine and 63 multivisceral. Only major BI were considered, namely, those associated with serious morbidity/mortality requiring specific therapy. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: 92.7% patients showed BI. There were 327 episodes, representing 2.6 episodes/patient (2.8/patients with infection): 193 episodes of bacteremia (1.7/patient with BI) including 29.5% due to catheter related sepsis, 16.5% from abdominal source, 5.7% from respiratory origin and 4.1% from the wound. The organ locations includes 46 respiratory infections, 33 intraabdominal abscesses or infected fluid collections, 8 diffuse peritonitis, 34 wound infections and other miscellaneous sites: empyema, soft tissue infections, cholangitis em leader etc. Median time of infection was nine days after surgery (mean 22+/-3 days), with 67.7% patients having at least one BI before the end of the first month. Infection was present in 76.2% of the 63 deceased patients. An infectious episode during month 1, a clinically manifest abdominal infection and a positive intraabdominal culture had negative impacts on patient survival. CONCLUSIONS: BI are common and early complications after IT. The high rate of bacteremia, line sepsis and abdominal and respiratory infections reflect the recipient's condition, with chronic deterioration superimposed with the effects of prolonged abdominal visceral surgery.

Adult↗

PubMed2003

Intestinal transplantation: advances in immunosuppression and surgical techniques.

Campath-1H is being used as induction immunosuppression for intestinal/multivisceral transplantation. Patient and graft survival in this preliminary experience is similar to previous studies but there has been a significant decrease in the incidence and severity of acute rejections without increase of opportunistic infections. Collage of the abdominal wall (transplantation of a composite graft of the abdominal wall) can provide biologic coverage of the newly transplanted abdominal organs if necessary. Partial abdominal exenteration, ex vivo resection, and intestinal autotransplantation may be useful in removing otherwise unresectable lesions of the root of the mesentery.

Graft Rejection↗

PubMed2003

Relationship of regional adiposity to serum leptin level in nonobese Japanese type 2 diabetic male patients.

BACKGROUND: The aim of the present study was to investigate the relationships between serum leptin levels and regional adipose fat area, BMI, and the measures of variables including serum insulin in nonobese Japanese type 2 diabetic patients. METHODS: A total of 121 nonobese Japanese type 2 diabetic patients [aged 35 to 83 years, body mass index (BMI) (15.4 to 26.8 kg/m(2))] were studied. They all were male patients. In conjunction with serum leptin level, BMI, glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose and serum insulin and lipids (triglycerides, total and HDL cholesterol) were measured. RESULTS: Univariate regression analysis showed that serum leptin levels were positively correlated to subcutaneous (r=0.566, P<0.0001) and visceral (r=0.481, P<0.001) fat area in our diabetic patients. Furthermore, serum leptin levels were positively correlated to serum insulin (r=0.517, P<0.0001), BMI (r=0.428, P<0.0001), serum triglycerides (r=0.279, P<0.005), and age (r=0.225, P<0.05). There was, however, no relationship between serum leptin levels and measures of other variables including total and HDL cholesterol. Multiple regression analyses showed that serum leptin levels were predicted by subcutaneous fat area (F=5.92, P<0.0001) and serum insulin level (F=5.60, P<0.0001), which explained 29.0% of the variability of serum leptin concentrations in our nonobese Japanese type 2 diabetic male patients. Visceral fat area, BMI, serum triglycerides, and age, however, were not independently associated with serum leptin levels in our patients. CONCLUSIONS: These results indicate that serum leptin levels are reflective of subcutaneous fat area in nonobese Japanese type 2 diabetic male patients.

Adipose Tissue↗

PubMed2003

Successful treatment of bcr/abl-positive acute mixed lineage leukemia by unmanipulated bone marrow transplantation from an HLA-haploidentical (3-antigen-mismatched) cousin.

We describe a patient with bcr/abl-positive acute mixed lineage leukemia who successfully underwent transplantation in primary induction failure, using unmanipulated bone marrow from a human leukocyte antigen (HLA)-haploidentical cousin. The tumor burden was successfully reduced by the administration of imatinib mesylate (STI571) before transplantation. As graft-versus-host disease (GVHD) prophylaxis, a combination of tacrolimus and a short course of methotrexate, methylprednisolone, and mycophenolate mofetil was used. Hematopoietic reconstitution was rapid, and acute GVHD was limited to the skin (grade I). The patient is still in complete remission past day +400. This successful case suggests that HLA-haploidentical transplantation using unmanipulated marrow from a distantly related relative can be considered for patients in urgent situations who do not have HLA-identical donors.

Adult↗

PubMed2003

Seminal immunoreactive relaxin in domestic animals and its relationship to sperm motility as a possible index for predicting the fertilizing ability of sires.

Although immunoassayable relaxin has been detected in human and boar seminal plasma, there is no evidence suggesting the existence of immunoreactive relaxin in the seminal plasma of other domestic animals. The first objective of this study was to determine whether immunoreactive relaxin was present in the seminal plasma of bulls, rams and he-goats. In addition, the correlation of immunoreactive relaxin with sperm motility as an index for predicting the fertilizing ability of bull sires was investigated. Semen with normal sperm motility was collected from bulls, rams and he-goats, and the relaxin immunoreactivity of the semen samples was measured using a time-resolved fluoroimmunoassay (TR-FIA) for porcine relaxin that we developed. The presence of relaxin immunoreactivity was demonstrated in seminal plasma from bulls, rams and he-goats. The level of immunoreactive relaxin in seminal plasma was the highest in bulls followed by humans, rams, boars and he-goats in that order, when relaxin levels in boar and human semen having normal sperm motility were also assayed under the same conditions. When the correlation between the seminal plasma level of immunoreactive relaxin and sperm motility was examined in bull semen samples as an index for predicting fertilizing ability, it was found that the relaxin level was significantly correlated with the percentage of spermatozoa showing the most intensive motility (r = 0.64, p < 0.05). These results indicate that immunoreactive relaxin is widely found in the seminal plasma of domestic animals and that measuring the relaxin concentration of seminal plasma may be useful to identify subfertile sires or predict the fertility potential of individual sires.

Animals↗

PubMed2003

Induction of apoptosis in HL-60 cells treated with medicinal herbs.

In order to develop a new apoptosis inducer, we screened 22 crude drugs for their apoptosis-inducing activity. It was found that Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora induced the death of HL-60 cells. To investigate the mechanism of apoptosis induced by these six crude drugs, the mitochondrial transmembrane potential and the activity of caspase-3 were measured. Reduced mitochondrial transmembrane potentials within 12 hours after the administration of Glycyrrhiza uralensis, Cynomorium songaricum, Phellodendron amurense and Paeonia lactiflora, and within 24 hours after the administration of Eucommia ulmoides and Cinnamomum cassia were observed. All of the six apoptosis-inducing crude drugs increased caspase-3 activity within 12-36 hours after administration. After further examining the apoptosis-inducing activity of berberine, palmatine, panelofuroline and glycyrrhizin, which were the ingredients obtained from Phellodendron amurense, Glycyrrhiza uralensis and Paeonia lactiflora, it was found that only berberine could induce apoptosis. From these results, it was concluded that the apoptosis induced by the six crude drugs (Glycyrrhiza uralensis, Cynomorium songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and Paeonia lactiflora) occurred via the mitochondrial route and that the apoptosis-conducting mechanism acted through a cascade involving caspase-3.

Antineoplastic Agents, Phytogenic↗