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Biomedical subjects

M Miki

Publications and source records attributed to M Miki.

At least 91 records · Page 5Linked to original sources
PubMed1995

Hepatic damage induced by perfusion of radical generating azo compound and its inhibition by vitamin E.

The damaging effect of perfusion of hydrophilic radical generating azo compound on the liver of normal and vitamin E-deficient rats and its inhibition by antioxidants were studied in order to increase understanding of the action of free radicals on biological tissues. The hepatic damage was evaluated from the release of cytosolic enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, mitochondrial oxidation metabolism and morphological change. Two kinds of hydrophilic azo compounds were used, one which decomposes spontaneously at a uniform rate to generate free radicals and the other which does not. The former induced hepatic damage in a dose-dependent manner, while the latter did not exert any damage. Both endogenous vitamin E in the membranes and a water soluble vitamin E analogue added simultaneously with a radical initiator suppressed the hepatic damage. These results show that the hepatic damage induced by perfusion of radical generating azo compound is caused not by the azo compound itself but by free radicals.

Alanine Transaminase↗
PubMed1995

Plasma copper and antioxidant status in Wilson's disease.

It has been demonstrated that the level of serum copper unbound to ceruloplasmin (loosely bound copper) is increased in Wilson's disease, although the total serum copper concentration is usually low, reflecting a low ceruloplasmin level. To assess the contribution of free radical reactions catalyzed by nonceruloplasmin copper to the development of complications in this disease, we investigated copper and antioxidant status in four untreated patients who had hepatic dysfunction with or without hemolytic anemia and made a comparison with five patients controlled on penicillamine therapy and 19 age-matched healthy children. We found that loosely bound copper in plasma measured by the phenanthroline assay was detectable in three of four untreated patients with Wilson's disease, but was not detectable in the patients during therapy or in the healthy controls. Among the various antioxidants, the ascorbate and urate levels were markedly reduced before treatment (mean +/- SD, 23 +/- 16 microM for ascorbate and 90 +/- 59 microM for urate) compared with the values in the patients during treatment with penicillamine (67 +/- 19 and 302 +/- 78 microM, p < 0.05) and in control children (60 +/- 8 and 254 +/- 48 microM, p < 0.05). We also demonstrated that the plasma concentration of allantoin, an oxidation product of uric acid and a possible marker of radical generation in vivo, was markedly elevated in the untreated patients (11.0 +/- 1.8 versus 4.3 +/- 0.5 microM in patients on therapy and 6.5 +/- 0.8 microM in controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Allantoin↗
PubMed1995

Establishment of a cell line from an adenocarcinoma of the lung producing carcinoembryonic antigen (CEA) and CA19-9.

An adenocarcinoma cell line was established from pleural effusion of a 67-year-old woman and designated as TK-SA. The population doubling time of the cells was 100.4 hr. Chromosomal analysis revealed the TK-SA to have human aneuploid chromosomes with a near-triploid mode. Ultrastructurally, the TK-SA was compatible with adenocarcinoma. The cell line was highly tumorigenic. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye assay demonstrated resistance of the cell line to Cis-platin (CDDP), Cyclophosphamide (CPM) and Tegafur/Uracil (UFT). High carcinoembryonic antigen (CEA) and CA19-9 levels were similar in patient's serum and conditioned medium.

Adenocarcinoma↗
PubMed1995

Expression of intercellular adhesion molecule 1 on pancreatic beta-cells accelerates beta-cell destruction by cytotoxic T-cells in murine autoimmune diabetes.

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) by being involved in the extravasation of lymphocytes from the circulation into the inflamed pancreas. However, the mechanism of beta-cell destruction by which expression of ICAM-1 on beta-cells may facilitate adhesion of effector cells still remains to be elucidated. Several lines of evidence suggest that this adhesion molecule is involved in the destruction of pancreatic beta-cells by killer lymphocytes in the NOD mouse, which shows an autoimmune diabetic syndrome similar to that of human IDDM. Immunohistochemical study under light microscopy demonstrated that all of the mononuclear cells infiltrating the islets strongly expressed ICAM-1 and leukocyte function-associated antigen 1 (LFA-1), a counterreceptor of ICAM-1, whereas ICAM-1 expression on islet cells was not apparent. However, immunohistochemical staining under electron microscopy revealed that islet beta-cells adjacent to infiltrating lymphocytes were clearly stained by an anti-ICAM-1 monoclonal antibody (mAb). Flow cytometric analysis showed that the ICAM-1 expression on NOD islet cells and NOD-derived insulinoma cells (MIN6N8a) was inducible by interferon (IFN)-gamma or tumor necrosis factor-alpha. These cytokines had an additive effect on the ICAM-1 induction. Susceptibility of MIN6N8a cells to lysis by a NOD islet-derived CD8+ cytotoxic T-cell clone was greatly enhanced by IFN-gamma pretreatment, and this enhancement was abolished by anti-ICAM-1 and anti-LFA-1 mAbs. When both mAbs were administered into NOD mice with spontaneous or adoptively transferred diabetes, the development of diabetes was significantly prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Clinical results of IV-compa (cisplatin, vincristine, methotrexate, peplomycin and adriamycin) chemotherapy for advanced urothelial cancer].

We have developed a new combination intravenous chemotherapy regimen called COMPA (IV-COMPA). The clinical value of IV-COMPA chemotherapy was evaluated based on the results of 24 patients with urothelial cancers. From October 1989 through October 1993, a total of 24 patients (20 males and 4 females) received IV-COMPA chemotherapy at Tokyo Medical College Hospital and Tokyo Medical College Hachioji Medical Center. All patients had advanced transitional cell carcinoma or adenocarcinoma of the urothelial tract (renal pelvis, ureter or bladder). One course of IV-COMPA was delivered at 2-week intervals and consisted of 30 mg/m2 CDDP on day 4 and 5, 0.6 mg/m2 VCR (Oncovin) on day 1 and 2, 5 mg/m2 MTX on day 2 and 3, 5 mg/m2 PEP on day 1, 2 and 3, 20 mg/m2 ADM on day 4. A few patients received the same regimen without peplomycin called IV-COMA to avoid pulmonary fibrosis. Fifteen patients with surgically confirmed invasive carcinoma were defined by at least 1 of the following criteria: multiple tumors or size greater than 5 cm, grade 3, stage P3 or P4, pN+, pR1, pL1, pV1, or secondary carcinoma in situ. These patients were treated with 2 or 3 corpses of postoperative IV-COMPA chemotherapy to improve prognosis. In this group, 14 of 15 (93%) are alive at a median follow-up of 22 months (range, 8-57 months) and actuarial survival rates of 1 and 3 years were 100%, 90.9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

[Retroperitoneoscopic nephrectomy without pneumoperitoneum--experiments in pigs].

Laparoscopic nephrectomy has been performed widely for minimally invasive therapy. However, the procedure of insertion of needles and trocars can cause vascular and intestinal injuries. In addition, pneumoperitoneum using high pressure CO2 gas can cause circulatory and respiratory problems. In order to avoid these problems, we tried retroperitoneoscopic nephrectomy without CO2 gas in 8 kidneys of 4 pigs. A 1.5 cm skin incision was made just below the lowest rib and a small retroperitoneal space was made with the forefinger. The sheath of a 27 Fr rigid nephroscope was covered with a condom balloon and inserted into the retroperitoneal space. Under observing through the nephroscope, the condom was filled with 150-200 ml saline to make a space for the operation. After removing the nephroscope with condom, a scope and trocars were inserted into the space and retroperitoneoscopic nephrectomy was performed. Making the space with condom balloon in the retroperitoneal space was very efficient. The procedures succeeded in 8 and average procedure time was 3 hours. Retroperitoneoscopic nephrectomy without gas is a very attractive minimally invasive technique.

Animals↗
PubMed1995

Inhalation of pertechnegas: similar clearance from the lungs to that of inhaled pertechnetate aerosol.

It has been reported that the inhalation of pertechnegas (TGO3) generated under an atmosphere of 3% oxygen (O2) in argon (Ar) instead of 100% Ar without O2 in the technegas generator, offers a simple but accurate quantification of clearance from the lungs, permitting it to be used in place of 99Tcm-diethylenetriamine pentaacetic acid (DTPA). The disappearance from the lungs of inhaled TGO3 was so similar to that of inhaled pertechnetate aerosol (TcO4) in this study, that there was neither a statistically significant difference in the clearance half-time (t1/2), nor a difference in the lung images between them. Neither TGO3 nor TcO4 inhalation could distinguish smokers from non-smokers using t1/2. When inhaled, TGO3 appears to behave in a similar manner to TcO4 in the lungs and hence cannot be used in place of 99Tcm-DTPA in clinical practice.

Administration, Inhalation↗
PubMed1995

[Bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease: a case report].

A 42-year-old man diagnosed with von Willebrand disease 7 years earlier visited his home doctor with a chief complaint of gross hematuria. Abdominal ultrasonography showed bilateral renal tumors. He was referred to our hospital on June 15, 1993. His mother also had von Hippel-Lindau disease and was treated by hemodialysis after bilateral nephrectomy. The examination and imaging revealed bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease. Partial nephrectomy and enucleation for a small tumor on the right side and enucleations for five tumors on the left side were performed. Histological diagnosis of all tumors were renal cell carcinoma, clear cell subtype, grade 1 approximately 2. The patient has been well without local recurrence or distant metastasis for 16 months since the operation. This is the first case of bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease in Japan.

Adult↗
PubMed1995

Binding affinity of N3-substituted uridine for synaptic membrane and their CNS depressant effects.

The binding affinity for synaptic membrane from bovine thalamus of N3-phenacyl substituted pyrimidine nucleosides having CNS depressant activity was examined by radio receptor assay. N3-Phenacyl derivatives of uridine, thymidine, deoxyuridine, 6-azauridine and arabinofuranosyluracil inhibited specific [3H]uridine binding and exhibited hypnotic activity. However, N3-phenacyl-2',3'-O-isopropylideneuridine, of which structure was different from sugar moiety of N3-phenacyluridine, showed neither the binding affinity nor the hypnotic activity. The results indicated that CNS depressant effect of pyrimidine nucleoside derivatives might relate to uridine binding affinity, so called uridine receptor.

Animals↗
PubMed1994

Induction of Fos-like immunoreactivity in the rat hypothalamus by an endogenous feeding suppressant (2-buten-4-olide).

Central influence of 2-buten-4-olide (2-B4O), an endogenous feeding suppressant, was studied through immunohistochemical detection of Fos expression in the rat hypothalamus. Animals received 2-B4O (100 or 200 mg/kg i.p.) or saline 2 h before perfusion with 4% phosphate-buffered paraformaldehyde. The hypothalamus was removed and cut into vibratome sections. Immunohistochemical analysis revealed that injection of 2-B4O induced Fos-like immunoreactivity significantly in the paraventricular, dorsomedial and arcuate nuclei and the periventricular and lateral hypothalamic areas. These hypothalamic regions may control feeding under the influences of endogenous 2-B4O.

4-Butyrolactone↗
PubMed1994

Domain motion in actin observed by fluorescence resonance energy transfer.

Actin is composed of two well-separated globular domains which are further subdivided into two subdomains [Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., & Holmes, K. C. (1990) Nature 347, 37-44]. Subdomains 1 and 2 constitute the small domain, and subdomains 3 and 4 comprise the large domain. In order to test a hinge bending domain motion in actin such as observed in many kinases, fluorescence resonance energy transfer between two probes attached to each of the two domains was measured by steady-state and time-resolved fluorometers. The adenine base is bound in a hydrophobic pocket between subdomains 3 and 4, and Tyr-69 is located at subdomain 2. In the present study, the adenine moiety was labeled with a fluorescence donor, epsilon ATP, and tyrosine-69 was labeled with the energy acceptor, dansyl chloride. Assuming the random orientation factor k2 = 2/3, the distance between epsilon-adenine moiety and dansyl chloride attached to Tyr-69 in G-actin was determined to be 2.46 nm from steady-state fluorescence measurements. The addition of DNase I did not appreciably change the distance (less than 0.1 nm). The distance decreased to 2.27 nm during polymerization by the addition of phalloidin under physiological salt conditions. On the other hand, time-resolved fluorescence energy transfer measurements have been used to investigate a distribution of distances for a donor-acceptor pair. In G-actin, the mean distance between probes was 2.79 nm with a full width at half-maximum of 3.91 nm, indicating a large number of conformational substates in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Structural similarity of cytochrome c2 from Rhodopseudomonas viridis to mitochondrial cytochromes c revealed by its crystal structure at 2.7 A resolution.

The crystal structure of cytochrome c2 from Rhodopseudomonas viridis has been refined using molecular dynamics and restrained least-squares methods to a crystallographic R-factor of 0.216 at 2.7 A resolution. A structural comparison between Rps. viridis cytochrome c2 and the other bacterial cytochromes c2 or mitochondrial cytochromes c indicates that the overall protein foldings are very similar to each other with the exception of the surface loop and terminal region of the polypeptide chain. However, the position and hydrogen-bond pattern of the evolutionarily conserved water molecule buried within the heme binding pocket in Rps. viridis cytochrome c2 are common to those in the mitochondrial cytochromes c. This fact indicates that Rps. viridis cytochrome c2 is structurally more similar to mitochondrial cytochromes c than to the other bacterial cytochromes c2.

Crystallography, X-Ray↗
PubMed1994

Application of an automatic molecular-replacement procedure to crystal structure analysis of cytochrome c2 from Rhodopseudomonas viridis.

An automatic molecular-replacement procedure has been applied to solve the crystal structure of cytochrome c(2) from Rhodopseudomonas viridis. The structure was solved on the basis of the structure of tuna cytochrome c as a search model using an automatic processing program system, AUTOMR. The refinements by molecular dynamics and restrained least-squares methods result in a current crystallographic R factor of 0.219 for diffraction data at 3 A resolution.

Journal Article↗
PubMed1994

Membrane potential-linked reversed electron transfer in the beef heart cytochrome bc1 complex reconstituted into potassium-loaded phospholipid vesicles.

The cytochrome bc1 complex purified from beef heart mitochondria was incorporated into potassium (K+)-loaded phospholipid vesicles by a cholate dialysis method to study the reverse reaction of electron transfer in the complex. The reduction of cytochrome b in the presence of sodium ascorbate was observed on addition of valinomycin to the K(+)-loaded proteoliposomes in a medium containing no external KCl; it was followed by the gradual oxidation. Nigericin accelerated the reoxidation of reduced cytochrome b, indicating that a K+ diffusion potential (negative inside) induced the reduction of cytochrome b. The extent of the cytochrome b reduction depended on the magnitude of the diffusion potential across the liposomal membranes, and its maximal reduction was attained at more than 210 mV of the diffusion potential. It was cytochrome b562 that was reduced during the establishment of the K+ diffusion potential in the presence of ascorbate, and about 90% of cytochrome b562 was estimated to be reduced. Antimycin A and myxothiazol inhibited the diffusion potential-induced reduction of cytochrome b562, and ubiquinone was proved to be essential for the reversed electron transfer. The K+ diffusion potential also induced the partial reduction of cytochrome b566 when cytochrome b562 had previously been reduced with ascorbate plus tetramethyl-p-phenylenediamine. These results were interpreted well based on the Q cycle scheme which assumed the energy-dependent reduction of ubiquinone at center o. Dicyclohexylcarbodiimide, which did not perturb the ability of proteoliposomes to generate the K+ diffusion potential, inhibited the energy-dependent reduction of cytochrome b562 without a significant loss in the catalytic activity of the complex. The half-inhibition was brought about by 200 mol of dicyclohexylcarbodiimide/mol of cytochrome c1. These results strongly suggest the coupling of a proton flow with the reversed electron transfer in the bc1 complex.

Animals↗
PubMed1994

Quantitative study of local distribution of noncholesterol sterols and cholesterol in gallstones.

Quantitative analysis of the local distribution of four noncholesterol sterols, 24-methylene cholesterol, campesterol, stigmasterol, and beta-sitosterol, and of the local distribution of cholesterol in gallstones was performed by mass spectrometry, with D6-cholesterol as an internal standard. The role played by trace amounts of these four noncholesterol sterols in the formation of gallstones was investigated by comparing the amounts of these sterols in different parts of gallstones. It was found that the amounts of the noncholesterol sterols in the inside part were significant greater than the amounts in the outside part of various structural types of gallstones. However, the distribution of the cholesterol did not show such variation. The amounts of noncholesterol sterols distributed locally suggested that these sterols play a role in the formation of gallstones.

Cholelithiasis↗
PubMed1994

Newly developed ultrasonic aspirator and its application for endoscopic surgery.

The authors have developed an ultrasonic aspirator to assist in urologic endoscopic surgery. It appeared that ultrasonic aspiration of bladder tumors was clinically efficient in transurethral surgery. Tumors 1 to 2 cm in diameter could be aspirated completely with this instrument alone. The application of the ultrasonic aspirator, which has also been designed with a coagulating function, to laparoscopic lymphadenectomy was evaluated. A special probe sheath was used to insulate it when using coagulation current. During operation, perivascular fatty tissue was removed safely with the aspirator. In the near future, the ultrasonic aspirator will be one of the most effective tools in laparoscopic surgery.

Aged↗
PubMed1994

Technegas versus krypton-81m gas as an inhalation agent. Comparison of pulmonary distribution at total lung capacity.

Exactly how the pulmonary distribution of inhaled radioactive gas and Technegas, or ultra-small aerosol particulates, differs from each other, is still uncertain. The authors compared the distribution of inhaled Kr-81 m gas and Technegas in the lungs at total lung capacity in 13 control subjects with no clinical conditions and 13 patients with various chest diseases. In normal lungs, there was no difference in the distribution ratios in the right and left lungs between inhaled Kr-81m gas and Technegas. However, there was a significant difference in the lungs of patients with pulmonary disease. Technegas tended to deposit more in the lung bases than did Kr-81m gas. Despite these statistical differences, they were visually, or qualitatively, similar. From a practical and clinical standpoint, Technegas seems to be useful as an inhalation agent, unless quantitative analyses are required.

Administration, Inhalation↗