Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 163 records · Page 9Linked to original sources

PubMed1998

[The majority of emergency calls are erroneous].

An emergency call system has been used to summon specialists for cardiopulmonary resuscitation in Kumamoto University Hospital since 1986. Many improvements have been made to the system since it was established. We performed a prospective evaluation of calls made during the period from April 1, 1996 to March 31, 1997. There were a total of 36 calls, but only two of them were judged to be true emergencies. While at first we considered the number of calls reflected a growing awareness of the cardiopulmonary resuscitation team in the hospital, the large number of erroneous calls (94%) indicated other factors needed to be considered. Further investigation revealed the existence of a special, and little-known, telecommunication system connecting various administrative offices of the Japanese Government. Some of the phone numbers in this system are similar to the emergency call number. Thus many of the emergency calls were probably caused by administrative officers who misdialed. We are proposing to change this emergency call number.

Cardiopulmonary Resuscitation↗

PubMed1998

Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice.

To clarify the role of type I and type II macrophage scavenger receptors (MSR-A) in the progression of diet-induced atherosclerosis, we generated mice lacking both MSR-A and low-density lipoprotein receptor (LDLR). After 4 or 12 weeks of a high-fat diet, the sizes of atherosclerotic lesions in MSR-A/LDLR double knockout mice were significantly reduced (p < 0.05) compared with those in LDLR single knockout mice. However, atherosclerotic lesions mainly composed of foamy macrophages were still observed in double knockout mice. Formation of atherosclerotic lesions in double knockout mice was partially explained by the participation of scavenger receptors other than MSR-A such as MARCO, CD36, and macrosialin/CD68. These receptors were clearly demonstrated in the atherosclerotic lesions in double knockout mice as well as LDLR single knockout mice by immunohistochemistry or by reverse transcriptase-polymerase chain reaction. Because the very low density lipoprotein (VLDL) fraction was elevated in the double and single knockout mice, we further examined the possibility that VLDL may participate in foam cell formation in atherosclerotic lesions. When incubated with VLDL isolated from LDLR-deficient mice, cholesterol ester accumulation and foamy transformation occurred in MSR-A-deficient macrophages as well as in normal macrophages. These data indicate that MSR-A plays an essential role in the development of diet-induced atherosclerosis. It also appears that other scavenger receptors, such as MARCO, CD36, and macrosialin/CD68, as well as uptake of VLDL are involved in foam cell formation during atherogenesis in MSR-A/LDLR double knockout mice.

Animals↗

PubMed1998

[Prospective study on evaluation of the ischemic heart disease for preoperative patients with lung cancer].

One hundred twenty-four patients with lung cancer undergoing operation in our hospital were prospectively studied on evaluation of the ischemic heart disease before operation. They performed master double electrocardiogram and exercised T1 scintigram before operation. The patient with positive master double electrocardiogram and/or exercised T1 scintigram was taken into high risk group. All patients in high risk group performed coronary angiography. This high risk group consisted of 37 patients (29.8%), including 6 single vessel disease (4.8%), 2 double vessel disease (1.6%), and 1 triple vessel disease (0.8%). Preoperative revascularization was done 8 patients (6.5%). These revascularization patients had uneventful course during and after lung operation. However 2 cases of vasospastic angina (VSA) occurred in non-risk group during operation. It was impossible to anticipate VSA before lung operation in our series. Therefore our preoperative evaluation and care of organic ischemic heart disease was effective in preventing cardiac complications.

Adult↗

PubMed1997

Local synthesis of natriuretic peptides in the eel intestine.

The intestine is a major osmoregulatory organ in euryhaline fishes which allows them to survive in the sea, and natriuretic peptides have been implicated in regulation of transmural transport. Atrial (ANP) and ventricular natriuretic peptide (VNP) were identified in eel intestine. Elution profiles of ANP and VNP from high-performance liquid chromatography (HPLC) were determined by radioimmunoassay using highly specific antisera. Elution times of immunoreactive ANP and VNP in HPLC were identical to those of authentic peptide standards and were consistent with the relative molecular masses of these peptides. Tissue localization of ANP and VNP was accomplished by fluorescence immunohistochemistry. Immunoreactive cells were observed in the epithelium of anterior, middle, and posterior regions of intestine. Reverse transcription of mRNA isolated from intestine and subsequent polymerase chain reaction amplification yielded appropriate-size products consistent with ANP and VNP expression. Together, these data show that natriuretic peptides are synthesized locally in eel intestine, rather than trapped from the circulation.

Anguilla↗

PubMed1997

Early song-deprivation affects the expression of protein kinase C in the song control nuclei of the zebra finch during a sensitive period of song learning.

Male zebra finches learn to imitate a tutor's song through auditory and motor learning during a sensitive period. The molecular aspects of auditory-dependent learning was investigated using protein kinase C (PKC) as a molecular marker for synaptic plasticity. We found a transient increase in the expression of PKC in the robust nucleus of the archistriatum (RA) during a sensitive period. Furthermore, both early deafening by cochlea removal and song deprivation inhibited the increase of PKC enzyme activity. The results strongly suggest that PKC is an important enzyme related to the synaptic plasticity of RA neurons during a sensitive period of song learning in the zebra finch.

Animals↗

PubMed1997

Cholinergic innervation of the song control nuclei by the ventral paleostriatum in the zebra finch: a double-labeling study with retrograde fluorescent tracers and choline acetyltransferase immunohistochemistry.

During the sensitive period of song learning, the content of acetylcholine and the enzyme activity of choline acetyltransferase (ChAT) increase remarkably in the song control nuclei of a young male zebra finch. Cholinergic fibers innervate the two main song control nuclei of the forebrain: the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA). The present study combines the retrograde tracer, Fluoro-Red (FRe), with ChAT immunohistochemistry. The results indicate that the cholinergic fibers which innervate the RA and HVC originate from the ventral paleostriatum (VP) in the basal forebrain, and that there is an anterior-posterior topography in the location of the cholinergic neurons in the VP that project to the HVC and RA, although there are a few neurons which project to both nuclei. These findings suggest that the VP is homologous to the nucleus basalis of Meynert of the basal forebrain cholinergic system of mammals which is associated with learning and memory processes, and that the cholinergic neurons in the VP play an important role in avian song learning.

Animals↗

PubMed1997

TNF-alpha stimulates the biosynthesis of complement C3 and factor B by human umbilical cord vein endothelial cells.

The human umbilical cord vein (HUVEC) endothelial cells synthesize and secrete complement components. We analyzed the regulation of biosynthesis of the third component of complement (C3) and factor B (Bf) by cytokines in endothelial cells. Production of C3 increased after stimulation with TNF-alpha or IL-1beta and that of Bf with TNF-alpha, TNF-beta and IFN-gamma. TNF-alpha was the most effective in stimulating the secretion of C3 and Bf or the expression of mRNA of C3 or Bf. Preincubation with TNF-alpha for at least 36 or 24 h was needed for the stimulation, respectively. TNF-alpha, together with IFN-gamma had synergistic effects and the release of C3 or Bf increased to about 40- and 26-fold higher than those in control cells after incubation with both cytokines.

Cell Line↗

PubMed1997

Expression of E-cadherin and alpha- and beta-catenin mRNAs in ovarian cancers.

To know the biological role of the adherens junction, mainly consisting of E-cadherin and alpha- and beta-catenins, associated with invasion and metastasis of ovarian cancers, we studied the expressions of E-cadherin and alpha- and beta-catenin mRNAs in the cancers in comparison with those in normal counterparts. The integral expression of E-cadherin and alpha- and, beta-catenin mRNAs was suppressed in the metastatic lesions of advanced ovarian cancers, while it was not in the primary tumors. Therefore, the suppressed expression of main adhesion molecules in the adherens junction might contribute to adherens junctional dysfunction, which might lead to the acquirement of invasiveness and metastatic potential by advanced ovarian cancers as one of the rate-limiting steps.

Adult↗

PubMed1997

A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Animals↗

PubMed1997

Plausible novel therapeutic strategy of uterine endometrial cancer with reduction of basic fibroblast growth factor secretion by progestin and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470).

To know the potential of growth, invasion and metastasis of endometrial cancer associated with neovascularization, the effects of sex steroids and O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) on basic fibroblast growth factor (FGF) expression and secretion and its mRNA expression were investigated in well-differentiated endometrial cancer cell line Ishikawa and in undifferentiated endometrial cancer cell line AN3 CA. Basic FGF expression and secretion and its mRNA expression in Ishikawa cells, but not in AN3 CA cells, were increased by estrogen, while progesterone diminished the estrogen-induced increases. TNP-470 reduced the levels regardless of estrogen treatment in AN3 CA cells. Therefore, basic FGF secretion may be inhibited by progestin in differentiated cells, and by TNP-470 in undifferentiated cells. Since endometrial cancer consists of differentiated and undifferentiated cells as heterogeneity, a combination therapy for endometrial cancer with progestin and TNP470 might be effective.

Antibiotics, Antineoplastic↗

PubMed1997

Expression of basic fibroblast growth factor and its mRNA in advanced uterine cervical cancers.

To know the potential of growth, invasion and metastasis of uterine cervical cancer cells associated with neovascularization, the expression of basic fibroblast growth factor (FGF) and its mRNA in uterine cervical cancers and normal uterine cervices as controls were determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction-Southern blot (RT-PCR-SB), respectively. Then, the relations between the expression and the histological grading and clinical staging in cervical cancers were analyzed. The levels of basic FGF and its mRNA were significantly higher in advanced primary uterine cervical cancers, regardless of histological type. Therefore, this status might contribute to the acceleration of growth, invasion, and metastasis with neovascularization in advanced uterine cervical cancers.

Adult↗

PubMed1997

Induction of apoptosis in a human hepatocellular carcinoma cell line by a neutralizing antibody to transforming growth factor-alpha.

A cell line derived from a Japanese man with hepatocellular carcinoma was established in culture and designated OCUH-16. The cell line has the morphological and chromosomal features of hepatocellular carcinoma cells and has a short doubling time (approximately 33 h). OCUH-16 cells were shown to express transforming growth factor-alpha (TGF-alpha) in addition to albumin, DNA polymerase-alpha, c-JUN, and the retinoblastoma gene product. Electron microscopy revealed TGF-alpha immunoreactivity associated with the cell membrane, but TGF-alpha was not detected in medium conditioned by OCUH-16 cells by enzyme-linked immunosorbent assay. Reverse transcription and polymerase chain reaction analysis revealed the presence of TGF-alpha messenger RNA in these cells. Culture of OCUH-16 cells in the presence of a neutralizing antibody to TGF-alpha inhibited cell proliferation and induced many cells to undergo apoptosis (programmed cell death). These observations suggest that endogenous TGF-alpha is necessary for OCUH-16 cell growth.

Antibodies, Monoclonal↗

PubMed1997

Evidence for the involvement of transforming growth factor-alpha in implantation in the rat.

This study was conducted to examine the possibility for participation of transforming growth factor-alpha (TGF-alpha), one of the epidermal growth factor (EGF) family of growth factors, in implantation in the rat. Immunostaining of TGF-alpha in the periimplantation uterus showed distinct staining in the luminal and glandular epithelium and moderate staining in stromal and myometrial cells. After implantation decidual cells and embryos were also positive stained for immunostaining. Immunocytochemistry of EGF receptor showed distinct staining in the luminal and glandular epithelium during the preimplantation period, and after implantation decidua at implantation sites and embryos were stained. Intraluminal injection of anti-TGF-alpha antibodies into uterine horns at 0600 h on day 5 of pregnancy decreased the number of rats showing implantation (blue dye reaction) at 0200 h on day 6 in a dose-dependent manner. Intraluminal injection of 100 pg of TGF-alpha on day 5 of pseudopregnancy elicited a greater decidual response when compared with the vehicle-injected contralateral uterine horn. Intraluminal injection of 20 pg of TGF-alpha into each uterine horn induced implantation in 50% of the ovariectomized progesterone-treated delayed implanting rats. These results suggest that TGF-alpha is involved in the implantation process in the rat.

Animals↗

PubMed1997

Intranuclear mitochondria in human myocardial cells.

Intranuclear mitochondria have occasionally been reported in various cells including cardiac myocytes, but the incidence and details including the specific mechanism(s) whereby mitochondria exist in the nuclear matrix are unknown. We studied the ultrastructure of a total of 91 consecutive endomyocardial biopsy specimens obtained from 50 patients with various cardiac diseases. Intranuclear mitochondria were found in three patients: two with hypertrophic cardiomyopathy and one with chronic myocarditis. Their myocytes were markedly hypertrophic and the shapes of the nuclei were bizarre. Specimens from these patients were further studied on serial sections, and some of the nuclei with mitochondria showed ruptured nuclear envelope. Intranuclear mitochondria were found in at least 6% of the patients with cardiac diseases (3% of the specimens examined), and a novel mechanism of the pathogenesis was documented: communication between the nuclear matrix and cytoplasm through the rupture in the nuclear envelope. The nuclear rupture might be simply due to a laboratory artifact. On the other hand, it might imply some pathophysiological significances in the degeneration of myocytes in cardiac diseases.

Aged↗

PubMed1997

Clinical implication of expression of progesterone receptor form A and B mRNAs in secondary spreading of gynecologic cancers.

This study was designed to determine the clinical implication of expression of progesterone receptor form A (PR-A) and B (PR-B) mRNAs in secondary spreading of gynecologic cancers. Approximately equal expression of PR-A and PR-B mRNAs was designated as type AB and dominant expression of PR-B mRNA as type B. Alteration from type AB to type B in the metastatic cancers occurred in 3/8 cases of uterine endometrial cancers, 2/8 cases of uterine cervical cancers, and 2/8 cases of ovarian cancers. Other cancers revealed type B regardless of primary or metastatic status. Thus, all metastatic cancers studied revealed type B. These results suggest that transcription of PR-A mRNA may be damaged, which might lead to uncontrolled overexpression of PR-B mRNA in metastatic lesion, and that the type B status could reveal a highly malignant phenotype in these three gynecologic cancers.

Adult↗

PubMed1997

Transient liver accumulation of Tc-99m phytate in hepatocellular carcinoma after percutaneous ethanol injection.

PURPOSE: We report that colloid liver scanning gave early evidence of the return to normal of Kupffer cell functions after ethanol injections into the liver. PATIENT AND METHODS: A 71-year-old man with hepatocellular carcinoma received percutaneous ethanol injections twice of 15 mL of ethanol, 1 week apart. RESULTS: Abdominal CT after the second injection showed an irregularly shaped low-density area in the left side of the tumor, extending outside the tumor. Liver imaging with To-99m phytate 10 days later showed increased activity at the corresponding site. Thirty days after the second injection, liver imaging did not show high activity. CONCLUSIONS: Ethanol that leaked into the normal part of the liver probably temporarily activated Kupffer cell function.

Aged↗

PubMed1997

Myosin light-chain phosphorylation controls insulin secretion at a proximal step in the secretory cascade.

The aim of this study was to investigate how insulin secretion is controlled by phosphorylation of the myosin light chain (MLC). Ca2+-evoked insulin release from pancreatic islets permeabilized with streptolysin O was inhibited by different monoclonal antibodies against myosin light-chain kinase (MLCK) to an extent parallel to their inhibition of purified MLCK. Anti-MLCK antibody also inhibited insulin release caused by the stable GTP analog guanosine 5'-O-(3-thiodiphosphate), even at a substimulatory concentration (0.1 microM) of Ca2+. Free Ca2+ increased MLC peptide phosphorylation by beta-cell extracts in vitro. In contrast to the phosphorylation by purified MLCK or by calmodulin (CaM) kinase II, the activity partially remained with the beta-cell under nonstimulatory Ca2+ (0.1 microM) conditions. The MLCK inhibitor ML-9 inhibited the activity in the beta-cell with both substimulatory and stimulatory Ca2+, whereas KN-62, an inhibitor of CaM kinase II, only exerted an influence in the latter case. ML-9 decreased intracellular granule movement in MIN6 cells under basal and acetylcholine-stimulated conditions. We propose that MLC phosphorylation may modulate translocation of secretory granules, resulting in enhanced insulin secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1997

Comparative study on expression of plasminogen activator inhibitor 1 and its mRNA in endometrial cancers and normal endometria.

The effects of the endocrine milieu on growth, invasion and metastasis, associated with neovascularization of endometrial cancer, the expression of plasminogen activator inhibitor 1 (PAI-1), and its mRNA in endometrial atypical hyperplasia and cancer, and normal endometria as controls were determined in premenopausal and postmenopausal women. In premenopausal women, the levels of PAI-1 and its mRNA in normal endometria were significantly higher than in endometrial atypical hyperplasia and cancer. On the other hand, in postmenopausal women, the results were reversed. There was no difference in the expression of PAI-1 and its mRNA in the various histological grades and clinical stages in endometrial cancers, while the expression of PAI-1 in other cancers increased during tumor progression. In our previous study, the expression of PAI-1 and its mRNA in well-differentiated endometrial cancer cell lines was dependent upon estrogen and progesterone. This might be partially related to the endocrine milieu, especially in endometrial atypical hyperplasia and well-differentiated endometrial cancer, which seems to be dependent on sex steroids. Therefore, endometrial cancer of any histological grade and clinical stage might maintain PAI-1 expression in both premenopausal and postmenopausal women, which may modulate, at least in part, growth, invasion and metastasis associated with neovascularization of endometrial cancer.

Adult↗