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Biomedical subjects

H Yamada

Publications and source records attributed to H Yamada.

At least 289 records · Page 16Linked to original sources

Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis.

A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW. The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk). Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy.

Abortion, Induced↗

Immunohistochemical distribution of the endothelin-converting enzyme-1 in the rat hypothalamo-pituitary axis.

We prepared a rabbit polyclonal antibody against an endothelin converting enzyme-1 (ECE-1) to examine the distribution of ECE-1 in the hypothalamus and the pituitary of the rat. By the Western blot analysis, the antibody specifically recognized ECE-1 proteins in membrane fractions of the rat hypothalamus. Immunohistochemical staining revealed ECE-1 immunoreactivity in both cell bodies and axons in some hypothalamic neurons. The immunopositive cell bodies were located in the paraventricullar and supraoptic nuclei; immunopositive axons were distributed in the suprachiasmatic, paraventricullar (PVN), and supraoptic (SON) nuclei. However no immunoreactivity was detected in the posterior pituitary gland. The present results indicate that ECE-1 converts the endothelin-1 (ET-1) from precursor big ET-1 to mature ET-1 in the PVN/SON. The big ET-1 existing in the posterior pituitary gland is thought to be escaped from the converting by ECE-1 in the hypothalamus.

Animals↗

Synthesis of a model compound related to an anti-ulcer pectic polysaccharide.

A stereocontrolled synthesis of the model compound for an anti-ulcer active polysaccharide (Bupleuran 2IIc) is described. Glycosidation of the disaccharide acceptor, 2-O-acetyl-3-O-benzyl-4-O-(p-methoxybenzyl)-alpha-L-rhamnopyranosyl-(1-- >4)-2,3,6-tri-O-benzyl-alpha-D-galactopyranosyl trichloroacetimidate, with the disaccharide receptor, allyl 3,4-di-O-benzyl-alpha-L-rhamnopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta- D-galactopyranoside, using silver triflate (AgOTf) as a promoter gave the desired tetrasaccharide derivative, which was transformed into the acidic tetrasaccharide, corresponding to a segment of the rhamnogalacturonan (Bupleuran 2IIc) polysaccharide, propyl alpha-L-Rha-(1-->4)-alpha-D-GalA-(1-->2)-alpha-L-Rha-(1-->4)-beta-D-GalA , via removal of the corresponding ether and ester protecting groups, followed by oxidation.

Anti-Ulcer Agents↗

Rapid internal dynamics of BPTI is insensitive to pressure. (15)N spin relaxation at 2 kbar.

Pressure effects on the backbone dynamics of a native basic pancreatic trypsin inhibitor (BPTI) have been measured by (15)N spin relaxation and chemical shifts at 30 and 2000 bar. The experiments utilized the on-line variable pressure cell nuclear magnetic resonance system on (15)N-uniformly labeled BPTI at a proton frequency of 750.13 MHz at 36 degrees C. Longitudinal (R(1)) and transverse (R(2)) (15)N relaxation times and ((1)H)-(15)N nuclear Overhauser effects were measured for 41 protonated backbone nitrogens at both pressures. The model free analysis of the internal dynamics gave order parameters for individual H-N vectors at both pressures. The results indicate that rapid internal dynamics in the ps-ns range for the polypeptide backbone is not significantly affected by pressure in the range between 30 bar and 2 kbar. The result is consistent with the linear pressure dependence of (1)H and (15)N chemical shifts of BPTI, which suggests that local compressibilities and amplitudes of associated conformational fluctuation are nearly invariant in the same pressure range. Overall, we conclude that at 2 kbar BPTI remains within the same native ensemble as at 1 bar, with a small shift of population from that at 1 bar.

Aprotinin↗

Detection of DNA fragmentation of myonuclei in myotonic dystrophy by double staining with anti-emerin antibody and by nick end-labeling.

To clarify the occurrence of apoptosis in skeletal muscle in pathological conditions, we studied 44 muscle biopsy specimens by immunohistochemical staining with monoclonal antibody against emerin, which is localized in muscle nuclear membrane, and by ApopTag Plus to detect DNA fragmentation. Five of six patients with myotonic dystrophy (DM) showed three to 35 myonuclei stained with anti-emerin antibody and ApopTag Plus in 1500 muscle fibers. Four of the 18 patients with polymyositis, one of those with thyroid myopathy and one with neurogenic atrophy showed a few myonuclei stained positively by these methods. Our study revealed that DNA fragmentation in myonuclei occurred in skeletal muscle fibers regardless of the type of disease, although the frequency was rather low in all of these diseases except DM. The DNA fragmentation detected in most of the patients with DM suggested a significant role of apoptosis in the pathomechanism of this disease.

Adolescent↗

TCR-independent activation of extrathymically developed, self antigen-specific T cells by IL-2/IL-15.

Naive intrathymically developed T cells, which express foreign Ag-specific TCR, do not express IL-2R. After antigenic stimulation, they express high affinity IL-2R, which enables IL-2 to be used as an autocrine growth factor. On the contrary, extrathymically developed T cells, which express self Ag-specific TCR but are unresponsive to antigenic stimulation, spontaneously express low affinity IL-2R. In this study, we compared the responses of these two subsets of T cells to IL-2R stimulation and examined the influences of TCR-mediated signaling on the responses. IL-2 or IL-15 augmented the proliferative response of Ag-stimulated, intrathymically developed T cells. On the other hand, extrathymically developed T cells proliferated in response to IL-2 or IL-15, independently of Ag stimulation. Furthermore, both IL-2 and IL-15 induced IFN-gamma production of these T cells, which is strikingly augmented by the presence of IL-12. These results revealed functional differences between intrathymically developed, foreign Ag-specific T cells and extrathymically developed, self Ag-specific T cells. The latter can be activated by some inflammatory cytokines, in an Ag-independent manner, similar to NK cells.

Animals↗

Preparation of 5-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyloxy)-6-hydroxynap htho[2,3- f]quinoline-7,12-dione (FT-Alz), a new-type, potentially antitumor substance with various biological activities.

The title compound (6), its structure being imaginatively created, has been prepared through coupling of alizarine blue (2), a classical dye, and 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (3). Compound 6 has considerably higher and different antitumor activity from that of doxorubicin or its analogue (10), and, further, has properties to reverse multidrug resistance (by P-glycoprotein), to inhibit topoisomerase II, and to induce apoptosis.

Animals↗

Energy confinement time and heat transport in initial neutral beam heated plasmas on the large helical device

The confinement characteristics of large net-current-free plasmas heated by neutral-beam injection have been investigated in the Large Helical Device (LHD). A systematic enhancement in energy-confinement times from the scaling derived from the medium-sized heliotron/torsatron experiments have been observed, which is attributed to the edge pedestal. The core confinement is scaled with the Bohm term divided by the square root of the gyro radii. The comparative analysis using a dimensionally similar discharge in the Compact Helical System indicates gyro-Bohm dependence in the core and transport improvement in the edge region of LHD plasmas.

Journal Article↗

Inflammation influences vascular remodeling through AT2 receptor expression and signaling.

The AT(2) receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model of vascular remodeling and compared the responses in wild-type (Agtr2(+)) and AT(2) receptor knockout (Agtr2(-)) mice. Polyethylene cuff placement on the femoral artery led to the vascular expression of cytokines, the transcriptional factor interferon regulatory factor-1 (IRF-1), and both the AT(1) and AT(2) receptors. Although the expressions of IRF-1 and AT(1) receptor were induced to comparable levels in both the Agtr2(+) and Agtr2(-) mice, the neointimal lesion size and the smooth muscle cell proliferation were twice greater in the Agtr2(-) than in the Agtr2(+) mouse. Correlated with this difference, AT(2) receptor expression was induced predominantly in the smooth muscle cells of Agtr2(+) mouse. These results demonstrate that the AT(2) receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.

Angiotensin Receptor Antagonists↗

Inhibition of food intake by central injection of anti-orexin antibody in fasted rats.

It has been shown that intracerebroventricular injection of synthetic orexins stimulated food intake in rats. This pharmacological evidence suggests that orexins may have a role for the central regulation of feeding. In the present study, we investigated the hypothesis of whether endogenous orexins indeed play a vital role in feeding behavior. An anti-orexin polyclonal antibody was used throughout the study. First, we examined the specificity of the antibody to orexin by Western blot analysis and immunohistochemistry. Next, the effects of central injection of the orexin antibody on food intake in 24-h-fasted rats were evaluated. Western blot analysis revealed that the orexin antibody detected synthetic orexin-A. Immunohistochemical study showed that orexin-positive neurons were identified only in the lateral hypothalamic area, in agreement with previous reports. Neither control antibody nor the orexin antibody preabsorbed with excess amount of orexin-A detected neurons, indicating that the orexin antibody is specific. Intracisternal but not intraperitoneal injection of the orexin antibody dose-dependently suppressed feeding. All these results suggest that immunoneutralization of endogenous orexins in the brain reduced food intake. In other words, we suggest that endogenous brain orexin may have a physiologically relevant action on feeding behavior.

Animals↗

Edge thermal transport barrier In LHD discharges

In LHD discharges a significant enhancement of the global energy confinement has been achieved for the first time in a helical device with an edge thermal barrier, which exhibits a sharp gradient at the edge of the temperature profile. Key features associated with the barrier are quite different from those seen in tokamaks: (i) almost no change in particle (including impurity) transport, (ii) a gradual formation of the barrier, (iii) a very high ratio of the edge temperature to the average temperature, and (iv) no edge relaxation phenomenon. These features are very attractive in applying the thermal barrier to future reactor grade devices.

Journal Article↗

Cell injury unmasks a latent proangiogenic phenotype in mice with increased expression of FGF2 in the retina.

Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial cells and exogenous administration of FGF2 stimulates angiogenesis. However, increased expression of FGF2 in the retina does not cause angiogenesis. One possible explanation is that FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another angiogenic factor. Alternatively, there may be control mechanisms that sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express FGF2 in the retina with mice that express vascular endothelial growth factor (VEGF) in the retina. Surprisingly, despite comparable levels of VEGF expression, mice that expressed both FGF2 and VEGF had significantly less neovascularization than mice that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice, choroidal neovascularization developed in areas of low-intensity laser. Both wild type and transgenic mice developed choroidal neovascularization in areas of intense laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased retinal expression of FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.

Animals↗

A new sensitive determination method of estradiol in plasma using peroxyoxalate ester chemiluminescence combined with an HPLC system.

A new sensitive determination method of estradiol in a plasma sample using peroxyoxalate ester chemiluminescence was developed. Estradiol, which was extracted by liquid-liquid extraction using ethyl acetate from plasma, was derivatized with dansyl-chloride (DNS-Cl) and separated by reverse-phase HPLC. The performance of four oxalates, bis(trichlorophenyl)oxalate (TCPO), bis(2,4-dinitrophenyl)oxalate (DNPO), bis(pentafluorophenyl)oxalate (PFPO), and bis[4-nitro-2-(3,6, 9-trioxadecyloxycarbonyl)phenyl] oxalate (TDPO), were evaluated using the static system, and DNPO was found to have the most sensitive and stable chemiluminescence at a H(2)O(2) concentration of 30 mM. HPLC-chemiluminescence system using DNPO for the determination of estradiol was established. The detection limit of dansylated-estradiol (DNS-E2) was 15 fmol (4 pg) in the standard solution and 44 fmol (12 pg) in the rat plasma sample at S/N = 3.

Animals↗

Roles of melatonin in gonadal maturation of underyearling precocious male masu salmon.

Testicular maturation of underyearling precocious male masu salmon (Oncorhynchus masou) is affected by photoperiod. It is accelerated by a short photoperiod (light-dark cycles of 8:16 h; LD 8:16) and delayed by a long photoperiod (LD 16:8). Circulating melatonin levels are high during the night and low during the day:the duration of the nocturnal elevation is longer under a short than under a long photoperiod, suggesting mediation of photoperiodic signals by melatonin. This study examined whether melatonin administration mimics short photoperiodic effects and whether it accelerates the testicular development of underyearling male masu salmon reared under a long photoperiod. Fish were randomly selected in June and were divided into two groups. They were reared under LD 16:8 (lights on 04:00-20:00 h) and fed pellets sprayed with melatonin (0.5 mg melatonin/kg body weight/day) or vehicle once a day at 11:00 h until October. The plasma melatonin profile of the melatonin-treated group was similar to that expected under a short photoperiod. Melatonin treatment had a stimulatory effect on the gonadosomatic index and pituitary gonadotropin (GTH) I contents. Plasma testosterone levels were significantly higher in the melatonin-treated group than in the control group in August. However, spermiation was observed in October in both groups and no significant differences were observed in GTH II contents in the pituitary in the two groups throughout the experiment. These results suggest that mimicking a short photoperiod by melatonin administration stimulated testicular development but did not completely activate the brain-pituitary-gonadal axis in precocious male masu salmon. Thus, melatonin is suggested to be one of the factors that mediates the transduction of photoperiodic information to the brain-pituitary-gonadal axis.

Administration, Oral↗

Prognostic significance of lymph node metastasis and clear cell histology in ovarian carcinoma limited to the pelvis (pT1M0 and pT2M0).

BACKGROUND: The prognostic significance of lymph node (LN) metastasis in clinically early-stage (pT1M0 or pT2M0) ovarian carcinoma has not yet been fully elucidated. METHODS: From 1988 to 1997, 94 patients with ovarian carcinoma of pT1M0 (n = 78) or pT2M0 (n = 16) classification underwent surgery including systematic pelvic and paraaortic LN dissection. We investigated the prognostic factors of intraperitoneally determined early-stage ovarian carcinoma focusing on LN metastasis. RESULTS: LN metastasis was seen in 5.1% of pT1M0 and in 31.3% of pT2M0 tumors. Univariate analysis of grade, histology (clear cell vs others), size of primary tumor, peritoneal cytology, and LN metastasis revealed that histology (P < 0.01), size of tumor (P < 0.05), and LN metastasis (P < 0.0005) were related to patient survival of early-stage ovarian carcinoma. Peritoneal cytology (P = 0.053) and grade (P = 0.059) had marginal statistical significance. A multivariate Cox regression analysis showed that clear cell histology (P < 0.05) and LN metastasis (P < 0. 005) are significant independent prognosticators of patient survival. Three (two with clear cell adenocarcinoma and one with mucinous adenocarcinoma) of nine patients with LN metastasis had died of the disease by the time of the present analysis. Two of the three deceased patients had recurrent tumors in distant organs (bone and brain/liver), one had pleural and peritoneal carcinomatosis, and no patients had retroperitoneal recurrence. This suggests that LN metastasis indicates that tumor cells may have already spread systemically at the time of treatment and, at the same time, retroperitoneal lymph node dissection (RPLND) may be effective in eradicating retroperitoneal metastasis in some instances of ovarian carcinoma. CONCLUSION: Clear cell histology and LN metastasis are indicators of poor prognosis for patients with tumors limited to the pelvis. Therapeutic significance of systematic RPLND for pT1M0/pT2M0 ovarian carcinomas needs to be further investigated by randomized studies.

Adenocarcinoma, Clear Cell↗

Two cases of endometrial cancer meeting new clinical criteria for hereditary nonpolyposis colorectal cancer.

BACKGROUND: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC) that includes extracolonic cancers were recently proposed. We present 2 endometrial cancer patients who met the new criteria of 161 endometrial cancer patients. CASE REPORTS: Case 1: A 55-year-old female was operated on for synchronous double primary cancers of the endometrium and rectum. She had also undergone an operation for metachronous ascending colon cancer at the age of 44. She had five relatives with a history of colorectal cancer. The rectal cancer tissue revealed no microsatellite instability (MSI). Case 2: A 48-year-old female underwent a radical operation for synchronous double primary cancers of the endometrium and ovaries. She had three relatives with a history of colorectal cancer. The endometrial cancer tissue showed high MSI. CONCLUSIONS: The frequency of endometrial cancer patients meeting the new HNPCC criteria was 1.2% (2/161). These are the first case reports selected from consecutive endometrial cancer patients.

Carcinoma, Endometrioid↗

Complications relating to intraperitoneal administration of cisplatin or carboplatin for ovarian carcinoma.

BACKGROUND: Complications associated with intraperitoneal (ip) chemotherapy is one of the factors that should be taken into consideration upon performing long-term intraperitoneal administration of chemotherapeutic agents for ovarian carcinoma. METHODS: From 1987 to 1996, 78 patients with primary ovarian carcinoma were treated with a total of 365 courses of ip administration of cisplatin (CDDP) or carboplatin (CBDCA) as a part of an initial chemotherapy regimen in combination with surgery including systematic retroperitoneal lymph node dissection using an implantable peritoneal cavity access catheter system. The complications that occurred in association with ip chemotherapy were analyzed. RESULTS: Complications associated with ip chemotherapy were seen in 27 of 78 (34.6%) patients, which included extensive intestinal adhesion, abdominal pain, local infection, ileus, bleeding at the site of implanted port, obstruction of the catheter, vaginal vault perforation, and bowel perforation. Major complications that required surgical treatment occurred in 3 patients, which included ileus, vaginal perforation, and an intestinal perforation. The perforations occurred after 18 and 36 months after the implantation of the catheter, respectively. CONCLUSIONS: It has been suggested that primary CDDP/CBDCA ip chemotherapy using an implantable catheter system can be carried out safely with rare major complications if employment of this method is restricted in 12 months after the installation of catheter.

Adult↗