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Biomedical subjects

M Mikami

Publications and source records attributed to M Mikami.

At least 19 recordsLinked to original sources
PubMed1995

Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation.

Two human epithelial cell lines, trophoblastic teratocarcinoma HT-H and endometrial adenocarcinoma SNG-M cells, adhere to each other at their respective apical cell surfaces in a divalent cation-independent manner. Two novel molecules responsible for the adhesion between these two cell types were identified by expression cDNA cloning. One, named trophinin, is an intrinsic membrane protein and mediates homophilic self-binding. Another, named tastin, is a cytoplasmic protein and is necessary for trophinin to function as a cell adhesion molecule. Trophinin and tastin appear to be associated with the cytoskeleton in HT-H and SNG-M cells. These molecules are normally not expressed in various types of human cells in tissues, with the exception of macrophages. Strong expression of these molecules was detected in the trophectoderm surface of monkey blastocyst. These molecules are also expressed in human endometrial surface epithelium on day 16/17 at the early secretory phase of human endometrium, the time consistent with that expected for the "implantation window."

Adenocarcinoma↗
PubMed1995

Purification and characterization of the cytotoxic factor in rat peritoneal exudate cells: its identification as the calcium binding protein complex, calprotectin.

We previously reported the existence of a growth inhibitory factor for mitogen-stimulated lymphocytes and murine tumor cell lines, MM46 and L-929, in inflammatory polymorphonuclear leukocytes. In this study, by using mouse MM46 mammary carcinoma as target, we purified the inhibitor from lysate of rat inflammatory peritoneal exudate cells by ammonium sulfate precipitation, gel filtration, isoelectrofocusing, and anion exchange chromatography. Although the in vitro inhibitory activity for MM46 growth was partitioned into three peaks in the final step, it was found that these inhibitory samples all consist of 8- and 13-kDa peptides. Analysis of amino acid sequences revealed that the partial sequences of the 8- and 13-kDa peptides completely agree with the smaller and larger components of rat calprotectin, which are predicted from cDNA, respectively, suggesting the cell growth inhibitory factor is calprotectin. In addition to MM46, the partially purified calprotectin inhibited the growth of a rat, three mice, and a human tumor cell line in similar dose-response relationships in vitro. Moreover, it exerted a cytolytic effect against all examined tumor cells. It was confirmed that the purified calprotectin induces growth inhibition and the lysis of MM46 cells and that the minimum effective concentration is between 50 and 100 micrograms/ml. The factor also inhibited the growth of bone marrow cells and macrophages. These results suggest that calprotectin is a negative regulatory factor for the growth and/or survival states of normal and tumor cells.

Amino Acid Sequence↗
PubMed1995

Induction of apoptotic cell death in mouse lymphoma and human leukemia cell lines by a calcium-binding protein complex, calprotectin, derived from inflammatory peritoneal exudate cells.

We have previously shown that the calcium-binding protein complex, calprotectin, purified from rat inflammatory peritoneal cells exerts marked cytotoxic activity against rat, mouse, and human tumor cells. We studied here whether the cytotoxicity is caused by induction of apoptosis, using mouse EL-4 lymphoma and human MOLT-4 leukemia lines as targets. The rat calprotectin sample inhibited [3H]thymidine incorporation into these cells by partially 24 h and almost completely in 48 h of culture at concentrations of 100-200 micrograms/ml. Morphological changes, that is, loss of cell volume and nuclear condensation and/or fragmentation, appeared in both cell types cultured with calprotectin from 20 h, and such apoptotic cells subsequently increased in number to compose the great majority of the cells at 40 h. Cell death, measured by stainability with trypan blue, lagged behind the emergence of the apoptotic morphology by about 2 and 10 h in EL-4 and MOLT-4 cells, respectively. DNA fragmentation was observed in EL-4 cells cultured with calprotectin, whereas it was not observed in MOLT-4 cells, consistent with results of flow cytometry showing that loss of cell DNA content caused by the factor was greater in EL-4 cells. The data indicate that calprotectin induces the apoptosis of certain tumor cells but that the occurrence of DNA fragmentation is dependent on cell type. Finally, the apoptosis-inducing activity of the calprotectin sample was abrogated by the presence of 10 microM zinc, whereas it was not affected by 5 mM calcium or magnesium.

Animals↗
PubMed1995

[The effects of the treatment with oxitropium bromide after one month or more in patients with pulmonary emphysema--evaluation of pulmonary function tests, exercise tests, and a questionnaire].

Chronic effects of oxitropium bromide were studied in patients with pulmonary emphysema. Pulmonary function tests, an exercise test, and a questionnaire were used. Seven subjects underwent two successive studies, including a questionnaire on QOL, pulmonary function tests, and an exercise test before and after one month or more of regular inhalation of ocitropium bromide (600 micrograms/day). The complaint of breathlessness was significantly reduced and the ability to perform activities of daily living had improved slightly after the treatment. There were no significant differences in the values of arterial oxygen pressure at rest. The VC, RV/TLC, and peak expiratory flow rate improved. A significant decrease in oxygen uptake at rest, a slight decrease in minute ventilation at rest, and a significant prolongation of exercise time were observed after the treatment. No other changes were noted. We conclude that oxitropium bromide may improve lung mechanics and reduce the work of respiratory muscles.

Administration, Inhalation↗
PubMed1993

[Effects of a synthetic progestin on ventilatory response to hypoxia in awake male rats].

The effect of progesterone is most likely exact by directly stimulating the central nervous system. However, it remains unclear whether progesterone and/or estrogen act through the peripheral chemoreceptor. The carotid body is thought to be the sole sensing organ of hypoxia. The present study was conducted to determine whether administration of female hormones, i.e., progestin and/or estrogen, augment ventilatory response to hypoxia in the awake male Wistar rat. The combined administration of a synthetic progestin (TZP 4238) and estradiol for 5 days significantly increased tidal volume and minute ventilation, reduced arterial PCO2, and enhanced the ventilatory response to hypoxic gas inhalation. Augmentation of hypoxic ventilatory response was achieved by a increment of respiratory rate with a shortening of expiratory time. Administration of either TZP 4238 or estradiol alone or vehicle had no effects on respiratory variables. Our results suggest that female hormones may act through the peripheral chemoreceptor as well as the central nervous system.

Animals↗
PubMed1992

Structural characteristics of the ceramides of neutral glycosphingolipids in the human female genital tract--their menstrual cycle-associated change in the cervical epithelium and uterine endometrium, and their dissociation in the mucosa of the fallopian tube with the menstrual cycle.

In human cervical epithelium, uterine endometrium, and mucosa of the fallopian tubes, neutral glycosphingolipids were exclusively represented by the globo-series glycosphingolipids, such as CMH, LacCer, Gb3Cer and Gb4Cer, but the molecular species of their ceramide moieties were characteristically altered in the cervical epithelium and uterine endometrium during the menstrual cycle. Individual neutral glycosphingolipids in the cervical epithelium and the uterine endometrium at the follicular phase gave two bands on TLC, whereas those at the luteal phase displayed three bands, the third being the lower migrating one. Neutral glycosphingolipids migrating to the same positions as these lower-migrating bands were constantly detected in the mucosa of the fallopian tubes, independent of the menstrual cycle. The lower-migrating bands for the cervical epithelium and the uterine endometrium at the luteal phase were due to molecules mainly constructed of phytosphingosine with alpha-hydroxy fatty acids having chain lengths of 18-24 and 4-sphingenine with alpha-hydroxy fatty acids having chain lengths of 16-22, whereas those in the mucosa of the fallopian tubes were exclusively N-alpha-hydroxypalmitoyl 4-sphingenine.

Ceramides↗
PubMed1992

Menstrual cycle-associated expression of 2-hydroxy fatty acyl phytosphingosine-containing GlcCer, LacCer and Gb3Cer in human uterine endometrium.

In the previous study, we found that sulfatide was characteristically expressed in the secretory phase of human uterine endometrium and that the metabolism of glycosphingolipids was strictly controlled by sex steroid hormones. Therefore, the neutral glycosphingolipid composition of human uterine endometrium in the proliferative and secretory phases was analyzed and was found to be characteristic in both phases. The major neutral glycolipids were GlcCer, LacCer, Gb3Cer and Gb4Cer. The concentrations of GlcCer, LacCer and Gb3Cer in the secretory phase were higher than those in the proliferative phase. Furthermore, on TLC, GlcCer, LacCer and Gb3Cer in the proliferative phase gave three bands, the 3rd band, which migrated to the lowest position, being much more predominant in the secretory phase. The individual band materials in both phases were purified by silica gel column chromatography, and their structures were analyzed by FABMS and GLC. The lower-migrating bands of GlcCer, LacCer and Gb3Cer were found to contain molecules with 2-hydroxy fatty acyl phytosphingosine, indicating that hydroxylation of the fatty acid and sphingosine moieties to give 2-hydroxy fatty acid- and phytosphingosine-containing glycosphingolipids, respectively, is induced selectively in the secretory phase on a change in the hormonal environment.

Cerebrosides↗
PubMed1992

Human uterine endometrial adenocarcinoma: characteristic acquirement of synthetic potentials for II3SO3-LacCer and ganglio series sulfoglycosphingolipids after transfer of the cancer cells to culture.

The acidic glycosphingolipid composition of human uterine endometrial adenocarcinoma was compared with those of normal uterine endometrium at the proliferative and the secretory phases. Upon chemical composition analysis, no significant transformation-associated change of these glycolipids was observed. However, when cancer cells from the patients with human uterine endometrial adenocarcinoma were transferred to culture, the composition of glycosphingolipids, particularly sulfoglycosphingolipids, was significantly altered after the 70th doubling time. I3SO3-GalCer, which was contained in the original tissues of uterine endometrial adenocarcinomas, disappeared completely from the cultured cells at the 70th doubling time, whereas II3SO3-LacCer and ganglio series sulfoglycosphingolipids, which were originally contained in a trace amount or not present at all in the cancer tissues, became the major components in the total acidic glycosphingolipids in the cultured cells. Also, among cell lines established from several gynecological cancers, which include uterine cervical squamous carcinoma, uterine endometrial adenocarcinoma, ovarian clear cell carcinoma, choriocarcinoma, uterine sarcoma, ovarian sarcoma, and vulvar melanoma, only those cells derived from uterine endometrial adenocarcinoma expressed II3SO3-LacCer and ganglio series sulfoglycosphingolipids and the synthetic activities of these sulfoglycolipids, indicating that uterine endometrial adenocarcinoma cells characteristically lose the sulfotransferase to GalCer and acquire the sulfotransferase to LacCer after being transferred to culture in vitro. Thus, the unique sulfoglycosphingolipids and sulfotransferase are useful markers for the characterization of uterine endometrial adenocarcinoma among human gynecological cancers.

Adenocarcinoma↗
PubMed1992

Effects of gentamicin on catecholamine levels in the striatum, hypothalamus, adrenal gland and vas deferens.

The effects of gentamicin, an aminoglycoside antibiotic, on changes in the catecholamine levels in the rat striatum, hypothalamus, adrenal medulla and vas deferens were studied. When rats were i.v. injected with gentamicin (1.0 mg/kg), the catecholamine content of all tissues increased 2-4 h after injection. The increases in catecholamine levels induced by gentamicin were about 1.4- to 2.3-fold those induced by saline. The effect of gentamicin was observed at 0.1 or 0.5 mg/kg, and was maximal at 2.0 mg/kg. The activity of tyrosine hydroxylase, a rate-limiting enzyme in catecholamine biosynthesis, was markedly increased in all four tissues of rats treated with gentamicin (1.0 mg/kg, 4 h). However, direct addition of gentamicin to the tyrosine hydroxylase assay medium did not affect tyrosine hydroxylase activity. These data indicate that gentamicin administration to rats increases the catecholamine content of both central and peripheral catecholamine-containing tissues. The results also suggest that the effect of gentamicin is due to an indirect activation of tyrosine hydroxylase.

Adrenal Medulla↗
PubMed1992

Small cell colonies appear in the primary culture of adult rat hepatocytes in the presence of nicotinamide and epidermal growth factor.

Colonies of small hepatocytes appeared after the culture of primary adult rat hepatocytes for 4 days in serum-free modified Dulbecco's modified Eagle's medium containing 10 mmol/L nicotinamide and 10 ng/ml epidermal growth factor. Each colony consisted of cells that had a single nucleus and a higher nucleus/cytoplasm ratio than surrounding hepatocytes, and immunocytochemically these cells were stained with albumin and transferrin. Ultrastructurally these cells had mitochondria, peroxisomes and desmosomes, indicating that they were derived from hepatocytes. When 6 x 10(5) cells were plated on 35-mm dishes, about 5.5 colonies/mm2 were observed. This result suggested that about 1.5% of adult rat hepatocytes has the potential for multiple replications and of forming a focal colony. These cell populations had higher proliferative activities than surrounding hepatocytes. DNA synthetic activity could not be inhibited by 2% dimethyl sulfoxide. Flow cytometric analysis showed that both 2N and 4N nuclei synthesized their DNA until day 4 but that the number of 2N nuclei rapidly increased at day 5. This result correlated with the observation of the appearance of small cell populations indicating that the cells of these focal colonies were predominantly diploid.

Animals↗
PubMed1992

[Continuous monitoring of coronary venous oxygen saturation during PTCA and its relation to electrocardiographic ST changes].

The purpose of this study was to investigate change in coronary venous oxygen saturation (CSO2-Sat) during percutaneous transluminal coronary angioplasty (PTCA) and to compare the results with those of standard 12-lead ECGs (s-ECG) and epicardial ECG induced using an intracoronary guidewire (ic-ECG). CSO2-Sat was measured continuously in 10 patients undergoing PTCA; 5 patients with lesions in the left anterior descending coronary artery (LAD), one with lesions in the left circumflex artery (LCX), and 4 with right coronary artery (RCA) lesions. The results were as follows: 1. In all 6 patients with stenotic lesions in the left coronary artery, CSO2-Sat decreased by 5 to 22% immediately after balloon inflation. Significant changes in ic-ECG (ST deviation > or = 0.1 mV) were observed in 5 of the 6 patients, while significant changes in s-ECG (ST deviation > or = 0.1 mV) were observed in only 3 of the 6 patients. The s-ECG did not seem to be sensitive enough to represent myocardial ischemia in the LCX. 2. The interval from the balloon inflation to the significant change was shorter for CSO2-Sat than for the ECGs in 4 of the 5 patients with LAD lesions, except Case 4. The recovery time of CSO2-Sat to the basal level on balloon deflation was longer than the recovery times of ic-ECG and s-ECG. 3. There was no significant change in the CSO2-Sat in 3 of the 4 patients undergoing PTCA for RCA lesions, while significant changes were observed in the ic-ECG and s-ECG in all 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

[Inverse relationship between coronary flow velocity and myocardial oxygen extraction during intracoronary infusion of papaverine].

The relationship between coronary blood flow velocity (CBFV) and myocardial oxygen extraction (O2-Ext) was investigated during rapid changes of CBFV after intracoronary papaverine infusion. In 6 patients without stenosis of the left anterior descending artery (LAD), one with hypertrophic cardiomyopathy, 2 with syndrome X and 3 with effort angina pectoris, simultaneous measurements of CBFV using the Doppler catheter system and coronary venous oxygen saturation using the fiberoptic catheter system were continuously performed before and during intracoronary infusion of papaverine. When O2-Ext was related to CBFV in every cardiac cycle, there was a good, inverse linear relationship, both in the increase (r = 0.81 +/- 0.24) and decrease (r = 0.93 +/- 0.04) phases of CBFV. The increase in cross-sectional area of segment 6 in the LAD as observed on orthogonal coronary angiograms was 6.0 +/- 2.0%. These results imply that the increase in CBFV during intracoronary papaverine infusion seems parallel to that of coronary blood flow, and that papaverine induces no significant change in myocardial oxygen consumption. Myocardial oxygen extraction in response to changes in coronary flow is regulated readily to meet the myocardial oxygen demand.

Adult↗
PubMed1992

[Are the first repetitive reentrant VPCs a trigger or an initiation of reentrant circuit for VPCs?: Evaluation by Holter ECG in patients with reentrant sustained ventricular tachycardia].

To evaluate whether the first repetitive reentrant VPCs are a trigger or an initiation of a reentrant circuit for VPCs, we studied Holter ECGs in 13 patients with sustained ventricular tachycardia, the morphology of reentrant VPCs, the relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V), and the relationship of the coupling interval (N-V) between single VPC and repetitive VPCs. In 7 patients who showed episodes of repetitive VPCs more than twice on one recording of Holter ECG, most of VPCs in the first and second beats were the same in shape (1195 out of 1466 episodes, 82%). No obvious relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V) was found in 5 patients, whereas a weak inverse relationship (r = 0.32) was found in one patient, and a weak positive relationship (r = 0.38) was found in another patient. In addition, the coupling interval in repetitive VPCs was longer than that in single VPCs in 4 out of 7 patients. These results imply that, in most cases, the first VPC is the expression of initiation of a reentrant circuit for repetitive reentrant VPCs developing spontaneously.

Adult↗
PubMed1992

[A case of atrial standstill associated with combined valvular disease].

A 62-year-old man was admitted to our hospital because of general malaise. The chest X-ray film showed severe cardiomegaly (CTR = 81%). The electrocardiogram demonstrated absence of P wave in 12-leads and regular junctional rhythm with incomplete right bundle branch block. Echocardiogram and color Doppler led to the diagnosis of mitral stenosis and regurgitation, tricuspid regurgitation with enlarged left and right atrium. Cardiac catheterization study revealed elevation of the pulmonary artery wedge pressure and the right atrial pressure without A wave. In the electrophysiologic study, no atrial electrical activity was recorded in the right atrium and the coronary sinus. However, when atrial pacing was attempted at multiple sites with stimulum strength of 10 V, there was no atrial activity at various sites. We considered that the atrial overload due to combined valvular disease for seventeen years had resulted in total and persistent atrial standstill. In this report, we discussed atrial standstill in 67 cases recorded in the medical literatures in our country.

Echocardiography↗
PubMed1991

Respiratory stimulation by female hormones in awake male rats.

The respiratory effect of progestin differs among various animal species and humans. The rat does not hyperventilate in response to exogenous progestin. The present study was conducted to determine whether administration of combined progestin and estrogen prompts ventilatory stimulation in the male rat. Ventilation, blood gases, and metabolic rates (O2 consumption and CO2 production) were measured in the awake and unrestrained male Wistar rat. The combined administration of a synthetic potent progestin (TZP4238) and estradiol for 5 days significantly increased tidal volume and minute expiratory ventilation (VE), reduced arterial PCO2, and enhanced the ventilatory response to CO2 inhalation (delta VE/delta PCO2). On the other hand, respiratory frequency, O2 consumption, CO2 production, and body temperature were not affected. The arterial pH increased slightly, with a concomitant decrease in plasma [HCO3-]. Administration of either TZP4238 or estradiol alone or vehicle (Tween 80) had no effect on respiration, blood gases, and ventilatory response to CO2. The results indicated that respiratory stimulation following combined progestin plus estradiol treatment in the male rat involves activation of process(es) that regulate tidal volume and its augmentation during CO2 stimulus.

Animals↗
PubMed1991

Biochemical analysis of glycosphingolipids in murine uterus and human uterine endometrium with special reference to the sexual cycle.

Uterus is an organ in which cellular proliferation and differentiation are strictly controlled by sex steroid hormones. Since we found a characteristic expression of sulfatide (I 3SO3-GalCer) in the human endometrium during its secretory phase, we decided to analyze developmental changes of glycolipids in murine uteri with special reference to the estrous cycle. Moreover, we analyzed sulfotransferase activity for the synthesis of sulfatide in the endometria in the proliferative and secretory phases and that in the epithelial and stromal cells derived from the human uterine endometrium. In the murine uterus, contents of GlcCer, LacCer, and Gb4Cer were relatively constant both during estrus and diestrus, but those of Gb3Cer and Gg4Cer during estrus were significantly greater than those during diestrus. In contrast, GM3 and sulfatide contents during diestrus were higher than those during estrus. This increase in GM3 and sulfatide during diestrus was characteristically observed in the uterus after sexual maturity. In human uterine endometrium, sulfotransferase activity for the synthesis of sulfatide was found only in the epithelial cells, but not in the stromal cells. Furthermore, the synthetic potential of sulfatide in the human endometrium was higher in the secretory phase than in the proliferative phase. Thus, sulfatide metabolism in human endometrial epithelial cells as well as in the murine uterus is supposed to be well controlled under hormonal regulation, and sulfatide may participate in several reproductive functions of the uterus.

Animals↗
PubMed1991

Effects of carvedilol on serum lipids in patients with essential hypertension.

The purpose of this study was to investigate the effect of carvedilol on serum lipids in patients with mild-to-moderate essential hypertension. Twenty-one patients with blood pressure greater than or equal to 160/95 mm Hg after a 4-week placebo run-in period were initially given 10 mg of carvedilol once daily. The dose was increased to 20 mg after 4 weeks if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks of administration, blood pressure and the pulse rate (PR) declined significantly (blood pressure from 173/105 to 142/91 mm Hg, p less than 0.001; PR from 74 to 67 beats/min, p less than 0.001); however, serum lipids [total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein (HDL), HDL2, and HDL3], lipoprotein fraction (alpha, pre-beta, and beta), apoprotein fraction (A-I, A-II, CII, CIII, and E), and atherogenic index [(total cholesterol - HDL cholesterol) divided by HDL cholesterol] were not altered significantly. There were no side effects reported during the trial. From these results, it can be concluded that carvedilol has no adverse effect on the coronary risk profile as reflected by lipid measurements, and is an efficacious, safe, well-tolerated antihypertensive drug in patients with mild-to-moderate hypertension.

Adrenergic alpha-Antagonists↗