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Biomedical subjects

M Miki

Publications and source records attributed to M Miki.

At least 19 recordsLinked to original sources

The mechanism of inhibition of the actin-activated myosin MgATPase by calponin.

Calponin inhibits the actin-activated ATPase of smooth muscle myosin and thus has been proposed as a thin filament-based regulatory component in smooth muscle. To obtain information on the mechanism of inhibition by calponin we have used chemical modification of actin and cross-linking of actin and subfragment 1. Modification of Lys 61 of actin had no effect on the inhibition by calponin of acto-heavy meromyosin ATPase, i.e. different from tropomyosin-troponin. In addition, modification of the acidic N-terminal region of actin did not impair the ability of calponin to bind to F-actin. Finally, calponin was effective in inhibiting ATPase activity of cross-linked acto-subfragment 1. Therefore the mechanism of inhibition by calponin is distinct from troponin-tropomyosin and caldesmon in that it does not involve either the N-terminal acidic region of actin nor the area around Lys 61 and does not fit a simple steric blocking model.

Actins

Malignant cell-specific gelatinase activity in human endometrial carcinoma.

BACKGROUND: The protease activity leading to degradation of the extracellular matrix was compared between human endometrial cancer and normal uterine endometrium. METHODS: Conditioned medium from tumor cells and normal endometrial cells was subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gel containing gelatin as a substrate. After electrophoresis, the gel was stained with Coomassie blue, and then the enzyme activity, expressed as the zone of dye clearing, was analyzed by densitometry. RESULTS: Densitometric analysis showed that all the endometrial cancers expressed a very high molecular weight enzyme activity (Mr 220,000), which was not detected in medium from normal endometrial cells. The analysis also showed that in endometrial cancer the activity of a Mr 92,000 enzyme was always superior to that of a Mr 64,000 enzyme, which was in contrast to the situation for normal endometrium. CONCLUSIONS: These results indicate that the expression of Mr 220,000 enzyme activity and the higher activity of the Mr 92,000 enzyme than the Mr 64,000 enzyme are involved in the malignant phenotype of native endometrial cancer.

Adenocarcinoma

Removing the two C-terminal residues of actin affects the filament structure.

We define conditions under which the two C-terminal residues of actin, Cys-374 and Phe-375, can be selectively removed by proteolysis with trypsin. This modification had little effect on the secondary structure of actin detected by Fourier-transform infrared spectroscopy. However, removing these residues caused small but significant decreases in the critical concentration of actin, in its ability to activate myosin ATPase, and in its interaction with tropomyosin and troponin. Removing residues 374-375 caused dramatic changes in the actin filament as seen by electron microscopy. The filaments had a much greater and more irregular curvature and were intertwined into disordered multifilament bundles. Removing 374-375 also significantly lowered the flow viscosity of filamentous-actin solutions. These data suggest an increase in the flexibility and fragility of the filament, supporting the idea that the C-terminus forms one of the major intermonomer contacts in the filament.

Actin Cytoskeleton

Portosystemic collateral shunts originating from the left portal veins in portal hypertension: demonstration by color Doppler flow imaging.

Color Doppler flow imaging was performed in 121 patients with portal hypertension. Portosystemic collateral shunts originating from the left portal veins were seen in 41 of the patients. A single collateral shunt was seen in 27 of these, and multiple collateral shunts were seen in the other 14. Collateral shunts running in the ligamentum teres were seen in 26 of the 41 patients; the veins ran through the liver parenchyma in 25 of these. B-mode ultrasound imaging could not clearly demonstrate vascular structures in 55% of the collateral shunts. Color Doppler flow imaging provided a clear picture of the course of the portosystemic collateral shunts originating from the left portal vein.

Adult

Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy.

In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.

Animals

Difference in inhaled aerosol deposition patterns in the lungs due to three different sized aerosols.

Deposition patterns of inhaled aerosol in the lungs were studied in five normal subjects and 20 patients with lung disease by inhaling radioaerosols with three different particle size distributions. These aerosols were generated from BARC, UltraVent, and Mistogen-EN-142. Particle size distributions generated by these three nebulizers were 0.84, 1.04 and 1.93 microns in activity median aerodynamic diameter (AMAD) with its geometric standard deviation (sigma g) of 1.73, 1.71 and 1.52, respectively. Deposition patterns of inhaled aerosols were compared qualitatively and quantitatively by studying six different parameters: alveolar deposition ratio (ALDR), Xmax, Xmean, standard deviation (S.D.), skewness and kurtosis of the radioactive distribution in the lungs following inhalation. It has been found that aerosol deposition patterns varied with particle size. The unevenness of aerosol deposition, Xmax, Xmean and the number of 'hot spots' became more prominent with the increase in particle size, whereas values of ALDR and S.D. decreased as particle size increased. Knowing these deposition characteristics would facilitate a judicious application of aerosol inhalation to medical use.

Administration, Inhalation

[The kinetic changes in murine lymphocyte subsets in regenerating liver].

The regeneration of the liver is frequently observed after the resection of liver tumor and partial liver transplantation, and it is assumed that the modification of the hematolymphoid system in the liver will occur during this process and influence not only the progress of the primary disease but also liver regeneration itself. In this study, we investigated by flow cytometric analysis the modification of the cell subpopulation in the peripheral blood lymphocytes (PBL), intrahepatic lymphocytes fraction 1, which come into marginal contact with the liver (IHL Fr. 1), and intrahepatic lymphocytes fraction 2, which come into close contact with the liver (IHL Fr.2). (1) The positive cells of each antigen (Thy 1.2, alpha beta TCR, gamma delta TCR, CD4 and CD8) exist in the normal liver as PBL. (2) CD8/CD4 ratio is 0.3-0.4 in PBL and IHL Fr.1 and significantly higher in IHL Fr.2 (0.7). (3) Compared with other fractions, the ratio of alpha beta TCR dull positive cells to whole alpha beta TCR positive cells is low, while (4) the percentage of gamma delta TCR positive cells is high in IHL Fr.2. These facts suggest that lymphocyte populations in the liver differ from those of PBL. Furthermore, one day after partial hepatectomy, (5) the percentage of the alpha beta TCR dull positive cells decreases in PBL, but remarkably increases to 2.6 times the normal level in IHL Fr.2 and (6) the ratio of CD8/CD4 increases to 1.4 times in IHL Fr.2. (7) The percentage of gamma delta TCR positive cells decreases in PBL, but does not significantly change in IHL Fr. 2 during the liver regeneration. These findings reveal that lymphocyte populations different from PBL exist in the liver and respond to stimulus to the liver in different ways from PBL. The mechanism for the modification occurring in the IHL population during liver regeneration and its biological significance are discussed.

Animals

Functional expression of human myometrial endothelin receptors in Xenopus laevis oocytes.

We demonstrate the existence of functional endothelin receptors in human uterine myometrium using the Xenopus oocyte expression system. Fifty nanograms of poly(A)+RNA from myometrium was injected into Xenopus laevis oocytes and incubated for 70-80 h. The membrane potential of the oocyte was clamped at -60 mV and membrane current was measured during and after endothelin stimulation. Endothelin-1 elicited a large inward membrane current in the oocytes injected with poly(A)+RNA; endothelin-2 elicited a small current; while endothelin-3 did not induce any membrane current. These results indicate the existence of messenger RNA encoding functional endothelin-1 receptors in human uterine myometrium.

Animals

[Basic and clinical evaluation of the new kit for detection of serum prostate specific antigen (PSA)].

BALL-ELSA PSA is a monoclonal radioimmunometric assay kit for detection of serum prostate specific antigen (PSA) developed and generally used in Europe. Basic and clinical study of the kit was performed for evaluation of it's utility in Japanese patients. The sera from 56 patients with benign prostatic hyperplasia (BPH), 35 patients with prostate cancer (PCA) and 18 normal males were examined. Other kits such as EIKEN PSA and EIKEN PAP (prostatic acid phosphatase) were also evaluated in same sera. The results of the range in the measurement, within-assay error, between-assay error, dilution test, recovery test and others were well satisfied. In our clinical study, mean + 2SD of serum PSA values in normal males was 2.57 ng/ml. Serum PSA values determined by the two RIA kits, BALL-ELSA and EIKEN, showed a good correlation (r = 0.9909), but the BALL-ELSA PSA kit yielded values about 2.4 times higher than the EIKEN PSA kit on the same sample. We think that the difference might be largely due to differences in assigned PSA calibrators and diluents between the assay kits. Further investigations and discussions were expected on this point. In our study, the most suitable cut-off level for distinguishing PCA from BPH in BALL-ELSA PSA kit was 10.0 ng/ml.

Adult

[Intraarterial COMPA (cis-diammine-dichloroplatinum (II), vincristine, methotrexate, peplomycin, adriamycin) chemotherapy for bladder cancer].

Seventeen patients with bladder cancer were treated with semiselective intraarterial COMPA chemotherapy. One course of COMPA consisted of 20 mg/m2 cis-diammine-dichloroplatinum (CDDP) on days 4 and 5, 0.6 mg/m2 vincristine (VCR) (Oncovin) on days 1 and 2, 5 mg/m2 methotrexate (MTX) on days 2 and 3, 5 mg/body peplomycin (PEP) on days 1, 2 and 3, and 15 mg/m2 adriamycin (ADM) on day 4. These drugs were injected every 2 or 3 weeks through a polyurethane catheter the tip of which was placed just proximal to the aortic bifurcation and during injection both thighs were tied with a pressure of over 250 mmHg. From 2 to 6 courses (mean, 4.4 courses) were administered. Of the 17 patients, 4 achieved complete remission, 10 achieved partial remission and 3 showed no change. After this COMPA chemotherapy eight patients were able to retain their bladders while seven underwent immediate radical cystectomy. The adjuvant COMPA chemotherapy for two patients with pelvic metastasis after radical cystectomy showed good results. Mild degrees of anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, leukopenia and intestinal paralysis were observed. Instrumental troubles were seen in two cases; one involved dislocation of the tip of the catheter, the other was infection of the reservoir. Intraarterial COMPA chemotherapy is effective for neoadjuvant therapy of invasive bladder cancer, bladder-preserving treatment and adjuvant therapy of pelvic metastasis.

Aged

Incidence of cholelithiasis in the northern part of Thailand.

It may be concluded from comparisons of recent u/s examinations in Northern Thailand to studies in Japan and to the gallstone study conducted over two decades ago that gallstone disease in Thailand is starting to exhibit the same situation as in the West. In comparing overall rates over time the gallstone incidence in Thailand appears to have climbed from 2.61 to 3.10 per cent (Fig. F). The rate increase is even more significant when broken down by sex (male: 1.89%--> 2.50%, female: 3.23%--> 3.70%). In addition, the present rates of female and male gallstone incidence in Northern Thailand closely match the rates found in studies of the Japanese population. Because gallstone disease has become a major public health problem in the West, a number of studies have emphasized the epidemiological characteristics of the disease in order to implement controls. As Thailand's gallstone problem seems to be heading towards the same level of importance further studies involving epidemiological factor linkage may be necessary and the technological advances in Ultrasonography make such studies quite feasible.

Adult

[Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis].

This study was performed to investigate the mechanism by which 99mTc-DTPA molecules pass through the pulmonary epithelium following inhalation of 99mTc-DTPA aerosol. Interstitial pneumonitis was induced in 6-week-old male rats by instilling 1 mg/kg of bleomycin into the trachea. Disappearance of radioactivity from the lungs was measured with a gamma camera every 2 weeks to estimate pulmonary epithelial permeability, and light- and electron-microscopic histopathologic examinations were performed at the same intervals. There was a statistically significant increase in the pulmonary epithelial permeability at 2 weeks after the instillation of bleomycin. However, subsequent changes in pulmonary epithelial permeability were not uniform; some animals showed recovery and some showed further increase and/or partial recovery. Microscopically, increase in the capillary bed, round cell infiltration, and widening of the interstitial space were observed in addition to the presence of macrophages in the alveolar spaces at 2 weeks. Electron microscopic examination revealed vacuolization, thinning and detachment of the alveolar epithelium, and denudation of the basement membrane. Prominent fibrosis, honeycombing, thinning of the pulmonary epithelium, and increase in collagen fibers were observed after 18 weeks. We consider that vacuolization, thinning, and detachment of the pulmonary epithelium and denudation of the basement membrane are related to the increase in pulmonary epithelial permeability in bleomycin-induced interstitial pneumonitis.

Animals

[Relation between serum PAP (prostate acid phosphatase) and bone scintigraphy in prostatic cancer].

Seventy-seven patients with prostatic cancer were treated at our department in the last 5 years. Of these patients 30 cases were followed by bone scintigraphy and serum PAP. In 27 follow-up scintigraphy procedures changes of bone scintigraphy corresponded to changes in serum PAP levels Changes of PAP levels did not always correspond to changes of scintigraphy, but almost all cases in which the level of PAP increased in a short period showed progression of bone metastasis. A 3-month interval between bone scintigraphy procedure in stage D2 prostatic cancer patients is generally recommended. However, we think that in prostatic cancer patients follow-up bone scintigraphy at regular short intervals is unnecessary if there is no change in serum PAP levels, symptoms or physical condition. Bone scintigraphy should be performed when the tumor marker changes rapidly or when any physical symptom appears.

Acid Phosphatase

[Changes in pulmonary epithelial permeability due to thoracic irradiation].

The changes in pulmonary epithelial permeability during and following radiation therapy were studied in 10 patients with malignant diseases of the chest; 9 patients with bronchogenic carcinoma and one with thymoma. 99mTc-DTPA aerosol was inhaled during tidal breathing with the patient in supine position, and radioactivity was measured anteriorly by a gamma camera and recorded on a computer. Half time clearance (t1/2) was calculated from exponential fitting of time activity curves by regression analysis in various regions of interest in the initial 7 min following completion of aerosol inhalation. Studies were made every two weeks. In patients who developed radiation pneumonitis, t1/2 values decreased and reached the nadir at the time of manifest pneumonitis, indicating increased pulmonary epithelial permeability. Increased pulmonary epithelial permeability was observed not only in the pneumonic regions but also in the contralateral normal lung regions. Steroid therapy reversed these changes. Increased pulmonary epithelial permeability was observed in 2 out of 5 patients who did not develop radiation pneumonitis. In summary, pulmonary epithelial permeability changes occur not only in regions of radiation pneumonitis but also in non-irradiated lung regions following radiation therapy. We consider that the judicious use of this method enables detection of changes in pulmonary epithelial permeability prior to the development of clinical manifestations of radiation pneumonitis.

Aerosols

[Simultaneous double malignant tumors on functional solitary kidney: a case report].

A case of simultaneous double cancer on functional solitary kidney is reported. A 72-year-old man was admitted to the Department of Internal Medicine with angina, hypertension and diabetes mellitus. After treatment involving percutaneous transluminal coronary angioplasty, he was sent to the Department of Urology to check the microhematuria. Cystoscopy showed normal interior of urinary bladder. Drip infusion pyelography and computed tomography demonstrated a tumor mass on the upper pole of the right kidney and atrophic left kidney. Preoperative diagnosis was right renal cell carcinoma. However, an additional pelvic tumor was found during surgery, and a partial nephrectomy was performed. Histologic examination confirmed the presence of 2 separate and distinct malignant entities: a renal cell carcinoma and a non-invasive transitional cell carcinoma. Postoperative recovery has been uneventful and without hemodialysis for 16 months. This is the 19th case of simultaneous occurrence of renal cell carcinoma and transitional cell carcinoma in the same kidney and the 1st case in the patient with a functional solitary kidney in the Japanese literature.

Aged