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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 199 records · Page 11Linked to original sources
PubMed2001

Decline of hepatitis C virus load in serum during the first 24 h after administration of interferon-beta as a predictor of the efficacy of therapy.

BACKGROUND/AIMS: Hepatitis C virus (HCV) kinetics during interferon (IFN)-alpha treatment have been evaluated recently, however, little is known about the resultant viral kinetics in IFN-beta treatment. In this study, we evaluated HCV kinetics during the first 24 h of IFN-beta treatment, and also assessed their relationship to therapeutic outcomes. METHODS: We measured HCV RNA levels at 0 and 24 h after the initiation of IFN-beta treatment, and we calculated the decay slope, viral half-life, and viral production and clearance. Then we analyzed these factors as they related to therapeutic responses with IFN-beta as well as to clinical variables, i.e. genotype, diversity of hyper variable region, and histological findings. RESULTS: Patients with sustained responses (SR) displayed steeper decay slopes of the viral load than those without SR (2.87 +/- 1.41 vs. 1.82 +/- 1.66, P = 0.031). On the other hand, the decay slope was not affected by the clinical variables. The values of viral half-life and viral production and clearance showed no significant correlation to the response and the clinical variables. CONCLUSION: This study demonstrated that the decay slope of the viral load during the first 24 h is related to the virological response to IFN-beta treatment.

Adolescent↗
PubMed2001

History of ultrasound in nephrourology.

Abdominal ultrasound (US) started from nephrourology with the representation of sections of the kidney or urinary bladder in the 1950s. Doppler signals from renal vessels were first recorded in 1976. Prostatic US was only achieved after the practical use of transrectal sonography in 1967. At present, US is an indispensable tool for diagnosis in any organ in the field of nephrourology.

History, 20th Century↗
PubMed2001

Physiologic assessment of coronary artery stenosis by coronary flow reserve measurements with transthoracic Doppler echocardiography: comparison with exercise thallium-201 single piston emission computed tomography.

OBJECTIVES: We evaluated the value of coronary flow reserve (CFR), as determined by transthoracic Doppler echocardiography (TTDE), for physiologic assessment of coronary artery stenosis severity, and we compared TTDE measurements with those obtained by exercise thallium-201 (Tl-201) single-photon emission computed tomography (SPECT). BACKGROUND: Coronary flow reserve measurements by TTDE have been reported to be useful for assessing angiographic left anterior descending coronary artery (LAD) stenosis. However, discrepancies exist between angiographic and physiologic estimates of coronary lesion severity. METHODS: We studied 36 patients suspected of having coronary artery disease. The flow velocity in the distal LAD was measured by TTDE both at rest and during intravenous infusion of adenosine. Coronary flow reserve was calculated as the ratio of hyperemic to basal peak (peak CFR) and mean (mean CFR) diastolic flow velocities. The CFR measurements by TTDE were compared with the results of Tl-201-SPECT. RESULTS: Complete TTDE data were acquired for 33 of 36 study patients. Of these 33 patients, Tl-201-SPECT confirmed reversible perfusion defects in the LAD territories in 12 patients (group A). Twenty-one patients had normal perfusion in the LAD territories (group B). Peak CFR and mean CFR (mean value +/- SD) were 1.5 +/- 0.6 and 1.5 +/- 0.7 in group A and 2.8 +/- 0.8 and 2.7 +/- 0.7 in group B, respectively. Both peak and mean CFR < or = 2.0 predicted reversible perfusion defects, with a sensitivity and specificity of 92% and 90%, respectively. CONCLUSIONS: Noninvasive measurement of CFR by TTDE provides data equivalent to those obtained by Tl-201-SPECT for physiologic estimation of the severity of LAD stenosis.

Aged↗
PubMed2001

Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy.

OBJECTIVES: The purpose of this study was twofold: 1) to examine the relationship between menstrual cycle and coronary flow velocity reserve (CFVR) in young healthy women, and 2) to evaluate the effect of hormone replacement therapy by estrogen on CFVR in postmenopausal women, using transthoracic color Doppler echocardiography (TTCDE). BACKGROUND: Although the incidence of cardiovascular disease is lower in women before menopause compared with men, postmenopausal women have an incidence of coronary artery disease similar to that of men of the same age. This is mainly dependent upon estrogen deficiency. However, no clinical report has yet examined the effect of estrogen on CFVR, which is one index of coronary microcirculation. METHODS: We examined 15 male and both 15 premenopausal and 10 postmenopausal female healthy volunteers. We measured coronary flow velocity of the left anterior descending coronary artery at baseline and hyperemic conditions during adenosine triphosphate infusion by TTCDE and determined CFVR. Each premenopausal woman was studied two times (menstrual [M] and follicular [F] phases) in one menstrual cycle. Fifteen men were also studied at a time corresponding to women's menstrual cycle. The postmenopausal women were studied before and two hours after oral administration of conjugated estrogen (CE). RESULTS: Serum 17beta-estradiol level in premenopausal women increased in the F phase and decreased to the same levels as in men, as in the M phase and as in postmenopausal women (123 +/- 9 pg/ml vs. 28 +/- 6 pg/ml, 25 +/- 9 pg/ml and 19 +/- 11 pg/ml; p < 0.0001, respectively). The CFVR increased in the F phase compared with that in the M phase (4.8 +/- 0.4 vs. 3.7 +/- 0.8, p < 0.0001). We found that CFVR in men remained unchanged (3.7 +/- 0.6 vs. 3.8 +/- 0.5). After CE administration, CFVR increased compared with baseline in postmenopausal women (4.1 +/- 0.8 vs. 3.4 +/- 0.8, p < 0.005). CONCLUSIONS: In premenopausal women, CFVR determined by TTCDE varied during the menstrual cycle, and in postmenopausal women, CFVR increased after acute estrogen replacement.

Adult↗
PubMed2001

ROC analysis of detection of metastatic pulmonary nodules on digital chest radiographs with temporal subtraction.

RATIONALE AND OBJECTIVES: The authors' purpose was to evaluate the effect of temporal subtraction on digital chest radiographs in the detection of metastatic pulmonary nodules. MATERIALS AND METHODS: The study included 21 cases with metastatic pulmonary nodule and 21 cases without metastatic nodule. Eleven radiologists, including eight residents and three certified radiologists, provided their confidence levels for the presence or absence of pulmonary nodules without and with temporal subtraction. Their performances without and with temporal subtraction were evaluated by means of receiver operating characteristic analysis with both independent and sequential tests. RESULTS: For the independent test, the radiologists' Az (area under the receiver operating characteristic curve) values were 0.871 without and 0.954 with temporal subtraction, compared with 0.882 and 0.955, respectively, for the sequential test. Diagnosis accuracy was significantly improved with the use of temporal subtraction. There was no significant difference in Az values between the independent and sequential tests. CONCLUSION: Temporal subtraction is useful in the detection of metastatic pulmonary nodules, and this technique augments the value of digital chest radiography.

Adult↗
PubMed2001

The importance of glycolytically-derived ATP for the Na+/H+ exchange activity in guinea pig ventricular myocytes.

The cardiac subtype of Na+/H+ exchanger (NHE-1) plays an important role in the regulation of intracellular pH (pHi) and also can be a major route for Na+ influx. Although intracellular ATP is required for the optimal function of NHE-1, the regulation of the exchanger by ATP is less well characterized. This study was designed to investigate which intracellular ATP generated by oxidative phosphorylation or by glycolysis is dominant for the activation of NHE-1 in intact cardiac myocytes. Isolated guinea pig ventricular myocytes were loaded with the pHi-sensitive fluorescent indicator, 2'-7'-bis(carboxyl)-5',6'-carboxy fluorescein (BCECF), and exposed to 20 mM 2-deoxyglucose (2-DG) or 2 mM sodium cyanide (CN) to inhibit glycolysis or oxidative phosphorylation, respectively. The activity of NHE-1 was estimated with pHi recovery following transient application of 15 mM NH4Cl (NH4Cl prepulse). After the NH4Cl prepulse, pHi decreased from 7.00 +/- 0.03 (mean +/- S.E.) to 6.60 +/- 0.06 and recovered to 6.94 +/- 0.13 at 10 min (n = 7). The pHi recovery was suppressed in the presence of 2-DG (6.67 +/- 0.05, p < 0.01, n = 7), but was not changed in the presence of CN (6.88 +/- 0.18, n = 6). Since there was no difference in the intrinsic H+ buffering power, the estimation of the net acid efflux demonstrated that the activity of NHE-1 was significantly depressed in 2-DG. The inhibitory effect of 2-DG was not due to more extensive depletion of global intracellular ATP or secondary to the change in either intracellular Na+ or Ca2+ concentration. We concluded that ATP generated by glycolysis rather than by oxidative phosphorylation is essential to activate NHE-1 in ventricular myocytes.

Adenosine Triphosphate↗
PubMed2001

In vitro and in vivo properties of recombinant human serum albumin from Pichia pastoris purified by a method of short processing time.

PURPOSE: Recombinant human serum albumin (rHSA), secreted by a Pichia pastoris expression system, was purified by a fast and efficient method, the essential feature of which is strong but reversible binding of the protein to Blue Sepharose. The structural characteristics, stability, and ligand-binding properties of the resulting protein were examined, and pre-clinical studies were performed. METHODS: Protein structure was investigated by amino acid sequencing, sodium polyacrylamide gel electrophoresis, CD spectroscopy and chromatography. Stability was examined by denaturation by guanidine hydrochloride and by calorimetry, and ligand binding was studied by ultrafiltration. Rat experiments were performed with 125I-labeled albumin. RESULTS: Far-ultraviolet and near-ultraviolet CD spectra of rHSA were identical to those of human serum albumin isolated from serum (HSA). Mercaptalbumin and non-mercaptalbumin were separated by high-performance liquid chromatography using an N-methylpyridinium polymer-based column. 60% of rHSA existed as mercaptalbumin, a content that is higher than that of a commercial preparation of HSA. Fatty acids, N-acetyl-L-tryptophan and pasteurization had similar effects on the conformational stability of rHSA and HSA. Stereoselective ligand-binding properties (warfarin, phenprocoumon, pranoprofen and ibuprofen) of rHSA were the same as those of HSA. The effect of the neutral to base transition on warfarin (site I-ligand) and dansylsarcosine (site II-ligand) binding to rHSA was also similar to HSA. In vivo studies showed comparable half-lives, excretion and tissue distributions of the two albumin preparations. CONCLUSION: The present yeast expression system and purification procedure result in rHSA with structural and functional properties very similar to those of HSA.

Animals↗
PubMed2001

A novel point mutation (C571T) in the tissue-non-specific alkaline phosphatase gene in a case of adult-type hypophosphatasia.

OBJECTIVE: Hypophosphatasia (HOPS) is an inheritable disorder characterized by defective skeletal mineralization, deficiency of tissue-non-specific alkaline phosphatase (TNSALP) activity and premature loss of deciduous teeth. The gene for TNSALP is located on chromosome 1p34-36.1 and consists of 12 exons and 11 introns. In this study we analysed the genomic TNSALP gene from a patient with HOPS, her family, and unrelated normal controls. MATERIALS AND METHODS: The proband was a 52-year-old Japanese woman with adult onset HOPS. The patient showed deficiency in alkaline phosphatase (ALP) activity, increased urinary excretion of phosphoethanolamine and severe periodontal disease. Genomic DNA was extracted from the peripheral leukocytes of the subjects. Based on published sequence data in the TNSALP gene, 11 pairs of polymerase chain reaction (PCR) primers were used to amplify the coding exons. The PCR amplified samples were subjected to PCR-single strand conformation polymorphism (SSCP) analysis and PCR-allele specific oligonucleotide (ASO) analysis. RESULTS: By PCR-SSCP analysis of the patient's genomic DNA, fragments containing exon 5 revealed abnormal mobility. This abnormal mobility (exon 5) was also found in the genomic DNA in her mother's sister, but were not detected in her father, brothers or sisters, and unrelated normal controls. Sequencing analysis of the abnormal band extracted from the SSCP gel revealed a C to T transition at nucleotide position 571 (C571T) in exon 5. This mutation resulted in a substitution of Ala-115 with a Val in the mature TNSALP polypeptide. PCR-ASO analysis also confirmed this missense point mutation. The result of this study showed that the pro-band has inherited the C571T mutation in exon 5 from her mother alone and the disease in this family was inherited as an autosomal dominant trait from the pedigree. CONCLUSIONS: The C571T mutation is a new missense point mutation and appears to cause significant changes in the structure and function of TNSALP because Ala-115 is highly conserved in rat TNSALP and human tissue-non-specific, intestinal and placental ALPs.

Alanine↗
PubMed2001

Other primary cancers occurring after treatment of superficial oesophageal cancer.

BACKGROUND: Recent advances in endoscopic diagnosis and treatment have led to better prognosis for patients with superficial oesophageal cancer. The incidence of subsequent other primary cancer (SOPC) has become a new problem for patients who survive after treatment of superficial oesophageal cancer. METHODS: Between 1966 and 1998, 368 patients with superficial oesophageal cancer, histologically confirmed as squamous cell carcinoma after resection, were reviewed for the presence of SOPC. RESULTS: Among the 368 patients, 43 developed SOPC. The most frequent sites of SOPC were the stomach (11 patients) and hypopharynx (11). Subsequent cancers of the stomach and hypopharynx developed significantly more frequently in heavy smokers. The 5-year cumulative occurrence rate of subsequent cancers within the fields of endoscopy of the upper gastrointestinal tract (stomach, hypopharynx and residual oesophagus) was 15 per cent. CONCLUSION: Gastric and hypopharyngeal cancers were frequently found after resection of superficial oesophageal cancer. A history of heavy smoking at the time of initial resection may be a risk factor. To make an early diagnosis of subsequent cancers, follow-up observation by upper gastrointestinal endoscopy is important after treatment of oesophageal cancer.

Carcinoma, Squamous Cell↗
PubMed2001

Early gallbladder carcinoma does not warrant radical resection.

BACKGROUND: This study was designed to address whether gallbladder cancer invading the muscle layer (stage pT(1b)) is a local disease and whether radical resection is necessary. METHODS: A retrospective analysis of 25 patients with pT(1b) gallbladder tumours, 13 of whom underwent simple cholecystectomy and 12 radical resection with regional lymph node dissection, was performed. A total of 147 regional lymph nodes was examined for metastasis. The median follow-up time was 95 months. RESULTS: No patient had blood vessel or perineural invasion on histology. Lymphatic vessel invasion was seen in one patient. Both overt metastasis and micrometastases were absent in all lymph nodes examined. Overall 10-year survival was 87 per cent. The outcome after simple cholecystectomy was comparable to that after radical resection (P = 0.16). Two patients who underwent radical resection died from tumour relapse in distant sites. CONCLUSION: Most pT(1b) gallbladder carcinomas spread only locally. Additional radical resection is not necessary when the depth of invasion of gallbladder carcinoma is limited to the muscle layer after simple cholecystectomy.

Adult↗
PubMed2001

Morphometric assessment of gastric antral atrophy: comparison with visual evaluation.

AIMS: As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists. METHODS AND RESULTS: Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non-standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions' grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non-standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40x microscopic field. The discriminant function analyses verified all cases classified visually as either non-atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The kappa statistics were good or excellent for the majority of pathologists. CONCLUSIONS: The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.

Atrophy↗
PubMed2001

Intensive generation of NK1.1- extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens.

Whether intermediate TCR (TCRint) cells and natural killer T (NKT or NK1.1+TCRint) cells are extrathymically generated remains controversial. This arises from the fact that there are few of these T cells in athymic nude mice and neonatally thymectomized mice. However, when athymic mice were provided with appropriate microenvironments or stimulation, many TCRint cells (mainly NK1.1-) were found to arise in the liver. NKT cells are known to be positively selected by monomorphic major histocompatibility complex (MHC) -like antigens (e.g. CD1d). This is true even if they are CD4+. In other words, a MHC class I-like antigen is restricted to CD4 antigen. This rule is somewhat different from that seen in conventional T cells (i.e. the restriction of class II with CD4 and that of class I and CD8). In the case of NK1.1-TCRint cells, they were selected by polymorphic MHC antigens, but their MHC restriction to CD4 or CD8 antigen was incomplete. This was revealed by experiments of bone marrow transfer with class I (bm 1) or II (bm 12) disparity. Depending on the disparity, a unique cytokine profile in sera was detected. These results suggest that the development of T lineage lymphocytes and MHC restriction to CD4 and CD8 might have occurred in parallell as a phylogenic event, and that NK1.1- extrathymic T cells (i.e. NK1.1-TCRint) are at an intermediate position between NKT cells and conventional T cells in phylogeny.

Aging↗
PubMed2001

In situ observation of the initial growth process of carbon nanotubes by time-resolved high resolution transmission electron microscopy.

We succeeded in plan-view dynamic observation of the initial formation process of carbon nanotubes from beta-SiC( 1 1 1) surfaces by time-resolved high resolution transmission electron microscopy. At 1360 degrees C, the flakes of graphite layers of a fibre orientation were formed on the SiC( 1 1 1) surfaces. From the graphite layers, carbon nanotubes were formed perpendicular to the ( 1 1 1) plane of the SiC. A scanning tunnelling microscopy observation showed that the end of carbon nanotube was closed. These results indicate that the caps of the carbon nanotubes are formed by a lift of a part of the graphene along the [ 1 1 1] direction of the SiC through generation of pentagons and heptagons. Two types of carbon nanotube, single-wall and double-wall, were observed in plan-view images. Different image intensity between an outer ring and an inner ring in double-wall nanotubes suggests that the inner layers of multiwall nanotubes are formed after the outer ones.

Journal Article↗
PubMed2001

Ultrastructural changes in calvarial osteoblast cytoskeleton after prostaglandin E2 administration in rats.

Recent studies on the cytoskeleton of osteoblasts have been made mainly using cultured cells. However, the morphology of cultured cells may be altered during subculture. Therefore, cytoskeletal changes of calvarial osteoblasts were investigated in situ by electron microscopy using the detergent perfusion method to preserve cell morphology as well as selectively observing the cytoskeleton in the presence of a high concentration of prostaglandin E2 (PGE2) in the calvarial periphery in rats. Rats were perfused with a mixture of Triton X-100 and glutaraldehyde, then the cytoskeleton was observed by transmission electron microscopy. In osteoblasts of the control group, thick bundles of microfilaments ran parallel to the long axis of the cells immediately below the cell membrane adjacent to the osteoid layer. In contrast, in the osteoblasts of the PGE2-administered group, the external morphology was changed to an asteroid or cubic shape, and thick bundles of microfilaments immediately below the cell membrane adjacent to the osteoid were not observed, although microfilament fibres, with a diameter of 5-6 nm, were observed in the cytoplasm.

Actin Cytoskeleton↗
PubMed2001

Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm.

BACKGROUND: Apg-1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32 degrees C to 39 degrees C heat shock in somatic cells. In mouse testicular germ cells Apg-1 mRNA is constitutively expressed depending on the developmental stage. As human Apg-1 has recently been identified, the expression of Apg-1 in the human testis and sperm was investigated. METHODS: Expression and heat-inducibility of Apg-1 in the human testicular germ cell tumor cell line, NEC8, was analyzed. Using an antimouse Apg-1 antibody, expression of Apg-1 in the human testis and sperm was examined by western blotting after confirmation of the specificity of the antibody. The cells expressing Apg-1 in the testis were further determined by immunohistochemistry. RESULTS: Slight induction of Apg-1 mRNA was detected in NEC8 cells after 32 degrees C to 39 degrees C temperature shift. In the human testis, the antibody specifically recognized Apg-1, which was absent in the testis without germ cells (Sertoli-cell-only syndrome) or arrested at spermatogonia. Spermatocytes and spermatids, but not testicular somatic cells, were positively stained with the anti-Apg-1 antibody. By western blot analysis, Apg-1 was detected in the preparation enriched for sperm from normal volunteers and infertile patients, but not from azoospermia patients. CONCLUSION: Apg-1 is developmentally expressed in human testicular germ cells and sperm, suggesting its role in spermatogenesis and fertilization. Identification of substrates for Apg-1 chaperone activity will help elucidate its function.

Adult↗