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Biomedical subjects

Y Toyoda

Publications and source records attributed to Y Toyoda.

At least 55 records · Page 3Linked to original sources
PubMed2000

Modulating effects of the feeding route on stress response and endotoxin translocation in severely stressed patients receiving thoracic esophagectomy.

Experimental studies have demonstrated that the route of nutritional supply impacts the systemic metabolic responses after surgical injury. Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) or prolonged bowel rest, has been reported to enhance bowel endotoxin translocation. The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph-node dissection, is a particularly stressful surgery that requires long-term aggressive nutritional support and often results in the postoperative hypermetabolic state, leading to perturbation of postoperative immune function. Interleukin-6 (IL-6) plays an important role in host inflammatory responses, whereas IL-10 is linked to suppression of cellular immunity. The aim of this study was to investigate how the antecedent nutritional routes influence systemic IL-6 and IL-10 responses and endotoxin translocation after an operation for thoracic esophageal cancer. Twenty-nine patients who underwent esophagectomy with three-field lymphadenectomy were investigated. They were assigned to groups receiving either TPN (n = 18) or enteral nutrition (EN; n = 11) providing 35 kcal x kg(-1) x d(-1) of energy and approximately 1.2-1.5 g x kg(-1) x d(-1) of amino acids. These nutritional supports were conducted from 1 wk before the operation to 14 d after the operation. Serum IL-6, IL-10, and endotoxin concentration were measured before and during the operation and at 2 h and 1, 3, and 7 d after the operation. IL-6 in sera was significantly higher after the operation in both groups. In the EN group, however, significantly less IL-6 production was observed on the third and seventh postoperative days when compared with those patients in the TPN group. Similarly, serum IL-10 concentration in the TPN group showed a significantly higher level than that in the EN group. Serum IL-6 showed a significant positive correlation with IL-10 at 2 h and at 7 d after the operation, suggesting that the reduced inflammatory responses were related to the inhibition of the development of postoperative immunosuppression. Endotoxin concentration in sera was significantly lower in the EN group after the operation than in the TPN group. Perioperative EN provides better regulation of inflammatory cytokine responses and may contribute less to immunosuppression after major surgery than parenteral nutrition. The attenuated production of endotoxin induced by EN may play an important role in these phenomena.

Bacterial Translocation↗
PubMed2000

Contamination of passenger trains with Dermatophagoides (Acari: Pyroglyphidae) mite antigen in Japan.

Passenger trains were surveyed for contamination with Dermatophagoides farinae Hughes and Dermatophagoides pteronyssinus (Trouesart) mites in Japan. A total of 492 dust samples were collected from upholstered seats in six commuter trains, one long-distance express train and three night trains in October, 1996 and January, April, and July, 1997. Mite antigen levels contained in fine dust fractions of these samples were measured by an enzyme-linked immunosorbent assay. Most samples obtained from commuter trains showed relatively high mite antigen levels of > 10 microgm(-2) (corresponding to > 100 mites). Express and night trains showed lower antigen levels per square meter, but higher mite antigen levels per gram of fine dust than commuter trains, indicating relatively high mite antigen densities. Seasonal comparisons indicated that commuter trains showed the highest mean antigen level per square meter in winter (January), whereas the highest antigen level per gram of fine dust was observed in summer (July) in express and night trains.

Animals↗
PubMed2000

Epithelioid leiomyosarcoma in a non-immunocompromised infant: additional differential diagnosis of pediatric "round cell tumors".

We report an 18-month-old Japanese girl with purely epithelioid leiomyosarcoma presenting as a huge intraabdominal mass. The patient had been well from birth and had shown no signs of immunodeficiency. She was negative for human immunodeficiency virus. Blood examination revealed elevated serum neuron specific enolase (NSE). Histologically, the tumor was comprised of solid growths of round or polygonal cells with vesicular nuclei and often vacuolated cytoplasm rich in glycogen. The tumor cells were positive for vimentin, NSE, and MIC2, and were negative for desmin and neurofilament. The age, clinical presentation, and histologic findings mostly favored Ewing's sarcoma/primitive neuroectodermal tumor. Silver stain, however, demonstrated well-developed reticulin fibers often outlining individual tumor cells. An expanded panel of immunostains showed that the tumor cells were intensely positive for smooth muscle actin, and ultrastructural study revealed abundant fine cytoplasmic filaments with focal subsarcolemmal densities, various amounts of glycogen, and irregularly arranged, thick basal lamina. The diagnosis of epithelioid leiomyosarcoma was made. Following reduction in tumor size by chemotherapy, the serum NSE level was normalized. From the surgical finding, the primary site was presumed to be the urachus or the urinary bladder dome. Although extremely rare, epithelioid leiomyosarcoma should be added in the list of differential diagnoses of pediatric "round cell tumors."

Abdominal Neoplasms↗
PubMed2000

Long-term follow-up of childhood acute lymphoblastic leukemia in Tokyo Children's Cancer Study Group 1981-1995.

The objectives were as follows: Firstly, to estimate the overall probability of event-free survival (EFS) and isolated CNS relapse in the studies for children with acute lymphoblastic leukemia (ALL) during the 1980s and 1990s. Secondly, to report the EFS according to presenting features and lineage. Thirdly, to evaluate the treatment results re-classified by the risks of NCI criteria. Four consecutive protocol studies were performed in the Tokyo Children's Cancer Study Group: L81-10 protocol (1981-1984, 189 patients), L84-11 (1984-1989, 484 patents), L89-12 (1989-1992, 418 patients) and L92-13 (1992-1995, 347 patients). Overall EFS at 5 years in each protocol was 56.5 +/- 3.8(1 s.e.)%, 71.0 +/- 2.1%, 67.8 +/- 2.3%, and 63.4 +/- 2.7%, respectively. The cumulative isolated CNS relapse rate at 5 years was 8.1 +/- 2.1%, 3.5 +/- 0.9%, 3.6 +/- 1.0%, 1.0 +/- 0.6. The EFS in SR/HR (standard risk/high risk) according to the NCI criteria in B-precursor ALL at 5 years was 61.9 +/- 4.3%/41.4 +/- 7.4% (lineage was not confirmed.), 72.5 +/- 2.6%/63.4 +/- 5.0%, 77.4 +/- 2.7%/56.3 +/- 4.7%, and 67.8 +/- 3.4%/56.7 +/- 5.4% in each protocol. Also EFSs according to NCI SR/HR at 5 years of T-ALL in protocols L84-11, L89-12 and L92-13 were 55.6 +/- 16.6%/60.9 +/- 10.1%, 72.7 +/- 13.4%/51.6 +/- 9.1%, and 77.1 +/- 14.4%/53.6/10.1%, respectively. The truncation of maintenance therapy to 6 months resulted in a decreased EFS in L92-13, particularly due to an increase of bone marrow relapse after cessation of therapy in SR and HR. The NCI risk criteria work properly even in the patients treated by different intensities, so that it makes the comparison possible among the patients in various groups. The overall EFSs in childhood ALL improved in 1980s, but it seemed stable or decreased in 1990s. The short maintenance therapy resulted in poor outcome in SR on the L92-13 protocol. Many of these late relapsers were effectively rescued and overall survival remained at a high level. The proportion of patients who received cranial irradiation reduced without any increase of the CNS events.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The influence of HLA genotyping compatibility on clinical outcome after cord blood transplantation from unrelated donors.

We performed retrospective DNA typing of class I (A, B, Cw) and class II (DRB1, DQB1, DPB1) HLA alleles in 27 unrelated cord blood transplantation (CBT) cases donated from a single cord blood bank (Kanagawa Cord Blood Bank). The influence of HLA genotype matching on clinical outcome was evaluated. From Cox's model, we found that incompatibility of two or more HLA alleles between the donor and recipient of an unrelated CBT was suggested to be a risk factor for a worse event-free survival (EFS) (p = 0.04; RR, 4.06; 95% CI, 1.06-15.61). Furthermore, mismatches including HLA-DRB1 alleles had an adverse effect on EFS (p = 0.04; RR, 4.91; 95% CI, 1.01-24.02). For definite conclusions on the role of HLA allele typing in unrelated CBT, more accumulation of data and analysis will be required.

Actuarial Analysis↗
PubMed2000

Maturation/M-phase promoting factor: a regulator of aging in porcine oocytes.

Deterioration in the quality of mammalian oocytes during the metaphase-II arrest period is well known as "oocyte aging." Oocytes in which aging has occurred are called aged oocytes, and these oocytes show enhanced activation and higher fragmentation rates after parthenogenetic activation. Previously we showed that porcine aged oocytes had low maturation/M-phase promoting factor (MPF) activity, and we suggested that this low MPF activity contributed at least in part to the aging phenomena. In the present study, we examined the relationship between MPF activity and these aging phenomena by artificially regulating MPF activity in porcine metaphase-II-arrested oocytes. Since we have shown recently that aged porcine oocytes contain abundant phosphorylated inactive MPF, so-called pre-MPF, we used vanadate and caffeine, which affect the phosphorylation status of MPF, to regulate MPF activity. Incubation of 48-h-matured oocytes with vanadate for 1 h increased the phosphorylation of MPF and decreased MPF activity. The parthenogenetic activation and fragmentation rates were significantly increased compared with those of control oocytes. Conversely, treatment of 72-h-cultured aged oocytes with caffeine (last 10 h of culture) decreased the level of pre-MPF and elevated MPF activity. These oocytes revealed significantly lower parthenogenetic activation rates and a lower percentage of fragmentation than did untreated aged oocytes. These results indicate that not only the increased ability for parthenogenetic activation but also the increased fragmentation rate observed in porcine aged oocytes may be attributable in part to the gradual decrease in MPF activity during prolonged culture. Control of MPF phosphorylation with these agents may allow for some degree of manipulation of oocyte aging.

Animals↗
PubMed2000

Clinicopathologic study of mass-screened neuroblastoma with special emphasis on untreated observed cases: a possible histologic clue to tumor regression.

Spontaneous regression and maturation of neuroblastoma (NB) are well documented and occur frequently in infants, including those detected by mass screening. To seek histologic clues for regression/maturation in mass-screened NB, clinicopathologic features of 12 tumors that were resected after 2 to 18 months of untreated observation were reviewed. Unobserved screened and age-matched unscreened patients were also studied. To evaluate the possible important role of apoptosis, apoptotic cells were detected by in situ deoxyribonucleic acid (DNA) nick end labeling and immunohistochemical stain for activated caspase-3. Nests with a varying degree of reduced cellularity ("less cellular" and "hypocellular" nests) were common in patients younger than 18 months of age, and were rare in older patients. Two characteristic cells, which have not been focused previously, were frequent, especially in the hypocellular nests. One showed amorphic eosinophilic cytoplasm with pyknotic nuclei and the other contained plump cytoplasm with well-maintained nuclei. These cells were also observed in 89% of the unobserved screened NBs and 79% of the age-matched unscreened patients with good outcome, whereas they could not be confirmed in any of the age-matched unscreened NBs with poor outcome. The amorphic and plump cells were negative for activated caspase-3 and in situ DNA nick end labeling. From these results, the authors hypothesize that these cells most likely represent a degenerative process, in either a state before the activation of caspase-3 or a caspase-independent form of cell death. The presence of less cellular and hypocellular nests with amorphic/plump cells may serve as one of the important clues in predicting tumor prognosis.

Age Factors↗
PubMed2000

Differential role of sarcolemmal and mitochondrial K(ATP) channels in adenosine-enhanced ischemic preconditioning.

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium (K(ATP)) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of K(ATP) channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific K(ATP) blocker glibenclamide (Glb), the mitochondrial (mito) K(ATP) channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) K(ATP) channel blocker HMR-1883 (HMR). Infarct size was significantly increased (P < 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery (P < 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery (P < 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mitoK(ATP) channels primarily during ischemia and suggest that functional recovery is modulated by sarcK(ATP) channels during ischemia and reperfusion.

Adenosine↗
PubMed2000

Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution.

PURPOSE: To describe various favorable courses of neuroblastoma (NBL) detected by mass screening and to present our observation program as a temporary treatment option, to be used until a final decision is made regarding the mass screening program for 6-month-old infants. PATIENTS AND METHODS: Between October 1993 and November 1999, 26 of 51 patients with NBL detected by mass screening were enrolled in our observation program. The criteria for observation included urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than 50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and granted informed consent. Patients were divided into four groups according to changes in urinary VMA and HVA values and tumor size. Patients who no longer fulfilled criteria underwent surgery. RESULTS: The observation period ranged from 4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often by age 16 months. Eighteen patients had regressing tumors, and in 10 of these cases, the tumor was undetectable or barely detectable by imaging techniques. Four patients younger than 12 months had increased tumor marker levels and tumor volume, histologically reflecting neuroblastic proliferation. The remaining three patients, all older than 18 months, had varied tumor marker levels but increased tumor volume, histologically reflecting an increase in Schwann cells. No upgrading of tumor stage or unfavorable biologic factor was noted in any patient. CONCLUSION: None of our patients showed evidence of transition from favorable to unfavorable prognosis, a finding that points to a reduction in the significance of screening as a public health measure. Until results of ongoing screening trials involving older patients have been evaluated, the observation program can be used as a temporary measure to avoid, with little risk, unnecessary surgical intervention.

Abdominal Neoplasms↗
PubMed2000

Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood.

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92-13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (+/- SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% +/- 3.4% and 81.5% +/- 2.2%, respectively, at 5. 5 years after diagnosis. EFS rates by risk category were similar (60. 2% +/- 6.0% for standard risk, 57.7% +/- 5.6% for high risk, and 62. 5% +/- 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% +/- 2.7%, 80.0% +/- 4.1%, and 72.1% +/- 4.5%, respectively, P <.0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% +/- 7. 9% (standard risk), 42.6% +/- 8.1% (high risk), and 9.6% +/- 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

Adolescent↗
PubMed2000

Localization of glucokinase-like immunoreactivity in the rat lower brain stem: for possible location of brain glucose-sensing mechanisms.

Pancreatic glucokinase (GK) is considered an important element of the glucose-sensing unit in pancreatic beta-cells. It is possible that the brain uses similar glucose-sensing units, and we employed GK immunohistochemistry and confocal microscopy to examine the anatomical distribution of GK-like immunoreactivities in the rat brain. We found strong GK-like immunoreactivities in the ependymocytes, endothelial cells, and many serotonergic neurons. In the ependymocytes, the GK-like immunoreactivity was located in the cytoplasmic area, but not in the nucleus. The GK-positive ependymocytes were found to have glucose transporter-2 (GLUT2)-like immunoreactivities on the cilia. In addition, the ependymocytes had GLUT1-like immunoreactivity on the cilia and GLUT4-like immunoreactivity densely in the cytoplasmic area and slightly in the plasma membrane. In serotonergic neurons, GK-like immunoreactivity was found in the cytoplasm and their processes. The present results raise the possibility that these GK-like immunopositive cells comprise a part of a vast glucose-sensing mechanism in the brain.

Animals↗
PubMed2000

Impairment of glucokinase translocation in cultured hepatocytes from OLETF and GK rats, animal models of type 2 diabetes.

We examined sugar-induced translocation of glucokinase in cultured hepatocytes from Otsuka Long-Evans Tokushima Fatty and Goto-Kakizaki rats, animal models of type 2 diabetes, and compared this with that in Long-Evans Tokushima Otsuka and Wistar rats, respectively, as control strains. When hepatocytes from the four strains were incubated with 5 mM glucose, glucokinase was present predominantly in the nuclei. Higher concentrations of glucose, 5 mM glucose plus 1 mM fructose, and 5 mM glucose plus 1 mM sorbitol all induced the translocation of glucokinase from the nucleus to the cytoplasm in hepatocytes from these rats. The extent of glucokinase translocation under these conditions, however, was less marked in both diabetic rat types than in the control rats. The extent of the phosphorylation of glucose as estimated by the release of 3H2O from [2- 3H] glucose is significantly lower in Goto-Kakizaki rats than in Wistar rats. The results indicate that the translocation of glucokinase is impaired in the hepatocytes of diabetic rats. They also suggest that the impaired translocation of glucokinase is associated with abnormal hepatic glucose metabolism in type 2 diabetes.

Animals↗
PubMed1999

Antibody reactivity in mice and cats to feline enteroepithelial stages of Toxoplasma gondii.

The reactivity of antibodies in mice and cats to feline enteroepithelial stages of Toxoplasma gondii was examined by means of an indirect immunofluorescent antibody test. Mice immunized with feline enteroepithelial stage (FES) parasites produced antibodies not only against FES, but also against tachyzoites, sporozoites/oocysts, tissue cysts and one part of the infected feline enterocytes. After absorption with tachyzoites, the titer of antibodies reactive to enterocytes was significantly reduced. In contrast, the titer of antibodies reactive to FES remained unchanged. The antibodies from cats immunized with FES, reacted specifically to FES, but not to tachyzoites, tissue cysts or enterocytes. These results suggest that FES parasites may have stage-specific antigen(s).

Animals↗
PubMed1999

Mammalian transgenesis by intracytoplasmic sperm injection.

Coinjection of unfertilized mouse oocytes with sperm heads and exogenous DNA encoding either a green fluorescent protein (GFP) or beta-galactosidase reporter produced 64 to 94 percent transgene-expressing embryos, reflecting DNA-sperm head association before coinjection. Nonselective transfer to surrogate mothers of embryos in the GFP series generated about 20 percent offspring expressing the integrated transgene. These data indicate that exogenous DNA can reproducibly be delivered into an oocyte by microinjected spermatozoa and suggest an adaptable method of transgenesis.

Animals↗