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Biomedical subjects

I Ito

Publications and source records attributed to I Ito.

At least 19 recordsLinked to original sources

Cloning and sequencing of a rat type II activin receptor.

A full-length cDNA for a rat type II activin receptor was cloned by hybridization from a rat ovary cDNA library. The deduced amino acid sequence (513 residues) containing a single membrane-spanning domain and an intracellular kinase domain with predicted serine/threonine specificity. The amino acid sequence is 99.8% and 99.4% identical in the coding region with the previously cloned mouse and human type II activin receptor, and only 66.7% identical in the coding region with the previously cloned rat type IIB activin receptor. We examined the effect of PMSG-hCG on the mRNA level of type II activin receptor in immature rat ovaries. Northern blot analysis of ovarian RNA revealed two mRNAs (3.0 kb and 6.0 kb).

Activin Receptors

Medical treatment of Takayasu arteritis.

The guidelines for medical treatment of Takayasu arteritis established in 1987 by the Systemic Vascular Disorders Research Committee, Ministry of Health and Welfare of Japan are presented. The first part of the guidelines concerns treatment with adrenocorticosteroids and the second part concerns other medical treatment. A review of the literature referring to steroid therapy and other medical treatment of Takayasu arteritis is also included.

Anti-Inflammatory Agents, Non-Steroidal

Linkage between HLA-DRB1 and -DRB3 types in the Japanese population analyzed by oligonucleotide genotyping.

We analyzed linkage between HLA-DRB1 and -DRB3 types in 219 Japanese donors by oligonucleotide genotyping. In the Japanese population, DRB1*1201 was linked with DRB3*0101 in all donors analyzed; in contrast, most Caucasian DRB1*1201 is known to be linked with DRB3*02(01/02) (*0201 or *0202). However, most DRB1*1202 was linked with DRB3*0301. Thus, the two DRw12-related DRB1 types are linked with DRB3 types distinct from each other. All the three DRw14-related DRB1 types, DRB1*1401, DRB1*1402, and DRB1*1405, were linked with DRB3*02(01/02) in the Japanese population, contrasting with the known linkage between DRB1*1402 and DRB3*0101 in other ethnic populations. The serologically "blank" DR type, DRB1*1403, was linked with DRB3*0101. Other DRB1 types, DRB1*0301, DRB1*11(01/04) (*1101 or *1104), and DRB1*13(01/02) (*1301 or *1302) in the Japanese population were linked mostly with the same DRB3 types, like those known in other ethnic populations.

Alleles

Endocytosis of soluble IgG immune complex and its transport to lysosomes in hepatic sinusoidal endothelial cells.

Both Kupffer cells and sinusoidal endothelial cells are engaged in the hepatic uptake of soluble IgG immune complex (IgG-IC) through Fc-receptors on their surface. Hepatocytes have also been reported to take up IgG-IC. It remains unclear, however, whether the endothelial cell degrades IgG-IC and whether the hepatocyte participates in IgG-IC clearance. In this study, normal mice received a single intravenous injection of soluble immune complex preformed in antigen excess, i.e. bovine serum albumin (BSA) anti-BSA-mouse-IgG complex (BABIgG) or BSA anti-BSA-mouse-F(ab')2 complex (BABF(ab')2), or BSA alone. An immunoperoxidase study for BSA showed that from 1 to 120 min after injection only BABIgG was ingested by both endothelial cells and Kupffer cells but not by hepatocytes. The staining intensity of BABIgG was maximal at about 15 min and decreased subsequently. Endocytosis of BABIgG occurred through coated pits in the endothelial cells. Within a few minutes, endocytosed BABIgG was found in tubulovesicular structures and large vesicles. The occasional large vesicles were shown to be lysosomes by simultaneous demonstration of BABIgG with acid phosphatase. BABIgG was not found on either of the endothelial and hepatocellular surfaces facing the space of Disse or in hepatocytes. These results indicate that soluble IgG-IC is endocytosed by sinusoidal endothelial cells and degraded in the lysosomes and that the participation of hepatocytes in the clearance of IgG-IC is improbable.

Acid Phosphatase

Left atrial function in ischemic heart disease assessed by intravenous digital subtraction angiography.

To investigate changes in left atrial morphology and dimensions during the cardiac cycle, the atrium was visualized by intravenous digital subtraction angiography (DSA). The study subjects consisted of 22 male patients whose average age was 54.5 +/- 8.6 years. They had ischemic heart disease without mitral valve disease and were in sinus rhythm. They were 11 patients with old myocardial infarction (OMI group) and 11 who had chest pain without evidence of infarction (AP group). DSA was performed in the continuous mode. Contrast material (35 ml) was injected at a rate of 18 ml/sec via a catheter in the superior vena cava and subtraction images were obtained at a speed of 30 frames/sec in the right anterior oblique projection. The left atrial and left ventricular margins were traced manually, their areas were calculated, and fractional changes in area were analyzed. The left ventricular ejection fraction (LVEF) was calculated by densitometry. Cardiac catheterization was performed in 16 patients and the left ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial wedge pressure (PAWP) were measured. The entire left atrium was clearly imaged using DSA. Phase analysis of the time-area curves in the right anterior oblique projection revealed that the left atrial area was maximal during left ventricular end-systole (%LA1 = 100%), it decreased during early left ventricular diastole (%LA2), and then increased slightly again during mid-diastole (%LA3). After left atrial contraction, the minimum area was obtained (%LA4). The left atrium showed a two-stage decrease in the area due to passive emptying and active contraction during left ventricular diastole. Passive emptying (%LA1-%LA2) was significantly less in the OMI group than in the AP group (6.3 +/- 3.6 vs 13.3 +/- 4.8%, p < 0.01, respectively). In all 22 subjects, passive emptying correlated with LVEF (r = 0.70, p < 0.001) and LVEDP (r = -0.58, p < 0.05). There was no difference in active contraction (%LA3-%LA4) between the 2 groups (26.0 +/- 5.7% in the OMI group, 28.2 +/- 8.4% in the AP group), and it did not correlate with LVEF or LVEDP. The ratio of passive emptying to active contraction [(%LA1-%LA2)/(%LA3-%LA4)] correlated with LVEF (r = 0.63, p < 0.01). These findings suggested that impaired left ventricular diastolic function and a relative increase in atrial contraction were present in patients with a lower LVEF. The %LA4 correlated with LVEDP and PAWP (r = 0.65, r = 0.63, p < 0.01, respectively). In conclusion, DSA proved to be a useful method for investigating left atrial morphology and function.

Aged

3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors.

An amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluR1. Apparent EC50 of DHPG for mGluR1 was slightly lower than that of (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD). DHPG responses were partially inhibited by 2-amino-3-phosphonopropionic acid (AP-3). DHPG had no effect on ionotropic glutamate receptors whose expression was induced in the oocytes following injection of poly(A)+ mRNA of rat brains. In hippocampal slices, DHPG produced slow excitation of pyramidal cells, resulting from a depression of Ca(2+)-dependent K+ current and a voltage-dependent K+ current. These results indicate that DHPG is a specific and potent agonist of mGluRs.

2-Amino-5-phosphonovalerate

[Application of image cytometry to cytological diagnosis of breast tumors].

Computerized morphological analysis of the cell nuclei was performed on 66 cases (2222 nuclei) of aspirated materials from breast tumors: 25 benign cases (302 nuclei), 41 malignant cases (1420 nuclei). Its diagnostic significance and the correlation between nuclear analysis and clinical staging were studied. Nuclear diagram and intranuclear chromatin distribution pattern were evaluated using computer system named 6400. The malignant tumor had larger, more round-shaped nuclei and less uniform chromatin distribution. Under tnm classification, stage IV tumors had larger, more flattened nuclei and more irregular chromatin distribution pattern than the others. Computerized morphological analysis of breast tumors may give a quantitative aspect to classical diagnostic process. Furthermore, this analytical method provides information on clinical stage of breast cancer.

Adult

Effects of KN-62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, on long-term potentiation in the rat hippocampus.

Effects of KN-62 (1-[NO-bis-1,5-isoquinolinesulfonyl]-N-methyl-L-tyrosyl- 4-phenylpiperazine), a specific inhibitor of calcium/calmodulin-dependent protein kinase II, were examined using rat hippocampus slices in vitro. The inhibitor, when applied in bathing solutions prior to and present during the tetanic stimulations, blocked the generation of long-term potentiation (LTP) in CA1 regions without affecting basal synaptic transmission itself, suggesting an important role of this kinase in the molecular mechanism of CA1 LTP. In contrast, mossy fiber LTP in CA3 regions was not affected significantly by the inhibitor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Possible heterogeneity of metabotropic glutamate receptors induced in Xenopus oocytes by rat brain mRNA.

Pharmacological properties of metabotropic glutamate receptors were studied in Xenopus oocytes injected with rat brain mRNA. trans-1-Amino-cyclopentyl-1,3-dicarboxylic acid (t-ACPD), a conformationally restricted analog of glutamate, induced oscillatory inward currents in mRNA-injected oocytes. These t-ACPD responses showed several characteristics identical to those of the other metabotropic responses including the metabotropic glutamate responses stimulated by quisqualate. D,L-2-Amino-3-phophonopropionate (D,L-AP3) effectively suppressed the t-ACPD and ibotenate responses. However, quisqualate responses were not affected substantially by D,L-AP3. These findings suggest that the metabotropic glutamate receptors in the oocytes may be classified into at least two subtypes according to their pharmacological properties: one preferentially activated by quisqualate and insensitive to AP3, and the other activated by t-ACPD and ibotenate and antagonized by AP3.

Alanine

Roles of glutamate receptors in long-term potentiation at hippocampal mossy fiber synapses.

We have investigated the roles of glutamate (Glu) receptors in the mechanism of long-term potentiation observed in rat hippocampal mossy fiber synapses (MF-LTP). The mossy fiber responses were almost completely suppressed by ionotropic Glu receptor (iGluR) antagonists both before and after the induction of LTP. However, tetanic stimulation produced robust LTP even when the synaptic transmission was blocked postsynaptically by iGluR antagonists. In contrast, when the transmission was blocked presynaptically by Ca(2+)-free media, tetanic stimulation produced no LTP. D,L-2-amino-3-phosphono-propionate(D,L-AP3), a metabotropic Glu receptor (mGluR) antagonist, inhibited the induction of MF-LTP. Perfusion with ibotenate, a mGluR agonist, induced long-lasting enhancement of the mossy fiber responses without tetanic stimulation, and this ibotenate-induced potentiation was antagonized by D,L-AP3.

6-Cyano-7-nitroquinoxaline-2,3-dione

HLA-DR gene frequencies in the Japanese population obtained by oligonucleotide genotyping.

We determined HLA-DRB types of 375 randomly chosen healthy Japanese donors using a set of 29 different sequence-specific oligonucleotide (SSO) probes directed against various DRB alleles. Except for a few cases, these SSOs enabled us to identify 33 different DRB types including those detectable only by SSO genotyping. Gene frequencies were calculated for each of the DRB types identified. The "blank" frequency calculated by our SSO typing was essentially zero, in contrast to the considerably high "blank" frequencies reported at serological HLA-DR or cellular HLA-D workshops. This indicates that almost all of the DRB types in the Japanese population are positively detectable by our SSO typing. By comparing the gene frequencies for each of the DR types obtained by our SSO typing with those obtained by immunological typing at workshops, significant differences were observed for several of the DR types.

Alleles

Cardiorespiratory responses to standing arm ergometry in patients with ischemic heart disease. Comparison with the results of treadmill exercise.

To compare cardiorespiratory responses to standing arm ergometry and treadmill exercise, two graded exercise stress tests were performed in 30 patients with ischemic heart disease (IHD). Cardiac catheterization and expired gas analyses were also done. Standing arm ergometry was discontinued because of arm fatigue in 15 (50%) patients, whereas treadmill exercise was stopped due to leg fatigue in 8 (27%) patients. Maximal increase in rate-pressure product and oxygen uptake, and magnitude of ST-segment depression during standing arm ergometry were significantly smaller (p less than 0.01, p less than 0.01 and p less than 0.05, respectively) than those during treadmill exercise. Furthermore correlations of maximal change in rate-pressure product, oxygen uptake and extent of ST-segment depression were not close between the two exercise tests (r = 0.76, r = 0.67 and r = 0.54, respectively). Our results indicate that the ability to detect IHD with standing arm ergometry is lower than that with treadmill exercise and that it is not possible to predict accurately one's capacity for arm exercise from the treadmill exercise test.

Adult

[The effect of human growth hormone on protein metabolism in the surgically stressed state].

The effects of human growth hormone (HGH) on protein metabolism were investigated. In the experimental study, thirty one male SD rats receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after burn in HGH group was significantly higher than in control group. (p less than 0.05) Rates of whole body protein turnover (Q), together with those of synthesis (S) and breakdown (B) were significantly higher in HGH group than in control group. (p less than 0.01) Nitrogen balance significantly correlated with urinary total catecholamine excretion in both groups. (p less than 0.01) The difference of correlations of nitrogen balance to urinary total catecholamine excretion between two groups was statistically significant (p less than 0.01) when compared by analysis of covariance. In the clinical study, 12 patients after sub-total esophagectomy receiving TPN were divided into 2 groups (control group & HGH group). Cumulative nitrogen balance after operation in HGH group was significantly higher than in control group. (p less than 0.01) Q,S, and B were higher in HGH group than in control group. Increase of S was statistically significant. (p less than 0.01). These results indicate that HGH may be greatly beneficial in improving protein metabolism in the surgically stressed state.

Adult

[Effects of aging on right and left ventricular function in patients with right bundle branch block].

The effect of aging on cardiac function in patients with right bundle branch block (RBBB) was commonly unknown, so left ventricular function and right ventricular function were investigated, using first-pass radionuclide angiography. Twenty-six patients with RBBB and 28 normal subjects were studied at rest and during bicycle exercise. Patients with RBBB but normal cardiovascular systems aged 33 to 75 years were divided into those within 60 years (n = 17) and those over 65 years (n = 9). Using the same method, normal subjects aged 38 to 83 years were divided into those within 60 years (n = 18) and those over 65 years (n = 10). Mean age between normal subjects and patients with RBBB didn't differ significantly. The response of left ventricular ejection fraction in normal groups rose during exercise, but its exercise tolerance function declined with aging. Left ventricular diastolic filling in normal groups declined at rest and during exercise with aging. Left ventricular function in RBBB groups showed the same results as those of normal groups. The response of right ventricular ejection fraction and its exercise tolerance function in normal groups was not influenced by aging. However, in contrast, right ventricular function in RBBB groups decreased with aging. We suggest that the mechanism of decrease of right ventricular function in aging patients with RBBB may be caused by the change of right ventricular contraction which is affected by the aging process.

Adult

Crystal-storing histiocytosis and crystalline tissue deposition in multiple myeloma.

Systemic distribution of crystal-storing histiocytes, increasing in number, and widespread crystalline tissue deposition were found in a 75-year-old man with a 5-year history of IgG-kappa-type multiple myeloma associated with corneal opacity and chronic renal failure. Characteristic crystalline inclusions were present not only in myeloma cells but also in cornea, epithelial cells of glomeruli, tubuli, Bowman's capsules, and choroid plexus. Histiocytes had particularly infiltrated the renal interstitium. These inclusions were positive by immunofluorescence for kappa light and gamma heavy chains. By electron microscopy, the inclusions were filled with fine crystalline hexagonal columns, each possessing a core structure. Of various factors generally considered responsible for renal failure in multiple myeloma, marked infiltration of histiocytes and the nephrotoxic effects of light chain appeared most relevant in the present case.

Aged

Mechanisms of stress-induced ST elevation and negative T-wave normalization studied by serial cardiokymogram in patients with a previous myocardial infarction.

Seventeen patients with a previous myocardial infarction were studied during pacing to characterize the clinical correlates of ST elevation, to analyze the relation between ST elevation and negative T-wave normalization and to investigate the mechanism of these electrocardiographic changes. Myocardial ischemia was evaluated by measurement of blood lactate, and wall motion was analyzed using cardiokymographs concurrently and serially. Results show that ST elevation and negative T-wave normalization were most marked in leads containing abnormal Q waves, that ST elevation greater than or equal to 1 mm during pacing was associated with a significant increase in left ventricular end-diastolic pressure and deterioration of left ventricular wall motion and that the magnitude of ST elevation and negative T-wave normalization was significantly correlated, but the latter appeared earlier and more markedly. In addition, there was no significant correlation between the extent of either ST elevation or negative T-wave normalization and myocardial lactate production. Thus, ST elevation and negative T-wave normalization are caused by abnormal left ventricular wall motion rather than myocardial ischemia. Negative T-wave normalization is a more sensitive marker of abnormal wall motion than ST elevation in patients with a previous myocardial infarction.

Cardiac Pacing, Artificial

Cardiac determinants of regression of left ventricular hypertrophy in essential hypertension with antihypertensive treatment.

To study the cardiac determinants of regression of left ventricular hypertrophy in hypertension, left ventricular mass, fractional shortening and end-systolic wall stress were measured echocardiographically in 36 patients with essential hypertension and left ventricular hypertrophy. The patients were classified into two groups. Group I consisted of 15 patients with subnormal end-systolic wall stress, and Group II consisted of 21 patients with normal end-systolic wall stress. There were no significant differences between groups in systolic or diastolic blood pressure. After treatment for 4.4 +/- 1.7 years, echocardiographic studies were repeated. There were no significant differences between groups in the duration of the follow-up period and the kinds of antihypertensive drugs. After treatment, blood pressure decreased significantly in both groups (p less than 0.001 for both), with no significant difference between groups. Left ventricular mass increased significantly in Group I (from 331 +/- 7 to 363 +/- 24 g, mean +/- SEM, p less than 0.05), whereas it decreased significantly in Group II (from 318 +/- 16 to 268 +/- 17 g, p less than 0.001). Myocardial contractility (the relation between end-systolic wall stress and fractional shortening) remained almost the same as before treatment. In conclusion, in patients with hypertensive ventricular hypertrophy with subnormal end-systolic wall stress (inappropriate hypertrophy, probably induced by a neurohumoral factor), a decrease in blood pressure with antihypertensive treatment does not lead to regression of left ventricular hypertrophy, but rather to an increase in left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents