Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 289 records · Page 16Linked to original sources

PubMed1998

Prenatal diagnosis of ornithine transcarbamylase deficiency by using a single nucleated erythrocyte from maternal blood.

We have developed a method that allows the prenatal DNA diagnosis of ornithine transcarbamylase (OTC) deficiency by using a single fetal nucleated erythrocyte (NRBC) isolated from maternal blood. OTC gene analysis of a male patient (TF) with early onset OTC deficiency was performed by single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing. To investigate the possible prenatal diagnosis of OTC deficiency, maternal blood was obtained at 13 weeks of gestation of a subsequent pregnancy, from the mother of patient TF. NRBCs in the maternal blood were separated by using the density gradient method and then collected with a micromanipulator. The entire genome of a single NRBC was amplified by primer extension preamplification (PEP). The human leukocyte antigen (HLA)-DQ alpha genotype and sex were determined from small aliquots of the PEP product. The HLA-DQ alpha genotype of each of the parents of the male patient was also determined. Once a single NRBC had been identified as being of fetal origin, the OTC gene was analyzed by using the restriction fragment length polymorphism (RFLP) method. DNA analysis revealed a point mutation in exon 9 of the OTC gene in the OTC-deficient patient (TF). All NRBCs retrieved from maternal blood were successfully identified as being of fetal origin by HLA-DQ alpha genotyping and sex determination. RFLP analysis demonstrated that the fetal OTC gene was normal. This is the first study to successfully diagnose OTC deficiency prenatally, by using a single fetal NRBC from the maternal circulation. Such prenatal DNA diagnosis is non-invasive and can be applied to other genetic diseases, including autosomal and X-linked diseases.

Erythrocytes↗

PubMed1998

Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family.

Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.

Adolescent↗

PubMed1998

Urgent total arch graft replacement in an elderly patient with acute type A dissection: report of a case.

There are many controversies regarding the treatment of acute aortic dissections. We herein present the case of an elderly patient over 80 years of age who underwent an urgent total arch graft replacement for a Stanford type A acute thrombosed aortic dissection complicating cardiac tamponade. An 81-year-old woman with chest discomfort and shock that developed 1 day earlier was transferred to our hospital by ambulance. A plain chest computed tomogram, aortogram, and an echocardiography revealed mild pericardial effusion and an ascending aortic aneurysm measuring 5 cm in diameter, but no evidence of an intimal tear in the ascending aorta and aortic arch. At operation, after the bloody pericardial effusion had been decompressed, her blood pressure was elevated and a type A acute thrombosed aortic dissection with the intimal tear in the aortic arch was confirmed, with a false channel filled with clotted blood. She underwent a successful emergency total arch graft replacement using selective cerebral perfusion and open distal anastomosis. The postoperative course was uneventful and the false lumen was closed. We thus conclude that early graft replacement should be performed on patients with Stanford type A acute thrombosed aortic dissection complicating cardiac tamponade, even in elderly patients over 80 years old.

Acute Disease↗

PubMed1998

Changes in high K+-evoked serotonin release and serotonin 2A/2C receptor binding in the frontal cortex of rats with thioacetamide-induced hepatic encephalopathy.

Serotonergic systems were investigated in the frontal cortex of rats with thioacetamide (TAA)-induced acute hepatic encephalopathy (HE). Extracellular basal levels of 5-HT showed no difference between control and HE animals, whereas the levels of 5-HIAA were significantly increased in HE rats. Unlike basal levels, high K+-evoked 5-HT release was significantly higher in HE rats than controls. Bmax of (+/-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I] DOI) binding, mainly labeling postsynaptic 5-HT2A receptors, was significantly decreased without any change in Kd in HE rats. These results suggest that there is no change in basal 5-HT release in the cortex of rats with TAA-induced HE despite the increase in intraneuronal 5-HT metabolism and in the size of releasable 5-HT pool, and that serotonergic neurotransmission via 5-HT2A receptor is altered in the brain area of rats with HE.

Acute Disease↗

PubMed1998

Idiopathic saccular azygos vein aneurysm.

We present a case of asymptomatic saccular aneurysm of the azygos vein. This abnormality is exceedingly rare. Dynamic computed tomography revealed strong enhancement of the mass, suggesting a vascular structure, which was very important for preoperative diagnosis. It is unclear whether the mass should be resected if the preoperative diagnosis has been made and the mass is not so large.

Aneurysm↗

PubMed1998

Relationship between the increase in Ca2+ transient and contractile force induced by angiotensin II in aequorin-loaded rabbit ventricular myocardium.

OBJECTIVES: Pieces of evidence have been accumulating that imply a crucial role of angiotensin II (Ang II) in initiation and progress of heart failure, but the signalling processes subsequent to Ang II receptor activation in cardiac myocytes are complex and still controversial. We examined the effects of Ang II on the relationship between the intracellular Ca2+ transient and isometric contraction in mammalian ventricular myocardium. METHODS: Isolated rabbit ventricular papillary muscle was loaded with the Ca2+ sensitive bioluminescent protein aequorin and electrically stimulated at a rate of 0.5 Hz at 37 degrees C. RESULTS: Ang II (10(-8)-10(-6) M), in the presence of bupranolol (3 x 10(-7) M) and prazosin (10(-7) M), elicited a positive inotropic effect (PIE) in association with an increase in the peak Ca2+ transient. The maximal PIE of Ang II was about 30% of the isoproterenol-induced maximum (ISOmax), while the maximal increase in the peak Ca2+ transient induced by Ang II was only 7% of ISOmax. Ang II tended to prolong the duration of contraction (both time to peak force and relaxation time) but did not produce a discernible change in the duration of Ca2+ transient. The relationship between the amplitude of Ca2+ transient and peak force was shifted to the left by Ang II, as compared with the relationship for elevation of [Ca2+]o (2.5-15.0 mM). The PIE and the increase in the amplitude of Ca2+ transient induced by Ang II were abolished by a selective angiotensin type 1 (AT1) receptor antagonist losartan (10(-5) M) but were not affected by a selective AT2 receptor antagonist PD123319 (10(-6) M). CONCLUSIONS: These results indicate that Ang II elicits a PIE through a dual mechanism via activation of AT1 receptors in rabbit ventricular myocardium: by an increase in the amplitude of Ca2+ transient; and in addition by an increase in the myofilament Ca2+ sensitivity.

Adrenergic alpha-Antagonists↗

PubMed1998

Red-green chromatic discrimination with variegated and homogeneous stimuli.

Chromatic discrimination thresholds were measured under conditions which yielded fine and degraded discrimination steps. Discrimination was assessed by identification of the location of one of four homogeneous equiluminant stimuli arranged in a square or with pseudoisochromatic (PIC) figures using the stimulus design of Regan, Reffin and Mollon (Vis Res 1994; 34: 1279-1299). Stimuli were presented on CRT monitors and specified in units of cone trolands. They were viewed within a surround metameric to the equal energy spectrum. L troland threshold versus retinal illuminance (TVR) functions were measured by four-alternative spatial forced-choice staircase procedures for (1) a four 1 x 1 degree equiluminant stimuli arranged in a square and (2) 'C' shaped pseudoisochromatic figures in which the observer had to identify the gap location. The 'C' was constructed of spatially discrete patches of varying size and luminance to ensure that the observer's responses depended on chromatic signals. The TVR functions appeared V-shaped and were similar for the two paradigms. The minimum occurred near the L excitation of equal-energy white. The PIC stimuli yielded poorer discrimination with the TVR function being displaced by approximately 0.5 log unit. Discrimination for stimuli degraded by luminance and spatial noise presented within an achromatic appearing surround is sharpest near the chromaticity metameric to the equal energy spectrum.

Adult↗

PubMed1998

A tensile test to facilitate identification of defects in dentine bonded specimens.

OBJECTIVES: To determine the efficacy of a miniaturized dumbbell test procedure designed to more easily identify defect(s) in bonded dentine test specimens. METHODS: Extracted human dentine substrates were pre-conditioned with 10-3 solution for 10, 30 or 60 s prior to dentine bonding with 4-META/MMA-TBB resin. Miniaturized dumbbell-shaped test specimens were prepared from the resin bonded samples. After 24 h storage in 37 degrees C water, the specimens were tensile-loaded to failure. Fractured surfaces and cross-sections were examined and compared under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Cohesive failure within the bonding resin was observed in specimens pre-conditioned for 10 s. The tensile bond strength of these was excellent. Bond strengths of specimens that were pre-conditioned for 30 and 60 s were significantly lower, and defects in these specimens, formerly difficult or impossible to identify, were readily identified under SEM and TEM microscopy. CONCLUSION: The proposed method of tensile stressing to failure and microscopically examining fractured miniaturized dumbbell-shaped test specimens is a simple and reproducible test procedure. The protocol is capable of clearly elucidating defective resin infiltration of demineralized dentine in bonded interfaces. These defects are difficult to visualize by conventional and/or ISO recommended methods.

Adult↗

PubMed1998

Effect of TYB-2285 on early and late bronchial responses and airway hyperreactivity in actively sensitized guinea pigs.

1. The effect of a new antiasthmatic drug, TYB-2285 [3,5-bis (acetoxyacetylamino)-4-chlorobenzonitrile], on dual bronchoconstriction and airway hyperreactivity in actively sensitized guinea pigs was investigated. 2. Immediate and late bronchial responses were induced at 1-10 min and 4-7 hr after antigen inhalation, respectively. Guinea pigs were pretreated with TYB-2285 (300 mg kg(-1) PO, as a single dose or consecutively for 7 days). 3. The immediate bronchial response was inhibited only by a multiple administration of TYB-2285. Late bronchial response was inhibited by both administration methods. 4. The numbers of eosinophils, neutrophils and macrophages, but not lymphocytes, in the bronchoalveolar lavage fluid were increased at 4 hr after antigen inhalation. TYB-2285, given singly and consecutively, decreased the numbers of total cells, eosinophils, neutrophils and macrophages. 5. Sensitized guinea pigs showed significant airway hyperreactivity to inhaled histamine. This airway hyperresponsiveness was reversed by a single administration of TYB-2285. 6. Luminol-dependent chemiluminescence of airway-infiltrated cells was slightly inhibited by TYB-2285 (20 microg ml(-1)). 7. The present study shows that TYB-2285 inhibits late asthmatic response and airway hyperresponsiveness, presumably by inhibiting the accumulation and activation of eosinophils and other inflammatory cells.

Animals↗

PubMed1998

Effect of TYB-2285 on peritoneal anaphylaxis in passively sensitized rats.

1. The effect of TYB-2285, a novel anti-inflammatory drug, was investigated on passive peritoneal anaphylaxis in rats, and compared with disodium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast. 2. As parameters of passive peritoneal anaphylaxis, histamine release into the peritoneal cavity and capillary permeability elicited by ascitis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitoneally at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylactic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 57.6% and 49.0%, respectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 79.6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 85.6% and 74.8%, respectively. 6. A time-course study showed that TYB-2285 (30 mg/kg) was effective for 30 min after oral administration. A dose-response study suggested that the inhibitory effect of TYB-22585 (postoperatively) on histamine release during PPA reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited antigen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependent manner, whereas TYB-2285 itself and other major metabolites of TYB-2285, TC-286 and TC-326, did not inhibit histamine release, even at 10(-4) M.

Anaphylaxis↗

PubMed1998

A case of effusive-constructive pericarditis: an efficacy of GD-DTPA enhanced magnetic resonance imaging to detect a pericardial thickening.

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.

Adult↗

PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗

PubMed1998

Novel antiallergic agents. Part I: Synthesis and pharmacology of pyrimidine amide derivatives.

We have synthesized many pyrimidine amide derivatives. Novel pyrimidine bis-glycolic amide derivatives showed moderate inhibition in the rat passive cutaneous anaphylaxis (PCA) assay by oral administration. Among these compounds, 2,4-bis(methoxyacetylamino)-6-piperidinopyrimidine (2i) exhibited significant inhibition. However the compound (2i) did not inhibit antigen-induced histamine or SRS-A release from lung fragments of the guinea-pig at less than 10(-4) M. Derivatives of 2i have also notable or moderate activity in the rat PCA assay. Compound 2h which has no oxygen atom at the alpha-position of the amide carbonyl group and, compound 17 which has no amide carbonyl group, showed no inhibition in the rat PCA assay. We supposed that both the amide carbonyl group and the oxygen atom at alpha-position of the amide carbonyl group play an important role in inhibiting the rat PCA reaction. These pyrimidine bis-glycolic amide derivatives have a novel structure and unique activity which suggests they may be potentially useful in the treatment of allergic diseases.

Administration, Oral↗

PubMed1998

Novel antiallergic and antiinflammatory agents. Part I: Synthesis and pharmacology of glycolic amide derivatives.

A series of mono-glycoloylamino derivatives was synthesized by treatment of the corresponding aromatic monoamine derivatives with glycoloyl chloride derivatives in pyridine or dichloromethane, in the presence of a base such as triethylamine or pyridine. Hydrolysis of acetoxy compounds in aqueous ammonia and methanol solution produced hydroxy derivatives with ease. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Thiazole and thiadiazole derivatives showed moderate inhibition in this assay. In contrast, benzothiazole and benzonitrile derivatives exhibited marked inhibition. In particular, compound 5t also showed marked inhibition of eosinophil adhesion to TNF (tumor necrosis factor) -alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M.

Administration, Oral↗

PubMed1998

Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds.

A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable inhibition of eosinophil adhesion to TNF- (tumor necrosis factor) alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.

Administration, Oral↗

PubMed1998

Characteristics and clinical outcome of proximal-third gastric cancer.

BACKGROUND: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.

Adult↗

PubMed1998

Optical rotation signals recorded from a single skeletal muscle fibre of a frog.

The optical rotation signal of a single frog skeletal muscle fibre was recorded and its properties were examined. To reduce movement of the fibre associated with its excitation, fibre was immersed in Ringer solution made of 90-95% D2O, stretched, and lightly pressed from above with a cylindrical lens. After these procedures no mechanical movements were recognizable under the dissection microscope, and the optical rotation signal appeared consistently as a brief transient increase in dextrorotation with a duration of about 23 ms. The shape and polarity of the signal did not change among preparations and remained unchanged when the direction of impulse conduction along the fibre was reversed. The influence of the birefringence change associated with excitation was found to be small in most preparations. Ryanodine (10 micron) reduced the amplitude of the signal to about half that of the control, and increased the duration slightly. Nitrendipine (10 micron) reduced the duration of the signal to about half that of the control, and reduced the amplitude to about two-thirds of the control. The effects of the chemicals took place within 10 minutes and remained constant for the periods examined. The intracellular action potentials were not appreciably altered by these chemicals. It is concluded that the optical rotation signal of the single muscle fibre reports the molecular conformational change of proteins during the early stage of the contraction process.

Animals↗

PubMed1998

Expression of extensin genes is dependent on the stage of the cell cycle and cell proliferation in suspension-cultured Catharanthus roseus cells.

To isolate cDNAs expressed at a specific phase of the cell cycle in a higher plant, we performed differential screening of a cDNA library prepared from the S-phase cells of synchronized cultures of Catharanthus roseus. Sequence analysis shows that two of the identified cDNAs, cyc15 and cyc17, encode extensins that represent a family of cell wall hydroxyproline-rich glycoproteins. Protein sequences deduced from the two cDNAs contain the characteristic pentapeptide repeat sequence, Ser-Pro-Pro-Pro-Pro, which is commonly observed in extensins. The protein sequences also share several other extensin characteristics such as the presence of a N-terminal signal peptide and a high content of Tyr and Lys residues. When C. roseus cell suspension cultures were synchronized by phosphate starvation, the mRNAs of both cyc15 and cyc17 were transiently expressed during the S and G2 phases of the cell cycle. However, significant amounts of the mRNAs also accumulated in phosphate-starved cells arrested in the G1 phase. In asynchronous cultures, both genes were expressed during the stationary phase, when cell proliferation ceased. The observed patterns of expression suggest that the extensin genes, cyc15 and cyc17, are under two types of regulation: one that depends on the stage of the cell cycle and another that is induced during the growth arrest. Thus, the products of these genes may function both during the progression through the cell cycle and in the strengthening of the cell wall after cell division.

Amino Acid Sequence↗