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Biomedical subjects

M Yasuda

Publications and source records attributed to M Yasuda.

At least 145 records · Page 8Linked to original sources

Immunohistochemical expressions of prohormone convertase (PC)1/3 and PC2 in carcinoids of various organs.

In order to clarify the expression of prohormone convertase (PC) 1/3 and PC2 in various carcinoids and non-carcinoid endocrine tumors, we performed indirect immunoperoxidase staining on total of 19 cases of carcinoids (9 cases of bronchial carcinoids, 4 cases of rectal carcinoids, 4 cases of gastric carcinoids and 2 cases of bile duct carcinoids). Our study also included 7 non-carcinoid endocrine tumors. Seventy-nine% and 26% of carcinoids highly or strongly expressed positive staining for PC1/3 and PC2, respectively. High and strong expressions (3+ or 4+) of both PC1/3 and PC2 were noted in only bronchial carcinoids. Strong expressions for only PC1/3 were noted in rectal carcinoids. Bile duct carcinoids also demonstrated higher expressions of PC1/3 than those of PC2. These results suggested that high expressions of both PC1/3 and PC2 in bronchial carcinoids might reflect their diverse and frequent peptide production. The expressions of PC1/3 mRNA and PC2 mRNA detected by in situ hybridization in the bronchial carcinoids and rectal carcinoids were correlated with immunoexpressions of both of the antigens. The granular immunoexpression pattern of PC1/3 and PC2 visualized by confocal laser scanning microscopy would suggest the site of post-translational processing in the secretory granules. Non-carcinoid endocrine tumors showed low expressions (+ or 2+) of PC1/3 and PC2, except for thyroid medullary carcinoma showing high immunoexpression of PC1/3. Other non-carcinoid endocrine tumors (parathyroid adenomas and adrenal pheochromocytomas) revealed low immunoexpressions for both PC1/3 and PC2.

Adolescent↗

[Bacillus Calmette-Guerin intravesical instillation treatment for carcinoma in situ of the bladder. Gifu BCG Instillation Therapy Research Group].

We performed a retrospective long-term study to evaluate the efficacy of intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guerin (BCG) on carcinoma in situ (CIS) of the bladder. Between 1989 and 1998, 42 patients with CIS of bladder underwent intravesical instillation of BCG. In the follow-up period from 6 to 116 months (mean: 37.3 months), the efficacy rate of intravesical BCG instillation for CIS of the bladder was 81.0%. Two patients died from the bladder cancer. The non-recurrence rate in patients with grade 2 carcinoma (19 cases) was not significantly different from that in those with grade 3 carcinoma (23 cases). However, the recurrence rate in patients with secondary CIS (15 cases) was significantly higher than in those with primary CIS (27 cases). The recurrence of CIS was observed in 7 of 42 cases. In 6 of 7 patients, CIS recurred within one year after treatment. Total cystectomy was performed in 10 of 42 patients, and pathological findings of muscle layer invasion were detected in 8 patients. Although side effects occurred in 33 patients (77.5%), no clinically significant side effects were observed. Our results suggest that intravesical BCG therapy may be useful for the treatment of CIS of the bladder.

Adjuvants, Immunologic↗

Establishment and characterization of cell lines derived from serous adenocarcinoma (JHOS-2) and clear cell adenocarcinoma (JHOC-5, JHOC-6) of human ovary.

The cell lines designated JHOS-2, JHOC-5 and JHOC-6 were established from epithelial ovarian carcinomas. JHOS-2 was established from a serous adenocarcinoma of a 45-year-old Japanese woman, JHOC-5 from a recurrent tumor of a clear cell adenocarcinoma of a 47-year-old Japanese woman and JHOC-6 from a tumor of a clear cell adenocarcinoma of a 43-year-old Japanese woman. These cell lines have grown well and serial passages were successively carried out more than 20 times. The monolayer cultured cells revealed neoplastic and pleomorphic features, and grew in multilayers. Electron micrographs revealed epithelial origins that had desmosomes and tonofilaments.

Adenocarcinoma, Clear Cell↗

Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog.

We have identified a C. elegans protein, ceBNIP3, homologous to the human BCL-2/EIB-19K interacting BCL-2 family pro-apoptotic protein BNIP3. In transiently transfected mammalian cells, ceBNIP3 complexes with CED-9, the worm homolog of BCL-2. CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain. Transfection of ceBNIP3 and CED-3 results in enhanced proteolytic processing of the CED-3 zymogen and in cooperative induction of apoptosis. Coexpression of CED-9 suppresses the cooperative cell death induced by ceBNIP3 and CED-3. In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex suggesting that CED-9 may suppress cooperative apoptosis induced by CED-3 and ceBNIP3 by simultaneous complex formation with CED-3 and ceBNIP3. Our results suggest that ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes.

Amino Acid Sequence↗

Response to head-up tilt testing in patients with situational syncope.

The results of head-up tilt testing were compared between 24 patients with situational syncope and 44 age-matched patients with typical vasovagal syncope. Patients with situational syncope showed poor positive responses, especially in the passive tilt results (8.3% vs. 39%, p = 0.0078).

Adult↗

Two novel oleanolic acid saponins having a sialyl Lewis X mimetic structure from Achyranthes fauriei root.

Two novel triterpene glycosides, achyranthosides E and F, were isolated as methyl esters from the root of Achyranthes fauriei, an antiinflammatory medicinal plant. Their structures were characterized as oleanolic acid glucuronides having unique substituents composed of C6H9O5 and C9H15O7, respectively, at the C-3 position of glucuronic acid. These compounds are active components which can inhibit the excess recruiting of neutrophiles to injured tissues 1,000 times more potently than sialyl Lewis X.

Magnetic Resonance Spectroscopy↗

Adenovirus E1B-19K/BCL-2 interacting protein BNIP3 contains a BH3 domain and a mitochondrial targeting sequence.

Adenovirus E1B-19K and BCL-2 anti-apoptosis proteins interact with certain BCL-2 family pro-apoptotic proteins. A conserved domain, BH3, present in these proteins is essential for their pro-apoptotic activity and for heterodimerization with anti-apoptosis proteins. Cellular protein BNIP3 (previously NIP3) interacts with E1B-19K, BCL-2, BCL-xL, and EBV-BHRF1. BNIP3 contains a motif similar to the BH3 domain. Deletion of the BH3-like motif in BNIP3 abrogates its ability to heterodimerize with E1B-19K and BCL-xL. Substitution of the BH3 domain of BNIP3 for the corresponding sequences of BAX functionally restores the pro-apoptotic and protein heterodimerization activities of BAX. BNIP3 exhibits a delayed cell death activity that is partially relieved by deletion of the BH3 domain. BNIP3 suppresses the anti-apoptosis activity of BCL-xL in a BH3-dependent manner. BNIP3 contains a C-terminal trans-membrane (TM) domain similar to other BCL-2 family proteins and BNIP1 (previously NIP1). The TM domains of BNIP3 and BNIP1 can functionally substitute for the TM domain of a BCL-2 family member EBV-BHRF1. The BNIP3 TM domain exclusively targets the heterologous green fluorescent protein (GFP) to mitochondria. These results suggest that BNIP3 is a member of the BH3-contaning BCL-2 family of pro-apoptotic proteins and functions in mitochondria.

Adenovirus E1B Proteins↗

Oligoclonal development of B cells bearing discrete Ig chains in chicken single germinal centers.

Chicken single germinal centers enable us to analyze the postbursal diversifications of B cells due to their easy isolation. Germinal center formation has peaked by day 7 of primary responses and begins to wane 14 days after immunization. To detail the kinetics of Ig mutation and selection, we analyzed Ig light chain sequences recovered from single germinal centers at 7 and 11 days postimmunization with an artificial Ag. Our observations show that multiple, Ag-activated B cells migrating into single germinal centers are diversified by gene conversion in the very early phase of the germinal center reaction and are subsequently subjected to point mutations and selection for oligoclonality.

Amino Acid Sequence↗

Modulation of actomyosin ATPase by goniodomin A differs in types of cardiac myosin.

Goniodomin A causes the conformational change of actin to modify actomyosin ATPase activity [Furukawa, K.-I., Sakai, K., Watanabe, S., Maruyama, K., Murakami, M., Yamaguchi, K., Ohizumi, Y., 1993. Goniodomin A induces modulation of actomyosin ATPase activity mediated through conformational change of actin. J. Biol. Chem. 268, 26026-26031]. Goniodomin A inhibited the ATPase activities of atrial myofibrils, myosin B and reconstituted actomyosin in a concentration-dependent manner. Interestingly, these ATPase activities of ventricular muscle were enhanced by goniodomin A (3 x 10(-8)-3 x 10(-7) M), but were decreased when the concentration was further raised. The stimulatory effect of goniodomin A was significantly inhibited by troponin tropomyosin complex. These results suggest that goniodomin A affects actin to modify cardiac actomyosin ATPase activity, and that this modulation differs in types of cardiac myosin.

Animals↗

Single-channel activity of the Ca2+-dependent K+ channel is modulated by FK506 and rapamycin.

Single-channel patch clamp recordings were performed in primary cultured neurons from rat dorsal hippocampi. Ca2+-dependent and TEA-sensitive K+ current was recorded from the neurons. Application of immunosuppressants FK506 and rapamycin to the channel inside the plasma membrane of the neurons significantly prolonged the mean open time of the channel. Calcineurin autoinhibitory fragment and W-7 induced no significant alteration in the mean open time of the channel. These results suggest that modulation of the activity of the Ca2+-dependent K+ channel by FK506 and rapamycin is directly through association of immunosuppressants with FKBP12.

Animals↗

Increase in odontoclast nuclei number by cell fusion: a three-dimensional reconstruction of cell fusion of human odontoclasts.

Osteoclasts and odontoclasts are known to increase their nuclear number by fusion of mononuclear precursors. However, the pattern of fusion remains morphologically unclear. One lower right deciduous canine of an 8-year-old male was investigated. Tartrate-resistant acid phosphatase activity (TRAP) positive cells on the resorbing surface of the tooth were serially sectioned into 0.5 microm-thick semithin sections. The sections were photographed, and cells possessing a light microscopic brush border facing a resorptive lacuna were identified as odontoclasts. Fourteen odontoclasts appearing as a continuous figure of cellular membrane between cells on one section were three-dimensionally reconstructed using NIKON COSMOZONE 2SA. A criterion for fusion was established in this study, requiring that there must be two or more nucleated cells which contacted each other at one site only in the three-dimensional reconstruction. Among 14 reconstructed cells, 10 odontoclasts satisfied the criterion for fusion. The observations of the three-dimensional structures of these odontoclasts showed that mononuclear and multinucleated odontoclasts participated in fusion. Cell fusion occurred between resorbing odontoclasts and cells not forming lacunae, and between resorbing odontoclasts. A case of odontoclastic fusion among three cells was also observed. The results establish that fusion resulting in multinucleation occurred among various odontoclasts with different numbers of nuclei including mononuclear odontoclasts.

Cell Fusion↗

Serum interleukin-2 receptor for the early diagnosis of rheumatoid arthritis.

The value of measuring soluble interleukin-2 receptor (sIL-2R) in the sera of patients with joint pain as a predicting parameter for the future development of rheumatoid arthritis (RA) was examined. sIL-2R was measured by the ELISA method. Sixty-four patients with joint pain (suspected RA: sus-RA) but no bone or joint destruction were enrolled over 2 years and 47 were selected for the study. Eleven patients whose diagnosis was sus-RA after a year of observation were successively followed-up for 5 years. Two-thirds of the patients whose sIL-2R levels were higher than those of normal healthy adults (< 82 pmol/l; mean +2SD) developed RA within a year. On the other hand, one-quarter of the patients with normal levels of sIL-2R also developed RA within a year. The presence of two or three of the following three items in patients with joint pain without any bone and joint destruction was thus indicated to be useful for the early diagnosis of RA: elevated CRP level (> or = 1.0 mg/dl), positive rheumatoid factor (RF) (> or = 30 IU/ml) and an elevated sIL-2R level (> or = 100 pmol/l). Sensitivity and specificity were 72.7% and 96.0%, respectively. The probability of development of RA is expressed as P = 1/[1 + exp(2.673 - 0.01784 x sIL-2R - 0.4398 x CRP - 0.004835 x RF)], with R2 = 0.3083 and p<0.0005. On the other hand, the sIL-2R levels did not correlate with any future bone or joint changes within a year of observation. The above criteria may therefore hopefully justify the early treatment of patients with joint pain using drugs that can modify the patients' immune function. However, the validity of these criteria still need to be examined more thoroughly in the future.

Adult↗

Induction of drug resistance to gold sodium thiomalate in a monocyte cell line, THP-1.

The expression of metallothionein, an intracellular heavy-metal-binding protein, and p-glycoprotein, an energy-dependent drug efflux pump, was examined to study the mechanism of cell resistance to gold sodium thiomalate (GST). THP-1, one of the monocyte-derived cell lines, was cultured for 6 months and resistance to 25 microg/ml of GST (GST-resistant cells) was thus induced. The GST-resistant cells were then cultured with bucillamine to examine the presence of cross-resistance. The intracellular GST concentration was examined by flameless atomic absorption spectroscopy. The cell viability was determined by the uptake of 3-4,5 dimethylthiazole-2,5 diphenyl tetrazolium bromide (MTT). The expression of p-glycoprotein was detected by Western blotting using monoclonal anti-p-glycoprotein antibody. The expression of metallothionein was detected using the indirect immunofluorescence technique. GST-resistant cells did not show any cross-resistance to bucillamine. The rate of cytoplasmic GST accumulation decreased in the GST-resistant cells, while the rate of GST efflux also decreased. The expression of p-glycoprotein in the GST-resistant cells was not significantly different from that in the cells not treated with GST. On the other hand, the GST-resistant cells showed a higher expression of metallothionein than cells not treated with GST. These findings suggest that the induced resistance to GST might partly be due to an induction of metallothionein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of long-term hormone replacement therapy on the bone in ovariectomized women with cancer.

OBJECTIVE: To evaluate longitudinally the effectiveness of long-term hormone replacement therapy (HRT) in preserving the bone mineral density (BMD) over a 5-year period in ovariectomized patients treated for gynecologic malignancies. METHODS: A total of 70 pre-menopausal women ovariectomized for gynecologic malignancies at our hospital were divided non-randomly into two groups: HRT (+) group (n = 59) and HRT (-) group (n = 11). HRT was administered in a sequential regimen of 0.625-1.25 mg conjugated estrogen for 24 days and 5-10 mg medroxyprogesterone acetate for 10 days. RESULTS: The BMD of the lumbar vertebrae decreased significantly in the HRT (-) group (pre-operative BMD was 91.8%, 91.0% and 91.3% at 1, 2 and 3 years post-ovariectomy), but no decrease in the BMD was observed in the HRT (+) group (pre-operative BMD was 98.4%, 99.0%, 99.4%, 98.8% and 98.7% at 1, 2, 3, 4 and 5 years post-ovariectomy); the difference in BMD between the two groups was statistically significant (P < 0.01). Serum alkaline phosphatase levels were significantly lower in the HRT (+) group than in the HRT (-) group (P < 0.01). There were four recurrences of cancer in the HRT (+) group. CONCLUSION: HRT appeared to have beneficial effects on bone metabolism by maintaining BMD for 5 years in ovariectomized patients for gynecologic malignancies.

Adult↗

Development of maternal IgG-free chick obtained from surgically bursectomized hen.

IgG-free eggs and chicks were developed, so as to study the role of maternal IgG in the development of the immune system. Surgical bursectomy on the 18th day of incubation deprived chickens of B cells and eliminated IgG synthesis. Bursectomized chickens are usually dead before sexual maturity under conventional conditions. When surgically bursectomized chickens were housed in an isolated clean room and antibiotics were administered to them, they could survive to sexual maturity. Finally, we succeeded in obtaining IgG-free fertilized eggs and maternal IgG-free chicks from surgically bursectomized hens. The amount of yolk IgG in IgG-free eggs was one-ten thousandth less than that in normal eggs. The level of IgM in the serum of maternal IgG-free chicks reached six times higher than that of normal chicks 5 days after hatching.

Animals↗

A comparative study of germinal center: fowls and mammals.

The mammalian germinal center is organized into a dark zone containing proliferating centroblasts and a light zone filled with nondividing B cells (called centrocytes), follicular dendritic cells and a few scattered T cells. We clarified these two zones in the chicken germinal center with immunohistology. Proliferating cells and immunoglobulin negative cells were detected in the circumference ring of the chicken germinal center. The central part of the chicken germinal center contained B cells expressing immunoglobulin, follicular dendritic cells and a few T cells. Most of the B cells in the central part of the chicken germinal center did not enter into the S phase. These results suggest that the chicken germinal center is also organized into the dark zone (the circumference ring of germinal center) and the light zone (the central part of germinal center).

Animals↗

Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum.

BACKGROUND/AIMS: Lipid peroxidation has been found to be associated with Ito cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between retinoids and hepatic fibrosis is complex. The aim of this study was to elucidate the role of retinoids as a fibrosuppressant: the effects of retinoids on hepatic fibrosis induced in rats by dimethylnitrosamine or pig serum, as well as on rat Ito cells in primary culture, were examined in order to assess the antioxidant activity of retinoids. METHODS: Male Wistar rats were given a single injection of 40 mg/kg dimethylnitrosamine or 0.5 ml PS twice weekly for 10 weeks. In each model, rats were treated with retinyl palmitate for 2 weeks before hepatotoxin treatments or for the last 2 weeks of the treatments. The cumulative amount of retinyl palmitate administered in each experiment was 2, 10, or 20x10(4) IU/rat. RESULTS: Retinyl palmitate treatment before or after administration of dimethylnitrosamine or pig serum suppressed the induction of hepatic fibrosis, restored hepatic retinyl palmitate levels, prevented increases in hepatic levels of collagen and malondialdehyde, a product of lipid peroxidation, and prevented increases in deposition of type III collagen and the number of alpha-smooth muscle actin (alpha-SMA) positive-Ito cells in the liver. Retinyl palmitate supplementation resulted in a dose-dependent reduction of alpha-SMA expression and an oxidative burst in cultured Ito cells. In addition, retinyl palmitate inhibited Fe2+/adenosine 5'-diphosphate-induced lipid peroxidation in rat liver mitochondria and showed radical scavenging activity. CONCLUSIONS: These findings suggest that retinyl palmitate may suppress the induction of hepatic fibrosis, at least in part, by the inhibition of Ito cell activation through its antioxidant activity.

Animals↗