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Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 181 records · Page 10Linked to original sources

Genetic and physical mapping of the McKusick-Kaufman syndrome.

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease-causing mutations.

Abnormalities, Multiple↗

Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and pseudomonas toxin.

We investigated the involvement of caspases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin in U937 cells. We found that caspase-3- and caspase-6-like activities, but not caspase-1-like activity, increased during toxin-induced apoptosis. Z-D-CH2-DCB, a caspase-like inhibitor, completely inhibited the generation of caspase-3- and caspase-6-like activities and blocked all features of apoptosis induced by toxins: nuclear morphological changes, DNA fragmentation, and cytotoxicity. However, three caspase-specific inhibitors, Ac-YVAD-CHO, Ac-DEVD-CHO, and Ac-VEID-CHO, had no effect, even though Ac-DEVD-CHO and Ac-VEID-CHO inhibited the increased caspase-3- and caspase-6-like activity, respectively. These results suggest that the generation of caspase-3- and caspase-6-like activities is redundant, and other caspases distinct from caspase-3 and -6 may be important in toxin-induced apoptosis. Furthermore, serine protease inhibitor, 3,4-dichloroisocoumarine (DCI), abolished the apoptotic cell death and DNA fragmentation caused by toxins, without affecting the increased caspase-3- and caspase-6-like activities. Our results suggest that multiple proteases with different preferences for apoptotic substrates participate in toxin-induced apoptotic death of U937 cells.

ADP Ribose Transferases↗

Detection of immunoglobulin G and A antibodies to rubella virus in urine and antibody responses to vaccine-induced infection.

Urine and serum samples from 89 healthy volunteers and three healthy individuals who underwent rubella vaccination were tested for immunoglobulin G (IgG), IgA, and IgM to rubella virus (RV) by enzyme-linked immunosorbent assay methods. Subjects with positive (n = 68) or negative (n = 21) results for serum IgG were exactly the same as those with the corresponding results for urinary IgG. Both urinary and serum IgG levels remained elevated from the 3rd or 4th week after vaccination until the end of the study. Both urinary IgA and serum IgM levels tended to increase rapidly between the 3rd and 5th week and then gradually decrease until the end of the study, but the levels of both remained positive except for one sample each at the end (26th week). On the other hand, the ratio of anti-RV IgA titer to anti-RV IgG titer in urine (urinary anti-RV IgA/IgG ratio) increased rapidly between the 3rd and 4th week after vaccination and then rapidly returned to the ratio levels of the subjects positive for serum IgG from among the healthy volunteers. In summary, detection of urinary anti-RV IgG should be useful for screening for previous RV infection, and measurement of urinary anti-RV IgA/IgG ratio might be useful for diagnosing recent infection.

Adult↗

[Amyloidogenic peptides such as beta-amyloid, amylin and calcitonin strongly enhance the susceptibility of rat hippocampal neurons to excitatory amino acids in vivo].

We have previously shown that in vivo injection of beta-amyloid (beta 1-40, beta 25-35) with non-toxic amounts of ibotenic acid, an excitatory amino acid, causes synergistic and drastic neuronal degeneration in rat hippocampus. It was, however, yet not clear whether the neuronal degeneration in vivo was associated with their primary amino acid sequences, their secondary beta-structure or their activities to suppress MTT reduction activity in vitro. In addition to beta-amyloid, other amyloidogenic peptides such as human amylin or calcitonin are known to deposit extracellularly in systemic and peripheral amyloidosis. In this study, we measured the activity of amyloidogenic peptides (beta 1-40, human amylin and calcitonin) to suppress cellular MTT reduction activity in vitro and their synergistic neurodegeneration with ibotenic acid in vivo. All amyloidogenic peptides, but not non-amyloidogenic peptides (beta 40-1, BSA), suppressed the MTT reduction activity in HeLa cells and in the primary cultured neurons in vitro, and also produced the synergistic neuronal cell loss in rat hippocampal region by enhancing the toxicity of ibotenic acid in vivo. The deposits of amyloidogenic peptides at the injection sites were thioflavin S fluorescence positive, suggesting the fibrillary beta-structures. These results indicate that the neurodegeneration in vivo by amyloidogenic peptides is strongly associated with their fibrillary beta-structure and their activity to suppress MTT reduction activity in vitro.

Amyloid↗

Hemagglutinating activity of extracellular alkaline metalloendopeptidases from Vibrio sp. NUF-BPP1.

Alkaline metalloendopeptidase (metalloprotease) AP1 (48 kDa) from Vibrio sp. isolated from the intestine of a five-barred goatfish (Parupeneus trifasciatus) was reported in our previous paper to produce AP2 (36 kDa) by releasing a peptide fragment (molecular mass of about 12 kDa) from the C-terminal end of AP1 by autodigestion. AP1 strongly agglutinated fish (flounder, Paralichthys olivaceus) and rabbit erythrocytes, and weakly chicken erythrocytes. In contrast, AP2 had no significant hemagglutinating activity toward any erythrocytes tested, except for weak activity on flounder erythrocytes, suggesting that the C-terminal region of AP1 may be required for the strong hemagglutinating activity. The optimum temperature for the hemagglutinating activity of AP1 was found to be lower than that for the proteolytic activity. At acidic pHs (below pH 7.5), the hemagglutinating activity of AP1 decreased, and its pH profile resembled that of the proteolytic activity. The hemagglutinating activity of AP1 was not observed in the presence of o-phenanthroline or synthetic and proteinous substrates, but different kinds of saccharides and lipids had no effect. While the proteolytic activity of AP1 was not affected by CaCl2, the hemagglutinating activity of AP1 decreased with increases in CaCl2 concentrations. These results suggested that the hemagglutinating activity of these proteases (AP1 and AP2) was most likely caused by their proteolytic action on erythrocyte cell surfaces.

Animals↗

Diisopropylfluorophosphate (DFP) inhibits ricin-induced apoptosis of MDCK cells.

Diisopropylfluorophosphate (DFP), a general serine protease inhibitor, inhibited the DNA fragmentation and cell death in MDCK cells treated with ricin, modeccin, Pseudomonas toxin, or diphtheria toxin. A trypsin-like serine protease inhibitor, N-tosyl-L-lysine chloromethyl ketone (TLCK) also prevented ricin-induced DNA fragmentation and cell death, albeit less effectively than DFP. Microscopic observation showed that the morphological changes of MDCK cells induced by ricin were prevented by DFP. DFP did not affect the binding, internalization, or subsequent excretion of ricin, but reduced the degradation of ricin in MDCK cells, suggesting that DFP inhibits at least the cellular protease that may be involved in the degradation of internalized ricin. In addition, SDS-PAGE analysis of cytosolic proteins suggested that DFP-sensitive endogenous proteases are activated in the ricin-treated cells. In the cells treated with DFP, the protein synthesis inhibitory activity of ricin was increased rather than inhibited. The activities of modeccin and Pseudomonas toxin were also slightly increased by DFP, but no effect of DFP on the activity of diphtheria toxin was observed. Therefore, these results suggest that protein toxins have a DFP-sensitive common pathway leading to apoptosis that is distinct from the pathway leading to the inhibition of cellular protein synthesis.

ADP Ribose Transferases↗

Transcatheter embolization of celiac artery pseudoaneurysm following pancreatico-duodenectomy for pancreatic cancer. A case report.

A case of transcatheter embolization of a celiac artery pseudoaneurysm in a 70-year-old man is reported. The pseudoaneurysm was considered to be the result of pancreatic anastomotic leakage and an intra-abdominal abscess following pancreaticoduodenectomy with irradiation of 66 Gy for pancreatic carcinoma. To avoid recanalization of the pseudoaneurysm due to retrograde blood flow, first all branches of the celiac artery were embolized with metallic coils, and then the celiac trunk was also occluded. Hepatic arterial flow was preserved by the right hepatic artery arising from the superior mesenteric artery. After the procedure, the patient had no noticeable complications associated with the embolization nor any recurrence of the pancreatic cancer, and he achieved a 2-year survival.

Aged↗

Supplementation of Bifidobacterium longum to a high-fat, low-calcium diet lowers cytolytic activity of fecal water in rats injected with 1,2-dimethylhydrazine dihydrochloride.

The effects of supplementing Bifidobacterium longum SBT 2928 and Lactobacillus acidophilus SBT 2062 to a high-fat, low-calcium diet on bile acid concentration, fatty acid concentration, cytolytic activity and intestinal alkaline phosphatase (ALP) activity of fecal water in rats injected with and without 1,2-dimethylhydrazine dihydrochloride (DMH) were examined. Male Wistar rats at 8 weeks of age were fed a diet containing 18% coconut oil, 2% corn oil and 0.1% calcium for 15 d. Lyophilized cultures were supplemented to test diets at a concentration of 1%. The feeding of a high-fat, low-calcium diet elevated the bile acid concentration, cytolytic activity and ALP activity of fecal water as compared to the AIN-76A diet, whereas the fatty acid concentration was not changed. None of the cultures had any effect on these parameters. Furthermore, 8 week-old rats were given a single subcutaneous injection of DMH at 40 mg/kg body weight, and fed the same diets for 15 d. The DMH injection had no effect on the bile acid concentration but increased the fatty acid concentration and cytolytic activity of fecal water. In contrast, ALP activity was lower in the DMH-treated rats than in the non-treated rats. The ingestion of B. longum lowered cytolytic activity but had no effect on the bile acids, fatty acids and ALP activity of fecal water. L. acidophilus had no effect on these parameters.

1,2-Dimethylhydrazine↗

Valve surgery in elderly patients 70 years or older: early and late results.

Between April 1986 and March 1997, 75 patients (Group E) who were 70 years or older underwent valvular operations, and another 73 patients who were under 70 years constituted a comparison group (Group Y). Valve replacement was performed on 131 patients (Group E; 65 patients, Group Y; 66 patients), reparative procedures on 11 patients (Group E; 7, Group Y; 4), and aortic root replacement on 5 (Group E; 3, Group Y; 2). Coronary artery bypass grafting was concomitantly performed on 13 patients (Group E; 7, Group Y; 6). In the elderly patients, preoperative clinical status, including cardiac and non cardiac organ functions, was not necessarily more severe than that in the younger patients, however, perioperative restoration of cardiac and pulmonary functions required a longer time in Group E than Group Y. There were no significant differences in operative mortality rate, long-term survival rate, the probability of freedom from all events related to native and prosthetic valves, and in activity of daily life between Group E and Group Y. These results suggest that valvular operation for elderly patients 70 years or older may be safely performed with operative risks similar to those of younger patients by application of modern surgical techniques.

Aged↗

[Targeted chemotherapy of hepatocellular carcinoma with SMANCS/Lipiodol--how to use SMANCS/Lipiodol].

The first drug only for arterial injection, SMANCS/Lipiodol, which offers targeted chemotherapy for hepatocellular carcinoma (HCC), now commercially available. Based on our experience using SMANCS/Lipiodol for 424 patients with HCC, the golden standard of how to use SMANCS/Lipiodol for complete necrosis of tumor was described. The initial dose of SMANCS/Lipiodol was varied 2 to 6 mg per body, mainly depending on the size of the tumor. All feeding arteries of HCC have to be verified on angiogram, and the drug must be injected via an adequate artery. Sometimes, a tumor changes its feeding arteries. Additional administrations with an interval of one month were done till the entire tumor was filled with SMANCS/Lipiodol (grade 4). One or two months after achievement of grade 4, we must examine how much drug was removed from tumor on CT. If the entire tumor is not filled with the drug, further injections are recommended to maintain grade 4. Almost all tumors shrank in 3 to 4 months while maintaining grade 4. Frequent administration of low doses (1-3 mg per body) is recommended. Discontinvation of administration was done on the following findings; tumor size reduction of over 90% or complete disappearance of tumor stain. With arterial injection therapy of SMANCS/Lipiodol, survival of patients with unresectable HCC was prolonged, especially in 272 patients who were good candidates for therapy. (Those with Child C liver cirrhosis, with a tumor occupying all four segments of the liver, and/or with extrahepatic spread at initial arterial injection of the drug were excluded.) The 1, 2, 5, and 10 year survival rates were 83%, 58%, 34%, and 25%, respectively.

Antineoplastic Agents↗

[Surgery for the treatment of infective endocarditis in the active and inactive stages].

Twenty-eight patients (16 M, 12 F, age 11 approximately 72 yr, mean 52.8 yr) underwent surgery for infective endocarditis. Of the 27 patients, 16 were in the active stage and 11 were in the inactive stage. In patients in the active stage, aortic valve replacement (AVR) was performed in 5, mitral valve replacement (MVR) in 7, AVR + MVR in 1, AVR + MVR + tricuspid valve plasty (TVP) in 1 and other procedures in 2. In patients in the inactive stage, AVR was performed in 3, MVR in 4, AVR + MVR in 2, and other procedures in 2. Causative organisms were detected in 56.3% of the patients in the active stage and 54.5% in the inactive stage. Also in patients in the active stage, infection was not prolonged. No deaths occurred among patients in the inactive stage but five patients (31%) died postoperatively; 4 of the five also died, for had severe heart failure before surgery, three died of multiple organ failure and one died of subarachnoid hemorrhage due to infective aneurysm. We recommend surgery for the treatment of infective endocarditis even in the active stage before emergence of heart failure.

Adolescent↗

[Change of cytokines and clinical efficacy of panipenem/betamipron in obstetric and gynecological infections. Yamagata Study Group of Panipenem/Betamipron in Obstetric and Gynecological Infections].

Efficacy and safety of panipenem/betamipron (PAPM/BP) in treatment of obstetric and gynecological infections, and change of interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in blood, as markers of infection, were investigated. The results were as follows; 1) Clinical efficacy of PAPM/BP by drip infusion of 1-2 g/day for 3-14 days against 52 patients with intrauterine infection (n = 29), pelveoperitonitis (n = 19), and other infections were 14 "Excellent" in 14 cases, "Good" in 35 cases, and efficacy rate was 94.2% (49/52). Both efficacy rate analy by causative organisms and eradication rate were 35/37 (94.6%). No subjective or objective side effects and no abnormal labolatory findings were observed. 2) Changes of IL-6 (> 4 pg/ml) levels in serum, as an infection marker, were observed in 8 cases out of 14 cases (57.1%), and correlation between CRP and IL-6 in the treatment process was noticed. However, changes of serum IL-8 (> 12.5 pg/ml) were observed in only 2 cases of those 14 cases (14.3%), indicative that IL-8 has no significance as a marker of infection.

Adolescent↗

Interleukin-8 and monocyte chemotactic protein-1 production by a human glioblastoma cell line, T98G in coculture with monocytes: involvement of monocyte-derived interleukin-1alpha.

We have previously demonstrated that a human glioblastoma cell line, T98G cells, produced high levels of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) when stimulated with IL-1 or tumor necrosis factor-alpha (TNF-alpha). In this study, we found that T98G cells are capable of producing large amounts of IL-8 and MCP-1 when cocultured with human peripheral blood monocytes or a monocytic cell line, U937 cells. Since it is possible that both glioblastoma cells and monocytes are capable of producing chemokines, we determined which type of cells actually produced IL-8 and MCP-1, by the fixation of one or the other cell type with 3% paraformaldehyde (PA). This procedure revealed that T98G cells were the main source and that PA-treated monocytes effectively stimulated IL-8 and MCP-1 production by T98G cells. Both IL-8 and MCP-1 gene expression and protein production by T98G cells were confirmed by northern blot as well as immunohistochemical staining methods. To analyze the molecules on human monocytes responsible for inducing IL-8 and MCP-1 by T98G cells, several antibodies (Abs) as well as IL-1 receptor antagonist (IL-1Ra) were tested. Anti-IL-1alpha Ab and IL-1Ra almost completely abolished the IL-8/MCP-1-inducing capacity of the PA-fixed monocytes, while no inhibition was obtained with anti-IL-1beta, anti-TNF-alpha or Abs against CD11b/18, L-selectin or ICAM-1, indicating that membrane-associated IL-1alpha is involved in the IL-8/MCP-1 induction, while secreted IL-1alpha plays a major role in this cell-to-cell, i.e., juxtacrine interaction in unfixed conditions.

Antibodies, Monoclonal↗

[A case of lung abscess caused by Eikenella corrodens].

We report a case of lung abscess caused by Eikenella corrodens and reviewed the literature. A 51-year-old man was hospitalized because of an infiltrative shadow in the left upper lung on chest X-ray. The patient was intravenously given CEZ (2 g/day) followed by CEZ (4 g/day) and AMK (200 mg/day). We nevertheless deteriorated and was subsequently treated with CTM (4 g/day) and LCM (6 g/day), and the shadow improved but remained. Only Eikenella corrodens was isolated from aspiration materials obtained from the resected lung. We examined the susceptibility of 60 strains of Eikenella corrodens to various antimicrobial against. The organisms were very susceptible to PCG, ABPC, PIPC, CTM, CTX and LMOX, but were all resistant to LCM, CLDM, GM and AMK.

Aminoglycosides↗

[Pulmonary edema due to acute airway obstruction immediately after tracheal extubation].

A 33-year-old male was scheduled for tonsillectomy and pharyngoplasty due to sleep apnea syndrome. The intubation was uneventful following induction with thiamylal and vecuronium. Anesthesia was maintained with O2-N2O-sevoflurane. No complications were observed during the 90 min operation. After the termination of the anesthesia, a hyperadrenergic state was observed: arterial pressure and heart rate rose to 230/135 mmHg and 135 bpm, respectively. Immediately after extubation, he developed dyspnea with tracheal tag and stridor, and became cyanotic despite the use of a simple oxygen mask and assisted ventilation. Laryngospasm was suspected. The patient was reintubated and suctioned; pink, frothy sputum was not obtained. Arterial blood gases 5 minutes after reintubation revealed a pH of 7.24, Pao2 86 mmHg (FIo2 1.0), and Paco2 54 mmHg. Chest X-ray 30 minutes after reintubation revealed bilateral diffuse alveolar infiltration. The diagnosis was interstitial pulmonary edema. The patient was ventilated mechanically by applying a positive end-expiratory pressure of 5cm H2O, and furosemide and dopamine were administered intravenously. The patient was extubated the next day, and discharged from hospital ten days later. We considered that the lung edema was induced by the severe negative pressure generated by inspirating against a closed upper airway, as well as by the hyperadrenergic state and severe hypoxemia observed during and after extubation.

Acute Disease↗

Induction by peroxisome proliferators and triiodothyronine of serine:pyruvate/alanine:glyoxylate aminotransferase of rat liver.

In rat liver, a single serine:pyruvate/alanine:glyoxylate aminotransferase (SPT or SPT/AGT) gene is transcribed from two transcription initiation sites. Transcription from the upstream site generates the mRNA encoding the precursor for mitochondrial SPT (pSPTm) and is markedly enhanced by the administration of glucagon or cAMP. In this report we show the increase in the downstream transcript, the peroxisomal SPT (SPTp) mRNA, caused by peroxisome proliferators and triiodothyronine (T3). In the case of T3, the pSPTm mRNA was also increased 72 h after a single administration of the hormone in addition to an earlier increase in SPTp mRNA.

Animals↗

Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12.

Notch proteins are a family of closely related transmembrane receptors proven to be instrumental in cell fate decisions. Recently, Notch ligands Delta and Jagged have been identified in Drosophila and rat, respectively. We have isolated the human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP-D20S186-cen). Alagille syndrome is an autosomal dominant disorder characterized by neonatal jaundice, paucity of intrahepatic bile ducts, and abnormalities of the heart, skeleton, and eyes. The human Jagged1 (JAG1), therefore, appears to be a strong candidate gene for this disease. Here we describe the identification, full-length cDNA cloning, expression patterns, and precise physical location of this gene within the Alagille syndrome critical region.

Alagille Syndrome↗