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Biomedical subjects

M Kataoka

Publications and source records attributed to M Kataoka.

At least 307 records · Page 17Linked to original sources

Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C.

Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long-acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate superoxide, which contributes to their cytocidal effects or side effects. We examined whether SOD-POE could prevent the side effects induced by superoxide generated by antitumor agents, and the following results were obtained. SOD-POE did not influence the antitumor effects of ADR and MMC either in vitro or in vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC in Donryu rats. The above results suggest that combination chemotherapy with SOD-POE would make it possible to increase the maximum permissible doses of antitumor agents, improving the efficacy of these agents.

Animals↗

Bacteriorhodopsin reconstituted from two individual helices and the complementary five-helix fragment is photoactive.

Bacteriorhodopsin (bR), a light-driven proton pump, consists of a bundle of seven membrane-spanning alpha-helices connected to each other by short extramembranous loops. Previously it has been shown that bR can be reconstituted from three fragments corresponding to the first helix, the second helix, and the remaining five helices, and that this reconstituted material reforms the native structure of bR. In this study, it is shown that the native function is also recovered. Low-temperature spectroscopy was used to examine the photochemical properties of bR reconstituted from three fragments. At room temperature at pH 6, the reconstituted material shows essentially the same absorption spectrum as native bR, while upon raising the pH at room temperature or cooling the sample in glycerol, a second, blue-shifted peak appears. The pH and temperature dependence of the absorption spectrum indicates that the reconstituted bR is in an equilibrium between two pigments, which we call P560 and P480. Both pigments convert to their own K intermediates, which differ in absorption maxima, upon illumination with green light at -180 degrees C. Each K intermediate can be reverted to its initial state by light. Similarly, both pigments convert to their own M intermediates upon irradiation with yellow light at -77 degrees C. The M intermediate of both species can be reverted only to P560 by light. Both pigments are therefore photoactive. These unique photochemical properties of bR reconstituted from three fragments may be attributable to the lack of a covalent linkage in the loop connecting the A and B helices, and thus possibly to a change in the orientation of the B helix.

Bacteriorhodopsins↗

Efficacy of oral administration of live herpes simplex virus type 1 as a vaccine.

Mice given herpes simplex virus type 1 (HSV-1) (Miyama +GC strain) intragastrically via a stainless-steel cannula were rendered immune to subsequent lethal intraperitoneal (i.p.) challenge with HSV-1. The orally administered HSV-1 was completely inactivated in the stomach within a few minutes of inoculation. However, systemic immunity was established 14 days after oral inoculation with the virus and retained for up to 6 months. The mechanisms of establishing systemic immunity were investigated by means of adoptive transfer comparisons. When splenic cells from HSV-1-immunized mice were transplanted into nonimmunized mice, all of the recipient mice survived after a lethal i.p. challenge with the virus. Immunity was not established in antithymocyte serum-treated mice or by transfer of serum from immunized to nonimmunized mice. In addition, all HSV-1-immunized mice died after lethal challenge with HSV-2 and influenza virus A. These findings suggest that the immunity was virus specific, with T lymphocytes playing a major role in its establishment. The present study therefore supports the possibility of oral immunization with live HSV-1 as a vaccine.

Administration, Oral↗

[Effect of SL-1010 (sodium hyaluronate with high molecular weight) on experimental osteoarthritis induced by intra-articularly applied papain in rabbits].

Sodium hyaluronate (HA) with a molecular weight of approximately 600,000-1,200,000 is reportedly effective against osteoarthritis (OA). However, since HA with higher molecular weight is expected to be more effective against OA, we investigated the effects of HA (SL-1010) newly produced by fermentation with a molecular weight of 1,800,000-2,100,000 on the experimental OA induced by intraarticular injection of papain, into the knee joint of the rabbit, in comparison with those of HA with a molecular weight of about 950,000 (HA-95). When 0.4, 0.8, and 1.6% papain (0.5ml) was injected into the knee joint of the animal twice with a 3-day interval, there were dose-dependent degenerative changes and a decrease in sulfated glycosaminoglycan (S-GAG) in the articular cartilage with slight synovial inflammatory changes 6 weeks after the final injection of papain. In this OA model, intraarticular application of SL-1010 slightly reduced the degeneration of articular cartilage, compared with the injections of HA-95 or saline (control). SL-1010 also caused a significant recovery in the S-GAG level which was decreased in the cartilage of the OA model, compared with the control. In addition, SL-1010 inhibited the release of 35S-GAG from the cartilage obtained from normal and OA model joints. These results suggest that SL-1010 is effective in inhibiting the degeneration of cartilage in the OA model, probably due to the recovery of the S-GAG level by reducing the release of S-GAG from the cartilage.

Animals↗

[Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet].

TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE-5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element-related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN.

Animal Nutritional Physiological Phenomena↗

Clinical features of 125 patients with sarcoidosis: Okayama University Hospital review of a recent 10-year period.

Clinical features were studied in 125 patients with sarcoidosis (72 females and 53 males) diagnosed at Okayama University Hospital during a recent 10-year period. The age distribution had two peaks in patients in their 20s and the 50s. Over half of the patients were detected at health screening check and were asymptomatic, while the remaining were symptomatic. Twelve patients were in stage 0, 41 were in stage I, 54 were in stage II, 16 were in stage III, and 2 were in stage IV according to the chest x-ray findings. Serum angiotensin converting enzyme levels and serum lysozyme levels were elevated in 60% and 76% of the patients, respectively. The bronchoalveolar lavage fluid showed lymphocytosis, especially of helper T-cells. The clinical features of sarcoidosis appear to depend on the duration of the disease.

Adolescent↗

[Urodynamic study on urinary disturbance after therapy of uterine cancer].

It is well known that urinary disturbance often appears after radical hysterectomy for uterine cancer and is aggravated by additional radiation therapy. The aim of this study is to elucidate the pathogenesis and to establish the treatment method of urinary disturbance after therapy for uterine cancer. Forty-five patients with urinary disturbance and ten normal controls were subjected to this study. Changes in clinical symptoms and findings in the Urodynamic study (UDS) in 12 severe cases were investigated before and after treatment with beta 2-stimulant (Mabuterol HCL). Clinical symptoms in cases treated by radiation therapy alone were rare and mild without any pad exchanges, and appeared 5 years after treatment for uterine cancer. Findings of UDS in these cases were mild low compliance of detrusor at maximum desire to void (Cmdv) and mild low bladder volume at maximum desire to void (Vmdv). In cases treated by radical hysterectomy alone, Cmdv decreased immediatelly after the operation and then maximum urethral closure pressure (cPura) gradually decreased. Concerning the cases treated by radical hysterectomy and radiation, severe low Cmdv and severe low Vmdv appeared 5 years after the treatment for uterine cancer in almost all cases, and low cPura appeared immediately after the operation in half of the cases. Treatment with beta 2-stimulant significantly improved urinary frequency, voided volume and urinary incontinence. In UDS findings, Vmdv and Cmdv were significantly improved by the treatment with beta 2-stimulant. The functional profile length and cPura value were not significantly changed. In uroflowmetry, the maximum flow rate and average flow rate were significantly improved by the treatment with beta 2-stimulant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

[Malignancies in patients with sarcoidosis].

We evaluated the occurrence and type of malignant tumors in 148 patients with sarcoidosis followed at the Okayama University Hospital. Nine patients had malignancies; in 2 of 9 patients the development of malignancy preceded that of sarcoidosis, and one patient presented with sarcoidosis and malignancy at the same time. Six patients developed six types of malignancy following the development sarcoidosis; one case each of stomach cancer, lung cancer, breast cancer, thyroid cancer, testicular tumor, laryngeal cancer, and chronic lymphocytic leukemia. There was no significant difference between sexes (3 males and 3 females). The mean age of the cancer group at the onset of sarcoidosis was 56 years, which was significantly higher (p less than 0.05) than that of the control group. In these 6 patients, the mean interval from onset of sarcoidosis to detection of cancer was 11.7 years (range 1.5 to 30.2 years). The relative risk of malignancy was calculated based on the data for 148 patients with sarcoidosis with a total of 1371 person-years. The expected incidences of cancer for all sites and specific sites were estimated by applying age- and sex-adjusted person-years. The observed incidence of cancer was significantly (p less than 0.05) greater than the expected incidence for thyroid cancer, laryngeal cancer, and leukemia. No significant difference in incidence was found for all sites or for the other sites of cancer. The increased cancer incidence in sarcoidosis may be secondary to immunological abnormalities associated with this disease.

Adult↗

[Release of interleukin-6 by alveolar macrophages in patients with sarcoidosis].

The supernatants from cultures of alveolar macrophages from 12 patients with sarcoidosis and 7 control subjects were assayed for interleukin-6 (IL-6) using an ELISA system. IL-6 was detectable without a stimulant in supernatants from all subjects with sarcoidosis and controls. However, the supernatants from 4 of 12 untreated patients with sarcoidosis contained significantly greater amounts of IL-6. When macrophages were stimulated by Propionibacterium acnes (P. acnes), the mean level of IL-6 in the supernatant of patients with sarcoidosis was 5.18 +/- 1.46 ng/ml, which was significantly higher than in controls (3.34 +/- 0.39) (p less than 0.05). Furthermore, in patients with sarcoidosis, the mean level of IL-6 in the supernatant was significantly correlated with the percentage of lymphocytes in bronchoalveolar lavage fluid (p less than 0.05), the level of interleukin-1 released by alveolar macrophages stimulated by P. acnes (p less than 0.05), and the phagocytic index of alveolar macrophages (p less than 0.05). The large amount of IL-6 in the supernatant after stimulation by LPS was measured in patients with sarcoidosis (24.49 +/- 13.36) and in controls (12.4 +/- 8.53), and there was no significant difference between patients with sarcoidosis and controls. Small amounts of IL-6 were detectable in bronchoalveolar fluid from only 2 of 26 patients with sarcoidosis; however, it was detected in none of 15 controls. It is suggested that the enhancement of IL-6 release by alveolar macrophages has a role in the activation of immune effector cells at sites of sarcoidosis.

Adult↗

A role of cytoplasmic free adenosine diphosphate in regenerating rabbit liver.

Cytosolic free adenosine diphosphate (ADP) concentration in remnant rabbit liver 24 hours after 70% hepatectomy was calculated from the measured components of the glyceraldehyde-3-phosphate dehydrogenase:3-phosphoglycerate kinase/lactate dehydrogenase reaction. The concentration of free cytoplasmic ADP of the remnant liver increased from the control value of 76.9 +/- 6.0 mumol/L to 208.8 +/- 31.9 mumol/L (mean +/- SEM) at 24 hours after hepatectomy. The calculated free ADP provides the following three interpretations with respect to mitochondrial respiration acceleration as a result of liver regeneration. First, the Michaelis-Menten equation for physiologic respiration relative to maximal respiration gave 1.16 as the value of acceleration. Next, the classical thermodynamic theory showed that the logarithm of [adenosine triphosphate]/[free ADP] [free inorganic phosphate], which is reciprocally correlated with mitochondrial respiration, was decreased by a factor of 0.78 after hepatectomy. Finally, the irreversible thermodynamic theory indicated that chemical affinity, which is linearly correlated to mitochondrial respiration, was increased 1.36 times. These interpretations suggest that the rate of mitochondrial respiration is accelerated after major hepatectomy.

Adenosine Diphosphate↗

[Intraoperative radiation therapy of carcinoma of the pancreas].

From May 1978 to December 1989, 54 patients with pancreatic carcinoma underwent electron beam intraoperative radiotherapy (IORT). Three died of preoperative complications within a month. In 19 patients, liver metastasis and/or peritoneal dissemination became obvious at laparotomy. They therefore underwent IORT with palliative intent. Relief of pain was obtained in 12 of the 14 patients with pain (85.7%), although three of them were treated in combination with splanchnic nerve block. Thirty-two patients with localized carcinoma underwent IORT with curative intent (total tumor resection in 6, partial resection in 6, and no tumor resection in 20). With additional IORT treatment, their survival was significantly (p less than 0.05 during the 18th month) longer than that of 40 patients without IORT (total tumor resection in 13, partial resection in 9, and no tumor resection in 18). Among the patients without tumor resection, the 20 patients who underwent IORT survived significantly (p less than 0.05 during the 7th month) longer than the 18 patients who did not. Twelve patients who underwent total pancreatectomy died earlier than the 23 patients treated with IORT in combination with partial tumor resection or no tumor resection (not significant). In 26 patients with partial tumor resection or no tumor resection, either additional external irradiation or IORT using a small field within a large field significantly (p less than 0.05 during the 7th and 8th month) improved survival compared with IORT using a single field. Of the 20 patients without tumor resection, relief from pain was obtained in 18 of 19 patients with pain (94.7%), although two of them were treated in combination with splanchnic nerve block. In terms of adverse effects possibly caused by IORT in 26 patients who survived longer than 6 months, gastrointestinal problems were serious in several (gastric ulcer in 2, duodenal stenosis in 1, gastric ulcer and duodenal stenosis in 1, and duodenal perforation and duodenal ulcer in 1). In conclusion, our experience suggests that IORT can relieve patients of serious pain and improve survival in patients with localized pancreatic carcinoma.

Adult↗

[Embolotherapy of varicocele by stainless steel coil].

Fifty-two patients with varicocele underwent embolotherapy using stainless steel coils. Forty-six of the patients complained of infertility, four of scrotal mass and two of scrotal pain. The procedure was successful in 42 of the 52 patients (81%). Positive semen analyses increased 53% (16/30), and the number of subsequent pregnancies was five of 33 (15%). We conclude that embolotherapy with the coils is a useful therapeutic procedure for varicoceles.

Adolescent↗

[MR imaging of adrenal masses smaller than 5 cm. Characterization with T2 relaxation time at 1.5 T].

The T2 relaxation times of 28 adrenal masses smaller than 5 cm obtained using a 1.5 Tesla MR imaging system were analysed to evaluate the ability of this parameter to characterize the tissue masses. The adrenal masses included 13 nonhyperfunctioning adenomas, five hyperfunctioning adenomas, five metastatic tumors, two pheochromocytomas, one nodular hyperplasia, one ganglioneuroma, and one cyst. The mean T2 value of nonhyperfunctioning adenomas was almost the same as that of hyperfunctioning adenomas. A significant difference was found in T2 (p less than 0.01) between nonhyperfunctioning adenoma (50 msec +/- 7 msec; mean +/- S.D.) and metastatic tumor (63 msec +/- 11 msec), whereas there was no significant difference in mass size between them. The two pheochromocytomas and the ganglioneuroma, which were derived from adrenal medulla, had relatively long T2 of over 70 msec. The T2 values of nodular hyperplasia and adrenal cyst were 58 msec and 123 msec, respectively. Although the T2 values of metastatic tumors tended to be longer than those of nonhyperfunctioning adenomas, differentiation between them with a T2 of 60 msec was not necessarily possible, especially in smaller masses. The T2 values of two metastatic tumors of less than 2 cm indicated 50 msec levels. There seemed to be a correlation between mass size and T2 in metastatic tumors. In adenomas, however, no significant correlation was demonstrated. We conclude that the characterization of small adrenal masses by T2 at 1.5 Tesla is unsatisfactory in differentiating metastatic tumors from nonhyperfunctioning adenomas.

Adrenal Gland Diseases↗

Crystallographic characterization by X-ray diffraction of the M-intermediate from the photo-cycle of bacteriorhodopsin at room temperature.

The structure of the M-intermediate appearing in the photo-cycle of bacteriorhodopsin was studied with X-ray diffraction techniques at room temperature. The lifetime of the M-intermediate was prolonged by treatment with an arginine solution at alkaline pH (Nakasako et al., FEBS Lett. 254, 211-214). The diffraction profile of membranes which had accumulated the M-intermediate had small but significant differences in the intensities of Bragg reflections and the lattice constant in comparison with that of membranes having trans-bacteriorhodopsin. Diffraction intensities were carefully evaluated and the structural changes during the formation of the intermediate were evaluated with difference Fourier analysis. We could find structural changes around helices G and B.

Bacteriorhodopsins↗

Small-angle X-ray scattering study of calmodulin bound to two peptides corresponding to parts of the calmodulin-binding domain of the plasma membrane Ca2+ pump.

The interaction between calmodulin (CaM) and two synthetic peptides, C20W and C24W, corresponding to parts of the calmodulin-binding domain of the Ca2+ pump of human erythrocytes, has been studied by using small-angle X-ray scattering (SAXS). The total length of the CaM-binding domain of the enzyme is estimated to be 28 amino acids. C20W contains the 20 N-terminal amino acids of this domain, C24W the 24 C-terminal amino acids. The experiments have shown that the binding of either peptide results in a complex with a radius of gyration (Rg) smaller than that of CaM. The complex between CaM and C20W revealed an interatomic length distribution function, P(r), similar to that of calmodulin alone, indicating that the complex retains an extended, dumbbell-shaped structure. By contrast, the binding of C24W resulted in the formation of a globular structure similar to those observed with many other CaM-binding peptides.

Amino Acid Sequence↗

Small-angle X-ray scattering studies of calmodulin mutants with deletions in the linker region of the central helix indicate that the linker region retains a predominantly alpha-helical conformation.

Two mutant forms of calmodulin were examined by small-angle X-ray scattering in solution and compared with the wild-type protein. Each mutant has deletions in the linker region of the central helix: one lacks residues Glu-83 and Glu-84 (Des2) and the other lacks residues Ser-81 through Glu-84 (Des4). The deletions change both the radii of gyration and the maximum dimensions of the molecules. In the presence of Ca2+, the observed radii of gyration are 22.4 A for wild-type bacterially expressed calmodulin, 19.5 A for Des2 calmodulin, and 20.3 A for Des4 calmodulin. A reduction in the radius of gyration by 1-2 A on removal of calcium, previously observed in the native protein, was also found in the wild type and the Des4 mutant; however, no significant size change was observed in the Des2 mutant. The large calcium-dependent conformational change in calmodulin induced by the binding of melittin [Kataoka, M., Head, J.F., Seaton, B.A., & Engelman, D.M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6944-6948] was observed in all the bacterially expressed proteins. Each protein appears to undergo a transition from a dumbbell shape to a more globular conformation on binding melittin in the presence of calcium, although quantitatively the changes in the wild-type and Des4 proteins greatly exceed those in Des2. Modeling shows the central linker region of the molecule. Thus, the structure of the linker region is stable enough to maintain the average orientation and separation of the lobes yet flexible enough to permit the lobes to approach each other upon binding a peptide.

Amino Acid Sequence↗

[Detection of common bile duct stones by hepatobiliary scintigraphy].

Hepatobiliary scintigraphy and direct X-ray cholangiography were compared in 29 patients with common bile duct (CBD) stones confirmed at surgery. The scintigraphic findings included no visualization of the biliary system (NV), pooling of bile in the biliary system (PB), prolonged transit time over 60 min (PTT), filling defect in the CBD image (FD), and reflux of bile toward the intrahepatic ducts after gallbladder stimulation (RB). The positive rates of NV, PB, PTT, FD, and RB in patients with CBD stones were 7%, 31%, 17%, 48%, and 14%, respectively. One or more of these five findings was found in 83%. Although the NV was a useful finding suggesting complete obstruction of the CBD, it shared little in the diagnosis of CBD stone. The positive rate of the PB was relatively high and it would be a useful finding as an indication of the presence of passage disturbance of the CBD. The PB was usually accompanied by the FD. The PTT had some usefulness in the detection of incomplete obstruction of the CBD in patients with a visualized gallbladder. In patients with no visualization of the gallbladder, however, the transit time tended to be shorter than that of gallbladder visualized patients. Therefore, the judgment of PTT in patients with no visualized gallbladder needed another criteria. The FD was the most frequent among the five findings and the sites of FD correlated well with CBD stones on direct X-ray cholangiography. The FD would be a reliable finding indicating CBD stone or CBD stenosis. Although the RB was a finding limited in patients with a visualized gallbladder, it seemed to be a helpful findings for the detection of CBD stone in patients with a mildly dilated CBD.

Adult↗