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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 73 records · Page 4Linked to original sources
PubMed1999

Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer.

p51, a novel family member of human p53, is a recently identified candidate tumor suppressor gene mapped at chromosome 3q28. Like p53, p51 was found to activate p21Waf1/Cip1 and to induce apoptosis. Since the DNA loss at 3q is reported in several cancers including non-small cell lung cancer (NSCLC), we screened for mutations in p51A (TAp63gamma), an isoform of p51 with short C-terminal region, in 80 NSCLCs as well as 85 breast cancers by RT-PCR single strand conformation polymorphism (SSCP) analysis and DNA sequencing. In NSCLCs, p51 was expressed in most tumors at variable levels and we found three missense and one silent mutations: Gln31His (transactivation domain) in two tumors, Ala148Pro (DNA-binding domain) and Leu248Leu (DNA-binding domain). In the tumor with Ala148Pro or the silent mutation, only the mutant gene appeared to be expressed. The modified FASAY method to test the ability of yeast expressing p51A cDNA to grow in medium lacking histidine has revealed that Ala148Pro results in a loss of function, while Gln31His does not. In contrast to NSCLC, no mutation was observed in all 85 breast cancers by the similar method. Our results suggest that, because of infrequent mutation, p51 may not be a Knudson type tumor suppressor in most NSCLCs and breast cancers. Nevertheless, in at least a part of NSCLC, p51 may play a certain role in carcinogenesis in a tissue-specific manner.

Adult↗
PubMed1999

Identification of a transactivation activity in the COOH-terminal region of p73 which is impaired in the naturally occurring mutants found in human neuroblastomas.

p73 is a recently cloned tumor suppressor gene that is highly homologous to p53, and the products of both possess similar functions in inhibiting cell growth and inducing apoptosis. Interestingly, the COOH-terminal region of p53 displays no significant homology with that of p73. Moreover, p73 has an additional segment at its COOH terminus. Recently, we have found two mutations of p73 with amino acid substitution (P405R and P425L) in primary neuroblastomas. Because the region (amino acid residues 382-491) contains a glutamine- and proline-rich domain, we hypothesized that it has a transactivation function, and the mutations found in tumors result in loss of function. To test it, we used the yeast GAL4 DNA-binding fusion system. Yeast transformants expressing a GAL4-p73(1-112) or a GAL4-p73alpha(380-513) fusion protein were grown in SD medium lacking histidine and tryptophan and exhibited a significant induction of beta-galactosidase activity. Transient transfection experiments revealed that both of fusion proteins could induce the chloramphenicol acetyltransferase activity in mammalian cells, indicating that the COOH-terminal as well as NH2-terminal regions of p73 had significantly high levels of transactivation activity. Furthermore, the former activity was severely impaired in two naturally occurring mutant forms found in neuroblastomas. These suggest that, unlike p53, p73 has two domains with transactivation function, one in the NH2-terminal region and the other in the COOH-terminal region. Loss of function mutation in the latter might be involved in tumorigenesis and/or tumor progression.

3' Untranslated Regions↗
PubMed1999

Prevention of lethal acute hepatic failure by antimacrophage migration inhibitory factor antibody in mice treated with bacille Calmette-Guerin and lipopolysaccharide.

During the past few years, the biological functions of macrophage migration inhibitory factor (MIF) have been extensively re-evaluated. This has been found to be protein involved in broad-spectrum pathophysiological states as an inflammatory cytokine, pituitary-derived hormone, and glucocorticoid-induced immunomodulator. In this study, we investigated the involvement of this cytokine in the pathogenesis of lethal liver injury. Injecting a small dose of lipopolysaccharide (LPS) into bacille Calmette-Guerin (BCG)-primed Jcl:ICR mice caused a lethal hepatic injury mimicking fulminant hepatitis, in which 8 of 11 mice died within 48 hours (27% survival rate). Massive necrosis of parenchymal hepatocytes with marked mononuclear cell infiltration was observed by histological examination. Immunohistochemical analysis showed that most of the infiltrating mononuclear cells were Kupffer cells, macrophages, and, to a lesser extent, T cells. In parallel, serum aminotransferase and tumor necrosis factor-alpha (TNF-alpha) levels were increased. When an anti-MIF polyclonal antibody (0.3 mg IgG fraction/mouse) was intraperitoneally injected into mice primed with BCG, it protected them from acute hepatic failure (90% survival rate) with concomitant improvement of histological features. Injection of the antibody also suppressed the up-regulation of TNF-alpha and T-cell infiltration induced by LPS. Taken together, these results suggested that treatment with the anti-MIF antibody suppresses the endotoxin-induced fatal hepatic failure by regulating production of inflammatory cytokines and T-cell infiltration.

Alanine Transaminase↗
PubMed1999

First case of cadaveric liver transplantation in Japan.

The first case of liver transplantation from a brain-dead donor in Japan is described. The recipient was a 43-year-old man with familial amyloid polyneuropathy who manifested various neuropathic symptoms and autonomic dysfunction at the time of transplantation. The graft had three arteries, for which a single trunk was created at the back table. A side-to-side cavacaval anastomosis was performed as an outflow reconstruction. To avoid portal congestion, a temporary shunt between the right posterior branch of the portal vein and the vena cava was constructed, instead of a venovenous bypass. The graft preservation time was 7.2 h and the operation time was 12.2 h. Although sufficient blood flow in the hepatic artery, portal vein, and hepatic vein was confirmed intra- and postoperatively, using Doppler ultrasound, transient graft dysfunction was observed immediately after surgery, but there was spontaneous improvement. The patient was discharged 100 days after transplantation.

Adult↗
PubMed1999

Protective role of nitric oxide in ischemia and reperfusion injury of the liver.

BACKGROUND: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfusion injury of the liver. But findings of the salutary effects of NO enhancement on such injury have been conflicting. In this study, we tested our hypothesis that NO enhancement would attenuate ischemic liver injury. For this purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour total hepatic vascular exclusion model in dogs. STUDY DESIGN: L-arginine was administered IV at a dose of 100 mg/kg twice (n = 5), while 300 mg/kg twice of FK409 was infused continuously into the portal vein (n = 5). The drugs were given to the animals for 30 and 60 minutes before and after ischemia, respectively. Non-treated animals were used as the control (n = 10). Two-week survival, systemic and hepatic hemodynamics indices, liver function tests, energy metabolism, and histopathology were analyzed. RESULTS: Both treatments comparably augmented hepatic tissue blood flow, decreased liver enzyme release, and increased high-energy phosphate restoration during the reperfusion period, all of which contributed to rescuing all of the treated animals from the 2-hour total hepatic ischemia. In contrast, ischemia caused 70% mortality in the control group. Histologically, structural abnormality and neutrophil infiltration were markedly attenuated by the treatments. Systemic hypotension was observed in the animals treated with FK409, however. CONCLUSIONS: Our data demonstrate that NO enhancement alleviates the liver injury caused by ischemia and reperfusion. The supplementation of L-arginine, rather than FK409, is considered more applicable to clinical use because of the absence of systemic adverse effects.

Adenine Nucleotides↗
PubMed1999

Cold preservation of the human colon and ileum with University of Wisconsin solution.

The inclusion of the colon in the intestinal graft resulted in worsening patient and graft outcome and increased the incidence of infection and rejection. In this study, we examine the role of ischemia on the barrier function of the epithelium during cold ischemia. Samples were collected from 15 harvested and transplanted human donor grafts (colon, 10; ileum, 6), which were immersed in University of Wisconsin (UW) solution. Ischemia (6, 12, 24, and 48 h) and reoxygenation were performed to evaluate the mucosal electrical status using the Ussing chamber technique. The functions of enterocytes and crypt cells were tested by glucose and theophylline challenge. Modified Park's classification was applied to evaluate the severity of mucosal damage under light microscopy. The colon had higher levels of baseline potential difference, short-circuit current, and resistance than the ileum during 6 48 h of ischemia. Colonic epithelial cells responded well to theophylline stimulation at 24 h of ischemia, while there was no ileal response. The colonic mucosa was histopathologically well preserved in UW solution for 48 h, and mucosal damage induced by reoxygenation was less than in the ileum. In conclusion, electrophysiologically and histopathologically, the colon is less susceptible to cold preservation damage than the ileum during storage with UW solution.

Adenosine↗
PubMed1999

Allogeneic hematopoietic stem cell transplantation for patients with hemophagocytic syndrome (HPS) in Japan.

Seventeen cases (age at onset, 1 month to 18 years; M/F, 9/8) of hemophagocytic syndrome which received allogeneic hematopoietic stem cell transplantation (SCT) in Japan during the period 1988-1998 are reported. The patients consisted of six familial inheritance-proven erythrophagocytic lymphohistiocytosis (FEL), five familial inheritance-unknown and infective agents-unknown HLH (of which two were highly likely to have been FEL with characteristic CNS signs), and six aggressive Epstein-Barr virus (EBV)-related HLH (of which two were natural killer cell-type large granular leukemia/lymphoma-associated hemophagocytic syndrome, EBV-NK-LGLL-HPS). All cases were treated intensively with immuno-chemotherapy, or with chemotherapy before SCT. As sources of SCT, 12 cases received bone marrow cells (sibling six, father one, URD five), two cord blood, two purified CD34-positive cells, and one PBSC. SCTs were successful in all 17 cases, apart from one receiving CD34-positive SCT. Following SCT, four patients relapsed and five died with a median follow-up of 23 months. Among the relapsed cases, the two EBV-NK-LGLL-HPS previously published as successfully transplanted were included. Among the fatal cases, three patients died from relapsed active disease and the remaining two from fatal post-SCT EBV-positive T cell lymphoma and extensive chronic GVHD, respectively. As of the end of September 1998, 10 patients are alive without disease for 3.5 months to 147 months, while two post-SCT patients are still having therapy for residual/recurrent disease. The Kaplan-Meier analysis showed a 2-year event-free survival after SCT as 54.0+/-13.0%.

Adolescent↗
PubMed1999

Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique.

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.

Administration, Oral↗
PubMed1999

[Echinococcosis].

Explore the source record for details and available documents.

Albendazole↗
PubMed1999

Anteroposterior and rotational movement of femur during knee flexion.

This study was designed to analyze anteroposterior and rotational movement of femoral condyles during knee flexion from 15 degrees to 90 degrees using magnetic resonance imaging. After a pilot study, scans were made in 10 healthy male Japanese volunteers. When centers of the circular profiles of posterior femoral condyles were used as reference points, the medial and lateral femoral condyles displaced posteriorly 1.9 +/- 0.8 mm and 2.3 +/- 0.5 mm, respectively (mean +/- standard error). Duplicate examinations on two separate occasions revealed the accuracy of this procedure was in the range of 1 to 2 mm. These results have confirmed that femoral rollback occurs in the unloaded normal knee during flexion from 15 degrees to 90 degrees, but its magnitude is small (2 mm). The results obtained in this in vivo measurement of anteroposterior movement of the femoral condyles have relevance for total knee replacement design.

Adult↗
PubMed1999

Effect of sliding locus on subsurface crack formation in ultra-high-molecular-weight polyethylene knee component.

The objective of this study was to evaluate the effect of sliding locus on fatigue destruction of ultra-high-molecular-weight polyethylene (UHMWPE) in order to design a durable total knee arthroplasty (TKA) articulation. Two-dimensional sliding fatigue testing was performed under two simplified patterns of articulating interface sliding locus. Scanning acoustic tomography (SAT) was used for observation of subsurface cracks in UHMWPE specimens. A high rate of subsurface crack formation was observed when the movement was reciprocated on two different loci, in contrast with that on a single linear locus. This finding suggests that crack formation or propagation in UHMWPE components is accelerated not only by the compressive stress but also by complicated articulating movement locus.

Biocompatible Materials↗
PubMed1999

Hemophagocytosis by leukemic blasts in a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22).

We report the case of a 2-year-3-month-old boy with acute megakaryoblastic leukemia showing hemophagocytosis by leukemic blasts. The chromosome analysis of his bone marrow revealed t(16;21)(p11;q22). In addition to the present case, we found 4 other acute myeloid leukemia (AML) cases associated with hemophagocytosis and t(16;21)(p11;q22) in the literature, of which 3 were megakaryoblastic. Although the syndrome of AML with FAB-M4/5 morphology, t(8;16)(p11;p13), and erythrophagocytosis is well known, leukemic blasts of FAB-M7 morphology showing t(16;21)(p11;q22) may be underscored for their phagocytic activity.

Child, Preschool↗