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Biomedical subjects

M Mikami

Publications and source records attributed to M Mikami.

At least 73 records · Page 4Linked to original sources

In vitro studies on a new method for islet microencapsulation using a thermoreversible gelation polymer, N-isopropylacrylamide-based copolymer.

Various materials for the semipermeable membrane for microencapsulation of islets, such as alginate complex and agarose, have been used. In this study, a thermoreversible gelation polymer, N-isopropylacrylamide based copolymer was used to make microencapsulated islets and was examined in vitro. The polymer has little or no cytotoxicity for human dermal fibroblasts. The characteristics of viscoelasticity below the soluble gel transition temperature (SGTT) and of thermoreversibility, the water soluble polymer below the SGTT (22 degrees C) becoming water insoluble upon heating, contributed to simplifying the encapsulation technique. We obtained viable islets at the center of the membrane with a thickness of approximately 20-50 microns, accounting for a 40% yield of encapsulated islets. Static glucose challenge test with microencapsulated islets revealed the insulin response to the concentration of glucose. The insulin concentrations of the culture medium in the microencapsulated islet group were the same as those in a similar free islet group up to 42 days. These results indicate that the morphological and functional stability of the new method for microencapsulation may be sufficient for it to be used for transplantation in diabetic animals.

Acrylamides↗

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↗

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↗

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↗

[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↗

Evaluation of serum uric acid to creatinine ratio in fulminant hepatitis.

Of the eight patients with fulminant hepatitis placed under total parenteral nutrition with an amino acid solution rich in branched chain amino acids and treated by plasma exchange, four survived and four died from hepatic failure. Serum uric acid levels in the non-survived group were significantly lower on days 1-6 compared with the survived group. The concentration ratios of uric acid to creatinine and prothrombin time were significantly lower on days 5-8 and days 3-8, respectively, in a similar comparison. Thus, the uric acid to creatinine ratio, which corrects for the possible renal dysfunction associated with acute hepatic failure, may serve as a clinically useful prognostic indicator for patients with fulminant hepatitis.

Adolescent↗

Administration of a branched-chain amino acid preparation during hepatic failure: a study emphasizing ammonia metabolism.

We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.

Adult↗

Characterization of cell growth-inhibitory factor in inflammatory peritoneal exudate cells of rats.

We characterized the nature and reaction mode of the cell growth-inhibitory factor (here designated CGIF) from rat peritoneal exudate cells (PEC). The soluble fraction separated from the lysate of Enterococcus faecalis-induced 24 hr PEC completely inhibited Con A-induced thymocyte mitogenesis. Gel filtration chromatography showed that CGIF has a molecular weight of approximately 23-25 kDa. Isoelectric focusing with Rotofor indicates that the factor has an isoelectronic point of 5.8-6.4. CGIF was inactivated by treatment at 70 C, for 30 min or by tryptic digestion, but the activity was not destroyed by the reduction with dithiothreitol. As well as thymocyte proliferation, CGIF completely suppressed 3H-thymidine incorporation of splenocytes which were stimulated by either Con A or LPS, suggesting the factor is effective on both T and B cells. The acting point of the inhibitor appeared to be a later stage of the lymphocyte activation sequence, since it was still effective when added 28.5 hr after the addition of Con A. CGIF also reduced the viability of these cells when added with mitogens such as Con A or LPS. CGIF thus appears to be distinct from interleukin-1 receptor antagonist or transforming growth factor-beta.

Animals↗

Hemostasis of gastric variceal hemorrhage by transileocoecal and transhepatic obliteration.

Obliteration for gastric or duodenal variceal hemorrhage was performed via transileocoecal or transhepatic portal catheterization in 8 patients with portal hypertension. The patients were 6 men and 2 women, whose average age was 59 years. All of the patients had cirrhosis of the liver. The obliteration was performed as an emergency procedure in 6 cases, and 2 patients were electively treated. Transileocoecal obliteration (TIO) and transhepatic obliteration (PTO) were selected for 6, and 2 patients, respectively. Variceal bleeding was successfully controlled in all patients after completion of the therapy. One patient died after 3 months when duodenal variceal bleeding recurred. Elective surgical operations were performed on 2 patients after the initial therapy, because the vein feeding toward the varices remained. Six of the patients have survived to date without bleeding. Transient oliguria and jaundice after the therapy were noticed in 2 patients. Histological examination revealed cast formation of polymerized cyanoacrylate in the obliterated gastric varices of 2 patients. TIO and PTO seem to be safe, effective procedures to stop bleeding from ectopic varices, gastric or duodenal. This therapy is useful either to obtain accurate information about the varices or to obliterate the collateral veins in patients with ruptured ectopic varices.

Adult↗

Pulmonary aspergilloma successfully treated with long-term intermittent inhalation therapy with miconazole.

A 63-year-old man developed pulmonary aspergilloma and was given antifungal agents systemically. However adverse reactions, including renal dysfunction and gastric ulcer necessitated discontinuation of the treatment. Transbronchial infusion of miconazole was also unsuccessful because of an asthmatic attack during the procedure. Inhalation of miconazole was started once a week, resulting in remarkable improvement after 6 months of treatment both symptomatically and radiologically without any adverse reactions. We believe that long-term intermittent inhalation therapy with miconazole is well tolerated and useful in patients with aspergilloma, particularly when systemic treatment is difficult because of other underlying diseases or adverse reactions.

Administration, Inhalation↗

[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↗

[Physicochemical properties of sputum from patients with immotile cilia syndrome].

Sputum samples were collected from 15 immotile cilia syndrome (ICS) cases, 12 diffuse panbronchiolitis (DPB) cases, and 11 bronchiectasis without ICS (BE) cases, during stable clinical state, to clarify the physicochemical properties of sputum from patients with ICS and to compare them with the properties of sputum from patients with DPB and BE. We measured sputum rheological properties and concentrations of several biochemical components. In ICS, spinnability was higher than that in DPB. No significant difference was seen between ICS and the other cases regarding other rheological properties. Albumin was lower, but fucose, sialic acid, and IgA were higher in ICS than in DPB. Although no significant difference was seen between ICS and BE, the sialic acid/albumin ratio was higher and the sialic acid/fucose ratio was lower in ICS than in BE. These results revealed that sputum from ICS cases was characterized by an absolutely or relatively increased mucus component with high spinnability and by a decreased extravascular transudate component. In view of these rheological properties, sputum from ICS cases was not always indicated to be associated with efficiency in cough clearance. The results suggested that chronic airway inflammation in ICS is not such a serious problem compared with DPB and BE.

Adolescent↗

Monoclonal gammopathy in atomic bomb survivors.

An analysis of monoclonal gammopathy in relation to radiation exposure was conducted on atomic bomb survivors examined between October 1979 and September 1981 and between June 1985 and May 1987. There was no overall increase in the relative risk of monoclonal gammopathy and only a suggestive increase in benign monoclonal gammopathy in the second survey which did not achieve statistical significance (P = 0.17). Thirty-one cases were detected among 8796 individuals studied in the first survey, whereas 68 cases were found among 7350 people in the second survey. Among the 31 cases found in the first survey, 9 individuals (29%) died before the second survey: 4 of cancer, 4 of vascular disease, and 1 of infection. Among the 8 individuals with benign monoclonal gammopathy examined in both surveys, 4 developed suppression of residual immunoglobulin(s), suggesting the progression of monoclonal gammopathy. The overall relative risks of monoclonal gammopathy in atomic bomb survivors in the two surveys were not significantly increased with increasing radiation dose. Only benign monoclonal gammopathy in 1985-1987 showed a suggestive increase with radiation exposure. The relative risk of benign monoclonal gammopathy in 1985-1987 was 2.64 in the group exposed to 0.01-0.49 Gy and 2.14 in the > or = 0.50-Gy group (95% confidence intervals = 0.90-8.82 and 0.69-7.31, respectively).

Female↗

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↗

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↗