Biomedical subjects

G Watanabe

Publications and source records attributed to G Watanabe.

At least 127 records · Page 7Linked to original sources

PubMed2000

Effects of third ventricle injection of norepinephrine analogue on LH secretion of the non-laying SIJI goose.

The effect of norepinephrine analogue (NA) and norepinephrine antagonists on luteinizing hormone releasing hormone (LHRH) secretion in geese was investigated by monitoring serum levels of LH. Twenty non-laying geese were selected and randomly assigned to 4 groups of 5 each. The geese received a single intraventricular injection of saline (control), NA (12 microg/6 microl), phentolamine (1 microg/6l) plus NA or yohimbine (10 microg/6 microl). Phentolamine, a non-selective adrenoreceptor blocker was given 5 min before NA, but yohimbine, an alpha2-adrenoreceptor blocker, was delivered without NA injection. The results showed that serum levels of LH began to increase 20 min after injection of NA, and that high serum levels of LH were maintained until 105 min, followed by a decline to the basal level 125 min later. Significantly high levels of serum LH were observed at 50 and 105 min after the injection as compared with the respective control. Treatment with phentolamine completely blocked the stimulatory effect of NA on serum levels of LH in NA treated geese. Serum levels of LH increased by yohimbine treatment 5 min after the injection and the high levels of serum LH were maintained until 125 min later. Five out of 8 points were significantly high as compared with their respective control values. The present study also suggested that there is presynaptic modulation in the a-noradrenergic neural pathways which mediate the release of LHRH, and that this modulation may be carried out by alpha2-adrenoreceptor blocker.

Adrenergic alpha-Agonists↗

PubMed2000

Changes in plasma concentrations of inhibin A and inhibin B throughout sexual maturation in the male chimpanzee.

Profiles of circulating plasma inhibin A and inhibin B during sexual maturation in male chimpanzees were investigated by using two-site enzyme-linked immunoassay (ELISA). Plasma concentrations of testosterone and pituitary gonadotropins were also measured. Concentrations of inhibin B, testosterone, luteinizing hormone (LH) and prolactin increased with age throughout prepuberty to adulthood, whereas inhibin A level was low and there were no age-related changes in concentrations of either inhibin A and follicle-stimulating hormone (FSH). Inhibin B showed an inverse correlation with FSH in adult (7 years or order) but not in immature (6 years or younger) male chimpanzees. There was no correlation between plasma levels of FSH and testosterone throughout the period of sexual maturation. However, testosterone levels were positively correlated with inhibin B levels. These results suggest that circulating inhibin B is involved in the regulation of FSH secretion after puberty in adult male chimpanzees, and also that circulating inhibin B is an important form of inhibin as a marker of Sertoli cell function in adult male chimpanzees.

Aging↗

PubMed2000

Induction of superovulation by inhibin vaccine in cyclic guinea-pigs.

Experiments were conducted to determine whether neutralizing endogenous inhibin affects follicular development and ovulation rate in guinea-pigs. Eighteen female guinea-pigs bearing 4 week progesterone implants were divided into three groups. At 1 week after removal of the progesterone implants, the animals were given a s.c. injection of 1 ml placebo (saline in oil emulsion; control), or 25 or 50 micrograms inhibin vaccine three times at 4 week intervals. Blood samples were collected once a week throughout the experiment for measuring inhibin antibody titres. After the third injection of inhibin vaccine, blood samples and ovaries were collected on the morning of day 8 after the day of oestrus. Inhibin vaccine increased the ovulation rate in a dose-dependent manner (placebo: 4.2 +/- 0.4; 25 micrograms inhibin vaccine: 6.2 +/- 0.9; 50 micrograms inhibin vaccine: 9.8 +/- 0.9) without any effects on the duration of the oestrous cycle. The results also showed that active immunization against inhibin increased the number of atretic follicles of 300-399 microns in diameter on day 8 after ovulation. The present study is the first to show that the active immunization against inhibin may be a useful method for inducing multiple ovulation in guinea-pigs.

Analysis of Variance↗

PubMed2000

TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma.

It has been demonstrated that vascular endothelial growth factor (VEGF) is associated with tumor progression as an angiogenic factor in esophageal squamous cell carcinoma (SCC)s. However, the role of other angiogenic factors such as transforming growth factor-alpha (TGF-alpha), platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF) are still unknown in esophageal SCCs. In this study, we detected the expression of VEGF, TGF-alpha, PD-ECGF and bFGF in tissue specimens from 96 patients with SCC of the esophagus by immunohistochemical staining. To evaluate angiogenesis, endothelial cells were stained immunohistochemically and microvessel density (MVD) was counted in 24 cases. The positive rates for VEGF, TGF-alpha, PD-ECGF and bFGF were 65% (62/96), 67% (64/96), 66% (63/96), and 49% (47/96), respectively. Only TGF-alpha expression had a strong correlation with the average MVD (p=0.0059). However, the MVD increased as the number of positive factors for these 4 factors increased (p=0.0023). The expression of all of these factors significantly correlated to the depth of tumor invasion, and lymph node metastasis. Finally, survival analysis of the patients revealed that VEGF, TGF-alpha, and PD-ECGF were significant prognostic factors. However, multivariate analysis revealed that these factors were not prognostic. Thus, we suggest that TGF-alpha as well as VEGF, PD-ECGF and bFGF may be associated with angiogenesis, and the progression and metastasis of esophageal squamous cell carcinoma.

Adult↗

PubMed2000

Angiotensin converting enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasminogen activator inhibitor-1 in healthy Japanese population.

Plasminogen activator inhibitor-1 (PAI-1) has a central role in the regulation of the fibrinolytic enzyme system. An elevated plasma PAI-1 level is associated with thrombotic disorders. In vitro and in vivo studies indicate that the renin-angiotensin system is involved in the regulation of PAI-1. A 287-bp insertion/deletion (I/D) polymorphism in the gene-encoding angiotensin converting enzyme (ACE) is associated with cardiovascular disorders. We evaluated the association between the ACE I/D polymorphism and plasma PAI-1 antigen levels in 110 healthy Japanese male subjects. Subjects with the D-allele of the gene-encoding ACE had higher levels of PAI-1 (26.3 +/- 14.7 ng/ml, mean +/- standard deviation) compared with those without (21.0 +/- 12.0; P = 0.0491). A multiple linear regression model with independent variables (age, body-mass index, total cholesterol level, triglyceride level, ACE I/D genotype, and PAI-1 genotype due to a single guanine I/D polymorphism in the PAI-1 gene) demonstrated that the triglyceride level (P = 0.0059) and ACE I/D genotype (P = 0.0372) were independent predictors of plasma PAI-1 antigen levels in a subset of the subjects without diabetes mellitus that were not taking lipid-lowering drugs. These findings suggest that the ACE I/D polymorphism is a genetic factor for the regulation of plasma PAI-1 antigen levels in the healthy Japanese population.

Adult↗

PubMed2000

Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects.

Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 +/- 0.81, 1.65 +/- 0.63, and 0.93 +/- 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P < 0.0001). This association was evident for each group studied (P < 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels.

Aged↗

PubMed2000

Improved haplotype analysis of human myelin basic protein short tandem repeat loci.

We report an improved haplotype analysis of the human myelin basic protein gene (MBP) short tandem repeat (STR) polymorphism. The polymorphic G-->A transition and 2 conventional STR polymorphisms, MBPA and MBPB, were simultaneously determined by an amplified product length polymorphism technique. After the MBPC fragments containing MBPA and MBPB were amplified, the linkage of these 2 STR loci was determined by a second amplification, using polymerase chain reaction (PCR) technique, of the isolated MBPC fragments. The present haplotype analysis dispensed with family studies for the haplotyping of MBPA and MBPB. Polymorphisms of the MBP loci studied in German and Japanese populations showed a high genomic variation. Haplotype analysis of the MBP loci showed distinct differences between the German and the Japanese populations. Consequently, haplotype analysis of the MBP loci promises to be useful in forensic identification and paternity testing.

Alleles↗

PubMed2000

[Evaluation of new TNM classification for lung cancer, especially T3N0M0, stage IIIA, stage IIIB, and pm].

The purpose of this study was to evaluate the results of new TNM staging system for lung cancer in 1997, especially T3N0M0, stage IIIA, stage IIIB, and pm. Five-year survival rates of the patients with stage IIIA and stage IIIB were 16% and 18% respectively (NS). Five-year survival rates of patients with T3N1M0, T1N2M0, T2N2M0, and T3N2M0 were 40%, 28%, 15%, and 3%, respectively. The prognosis of T3N2M0 was significantly worse than that of T3N1M0, T1N2M0, and T2N2M0. Five-year survival rates of the patients excluding pm 1 with T4N0M0, T4N1M0, T4N2M0, and T4N3M0 were 21%, 10%, 10%, and 0%, respectively. The prognosis of the patients with T4N0 was significantly better than that of T4N2 and T4N3. In the patients with pm, 5-year survival rates of the patients with pm 1 and pm 2 were 26% and 7%, respectively (p < 0.01). In the patients with pm 1, 5-year survival rates of the patients with N0 + N1 and N1 + N2 were 53% and 16%, respectively (p < 0.01). From our these results, we supported the new TNM system as putting T3N0M0 to stage IIB, putting pm 2 into stage IV. We proposed; 1) chest wall invasion with bone destruction stay in stage IIIA or is T4, 2) T3N1M0 is classified with stage IIB, 3) main stem bronchus invasion is classified with T2, 4) pm 1 is subdivide by N status. Furthermore, stage III seemed to be reasonably subdivided into T1-2N3M0, T4N0-1M0 as stage IIIA and T3-4N2, T1-4N3 as stage IIIB.

Humans↗

PubMed2000

[Application of the PCR-APLP method to determine ABO genotypes in forensic samples].

We carried out ABO genotyping of forensic samples by the amplified product length polymorphism (APLP) technique. We present two novel systems. One is termed as eight primers system, in which eight allele-specific primers are added into a single PCR reaction. Another is termed as six primers system. In both APLP systems, all alleles were clearly detected using DNA purified from forensic samples. In PCR amplification with direct addition of specimen, ABO genotyping was also possible to blood stain, seminal stain, blood, saliva and urine. Furthermore, ABO genotyping worked only to chimpanzee. This PCR-APLP method should be convepffnt and valuable for forensic practice.

ABO Blood-Group System↗

PubMed2000

Intrapulmonary lymph nodes detected by exploratory video-assisted thoracoscopic surgery: appearance of helical computed tomography.

The objective of this study was to analyze helical computed tomography (CT) findings of intrapulmonary lymph nodes (IPLNs), and to evaluate the diagnostic procedures to prevent unnecessary exploratory surgery. Between April 1997 and March 2000, we performed exploratory video-assisted thoracoscopic surgery (E-VATS) in 42 patients and in 8 patients (4 men, 4 women; 48 to 75 years of age, mean 57 years) IPLN was pathologically proven. Retrospectively, the appearances of IPLN in helical CT images were studied in detail. The diameter of the IPLNs varied from 4 to 10mm. Six nodules were located in the lower lobes and 2 nodule was in the lingula. Chest CT showed several malignancy-suggesting associated findings with pleural indentation (2/8), spicular radiation (2/8), fuzzy margins (4/8), and vascular involvement (2/8). Black colored anthracoses in 5 subpleural IPLNs were confirmed by thoracoscopy. One patient with two coin lesions was suggestive of lung metastasis of adenoidcystic carcinoma of the tongue, but one lesion was proven as IPLN, and the other as metastatic carcinoma. In conclusion, it is not possible to distinguish an intrapulmonary lymph node from a malignant lesion using the CT findings preoperatively. Therefore, a pathological study with E-VATS is necessary and sure procedure to exclude malignant disease under the present conditions.

Aged↗

PubMed1999

Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis.

The adenovirus E1A protein interferes with regulators of apoptosis and growth by physically interacting with cell cycle regulatory proteins including the retinoblastoma tumor suppressor protein and the coactivator proteins p300/CBP (where CBP is the CREB-binding protein). The p300/CBP proteins occupy a pivotal role in regulating mitogenic signaling and apoptosis. The mechanisms by which cell cycle control genes are directly regulated by p300 remain to be determined. The cyclin D1 gene, which is overexpressed in many different tumor types, encodes a regulatory subunit of a holoenzyme that phosphorylates and inactivates PRB. In the present study E1A12S inhibited the cyclin D1 promoter via the amino-terminal p300/CBP binding domain in human choriocarcinoma JEG-3 cells. p300 induced cyclin D1 protein abundance, and p300, but not CBP, induced the cyclin D1 promoter. cyclin D1 or p300 overexpression inhibited apoptosis in JEG-3 cells. The CH3 region of p300, which was required for induction of cyclin D1, was also required for the inhibition of apoptosis. p300 activated the cyclin D1 promoter through an activator protein-1 (AP-1) site at -954 and was identified within a DNA-bound complex with c-Jun at the AP-1 site. Apoptosis rates of embryonic fibroblasts derived from mice homozygously deleted of the cyclin D1 gene (cyclin D1(-/-)) were increased compared with wild type control on several distinct matrices. p300 inhibited apoptosis in cyclin D1(+/+) fibroblasts but increased apoptosis in cyclin D1(-/-) cells. The anti-apoptotic function of cyclin D1, demonstrated by sub-G(1) analysis and annexin V staining, may contribute to its cellular transforming and cooperative oncogenic properties.

Adenovirus E1A Proteins↗

PubMed1999

An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells.

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [(3)H]-thymidine incorporation, [(125)I]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein.

Aldehyde Reductase↗

PubMed1999

Protein kinase Cdelta inhibition of S-phase transition in capillary endothelial cells involves the cyclin-dependent kinase inhibitor p27(Kip1).

Distinct protein kinase C (PKC) isoforms differentially regulate cellular proliferation in rat microvascular endothelial cells (EC). Overexpression of PKCalpha has little effect on proliferation, whereas PKCdelta slows endothelial cell proliferation and induces S-phase arrest. Analyses were performed on EC overexpressing PKCalpha (PKCalphaEC) or PKCdelta (PKCdeltaEC) to determine the role of specific cell cycle regulatory proteins in the PKCdelta-induced cell cycle arrest. Serum-induced stimulation of cyclins D1, E, and A-associated kinase activity was delayed by 12 h in the PKCdeltaEC line in association with S-phase arrest. However, the protein levels for cyclins D1, E, and A were similar. Nuclear accumulation of cyclin D1 protein in response to serum was also delayed in PKCdeltaEC. In the PKCdeltaEC line, serum induced p27(Kip1) but not p16(Ink4a) or p21(Cip1). Serum did not affect p27(Kip1) levels in the control vascular endothelial cell line. Immunoprecipitation-Western blotting analysis of p27(Kip1) showed serum stimulation of the vascular endothelial cell line resulted in increased amounts of cyclin D1 bound to p27(Kip1). In the PKCdeltaEC line, serum did not increase the amount of cyclin D1 bound to p27(Kip1). Transfection of full-length p27(Kip1) antisense into the PCKdeltaEC line reversed the S-phase arrest and resulted in normal cell cycle progression, suggesting a critical role for p27(Kip1) in the PKCdelta-mediated S-phase arrest.

Animals↗

PubMed1999

pp60(v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60(v-src) signaling in breast cancer cells.

The cyclin D1 gene is overexpressed in breast tumors and encodes a regulatory subunit of cyclin-dependent kinases that phosphorylate the retinoblastoma protein. pp60(c-src) activity is frequently increased in breast tumors; however, the mechanisms governing pp60(c-src) regulation of the cell cycle in breast epithelium are poorly understood. In these studies, pp60(v-src) induced cyclin D1 protein levels and promoter activity (48-fold) in MCF7 cells. Cyclin D1-associated kinase activity and protein levels were increased in mammary tumors from murine mammary tumor virus-pp60(c-src527F) transgenic mice. Optimal induction of cyclin D1 by pp60(v-src) involved the extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase members of the mitogen-activated protein kinase family. Cyclin D1 promoter activation by pp60(v-src) involved a cAMP response element-binding protein (CREB)/activating transcription factor 2 (ATF-2) binding site. Dominant negative mutants of CREB and ATF-2 but not c-Jun inhibited pp60(v-src) induction of cyclin D1. pp60(v-src) induction of CREB was blocked by the p38 inhibitor SB203580 or by mutation of CREB at Ser133. pp60(v-src) induction of ATF-2 was abolished by the c-Jun N-terminal kinase inhibitor JNK-interacting protein-1 or by mutation of ATF-2 at Thr69 and Thr71. CREB and ATF-2, which bind to a common pp60(v-src) response element, are transcriptionally activated by distinct mitogen-activated protein kinases. Induction of cyclin D1 activity by pp60(v-src) may contribute to breast tumorigenesis through phosphorylation and inactivation of the retinoblastoma protein.

Activating Transcription Factor 2↗

PubMed1999

Rhophilin, a small GTPase Rho-binding protein, is abundantly expressed in the mouse testis and localized in the principal piece of the sperm tail.

Tissue distribution and cellular localization of rhophilin, a 71 kDa Rho-binding protein, were examined in mice. Rhophilin mRNA was highly expressed in adult testis, but was absent in the testis of W/WV mice deficient in germ cells. An anti-rhophilin antibody detected a band of an expected size in sperm extracts, which was enriched in the tail fraction. Immunofluorescence analysis revealed two lines of striated staining running in parallel in the principal piece of the sperm tail. These results suggest that rhophilin is expressed in germ cells and localized in the fibrous sheath of the sperm tail.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Determination of the HUMTH01 alleles by the APLP method.

We present a simple and rapid technique for determination of alleles at the HUMTH01 locus. The amplified product length polymorphism (APLP) method using two primers different in length, permits the differentiation between allele 9.3 and other alleles. The primers were designed to have an allele-specific nucleotide at the 3' terminal and 11 non-complementary nucleotides were added to the 5' terminal of one of the primers for the allele 9.3. The amplified fragment sizes for the alleles 9.3 and 10 were 80 bp and 70 bp, respectively. This method has proved to be very useful for forensic applications.

Base Sequence↗

PubMed1999

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.

BACKGROUND: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. RESULTS: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

Blood Pressure↗

PubMed1999

A new method of double cardiomyoplasty: "contractile muscular sling".

BACKGROUND: In several experimental studies, double cardiomyoplasty using both latissimus dorsi muscles did not provide sufficient assist to the failing heart and did not clearly show improvement compared with single cardiomyoplasty. This study demonstrated the superior efficacy of our method of double cardiomyoplasty compared with single cardiomyoplasty. METHODS: In 16 dogs, the two latissimus dorsi muscles were crossed in front of the heart and directly sutured to each other behind the heart. Control hemodynamic measurements were obtained, and acute heart failure was induced by intravenous administration of propranolol. After the hemodynamic changes with bilateral latissimus dorsi muscle assistance were measured, single cardiomyoplasty was done in the same dog, and the hemodynamic variables were measured. RESULTS: With our double cardiomyoplasty, aortic systolic pressure increased by 25% (p < 0.001); pulmonary artery systolic pressure, by 40% (p < 0.001); end-systolic elastance, by 155% (p < 0.001); and cardiac output, by 55% (p < 0.001). There were significant increases in aortic pressure, pulmonary artery pressure, end-systolic elastance, stroke volume, and cardiac output with our double cardiomyoplasty compared with single cardiomyoplasty. CONCLUSIONS: In this study, our double cardiomyoplasty provided significant hemodynamic improvement compared with single cardiomyoplasty.

Animals↗