Search PubMed⌕ Search

Biomedical subjects

A Sakamoto

Publications and source records attributed to A Sakamoto.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parathyroid hormone-related protein (C-PTHrP) in hematological malignancies with bone lesions and hypercalcemia].

We measured the levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parothyroid hormone-related protein (C-PTHrP) in serum of patients with hematological malignancies. ICTP and C-PTHrP levels in serum of multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and adult T-cell leukemia (ATL) patients with bone lesions and hypercalcemia were significantly higher than those of patients without bone lesions and hypercalcemia. ICTP and C-PTHrP levels in ATL were significantly higher than in MM and NHL. There was a correlation between ICTP and C-PTHrP in serum of ATL patients, but no correlation in MM and NHL. Serum ICTP levels tended to correlate with serum beta 2-microglobulin and survival in patients with MM. Therefore, ICTP and C-PTHrP levels in serum may be useful in the diagnosis of bone lesions and hypercalcemia in hematological malignancies. In particular, ICTP may be a useful bone resorption marker in MM.

Adult↗
PubMed1998

[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer].

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.

Aged↗
PubMed1998

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Histological classification of prostatic cancer].

Histological classification of prostatic cancer with a special focus on adenocarcinoma was reviewed according to "General Rule for Clinical and Pathological Studies on Prostatic Cancer (The 2nd Edition, 1992) published by Japanese Urological Association and The Japanese Society of Pathology. The points of the classification are as follows; (1) adenocarcinoma is separated into 3 categories, namely, well, moderately and poorly differentiated types, by structural features. (2) nuclear grading does not commit for making a subclassification of prostatic adenocarcinoma. The other types of primary malignancies are rare in the prostate. Prostatic intraepithelial neoplasia should be discussed in the further revision of the classification.

Adenocarcinoma↗
PubMed1997

Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, delta-sarcoglycan, in hamster: an animal model of disrupted dystrophin-associated glycoprotein complex.

Cardiomyopathy (CM) is a primary degenerative disease of myocardium and is traditionally categorized into hypertrophic and dilated CMs (HCM and DCM) according to its gross appearance. Cardiomyopathic hamster (CM hamster), a representative model of human hereditary CM, has HCM and DCM inbred sublines, both of which descend from the same ancestor. Herein we show that both HCM and DCM hamsters share a common defect in a gene for delta-sarcoglycan (delta-SG), the functional role of which is yet to be characterized. A breakpoint causing genomic deletion was found to be located at 6.1 kb 5' upstream of the second exon of delta-SG gene, and its 5' upstream region of more than 27.4 kb, including the authentic first exon of delta-SG gene, was deleted. This deletion included the major transcription initiation site, resulting in a deficiency of delta-SG transcripts with the consequent loss of delta-SG protein in all the CM hamsters, despite the fact that the protein coding region of delta-SG starting from the second exon was conserved in all the CM hamsters. We elucidated the molecular interaction of dystrophin-associated glycoproteins including delta-SG, by using an in vitro pull-down study and ligand overlay assay, which indicates the functional role of delta-SG in stabilizing sarcolemma. The present study not only identifies CM hamster as a valuable animal model for studying the function of delta-SG in vivo but also provides a genetic target for diagnosis and treatment of human CM.

Amino Acid Sequence↗
PubMed1997

Palmitoylation of human endothelinB. Its critical role in G protein coupling and a differential requirement for the cytoplasmic tail by G protein subtypes.

By site-directed mutagenesis, three cysteine residues (amino acids 402, 403, and 405) in the carboxyl terminus of human endothelinB (ETB) were identified as potential palmitoylation sites. Substitutions of all of the three cysteine residues with serine gave an unpalmitoylated mutant, C2S/C3S/C5S. When expressed in Chinese hamster ovary cells, C2S/C3S/C5S was localized on the cell surface, retained high affinities to ET-1 and ET-3, and was rapidly internalized when bound to the ligand. However, unlike the wild-type ETB, C2S/C3S/C5S transmitted neither an inhibitory effect on adenylate cyclase nor a stimulatory effect on phospholipase C, indicating a critical role of palmitoylation in the coupling with G proteins, regardless of the G protein subtypes. Truncation of the carboxyl terminus including Cys403/Cys405 gave a deletion mutant Delta403 that was palmitoylated on Cys402 and lacked the carboxyl terminus downstream to the palmitoylation site. Delta403 did transmit a stimulatory effect on phospholipase C via a pertussis toxin-insensitive G protein but it failed to transmit an inhibitory effect on adenylate cyclase. These results indicated a differential requirement for the carboxyl terminus downstream to the palmitoylation site in the coupling with G protein subtypes, i.e. it is required for the coupling with Gi but not for that with Gq.

Amino Acid Sequence↗
PubMed1997

In vivo gene transfection of human endothelial cell nitric oxide synthase in cardiomyocytes causes apoptosis-like cell death. Identification using Sendai virus-coated liposomes.

BACKGROUND: Nitric oxide (NO) has various actions on the cardiovascular system, although its pathophysiological significance in myocardial cells remains obscure. The aim of the present study was to identify direct NO actions on cardiomyocytes by gene transfection in vivo using a newly developed vector under physiological conditions. METHODS AND RESULTS: Liposomes containing the beta-galactosidase (beta-gal) gene alone or with the human endothelial cell nitric oxide synthase (ecNOS) gene were coated with UV-inactivated Sendai virus and injected into the left ventricular wall of rat heart in vivo. Histological examination confirmed that the transfection efficiency was comparable to adenovirus-mediated transfection and that the new vector per se caused no inflammation. beta-Gal expression was confined to cardiomyocytes between two intercalated discs, suggesting that the transfected gene did not permeate the discs. An immunohistochemical study showed that cotransfection of the ecNOS gene induced massive myocardial cell shrinkage in both transfected cells and the adjacent myocytes in a time- and dose-dependent manner. Histochemical findings in shrunk cells coincided with apoptosis as identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. Electron microscopy of the lesion revealed myofibrillar degradation and accumulation of mitochondria but no apoptotic bodies. Pre-treatment with the NOS inhibitor N omega-nitro-L-arginine methyl ester abolished these morphological alterations. CONCLUSIONS: The efficient expression of the human ecNOS gene in vivo suggests that NO or its toxic metabolite caused myocardial degradation, a part of which was compatible with apoptosis of the transfected cardiomyocytes themselves and the adjacent cells as a paracrine effect. These morphological features mimicked acute myocarditis or ischemic injury.

Animals↗
PubMed1997

Growth retardation of Mato's fluorescent granular perithelial (FGP) cells in scavenger receptor knockout (SRKO) mice.

BACKGROUND: Mato's fluorescent granular perithelial (FGP) cells are situated between the basal lamina of cerebral microvessels and the glia limitans covering astrocytic processes. Because they are potent enough to take up endo- and exogenous substances in a steady state, they are regarded as scavenger cells in the central nervous system. The scavenger receptor for oxidized low-density lipoprotein (LDL) is also expressed on their cytoplasmic membrane. We studied the differentiation and growth of FGP cells in wild-type and scavenger receptor knockout (SRKO) mice. METHODS: Wild-type (129 strain) and SRKO mice at 1, 3, 5, 8, 10, 14, and 28 days after birth were employed in this study. Stretch specimens of their cerebral cortices were used for immunohistochemical investigations, and Epon-embedded specimens of the same region were studied with an electron microscope. RESULTS: In wild-type mice, perivascular cells derived from the pial tissue were transformed at approximately 8 days after birth into the FGP cells, which, provided with several epitopes common to macrophage lineages, developed over a period of 14 days. The FGP cells possessed several inclusions and were surrounded by two defined sheets of basal lamina and continuous glia limitans. At 4 weeks, their morphology, enzymatic activity, and epitopes advanced with the aging of the mice. However, in SRKO mice, at 8 days, the perivascular cells took fibroblastoid forms with scarce lysosomal inclusions, and, even at 14 days, glia limitans remained discontinuous and most of FGP cells remained immature in their cytoplasmic organelles. Different from the case with the wild-type, the intensity of the labeling of epitopes remained at a low level. At 4 weeks, some of the FGP cells fell into degeneration, and the others were differentiated to a certain degree. CONCLUSIONS: The development of Mato's FGP cells in SRKO mice was retarded in the morphology, enzyme activity, and epitopes. The scavenger receptor, which reacted with the antibody 2F8, seems to be closely associated with the development of Mato's FGP cells.

Acid Phosphatase↗
PubMed1997

Efficacy of an ultrashort-acting beta-adrenoceptor blocker (ONO-1101) in attenuating cardiovascular responses to endotracheal intubation.

OBJECTIVE: To investigate the clinical effectiveness and safety of ONO-1101, a new ultrashort-acting (half-life 3-4 min), cardioselective beta-adrenoceptor blocker in attenuating the cardiovascular responses to endotracheal intubation in a dose-finding open study. METHODS: Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of succinylcholine, and saline or ONO-1101 0.1, 0.25 or 0.5 mg.kg-1, in 53 patients. Heart rate and blood pressure were continuously recorded beginning prior to administration until 5 min after administration of the drug, and the rate-pressure product was calculated. RESULTS: ONO-1101 was found to significantly blunt the increase in heart rate throughout the study. Administration of ONO-1101 0.25 or 0.5 mg.kg-1 decreased the incidence of tachycardia. However, these doses were not sufficient to suppress the increase in systolic blood pressure, although the maximal value in the ONO-1101 0.5 mg.kg-1 group was reduced. Rate-pressure product increased significantly after intubation in all groups, but the increase was suppressed in the ONO-1101 0.25 and 0.5 mg.kg-1 groups as compared with the saline group. Bradycardia was not observed in any patient, although hypotension might be caused by administration of ONO-1101 0.5 mg.kg-1. CONCLUSION: ONO-1101, especially at a dose of 0.25 mg.kg-1, due to its beta-adrenoceptor blockade and ultrashort action, was shown to be effective and well tolerated by patients in this study, when used to attenuate the cardiovascular responses to laryngoscopy and endotracheal intubation.

Adrenergic beta-Antagonists↗
PubMed1997

Growth and differentiation of periodontal ligament-derived cells in serum-free defined culture.

We have developed a serum-free medium for the growth and differentiation of periodontal ligament-derived cells (PLC). In addition, the expression of both fibroblast growth factor (FGF) and FGF receptor (FGFR) in the PLC was investigated by immunohistochemical examination, heparin affinity chromatography (HAC), and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Optimal growth of the cells was achieved in Iscove's modified Dulbecco's medium supplemented with insulin, transferrin, 2-mercaptoethanol, 2-ethanolamine, sodium selenite, and oleic acid in type-I collagen-coated dishes. Both FGF-1 and FGF-2 stimulated cell growth and inhibited differentiation as measured by inhibition of alkaline phosphatase activity of the cells. An immunohistochemical analysis of FGF-1 and FGF-2 revealed that immunoreactive FGF-1 and FGF-2 were detected predominantly in the cytoplasm of growing cells. In addition, perinuclear FGF-1 staining and nuclear FGF-2 staining were observed in the same growing cells. In contrast, a faint diffuse staining of FGF-1 and FGF-2 was detected in cytoplasm of the confluent differentiated cells. The 2.15 M NaCl eluate from HAC of the cell extracts exhibited growth-promoting activities for the PLC, and it also stimulated the growth of human umbilical vein-derived endothelial cells and inhibited binding of [125I]-FGF to its receptors, indicating the cells produced FGFs or FGF-like growth factors. RT-PCR analysis revealed that the cells expressed FGFR-1 mRNA but not mRNAs for FGFR-2, FGFR-3 and FGFR-4 mRNA. These results suggest that the FGF-FGFR-1 system plays an important role in the growth and differentiation of periodontal ligament-derived cells.

Alkaline Phosphatase↗
PubMed1997

Prevalence of ovarian endometriosis in epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to examine the occurrence of ovarian endometriosis in epithelial ovarian cancer in Japan. METHOD: The presence of ovarian endometriosis was determined by reviewing the sections of resected specimens in 172 epithelial ovarian cancers. RESULTS: The incidence of ovarian endometriosis in ovarian cancer (14.5%) was higher than that in Western countries. The rank order of incidence of endometriosis in each histologic type was clear cell (40.6%)>endometrioid (23.1%)>serous (8.7%)>mucinous (2.9%). The incidence in serous type was higher when compared with that reported in Western countries. The higher incidence of endometriosis in Japan can be explained by a greater proportion of clear cell type, comprising 18.6% of all the cases and a higher incidence of endometriosis in the serous type. CONCLUSION: The association of ovarian endometriosis with epithelial ovarian cancer was more frequently found in Japan.

Adenocarcinoma, Clear Cell↗
PubMed1997

Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants.

Plasma total homocysteine (tHcy) and serum folate (FA) concentrations were measured in 130 epileptic patients taking anticonvulsant drugs. A significant inverse correlation was found between FA and tHcy. This was greater in the older group (> or = 15 years) than in the younger group (1 to 14 years). There were four FA-deficient patients (FA concentration < 3 ng/mL regardless of symptoms), including three patients in the older group and one in the younger group. All FA-deficient patients had received long-term treatment (> 7 years) with multiple anticonvulsants. Their tHcy levels were higher than the 90th percentile of those in control subjects. Two patients showed extremely high levels of tHcy (57.9 and 29.1 mumol/L) and subnormal plasma methionine levels. After FA therapy, their tHcy decreased to levels the same as or less than those of control subjects and FA increased to above the normal range. Based on these findings, we conclude that measuring FA and tHcy concentrations may be useful for preventing thrombosis due to hyperhomocysteinemia in epileptic patients taking anticonvulsants, particularly those who receive long-term treatment with multiple agents.

Adolescent↗
PubMed1997

P-glycoprotein is positively correlated with p53 protein accumulation in human colorectal cancers.

To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocarcinomas. Serial frozen sections of 40 surgical samples were stained with an anti-Pgp (MRK16) and two different anti-p53 protein antibodies (Abs), PAb421 and PAb1801. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The samples that stained positively with PAb421 also stained positively with PAb1801. Pgp expression was detected in 13 (76.5%) of 17 samples that were positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using PAb1801. Thus, we found that p53 and Pgp were co-expressed in a significant number of samples (P < 0.002). There was no relationship between Pgp or p53 protein accumulation and histologic grade or stage. The present results demonstrate that Pgp expression is closely associated with p53 protein accumulation in human colorectal cancers. These data provide evidence to support the idea that mutant p53 activates the MDR1 gene in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Small cell undifferentiated carcinoma of the urinary bladder: a cytodiagnostic case report of its variant type.

Presented is a case report of a urinary bladder carcinoma that had an unusual morphology and phenotype. A 65-year-old Japanese man complained of gross hematuria. Cytological examination of the urine before a partial cystectomy revealed small, round atypical cells with a high nuclear/cytoplasmic ratio, scant cytoplasm, and hyperchromatic nuclei with coarse and granular chromatin in a bloody background. Several tumor cells had relatively large and vesicular nuclei with prominent eosinophilic nucleoli and obscure perinucleolar halos. A small number of large atypical urothelial cells were also recognized. The tumor recurred locally 3 months after the operation. The urine cytology during recurrence showed the same features without the atypical urothelial cells. These cytological findings suggested a case of small cell undifferentiated carcinoma (SCUC) combined with transitional cell carcinoma (TCC). An histology of the resected specimen before the recurrence revealed that the SCUC was consistent with a variant type of SCUC proposed for the lung and showed transition with TCC in situ. M-VAC chemotherapy after a total cystectomy was less effective. The patient died 6 months after diagnosis. A variant subtype of SCUC of the urinary bladder associated with TCC in situ has not been previously reported. Although this histological type is very rare, its earlier cytological detection is needed for appropriate therapy.

Aged↗
PubMed1997

Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer: an interim report on short-term effects. Prostate Cancer Study Group.

BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer. METHODS: Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy. RESULTS: Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.

Aged↗