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Biomedical subjects

T Gotoh

Publications and source records attributed to T Gotoh.

At least 145 records · Page 8Linked to original sources

Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study).

An elevated serum level of lipoprotein(a) (Lp[a]) may be an independent risk factor for atherosclerotic disease, but the relation of Lp(a) to aortic valve (AV) sclerosis has not been determined. We measured serum concentrations of Lp(a) and investigated their relation to the presence of echocardiographic AV sclerosis in residents of a rural village in Japan. We measured serum Lp(a) levels in 347 men and 437 women aged 35 to 90 years (mean +/- SD: 62 +/- 11 years) who participated in mass screening examinations in Wara village, Gifu, Japan. AV sclerosis was assessed by long- and short-axis 2-dimensional echocardiographic views and continuous-wave Doppler echocardiography. AV sclerosis was graded as follows: 0 = normal AV; 1 = increased echo density; 2 = thickening or calcific deposits > or = 3 mm; and 3 = same as 2 with mildly restricted motion (pressure gradient < 16 mm Hg). Lp(a) levels ranged from < 1 mg/dl to 153 mg/dl. The 25th, 50th, and 75th percentile values were 7, 16, and 28 mg/dl, respectively. Lp(a) levels were significantly higher in women than in men (p < 0.01), and did not increase significantly with age. The prevalence of AV sclerosis (grades 2 and 3) increased significantly with age (p < 0.001). AV sclerosis was present in 65 (36.1%) of 180 subjects with Lp(a) levels > or = 30 mg/dl and in 77 (12.7%) of 604 subjects with Lp(a) levels < 30 mg/dl (p < 0.001). There were no significant differences in the prevalence of AV sclerosis in terms of sex, blood pressure, or levels of total cholesterol, high-density lipoprotein cholesterol, triglycerides, or blood sugar. We conclude that increased serum levels of Lp(a), as well as aging, are closely related to AV sclerosis.

Adult↗

Electrospray ionization mass spectrometric determination of the complete polypeptide chain composition of Tylorrhynchus heterochaetus hemoglobin.

Electrospray ionization mass spectrometry (ESI-MS) of the native, reduced, and carbamidomethylated forms of the extracellular, 3.38-MDa hemoglobin from the marine polychaete Tylorrhynchus heterochaetus, when combined with a maximum entropy (MaxEnt) analysis, provided a complete description of the polypeptide chain composition. This hemoglobin, a hetero-multimeric complex of approximately 180 polypeptide chains, consisting of globin and linker subunits in an approximately 3:1 mass ratio, is among the largest protein complexes investigated by ESI-MS. The globin subunits consist of a monomer subunit (chain I, 15575.4 Da) and a disulfide-bonded trimer subunit, 50068.4 Da, consisting of globin chains IIA (16601.9 Da), IIB (16680.4 Da), and IIC (16,794.0 Da). Linker subunits L1-L5, 23233.8, 24835.4, 25326.9, 28202.2, and 26317.2 Da, respectively, were found together with a disulfide-bonded dimer of L2, 52609.4 Da. Using the exact masses of the subunits, a plausible model of the hemoglobin consisting of 144 globin chains (36 monomers and 36 trimers) and 36 linker chains provides a calculated mass of 3.42 MDa.

Animals↗

Carbohydrate gluing, an architectural mechanism in the supramolecular structure of an annelid giant hemoglobin.

We report a carbohydrate-dependent supramolecular architecture in the extracellular giant hemoglobin (Hb) from the marine worm Perinereis aibuhitensis; we call this architectural mechanism carbohydrate gluing. This study is an extension of our accidental discovery of deterioration in the form of the Hb caused by a high concentration of glucose. The giant Hbs of annelids are natural supramolecules consisting of about 200 polypeptide chains that associate to form a double-layered hexagonal structure. This Hb has 0.5% (wt) carbohydrates, including mannose, xylose, fucose, galactose, glucose, N-acetylglucosamine (GlcNAc), and N-acetylgalactosamine (GalNAc). Using carbohydrate-staining assays, in conjunction with two-dimensional polyacrylamide gel electrophoresis, we found that two types of linker chains (L1 and L2; the nomenclature of the Hb subunits followed that for another marine worm, Tylorrhynchus heterochaetus) contained carbohydrates with both GlcNAc and GalNAc. Furthermore, two types of globins (a and A) have only GlcNAc-containing carbohydrates, whereas the other types of globins (b and B) had no carbohydrates. Monosaccharides including mannose, fucose, glucose, galactose, GlcNAc, and GalNAc reversibly dissociated the intact form of the Hb, but the removal of carbohydrate with N-glycanase resulted in irreversible dissociation. These results show that carbohydrate acts noncovalently to glue together the components to yield the complete quaternary supramolecular structure of the giant Hb. We suggest that this carbohydrate gluing may be mediated through lectin-like carbohydrate-binding by the associated structural chains ("linkers").

Amino Acid Sequence↗

Nucleus-cytoplasm interactions causing reproductive incompatibility between two populations of Tetranychus quercivorus Ehara et Gotoh (Acari: Tetranychidae).

Partial reproductive incompatibility between two local populations of Tetranychus quercivorus Ehara et Gotoh derived from Sapporo (43 degrees N) and Tsukuba (36 degrees N), Japan, was found. The incompatibility was unidirectional: the Sapporo female was incompatible with the Tsukuba males, which resulted in a low egg hatchability and strongly male-biased sex ratio, whereas the reciprocal cross was compatible and produced normal progeny with a female-biased sex ratio. To determine the genetic mechanism responsible for the incompatibility, crosses were made between the two populations over five to six filial generations as well as backcrosses. The results suggested that the incompatibility could be caused by an interaction between the cytoplasm from the Sapporo population and a single nuclear gene from the Tsukuba population. Compatibility was not restored when individuals of the Sapporo population were treated with antibiotics or high temperature, indicating a possibility that the cytoplasmic factors are cytoplasmically inherited elements such as mitochondria rather than microorganisms.

Animals↗

Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G.

C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide-releasing factor, shows sequence similarity to CDC25 and Sos family proteins (S. Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, K. Matuoka, T. Takenawa, T. Kurata, K. Nagashima, and M. Matsuda, Proc. Natl. Acad. Sci. USA 91:3443-3447, 1994). The substrate specificity of C3G was examined by in vitro and in vivo experiments. C3G markedly stimulated dissociation of bound GDP from Rap1B but marginally affected the same reaction of other Ras family proteins (Ha-Ras, N-Ras, and RalA). C3G also stimulated binding of GTP-gamma S [guanosine 5'-3-O-(thio)triphosphate] to Rap1B. When C3G and Rap1A were expressed in COS7 cells, marked accumulation of the active GTP-bound form of Rap1A was observed, while Sos was not effective in the activation of Rap1A. These results clearly show that C3G is an activator for Rap1. Furthermore, expression of C3G with a membrane localization signal in a v-Ki-ras transformant, DT, induced a reversion of the cells to the flat form, possibly through the activation of endogenous Rap1.

Animals↗

Purification and properties of extracellular carboxyl proteinase secreted by Candida pulcherrima.

An extracellular proteinase secreted by Candida pulcherrima KSY 188-5 was purified about 60-fold to electrophoretical homogeneity from its culture supernatant, by ammonium sulfate fractionation, anion-exchange chromatography, and gel filtration. The proteinase had a molecular weight of approximately 36,500 and an isoelectric point of pH 4.7. The enzyme had an optimum pH of around 2.5-3.5 for activity and 3.0-5.0 for stability. The optimum temperature was around 45 degrees C at pH 3.0. The enzyme showed a broad substrate specificity for a variety of proteins to hydrolyze casein, BSA, hemoglobin keratin, and collagen. Among several proteinase inhibitors, pepstatin A completely abolished the enzyme activity; indicating that the extracellular proteinase from C. pulcherrima KSY 188-5 was classified in the group of carboxyl proteinases.

Amino Acids↗

Most thymocytes die in the absence of DNA fragmentation.

Most thymocytes are known to be depleted from the thymus during T cell development, with the process of thymocyte death considered to be apoptosis. In this study we examined the mechanism of thymocyte death in the thymus of 6-week-old mice by using terminal deoxynucleotidyl transferase to detect DNA fragmentation or double strand breaks (TUNEL method). The TUNEL positive thymocytes were scattered throughout the cortex. Double staining of the section with the TUNEL method and acid phosphatase (ACP) activity showed that all the TUNEL positive cells were phagocytosed by ACP positive macrophages. An ultra-structural study revealed the presence of a substantial number of extremely small, unphagocytosed thymocytes throughout the cortex. These small unphagocytosed thymocytes were apparently dead cells, as based on several morphological features: 1) The majority were much smaller than red blood cells; 2) the nuclei were also considerably small; and 3) the extent of chromatin condensation was enormous. Importantly, these unphagocytosed dead thymocytes were TUNEL negative. These results indicate that: 1) DNA fragmentation, which is detected by the TUNEL method, is not involved in the cell death process of small unphagocytosed dead thymocytes shown in the present study; and that 2) typical apoptosis, which is characterized by DNA fragmentation, is not the dominant type of cell death in the normal murine thymus. Processes of cell death other than typical apoptosis taking place in most thymocytes require further investigation.

Animals↗

[Clinical studies of 15 cases of renal angiomyolipoma].

Fifteen cases of renal angiomyolipoma seen between May, 1988 and October, 1994 in our hospital are presented. Surgical treatment was performed in 6 cases, 1 of which was falsely diagnosed as liposarcoma by frozen specimen during the operation. Nine cases were only followed-up by ultrasonography and/or computed tomography. In 2 cases, in which enucleation was performed after a follow-up period of more than one year, tumors were inclined to grow rapidly. In 5 cases, which were not operated and followed-up for more than one year, tumors were inclined to grow very slowly.

Adult↗

[Giant schwannoma in the pelvic cavity presenting as renal failure: a case report].

A case of giant schwannoma in the pelvic cavity detected with renal failure is reported. A 50-year-old man was referred to another clinic with chief complaints of general fatigue and edema of the face and dorsa of the feet. On March the 4th 1994, he was hospitalized in the clinic because of renal failure. Bilateral hydronephrosis and a giant pelvic tumor were found by computed tomography (CT) and ultrasonography. Because bilateral percutaneous nephrostomies failed to recover his renal function, he was referred to our clinic for the purpose of hemodialysis and the further examination of the tumor on March 16, 1994. The pelvic angiography showed that the tumor was fed by the vessel from the left internal iliac artery. After the chemo-embolization from the feeding artery, tumor resection was performed on May 9, 1994. The tumor was 16x13x10 cm in size, and 1,110 g in weight. The histological findings of the tumor revealed the mixed type schwannoma of Antoni A and B. Six months after the operation, he has had no tumor recurrence. This is a rare case of pelvic schwannoma which was detected with renal failure. We reviewed and discussed 56 cases of schwannoma in the pelvic cavity, including our case, in the Japanese literature.

Humans↗

[Recurrence of transitional cell carcinoma in bilateral upper urinary tracts and ileal conduit with invasion in the abdominal wall around nephrostomy after total cystectomy: a case report].

A case of recurrence of transitional cell carcinoma in bilateral upper urinary tracts and ileal conduit with invasion in the abdominal wall around nephrostomy after total cystectomy is presented. A 33-year-old man with right nephrostomy, after total cystectomy, construction of ileal conduit, bilateral partial ureterectomy and left nephrectomy for transitional cell carcinoma at another hospital was referred to our hospital because of further recurrence in the right renal pelvis and ileal conduit. He had had left nephrostomy before the left nephrectomy was performed. Right nephrectomy and total extirpation of ileal conduit were performed and hemodialysis was started from the day after the operation. However, several weeks later, transitional cell carcinoma was detected pathologically in the left abdominal wall around the left nephrostomy which had been inserted. The renal pelvis was inferred to have leaked urine around the nephrostomy and invasion arose in this region. After radiation therapy he was discharged but he died from recurrence of carcinoma 9 months after the operation. After total cystectomy, examinations by percutaneous puncture of the renal pelvis are very effective for evidence of recurrence in the upper urinary tract. However, we emphasize that the percutaneous technique carries the risk of tumor invasion through the percutaneous urinary tract.

Abdominal Muscles↗

[Circadian rhythms in peak expiratory flow rate of asthmatic patients before and after treatment with beclomethasone dipropionate].

Asthmatic patients have a circadian rhythm in peak expiratory flow rate (PEFR). The present study was done to measure the effect of inhaled beclomethasone dipropionate (BDP) on the circadian rhythm of PEFR in asthmatic patients. After two weeks of observation, BDP (400 micrograms) was given by metered dose inhaler to nine asthmatic patients. The dose of inhaled BDP (800-1200 micrograms) was increased every two weeks until PEFR varied by no more than 20% each day. PEFR was measured four times daily: on waking, around noon, in the evening, and at bedtime. Nine asthmatic patients had a significant (p < 0.05) rhythm detectable by single cosinor analysis, both during the observation period and during treatment. Analysis by the group mean-cosinor method showed that the mean mesor was 397.3 +/- 6.8 l/min, the mean amplitude was 54.3 +/- 7.1 l/min, and the mean acrophase was at 16:31 +/- 0.27 before treatment. After treatment, the mean mesor was 543.8 +/- 4.4 l/min, the mean amplitude was 30.5 +/- 4.9 l/minm, and the mean acrophase was at 16:25 +/- 0.31. The mean mesor had increased significantly (p < 0.05), and the mean amplitude had decreased significantly (p < 0.05) after treatment. The mean acrophase did not change. These data indicate that inhaled BDP increases PEFR at a constant acrophase in asthmatic patients.

Adolescent↗

[A case of successful surgical retrieval of the intracoronary interlocked Palmaz-Schatz stent].

We presented a case of a 48-year-old male with failed delivery of the Palmaz-Schatz stent, who subsequently required CABG with successful retrieval of the stent. The patient had presented recurrent angina, approximately one and a half year since the last PTCA to the LAD. Re-PTCA was performed, but resulted in a severe local dissection. The stent implantation was tried, but was inadvertently dropped in the vessel. Since the patient was hemodynamically stable, we tried to remove the stent with Retriever endovascular snare, which ended up with interlocking the stent in the more proximal segment of the LAD and the snare itself was not removed. We, therefore, resort to the emergent operation, with successful retrieval of the snare device and the stent and carried on to the the bypass operation to the distal LAD without any complications. To our best knowledge, this is the first report in Japan for surgical retrieval of the Palmaz-Schatz stent, which was failed in delivery and interlocked in the vessel with retriever device.

Angina Pectoris↗

[Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father].

We report a case of a 19-year-old male with congenital aplastic anemia and multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and mental retardation. He was admitted to our hospital because of severe pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42% myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and underwent allo-BMT from an HLA-identical father. The conditioning regimen consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total body irradiation. Severe toxicity associated with the conditioning regimen was not observed. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is well and free of disease for 15 months since BMT. Very few cases of Fanconi's anemia with leukemic transformation treated by BMT have been reported. Long-term observation will be necessary to evaluate our conditioning regimen for Fanconi's anemia with leukemic transformation.

Adult↗

[Dextromethorphan maintains the function of the detached retina].

In order to evaluate the effect of dextromethorphan (DEX), an antagonist of N-methyl-D-aspartate receptors, on ischemic damage in the detached retina, transretinal electrical responses (trans-retinal electroretinogram: TR-ERG) to photic stimulation were recorded from the detached retina of rabbit eyes in vitro. In experiment 1, 0.1 ml of 0.1% DEX was injected into the subretinal space to produce retinal detachment (RD) of 8 mm diameter (DEX group). For the control, the same volume of Hanks' solution was injected instead of DEX (control group). In experiment 2, 0.1 ml of 0.1% DEX was dropped onto retina, and RD was produced by injecting 0.1 ml of Hanks' solution into the subretinal space (DEX group). For the control, the same volume of saline was dropped onto the retina instead of DEX (control group). In experiment 1, the averaged b-wave amplitude of the TR-ERG decreased significantly (p < 0.01) at 3 hrs after RD in the control group, but it was almost stable and did not show significant decrease in the DEX group. In experiment 2, the averaged b-wave amplitude of the ERG decreased significantly (p < 0.05) at 2 hrs after the RD in the control, but showed no significant decrease even at 3 hrs after RD in the DEX group. These results indicate that DEX injected into the subretinal space and dropped onto the retina before producing RD may reduce ischemic damage in the detached retina.

Animals↗

Role of nitric oxide in the peripheral vessels of patients with familial amyloidotic polyneuropathy (FAP) type I.

In order to establish the generation of endothelial derived relaxating factor (EDRF) in patients with familial amyloidotic polyneuropathy (FAP) type I, the muscle temperature of the lower limb was measured with a deep portion thermometer. The temperature of the gastrocunemius muscle in FAP patients was significantly decreased compared with control subjects. In order to investigate the generation of EDRF in FAP patients, we administered NG-monomethyl-L-arginine (L-NMMA), specific inhibitor of nitric oxide, from the brachial artery and measured the changes in blood flow. Although 61.7 +/- 18.2% of the blood flow was transiently decreased after administration of L-NMMA in control subjects, FAP patients showed poor responses. In contrast, in the same way as in control subjects, significant vasodilatation was seen in FAP patients after administration of L-arginine. The urinary secreted NO2-/NO3- levels per day, which reflect the synthesis of nitric oxide in the systemic circulation, was a great deal lower in FAP patients than in control subjects. These results suggest that, although peripheral vessels can be dilated when a large amount of the substrate for NO synthase, L-arginine, is supplied, production of nitric oxide may be suppressed, and, as the result of this phenomenon, blood flow is decreased in the peripheral tissues of FAP patients in a static state.

Adult↗

The delayed glucocorticoid-responsive and hepatoma cell-selective enhancer of the rat arginase gene is located around intron 7.

Liver-selective transcription of the gene for rat arginase, an ornithine cycle (urea cycle) enzyme, is induced by glucocorticoids in a delayed secondary manner; the mRNA induction by the hormones requires de novo protein synthesis, and is preceded by a time lag of several hours. We searched for a DNA element mediating the glucocorticoid induction of the arginase gene with a transient transfection system using hepatoma cell lines. Within the 233-base pair region that is located 11 kilobases downstream from the transcription start site and that spans the junction of intron 7 and exon 8, we detected an enhancer element that is glucocorticoid-responsive and hepatoma cell-selective. The time course of the glucocorticoid induction through this enhancer element was delayed compared to that through the primary glucocorticoid-responsive mouse mammary tumor virus promoter. Footprint analysis revealed four protein-binding sites in this enhancer region. In gel retardation analysis, each site exhibited a complicated profile characterized by a number of shifted bands, some of which were tissue-selective and others ubiquitous. Gel shift competition and antibody supershift/inhibition analysis demonstrated that two of the four sites are recognized by members of the CCAAT/enhancer binding protein (C/EBP) family, some of which are liver-enriched.

Animals↗