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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 127 records · Page 7Linked to original sources
PubMed2000

Anti-AB titer changes in patients with ABO incompatibility after living related kidney transplantations: survey of 101 cases to determine whether splenectomies are necessary for successful transplantation.

BACKGROUND: A shortage of organ donors for transplantation has become a serious problem throughout the world. To overcome this problem, transplantations across ABO blood barriers have been performed with some success. In general, however, the graft survival rate for transplantation with ABO incompatibility is lower than that of transplantation with ABO compatibility. Unfortunately, the mechanism by which isohemagglutinins might injure an ABO-incompatible graft remains uncertain. Here, the pre- and posttransplantation anti-AB titers in patients who received transplants from ABO-incompatible living donors are reviewed and the pathological findings are compared. METHODS: One hundred and one patients underwent ABO-incompatible living related kidney transplantation (i-LKT) between January 1989 and October 1999 at our hospital. Plasmapheresis and immunoadsorption were performed in all of the i-LKT patients before the transplantation to remove anti-AB antibodies. A splenectomy was also performed during the operation, followed by the local irradiation of the graft with a dose of 150 rad. The anti-AB titers and pathological findings for 93 i-LKT patients, excluding 8 patients who died, were then examined. RESULTS: Immediately after the i-LKT, the anti-AB titer dropped rapidly to below 1:4 in all 93 cases. Seventy of patients (70/93, 75%) showed no elevation in their anti-AB titer during their follow-up. However, the remaining 23 patients (23/93, 25%) showed a significant elevation of their anti-AB titer to over 1:16. Sixteen of these patients (16/93, 17%) exhibited an anti-AB titer of over 1:32. Out of these 16 patients, 11 patients (11/16, 69%) lost their grafts. The anti-AB titer in the remaining five patients (5/16, 31%) spontaneously decreased without any special treatment. Seven patients (7/93, 8%) exhibited an elevated titer of 1:16. Out of these patients, only one patient (1/7, 14%) lost his graft. The elevated titers in the remaining six patients (6/7, 86%) eventually decreased. The graft function improved in patients whose elevated anti-AB titers eventually decreased. Control patients (ABO-compatible kidney transplant patients) showed a normal elevation of their titer values compared with preoperative titers. Pathological findings showed severe humoral rejections in all cases with high anti-AB titers that lost grafts. Humoral rejection was also detected in most of the patients whose anti-AB titer was elevated to over 1:16 after the transplantation, but excellent renal function was resumed once the titers decreased to below 1:4. CONCLUSIONS: In 23 out of 93 i-LKT patients (25%), the anti-AB titers were significantly elevated after the splenectomy. In view of other reports of i-LKT without splenectomy, we feel that a splenectomy in i-LKT patients might be unnecessary. Pathological evidence suggests that the decrease in the anti-AB titer after transplantation might be the net result of plasmapheresis before the operation and the adsorption of antibodies to the endothelium of the transplanted organ after the operation, neither of which is influenced by a splenectomy.

ABO Blood-Group System↗
PubMed2000

Detection and measurement of a single blood cell surface antigen by thermal lens microscopy.

A highly sensitive method for detection of antigens on the surface of a single blood cell using thermal lens microscopy is described. Colloidal gold, coated with antibody, was used to stain membrane antigens of leukocytes. Human leukocyte antigens on the lymphocytes and mononuclear leukocytes were observed by new thermal lens microscopy, which involves spectrometry using a laser-induced thermal-lens effect. Antigens of HLA-A, -B, and -C loci on the lymphocytes were identified and quantitated using a single cell. The image of HLA-A, -B, and -C antigen distribution on a mononuclear leukocyte was obtained. Our laser microscope, newly devised for measuring convex surface cells, is a powerful analytical tool for detecting and quantitating localized antigens in a single cell and/or cell-surface-associated molecules.

Antigens↗
PubMed2000

Assessment of fresh and stored duck spermatozoa quality via in vitro sperm-egg interaction assay.

An in vitro sperm-egg interaction assay was used to measue the quality of duck spermatozoa in fresh and stored semen. The inner perivitelline layer (IPVL), which had been separated from laid duck eggs, was incubated with spermatozoa in vitro. The number of points of sperm hydrolysis in the IPVL in vitro was logarithmically correlated with the fertility of the eggs laid by inseminated females, for both fresh semen (r = 0.85, P < 0.001) and stored semen at 5 degrees C for 24 h (r = 0.84, P < 0.001). After semen storage, the ability of spermatozoa to hydrolyze the IPVL decreased by 67.4% compared with the values for fresh semen, whereas egg fertility and sperm motility decreased by 47.8% and 15.2%, respectively. These results suggest that the in vitro sperm-egg interaction assay accurately reflects the fertilizing ability of fresh and stored duck spermatozoa and detects spermatozoal damage due to semen storage more sensitively than motility or fertility tests.

Animals↗
PubMed2000

Induction of rat L-phosphoserine phosphatase by amyloid-beta (1-42) is inhibited by interleukin-11.

Alzheimer's disease (AD) is characterized by the presence of beta-amyloid (Abeta) protein deposits in the brain and increased Abeta (1-42) peptide production is thought to be one of the early events in the pathogenesis of AD that leads to progressive neurodegenerative processes and dementia. Using cDNA subtraction and reverse transcription-polymerase chain reaction, we examined the Abeta (1-42) peptide-induced gene expression in rat neuroblastoma B104 cells. In addition we hypothesized that interleukin-11 (IL-11) supports neuronal survival. We found that Abeta (1-42) activates L-phosphoserine phosphatase in neuronal cells which is inhibited by IL-11. Moreover, IL-11 inhibits Abeta (1-42)-induced neurotoxicity in a dose-dependent manner. Our study suggests that L-phosphoserine phosphatase may play a role in altered neuronal function in AD via enhancing glutamate-induced neurotoxicity by D-serine and the IL-11 receptor system may act as a neuroprotective cytokine in human brain.

Amyloid beta-Peptides↗
PubMed2000

Epidermal growth factor (EGF) in the goat uterus: immunohistochemical localization of EGF and EGF receptor and effect of EGF on uterine activity in vivo.

This study examined the distribution of immunoreactive epidermal growth factor (EGF) and EGF receptor (EGF-R) in the uterus and the effects of EGF on uterine activity in goats. Immunohistochemistry of EGF and EGF-R in the uteri showed distinct staining in the luminal and glandular epithelium and slight to moderate staining in the stromal and myometrial cells. To examine possible roles of the EGF system in the regulation of uterine activity, pressure changes in the intrauterine balloon were determined after intraluminal infusion of EGF into the uterine horn. Either at estrus or diestrus (9 to 14 days after the first day of estrus), treatment with 1 or 5 microg of EGF gradually reduced uterine activity, whereas infusion of the vehicle alone had no effect. The maximum reduction in uterine activity was seen 4 h after the treatment with 1 microg of EGF (40% to 45% reduction in the area surrounded by the contraction curve and its baseline), and the activity slowly returned thereafter. These results suggest that EGF in the uterus may play a role in regulating uterine activity in goats.

Animals↗
PubMed2000

Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia.

An attractive hypothesis is that in utero exposure of hematopoietic cells to oncogenic agents can induce molecular changes leading to overt acute lymphoblastic leukemia (ALL) in infants and perhaps older children as well. Although supported by studies of identical infant twins with concordant leukemia, and of nontwined patients with MLL gene rearrangements, this concept has not been extended to the larger population of B-lineage ALL patients who lack unique nonconstitutive mutations or abnormally rearranged genes. We therefore sought to demonstrate a prenatal origin for 7 cases of B-cell precursor ALL (either CD10(+) or CD10(-)) that had been diagnosed in infants and children 14 days to 9 years of age. Using a polymerase chain reaction-based assay, we identified the same clonotypic immunoglobulin heavy-chain complementarity determining region or T-cell receptor V(D)2-D(D)3 sequences in the neonatal blood spots (Guthrie card) and leukemic cell DNAs of 2 infants with CD10(-) ALL and 2 of the 5 older patients with CD10(+) ALL. Nucleotide sequencing showed a paucity of N or P regions and shortened D germ line and conserved J sequences, indicative of cells arising from fetal hematopoiesis. Our findings strongly suggest a prenatal origin for some cases of B-cell precursor ALL lacking specific clonotypic abnormalities.

Base Sequence↗
PubMed2000

Sialyl Lewis(x) (CD15s) monitoring as a means to select antirejection therapy in patients with rejection after renal transplantation: CD15s monitoring for treatment and diagnosis in patients with acute rejection after renal transplantation.

BACKGROUND: Sialyl Lewis(x) (CD15s), which is known to serve as a ligand for the cell adhesion molecules E-selectin and P-selectin, is expressed on peripheral lymphocytes in renal transplant patients with rejection. In this study, we examined whether CD15s monitoring could differentiate the patients with rejection in whom steroids were effective from those in whom steroids were not effective. METHODS: To investigate CD15s expression on peripheral lymphocytes, flow cytometry was performed before and after steroid pulse therapy in 20 recipients with rejection after renal transplantation, including 5 recipients resistant to steroid therapy. We also compared CD15s expression with pathological findings before and after steroid pulse therapy. RESULTS: CD15s expression was stronger before steroid pulse therapy in the 5 patients resistant to steroids than in the 15 patients responsive to steroid treatment. In addition, CD15s expression remained high without any pathological improvement in the 5 patients resistant to steroids after steroid treatment, although CD15s recovered to normal levels with remarkable improvement of pathological findings in the other 15 patients. Five patients in whom steroids were not effective, had full recovery of serum creatinine levels as well as CD15s expression after muromonab (OKT3) therapy. CONCLUSIONS: CD15s monitoring might help clinicians to select antirejection therapy.

Adult↗
PubMed2000

Doxapram accentuates white matter injury in neonatal rats following bilateral carotid artery occlusion.

The effect of the respiratory stimulant, doxapram, on white matter damage was investigated in neonatal rats under cerebral ischemia. Five-day-old rats underwent bilateral carotid artery occlusion with or without 50 mg/kg i.p. of doxapram. Their brains were neuropathologically examined 48 h later. Doxapram induced about a 20% decrease of PCO(2) for 90 min, but did not cause any neuropathological abnormalities. Bilateral carotid artery occlusion resulted in mild cerebrocortical lesions in 67% of pups, and white matter lesions in the internal capsule in 44%. Doxapram, in addition to bilateral carotid artery occlusion, produced more severe white matter injury in the internal capsule (injury score; 0.67+/-0.87 vs. 1.70+/-0.48, P<0.05) and in the subcortical white matter (0.33+/-0. 67 vs. 1.10+/-0.54, P<0.05). These results demonstrated that the use of doxapram under an ischemic condition accentuates white matter damage in neonatal rats.

Animals↗
PubMed2000

Clinical utility of monitoring sialyl Lewis(X) (CD15S) antigen on peripheral lymphocytes for the diagnosis and treatment of rejection after renal transplantation.

BACKGROUND: In organ transplantation, the grafts must be carefully monitored, but it is often difficult to make a quick and accurate diagnosis of unusual changes. Extensive research has failed to identify a useful marker for rejection. We investigated the clinical utility of sialyl Lewis(X) (CD15s) monitoring in 17 renal transplant patients with acute rejection. METHODS: The expression of CD15s on peripheral lymphocytes was examined using flow cytometry in renal transplant recipients with rejection (n=17), without rejection (n=23), recipients infected with cytomegalovirus (n=7), recipients with other diseases (n=7), and healthy volunteers (n=18). CD15s expression was compared with histological findings, and was also examined before and after steroid pulse therapy to investigate the effects of steroids on CD15s antigen expression on the surface of the peripheral lymphocytes. RESULTS: CD15s was strongly expressed in all patients with rejection, but was not expressed in any of the patients without rejection or in any healthy volunteers. Histologically, cell infiltration into the rejected graft was moderate or severe in all patients with strong expression of CD15s. In contrast, no or only mild infiltration was observed in patients with weak expression of CD15s. In addition, 14 of 17 patients (14/17, 82%) with strong CD15s expression improved upon administration of steroid pulse therapy, although there was no benefit from steroids in any of the patients with weak expression of CD15s. CONCLUSIONS: The CD15s antigen is expressed strongly on the peripheral lymphocytes at the time of rejection. It is interesting that the efficacy of steroid therapy in the patients with elevated creatinine could be predicted by CD15s expression on the peripheral lymphocytes before graft biopsy. There have been only few reports showing the relationship between CD markers and the efficacy of the treatment in patients with elevated creatinine. We report that the detection of CD15s on the peripheral lymphocytes by flow cytometry was an easy, helpful, and noninvasive means for the diagnosis and treatment of patients with elevated creatinine after renal transplantation.

Adult↗
PubMed2000

Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H+, K(+)-ATPase.

We purified a compound with strong inhibitory effect on H+, K(+)-ATPase from Paeoniae radix, which has been used in Japan for the treatment of gastritis and peptic ulcers. The compound was identified as 1,2,3,4,6,-penta-o-galloyl-beta-D-glucose by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and fast atomic bombardment mass spectrometry. The IC50 of the compound for H+, K(+)-ATPase was 166 nmol/l. Kinetic analyses indicated that the inhibition of the enzyme by pentagalloylglucose was noncompetitive with respect to K+. Pentagalloylglucose had relatively weak inhibitory effects for Mg(+)-ATPase (IC50: > 10 mumol/l) and Na+, K(+)-ATPase (IC50: 2.7 mumol/l). Pentagalloylglucose also inhibited the accumulation of [14C]aminopyrine in parietal cells that had been isolated from guinea pig stomach and stimulated by 10 mumol/l histamine (IC50: 7.8 mumol/l) and 1 mmol/l dbc-AMP (IC50: 10 mumol/l). These results suggest that pentagalloylglucose is a potent inhibitor of H+, K(+)-ATPase and may be responsible for inhibition of acid secretion by Paeoniae radix.

Aminopyrine↗
PubMed2000

N-Myc induction stimulated by insulin-like growth factor I through mitogen-activated protein kinase signaling pathway in human neuroblastoma cells.

Insulin-like growth factor I (IGF-I) stimulates proliferation, survival, and differentiation in many cell types, including pediatric neuroblastomas. The effect is mediated via the type I IGF-I receptor (IGF-IR), which is essential for growth in these cells. Several lines of evidence indicate that IGF-IR function may be particularly important in the pathogenesis of neuroblastoma. Amplification of the N-myc oncogene or overexpression of N-Myc oncoprotein has been reported to be associated with resistance to therapy and poor prognosis of neuroblastomas. It was therefore of interest to analyze whether IGF-I signaling regulated expression of N-myc in KP-N-RT human neuroblastoma cells as an experimental model that has amplified N-myc. We found that IGF-I induces N-myc mRNA and protein in the KP-N-RT with maximums of four and six times more than the basal level at 2 and 3 h after stimulation, respectively. These effects of IGF-I were blocked by a neutralizing antibody against IGF-IR (alpha-IR3). Exogenous IGF-I induced phosphorylation and activation of extracellular signal-regulated kinases p44/42 (ERK1 and ERK2), with a maximal level 30 min after the stimulation. The MEK1 inhibitor PD98059 reduced IGF-I-mediated p44/42 MAPKs phosphorylation and produced a parallel reduction of IGF-I-stimulated N-Myc induction. Furthermore, both alpha-IR3 and PD98059 inhibited G1-S cell cycle progression stimulated by IGF-I. Our results demonstrate that IGF-I induces N-Myc in the KP-N-RT neuroblastoma cell line at the RNA level and establishes a clear correlation between N-Myc induction and activation of p44/42 MAPK signaling.

Enzyme Inhibitors↗
PubMed2000

Neuronal differentiation in human neuroblastoma cells by nerve growth factor following TrkA up-regulation by interferon-gamma.

BACKGROUND: TrkA mRNA expression has been reported to be related to favorable outcome of neuroblastoma (NB). Previously, we found that interferon-gamma (IFN-gamma) can enhance TrkA mRNA expression in NB cell lines. In the present study, we examined the effect of nerve growth factor (NGF) on IFN-gamma-induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB. PROCEDURE: The effect of IFN-gamma on the TrkA mRNA expression was screened in six human NB cell lines and a freshly prepared sample, SK-rib, from a stage IV patient. Using two of them, we examined their morphological change during simultaneous loading of NGF and IFN-gamma. Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti-gp140(trkA) antibody and antiphospho tyrosine antibody. RESULTS: After a 4-day treatment with 500 IU/ml IFN-gamma, TrkA mRNA increased in five cell lines and SK-rib cells in association with growth inhibition. Although the degree of morphological differentiation did not increase in proportion to the TrkA expression induced by IFN-gamma, continuous loading of both IFN-gamma and NGF caused marked morphological differentiation in a cultured KP-N-RT cell line and SK-rib cells during 10 days. Moreover, 5 min of NGF stimulation after IFN-gamma treatment caused the phosphorylation of TrkA protein and downstream proteins. CONCLUSIONS: IFN-gamma could induce the functional NGF receptor even in the aggressive phenotype of NB.

Antineoplastic Agents↗
PubMed2000

Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.

The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect disease-causing mutations, to clarify their frequency and distribution, to determine whether genotype correlates with phenotype, and to determine the rate of abnormal findings in heterozygotes for the WD gene. We analyzed 41 unrelated Japanese WD families, including 47 patients. Twenty-one mutations, including nine novel ones, were identified. 2871delC (15.9%), 1708-5T-->G (11. 0%), and Arg778Leu (13.4%) were the most common mutations. 2871delC was detected mainly in eastern Japan and 1708-5T-->G in western Japan. The homozygotes for the 1708-5T-->G, 2871delC, or Arg778Leu mutations did not show a correlation with their phenotypes. Ceruloplasmin and copper levels were abnormally low in 28.6% and 35. 0% of heterozygotes, respectively. When patients and their families are screened for WD, a high rate of abnormal laboratory data in heterozygotes must be taken into account.

Adenosine Triphosphatases↗
PubMed2000

Serial analysis of MLL-AF4 chimeric message through successful bone marrow transplantation in a patient with t(4;11)-positive infant-ALL.

A 28-month-old girl with acute lymphoblastic leukemia (ALL) showing a t(4;11)(q21;q23) karyotype successfully underwent allogeneic bone marrow transplantation (BMT) at relapse. The chimeric MLL-AF4 message on her bone marrow (BM) specimens, examined by reverse transcriptase-polymerase chain reaction, was detectable at diagnosis, relapse, and just before BMT but became undetectable following BMT. She has since maintained complete remission. This observation suggests that detection of the chimeric message in BM may be useful to predict clinical outcome in patients with t(4;11) ALL.

Biomarkers, Tumor↗
PubMed2000

Risk of unfavorable character among neuroblastomas detected through mass screening. The Japanese Infantile Neuroblastoma Cooperative Study.

Current study shows that about 50% of neuroblastomas (NBs) detected through mass screening had factor(s) indicating an unfavorable biological nature and that early intervention after the screening might improve clinical outcome of the patients. On the other hand, favorable properties were detected in the remaining half of the mass-screening NBs. Some of them might have the ability to regress spontaneously. Therapeutic modality should be determined according to their biological nature. Further investigation for their biologic properties is necessary to evaluate the benefits of the mass screening.

Gene Expression Regulation, Neoplastic↗
PubMed2000

High proliferative activity is associated with dysplasia in ulcerative colitis.

PURPOSE: Ulcerative colitis is associated with an increased risk of colorectal neoplasia. Markers of proliferation are reported to be valuable in the diagnosis of dysplasia in ulcerative colitis. However, it is not known whether dysplastic change or proliferative change occurs first. Whether abnormal proliferation is present in normal-seeming mucosa in ulcerative colitis was investigated. METHODS: Eighteen cancer or high-grade dysplasia specimens and 9 low-grade dysplasia specimens from 5 patients and 51 specimens from 31 patients without neoplasia were studied. Immunostaining with anti-Ki 67 antibody was used to evaluate proliferative activity. Labeling index (in the superficial one-half of crypt) was calculated. Crypts with labeling index more than 0.3 were determined to have abnormal proliferation. RESULTS: The mean +/- standard error of the mean labeling index in specimens negative for dysplasia (0.056+/-0.004) was significantly lower than that in low-grade dysplasia specimens (0.418+/-0.024) and that in high-grade dysplasia specimens (0.503+/-0.027; P < 0.0001). In specimens negative for dysplasia, only 4 (4 cases) of 339 (1.2 percent) crypts had abnormal proliferation, whereas the ratio of crypts with abnormal proliferation was 76 percent (54/71) in low-grade dysplasia and 92.1 percent (35/38) in high-grade dysplasia. The labeling index in background mucosa was 0.139+/-0.009, which was significantly higher than that in specimens negative for dysplasia (P < 0.001). In background mucosa 15.7 percent of crypts showed abnormal proliferation. A follow-up study revealed that two of four cases developed cancer or high-grade dysplasia one and seven years after proliferative abnormality was detected in nondysplastic specimens. CONCLUSION: Ki-67 immunostaining can be an aid in the diagnosis of dysplasia. High proliferating activity in background mucosa suggests that proliferating activity change precedes dysplasia detected with hematoxylin-and-eosin staining.

Biomarkers↗
PubMed2000

Immunohistochemical study of tight junction-related protein in neovasculature in astrocytic tumor.

To clarify whether the neovasculature of brain tumors preserves blood-brain barrier (BBB) functions, we studied the expression of a tight junction-related protein, Zo-1, using immunohistochemistry. Twenty-six astrocytic tumors were examined using an anti-Zo-1 Mab, and Zo-1 expression was compared with the expression of vasicular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) (fit-1), and antiproliferative cell nuclear antigen (PCNA). A positive reaction for Zo-1 was seen in the endothelial cells in micro-blood vessels in all astrocytic tumors. The reactions for Zo-1 in the endothelial cells forming glomeruloid proliferations in newly formed micro-blood vessels in high-grade tumors were weaker than those in the endothelial cells of normal cerebral capillaries. Although there is a negative correlation between positive immunoreactions for BBB-related proteins and the expression of VEGF of the endothelial cells in micro-blood vessels, the proliferative activity of tumor cells, and histological grades, the present findings suggest that the endothelial cells of the neovasculature of high-grade tumors preserve partial BBB function at the cellular level. Because of the ease of immunohistochemical procedures compared with electron microscopic examination, the immunohistochemical detection of Zo-1 should provide a useful marker for tight junctions.

Adolescent↗