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Biomedical subjects

R Yamamoto

Publications and source records attributed to R Yamamoto.

At least 127 records · Page 7Linked to original sources

Cox multivariate regression models for estimating prognosis of patients with endometrioid adenocarcinoma of the uterine corpus who underwent thorough surgical staging.

The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical staging criteria in 1988. Many studies have shown that histologic grade, nuclear grade, lymph-vascular space invasion and cell type are also important predictors of survival. It has not been clarified, however, how to integrate these histopathologic variables into the process of estimating individual prognosis. We performed Cox multivariate regression analysis to create models that incorporate various histopathologic factors for estimating the prognoses of patients with endometrioid adenocarcinoma of the uterine corpus. Our study was based on data from 206 patients who underwent complete surgical staging, including systematic pelvic and para-aortic lymph node dissection. Two models resulted: one included depth of myometrial invasion, para-aortic node metastasis and the number of sites involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we designated as extracorporeal spread score, ECS) and the other incorporated nuclear grade and lymph-vascular space invasion as variables. These 2 models enabled the prognosis for patients with endometrioid adenocarcinoma to be stratified into several levels according to hazard ratio. Comprehensive integration of the histopathologic prognostic factors, categorized into those relating to tumor extent and those relating to tumor virulence, should facilitate the estimation of individual prognosis more accurately than FIGO staging alone.

Adenocarcinoma↗

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma.

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.

Adenocarcinoma, Clear Cell↗

Multiple genes for vacuolar-type ATPase proteolipids in Caenorhabditis elegans. A new gene, vha-3, has a distinct cell-specific distribution.

In the vacuolar-type H+-ATPase (V-ATPase), highly hydrophobic subunits known as the proteolipids are components of the integral membrane V0 sector. Previously, we described the identification of three different proteolipid genes in Caenorhabditis elegans (Oka, T., Yamamoto, R., and Futai, M. (1997) J. Biol. Chem. 272, 24387-24392): vha-1 and vha-2 encoded 16-kDa subunits, and vha-4, a 23-kDa isoform. We report here that a third 16-kDa gene, vha-3, has been identified on chromosome IV. This is the first example in which four proteolipid genes have been found in a single organism. vha-2 and vha-3 exhibited 85% nucleotide identity within the open reading frames which encoded the identical amino acid sequence. Northern blot analysis indicated that all four genes were expressed in a similar pattern during the worm life cycle; however, studies with transgenic worms indicated that the vha-3 gene was expressed differently from other proteolipid genes in a cell-specific manner. These results implied that the isoforms of the proteolipids may be related to functional differences of V-ATPases in various cell types. Another new gene, vha-11, contained seven exons and was found to be located immediately downstream of vha-3. The two genes constitute a single transcriptional unit. The VHA-11 protein had 384 amino acids and shared strong sequence similarities with the C subunit, a component of the peripheral V1 sector of the V-ATPase, from yeast, bovine, and human. Expression of the vha-11 cDNA complemented a null mutation of VMA5, the yeast C subunit gene, thus demonstrating that vha-11 was the functional C subunit of C. elegans.

Animals↗

A simple assay system for examination of the inhibitory potential in vivo of decoy RNAs, ribozymes and other drugs by measuring the Tat-mediated transcription of a fusion gene composed of the long terminal repeat of HIV-1 and a gene for luciferase.

Nucleic acid-based drugs, including antisense RNA and DNA, ribozymes and decoys appear to have potential for the suppression of the expression of specific genes. To allow the examination of the potential of such agents in vivo as anti-HIV drugs in standard laboratories, where facilities for handling live virions are not available, we constructed a simple assay system (HIV-1 model) that allows measurement of the extent of inhibition of Tat-mediated transcription of HIV-1 by nucleic acid-based drugs and other agents. In cells that harbor a stable chimeric long terminal repeat (LTR)-Luc construct (a fusion gene consisting of the LTR of HIV-1 and the gene for luciferase), total luciferase activity in an aliquot of cell lysate is dose- and promoter-dependent on transfection with a Tat expression plasmid, reflecting the character of the LTR promoter of HIV. When HeLa cells were co-transfected with the Tat expression plasmid and another plasmid that encoded the U6 promoter or the promoter of the gene for tRNA(Val) linked to the trans-activating response (TAR) sequence, total luciferase activity was inhibited by 60 or 40%, respectively. The inhibition was also dependent on the dose of the TAR expression plasmid. These results demonstrate the usefulness of this simple assay system for detection of the efficacy of a decoy RNA or a ribozyme in vivo, without a requirement for HIV-infected cells, by measurement of luciferase activity in vitro.

Artificial Gene Fusion↗

Bcl-2 expression and prognosis of patients with endometrial carcinoma.

Bcl-2 protein inhibits apoptosis, reduces the requirement for growth factors, and thereby extends the survival of cells. Recent findings of Bcl-2 in several solid tumors suggest that it might contribute to the genesis of some types of cancer. Over-expression of Bcl-2 might play a role in carcinogenesis and malignant progression of endometrial carcinoma. The aims of this study were to determine Bcl-2 expression in endometrial carcinoma in relation to other histopathologic prognostic factors, and to test its prognostic significance in patients with endometrial carcinoma. A total of 61 endometrioid-type endometrial carcinomas were immunohistochemically investigated for Bcl-2 expression on cryostat sections. Bcl-2 localization was observed in cytoplasm in 18 tumors, in nucleus in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl-2 was observed neither in cytoplasm nor in nucleus. There was not a statistically significant relationship between grade of tumor and Bcl-2 expression. Cytoplasmic Bcl-2 became less frequently expressed as the tumor invaded the myometrium deeper (p < 0.025). Retroperitoneal lymph-node dissection was performed in 57 patients. Multiple-regression analysis showed that lymph-vascular space invasion and nuclear expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001 and < 0.05 respectively). Univariate Cox regression analysis revealed that nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a significant prognostic factor for patients who underwent systematic retroperitoneal lymph-node dissection. Cox multivariate-regression analysis revealed that pelvic node metastasis and cervical invasion were the most important prognostic factors in this series of patients. When the analysis was made after exclusion of pelvic node metastasis, histologic grade (hazard ratio = 2.4), cervical invasion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard ratio = 11.5) were shown to be significant predictors of survival of the patients. These results indicate that aberrant Bcl-2 expression might be involved in malignant progression of endometrioid-type endometrial carcinoma. Site of Bcl-2 localization may be an important predictor of prognosis for patients with endometrioid-type endometrial carcinoma.

Adult↗

Structural basis for the electron transfer across the chromaffin vesicle membranes catalyzed by cytochrome b561: analyses of cDNA nucleotide sequences and visible absorption spectra.

We isolated cDNA clones for cytochromes b561 from sheep and porcine adrenal medullae using the RT-PCR technique. Comparison of the deduced amino acid sequences of various species showed that there are two fully-conserved regions in this cytochrome. In addition, one methionyl and six histidyl residues (potential heme ligands) are fully-conserved. Based on a plausible structural model in which a polypeptide spans the vesicle membranes six times and holds two heme B molecules, the first conserved sequence (69ALLVYRVFR77) is located on the extravesicular side of an alpha-helical segment and the second one (120SLHSW124) is located in an intravesicular loop connecting two alpha-helical segments, respectively. Consideration of the relative locations of the fully-conserved sequences, and the methionyl and histidyl residues in the model led to a proposal that the first and second conserved sequences are likely to form the binding sites for extravesicular ascorbic acid and intravesicular semidehydroascorbic acid, respectively. A mild alkaline-treatment of purified bovine cytochrome b561 in oxidized state led to a specific loss of an electron-accepting ability from ascorbic acid for a half of the heme center, suggesting a distinct role for each of the two hemes.

Adrenal Medulla↗

Receptors for natriuretic peptides in adrenal chromaffin cells.

Atrial, brain, and C-type natriuretic peptides of the atrial natriuretic peptide family are present in adrenal chromaffin cells, and are secreted with catecholamines by exocytosis. These peptides modulate the physiological functions of the cells such as synthesis and secretion of catecholamines in an autocrine manner interacting with natriuretic peptide receptors.

Animals↗

Attachment of gelatin films to tissue using argon beam coagulator.

Cross-linked gelatin films were bonded to heart muscle and to lung pleura and parenchyma using the electrical discharge of an argon beam radiofrequency coagulator. The bonds were stable in warm saline buffer for minutes to hours. Bonding was thought to partly occur through a mechanical interlock of film and tissue elements. The interdigitation of tissue and film arose during exposure to the argon beam, which denatured protein constituents of both, and created a fluidized state that rapidly coalesced.

Animals↗

Selective inhibition by riluzole of voltage-dependent sodium channels and catecholamine secretion in adrenal chromaffin cells.

We examined the effects of riluzole, a neuroprotective drug, on voltage-dependent Na channels, nicotinic receptors, and voltage-dependent Ca channels, as well as catecholamine secretion, in comparison with those of verapamil and nicardipine, in primary cultures of bovine adrenal chromaffin cells. Riluzole inhibited veratridine-induced 22Na influx via voltage-dependent Na channels even in the presence of ouabain, an inhibitor of Na,K-ATPase. Blockade of Na channels by riluzole was concentration-dependent with an IC50 of 5.3 microM. It was associated with a similar concentration-related reduction of veratridine-induced 45Ca influx via voltage-dependent Ca channels, and of catecholamine secretion. Riluzole had no effect on 45Ca influx caused by high K, which directly activates voltage-dependent Ca channels, and on nicotine-induced 22Na influx, which passes through the nicotinic receptors. Verapamil and nicardipine attenuated 22Na influx caused by veratridine or nicotine at the same concentrations as they suppressed high K-induced 45Ca influx. The inhibitory effect of riluzole on veratridine-induced 22Na influx disappeared at high concentrations of veratridine. A potentiation of veratridine (site 2 toxin)-induced 22Na influx caused by alpha-scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or brevetoxin PbTx-3 (site 5 toxin), occurred in the presence of riluzole in the same manner as in control cells. These results suggest that riluzole binds to the veratridine site in voltage-dependent Na channels. It does not impair the cooperative interaction between the functional peptide segments of Na channels, but selectively inhibits gating of Na channels, thereby reducing Ca influx via Ca channels and catecholamine secretion. In contrast, verapamil and nicardipine suppress Na influx both Na channels and nicotinic receptors.

Animals↗

Idiopathic mediastinal fibrosis: report of a case.

We report herein the case of a 28-year-old woman who presented with a mediastinal mass, subsequently confirmed to be idiopathic mediastinal fibrosis. Preoperative chest computed tomography (CT) showed a noncalcified mediastinal mass and surgery was performed to exclude malignancy. The mass was hard and dense, involved the left phrenic nerve, vagus nerve, and left upper lobe, and surrounded the subclavian artery, subclavian vein, superior vena cava, and left pulmonary artery. Pathologic examination showed the findings of mediastinal fibrosis and the mass was partially excised. Postoperative medical treatment was performed with prednisolone and tranilast, and a 3-year follow-up has not demonstrated any complications.

Adult↗

Inhibition of experimental gastric carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats, by sodium nitroprusside, a nitric oxide generator.

The effects of prolonged administration of sodium nitroprusside (SNP), a generator of nitric oxide (NO), on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the labelling index of the gastric mucosa were investigated in male Wistar rats. The rats received intra-peritoneal injections of 2 or 4 mg/kg body weight of SNP every other day after 25 weeks' oral treatment with the carcinogen. Prolonged administration of SNP at 4 mg/kg body weight, but not at 2 mg/kg body weight, significantly decreased the incidence of gastric cancers in experimental week 52. However, it did not affect the histological types or depths of involvement of gastric cancers. SNP at 4 mg/kg body weight, but not at 2 mg/kg body weight, also significantly decreased the bromodeoxyuridine labelling index of the antral epithelial cells. These findings indicate that SNP inhibits gastric carcinogenesis and suggest that this effect may be related to the suppression of proliferation of the antral epithelial cells.

Animals↗

Suppression by pravastatin, an inhibitor of p21ras isoprenylation, of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.

The effect of pravastatin, an inhibitor of p21ras isoprenylation, on hepatocarcinogenesis induced by N-nitrosomorpholine and on p21ras isoprenylation were investigated in male Sprague-Dawley rats. Rats received i.p. injections of pravastatin (10 and 20 mg kg(-1) body weight) every other day and, from the beginning of the experiment, were given drinking water containing N-nitrosomorpholine for 8 weeks. Visible white nodules and hepatic lesions staining positively for gamma-glutamyl transpeptidase or glutathione-S-transferase, placental type, were examined macroscopically or histochemically. In week 15, pravastatin at both dosages significantly reduced the incidence, number and volume of visible white nodules. Quantitative histological analysis also showed that prolonged administration of pravastatin at both dosages resulted in significant reductions in the number and percentage area of hepatic lesions positive for gamma-glutamyl transpeptidase and glutathione-S-transferase, placental type. Administration of pravastatin also significantly decreased the amount of membrane-associated p21ras in the tumour and the labelling index of neoplastic nodules and increased the apoptoic indices of neoplastic nodules. These findings indicate that pravastatin suppresses hepatocarcinogenesis and suggest that this effect might be related to pravastatin's inhibition of p21ras isoprenylation and its subsequent inhibition of cell proliferation and induction of apoptosis in neoplastic lesions.

Animals↗

Prolyl hydroxylase and tissue inhibitor of metalloproteinase in pure pancreatic juice in patients with chronic pancreatitis.

Prolyl hydroxylase is a key enzyme in collagen synthesis, and tissue inhibitor of metalloproteinase (TIMP) is known to suppress collagenolytic enzymes. To see whether the levels of these two enzymes in serum and human pure pancreatic juice (PPJ) are good indicators of pancreatic fibrosis in chronic pancreatitis (CP), we examined 15 controls, 14 alcoholics without evident pancreatic diseases (7 current drinkers and 7 former drinkers), and 19 patients with CP. Levels of the two enzymes were determined by a sandwich enzyme immunoassay method. TIMP-1 levels in PPJ were significantly higher in patients with CP than in controls and alcoholics, with overlap in only a few exceptional patients. A significant inverse correlation between TIMP-1 and bicarbonate output in PPJ was observed. Prolyl hydroxylase levels in PPJ, in contrast, were significantly higher in current drinkers than in patients with CP, controls, and former drinkers, with overlap in only a few exceptional patients with relapsing CP. Identical results were obtained even when the enzyme levels were expressed as nanograms per milligram of protein. Serum levels of prolyl hydroxylase and TIMP-1 showed no significant differences among controls, current alcoholics, former alcoholics, and patients with CP. These results indicate that the raised level of TIMP-1 in PPJ, unlike that of prolyl hydroxylase, is a good indicator of pancreatic fibrosis in CP.

Adult↗

Cerebral blood volume in the sleep measured by near-infrared spectroscopy.

We investigated the relationship between hemodynamic changes in the cortex measured by near-infrared spectroscopy (NIRS) and the polysomnographic changes during sleep. Four healthy male volunteers participated in the study. Near-infrared spectroscopy measuring and polysomnographic recordings were done simultaneously during sleep. In many case, oxy-hemoglobin (oxy-Hb) decreased and deoxy-hemoglobin (deoxy-Hb) increased during the transition from wakefulness to sleep, and oxy-Hb increased toward deep sleep. Oxy-Hb and deoxy-Hb had larger fluctuations during REM sleep than those during non-REM sleep. During REM sleep, oxy-Hb often showed a lower level and deoxy-Hb showed a higher level than those during the preceding and following non-REM sleep.

Adult↗

[A rapid determination of allantoin by high-performance liquid chromatography using tris(hydroxymethyl)aminomethane-HCl buffer as a mobile phase].

A rapid and simple method for the determination of allantoin in pharmaceuticals by reversed-phase ion-pair high-performance liquid chromatography using an ODS column was presented. In general, it is difficult to retain allantoin to the ODS column owing to its very low hydrophobicity. We solved these problems by the use of a Tris-HCl buffer (pH 7.5) containing tetra-n-hexyl-ammonium bromide (THAB) as an ion-pair reagent for the mobile phase. Comparatively low concentrations of Tris-HCl buffer (0.9 mM) and THAB (0.5 mM) gave a high capacity factor (k'). As a results of the examination of the chromatographic behavior, it is confirmed that the retention mechanism of allantoin to the ODS column on the present method was not the ion-pair mode, but the ion-exchange mode. Calibration curves for allantoin showed a good linearity in the range of 10 to 400 micrograms/ml (r = 0.9999). The reproducibility (R.S.D., n = 6) was invariably good (0.37%). The lowest concentration of allantoin for the determination was 200 ng per 20 microliters of injection. The present method was successfully applied to the determination of allantoin in commercial eyedrops with good recovery (99.4%). It was found that allantoin in pharmaceuticals could be determined by the present method in short time and without any complicated derivatization.

Allantoin↗

Contracture of the deltoid muscle. Results of distal release.

We prospectively studied the results of distal release, performed between February 1989 and December 1994 for the treatment of a contracture of the deltoid muscle, in forty patients (forty-nine shoulders). Forty-seven contractures (in thirty-eight patients) developed after multiple intramuscular injections of various medications. The two remaining contractures (in two patients) were congenital. The average age at the onset of the symptoms was thirty-two years (range, birth to fifty-eight years). The primary symptoms included pain around the neck and the shoulder girdle, dimpling of the skin, a palpable fibrous band, winging of the scapula, difficulty in combing the hair or reaching the contralateral side of the body for grooming, and inability to bring the arm adjacent to the body. The average age at the time of the operation was thirty-nine years (range, fifteen to sixty-three years). The average duration of follow-up was three years and eleven months (range, two years to six years and six months). After the distal release of the contracture, but on the same day, the patients started a physical-therapy program. Postoperatively, the pain, dimpling of the skin, palpable fibrous band, and winging of the scapula resolved in forty-eight shoulders (thirty-nine patients). Six patients (six shoulders) no longer had difficulty in combing the hair or adducting the shoulder. There were no infections or neuromuscular complications. Forty-seven (96 per cent) of the forty-nine shoulders (thirty-eight of the forty patients) had a good clinical result, and two shoulders (two patients) had a poor result. Anterosuperior subluxation of the humeral head, noted on preoperative radiographs of twenty-three shoulders (eighteen patients), was not present postoperatively. Drooping of the acromion, seen in six patients (six shoulders) in whom the contracture had developed before they were sixteen years old, improved postoperatively in five shoulders (five patients). Rotation of the scapula, seen in five shoulders (five patients), resolved after release of the contracture in all five. There were no clinical or radiographic signs of osteoarthrosis due to long-term anterior translation of the shoulder joint in the four patients (six shoulders) who had had the contracture for at least twenty years (average, twenty-three years; maximum, twenty-seven years).

Adolescent↗

Medical Internet exchange project in Japan.

The Internet has been widely used by medical institutes and hospitals around the world, however; its use for telemedicine is still low. The main reason for this is the availability of bandwidth and poor security through the net. Meanwhile, we have established and have been operating 'Cancer Information Network' among 11 Cancer Centers in Japan, mainly for Multipoint TV Conference using HDTV image. There are also similar projects among 9 cardiovascular centers in Japan. By March, all 240 national hospitals will have been connected by an IP network using an ATM backbone. The above network projects are operated independently, and have an 'Intranet' characteristics within them. There are also many hospitals and clinics connected to the Internet by commercial internet providers. To make a secure and efficient network between these medical networks and medical sites, we started the Medical Internet eXchange project (MDX project) constructing a Medical Network Operation Center to create a link between them. To provide the administrative policy of this project, we established the Medical Internet eXchange Association. We are planning to expand this project to Asian-Pacific countries using the Asian-Pacific Advanced Network (APAN), and also expand it to worldwide connections in the future. For this purpose, we are currently asking other countries to form a structure similar to MDX-Japan. The concept, hardware system, software system, firewall configuration, and routing policy will be also discussed.

Computer Systems↗

Factor G pathway reactive activity (GPRA) after surgery for abdominal aortic aneurysm.

BACKGROUND: Following major surgery, detection of endotoxaemia using the Toxicolor (Limulus) test has been reported. In addition to endotoxins, this test detects a reactant from human tissue, factor G pathway reactive activity (GPRA). We measured endotoxin and GPRA in 10 patients during and after elective surgery for abdominal aortic aneurysm. Additionally, we measured phosphokinase (CPK) and GPRA levels in the muscle of 10 patients during abdominal aortic aneurysm surgery and 6 during open laparotomy for other causes. METHODS: Samples were taken from the arterial lines prior to surgery, before cross-clamping of the aorta, immediately after and 1, 3, 6, and 18 hours after declamping. Muscle specimens were taken from the rectus abdominus and homogenized in many levels. Endotoxin concentrations were measured with the Endotoxin-Specific test. GPRA concentrations were determined by subtracting the values from the Endotoxin-Specific test from those given by the Toxicolor test (Limulus assay with achromogenic substrate). CPK was also measured. RESULTS: Endotoxin did not significantly increase during or after surgery, but GPRA was elevated. GPRA in muscle correlated significantly with CPK in muscle. CONCLUSIONS: We conclude that GPRA was elevated after surgery, while endotoxin did not increase significantly. The GPRA probably originated from human muscle tissue.

Aged↗