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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 559 records · Page 31Linked to original sources
PubMed1996

A transcranial doppler ultrasonography study of cerebrovascular CO2 reactivity in mitochondrial encephalomyopathy.

BACKGROUND AND PURPOSE: To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM). we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO2 reactivity. METHODS: The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO2 partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO2 partial pressure (PETCO2) to the exponential formula fm = a x e(K < PETCO2), where a is the theoretical fm at a PETCO2 of 0 mm Hg, the parameter K, an index of CO2 reactivity, was calculated. RESULTS: The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome. CONCLUSIONS: Our results suggest that there is a high incidence of impairment of cerebrovascular CO2 reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.

Adolescent↗
PubMed1996

Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia.

Hypophosphatasia is associated with a defect of the tissue-non-specific alkaline phosphatase gene. We performed a mutational analysis in a surviving patient diagnosed at birth as having hypophosphatasia, on the basis of a low level of serum alkaline phosphatase (ALP) activity and characteristic radiographical findings. She had two sisters, one of whom died of respiratory failure complicated by perinatal hypophosphatasia; the other seemed healthy, with a relatively low activity level of ALP. The patient's parents also had low ALP activity. Sequence analysis of the tissue-nonspecific alkaline phosphatase gene was performed, using genomic DNA and total RNA from the skin fibroblasts of the patient and the peripheral mononuclear cells of her parents. The conversion of Phe to Leu at codon 310 (F310L) and Gly to Arg at 439 (G439R) were identified in the patient. Interestingly, the reconstructive experiments demonstrated that the F310L mutant exhibited an ALP activity level 65% of the normal level, whereas the mutant G439R had no activity. Moreover, the digestion by StuI, after a PCR using complementary DNA extracted from fibroblasts of the patient and lymphocytes of her father, revealed a relatively low messenger RNA level of F310L. These findings suggest that the neonatal case of hypophosphatasia was associated with compound mutations, one of which caused the loss of ALP activity and the other of which caused a slight reduction of the ALP activity, with a relatively low level of messenger RNA.

Adult↗
PubMed1996

Dimethylarsenics reveal DNA damage induced by superoxide anion radicals.

We previously reported that DNA single-strand breaks (ssb) induced by exposure to dimethylarsinic acid (DMAA) were enhanced by the presence of paraquat (PQ), a superoxide anion radical 0 -(2)-producing agent, in cultured human alveolar type II (L-132) cells in vitro. In the present study, we examined the effect of sequential exposure of the cells to PQ and then DMAA under conditions causing no ssb by each alone, and observed a remarkable occurrence of ssb. The result suggests that 0 -(2) caused DNA damage, which became detectable as ssb by the treatment using DMAA. The DNA damage induced by the exposure to PQ alone was different from that by DMAA; PQ-induced damage was fully repaired after 24 h, while DMAA-induced damage was repaired only partially, and aphidicolin, an inhibitor of repair-serving DNA polymerases alpha, delta and/or epsilon, inhibited only the latter repair but not the former. These findings indicate that the DMAA treatment may be an effective tool to reveal DNA damage induced by 0 -(2), which to date has not been sufficiently clarified.

Aphidicolin↗
PubMed1996

Differential effect of UV-B and UV-C on DNA damage in L-132 cells.

Ultraviolet radiation is known to induce skin cancer. The induction of DNA damage caused by UV-B and UV-C was investigated using cultured L-132 cells. DNA strand breaks assayed by the alkaline elution procedure occurred in a dose-dependent manner, the extent of the strand breaks were inversely well correlated with the number of viable L-132 cells after 24 h incubation. About a 10-fold dose of UV-B irradiation was required to induce a similar degree of strand breaking to that induced by UV-C. Similarly about a 10-fold dose of UV-B was required to produce a similar amount of pyrimidine dimers, such as cyclobutane-type dimers and pyrimidine-(6-4)-pyrimidone photoproducts, which were determined by ELISA using the specific monoclonal antibody, to that produced by UV-C. Strand breaks induced by UV-B, however, were not fully repaired in viable cells remaining after incubation of cells for a longer period of time, although UV-C-induced strand breaks were repaired in a time-dependent manner. Furthermore, an experiment with a cell-free system, where the induction of strand breaks by repair enzymes did not take place, indicated that UV-B caused significantly more direct DNA strand breaks than that caused by one-tenth the dose of UV-C. The data shown here suggest that UV-B-induced DNA damage is mediated, at least in part, via a different mechanism from the UV-C induced one.

Antibodies, Monoclonal↗
PubMed1996

Effect of freeze-thawing on phospholipid/surfactant mixed bilayers.

The effect of freeze-thawing of egg phosphatidylcholine (PC) and octyl glucoside (OG) on vesicle growth and on liposomal formation by the subsequent removal of the OG was investigated. When increasing concentrations of OG were mixed with PC vesicles of 10 or 20 mM PC, vesicle growth was observed until the ratio of OG/PC reached about 3.0, and then micellization occurred at a higher concentration of OG, as determined by turbidity change and microscopic observation. On the other hand, a marked increase in turbidity was observed after freeze-thawing of the samples when the OG/PC ratio was less than 3.0. The frozen and thawed mixed bilayer composed of OG/PC = 2 formed closed vesicles having solute-trapping ability as determined by fluorescence microscopy. Interestingly, the trapping volume of liposomes generated after removal of OG from freeze-thawed samples was higher for those from mixed micelles than for those from mixed vesicles composed of OG and PC. When increasing concentrations of OG were mixed with PC vesicles of 0.8 or 2 mM PC, micellization started when the OG was at about its critical micelle concentration (cmc), although marked turbidity was observed when the OG/PC ratio was 2.0 after freeze-thawing. These data suggest that freeze-thawing affects the bilayer-micelle transition and liposomal formation after removal of OG even at concentrations of detergent lower than its cmc.

Detergents↗
PubMed1996

Estimations of average particle sizes and size distributions of commercially available human-insulin aqueous suspensions using laser-light diffraction spectroscopy.

The average diameter and size distribution of particles in commercially available isophane-insulin and zinc-insulin aqueous suspensions (11 products) were examined using laser-light diffraction spectroscopy (LLDS). Wide variation was observed between products in volume-weighted and number-weighted average diameters. The particles in the insulin aqueous suspensions were found to be mono-dispersed within relatively narrow size distributions. Sonication for a short time led to a downshift in the apparent average diameter, which was most remarkable with isophane-insulin aqueous suspensions. This could be ascribed to dispersion of aggregated needle-like crystals and/or crystal breakage. In the case of biphasic isophane-insulin aqueous suspensions, the average size as well as the size distribution shifted toward the smaller end of the scale with decrease in the isophane content.

Humans↗
PubMed1996

Acceptor specificity of cyclodextrin glucanotransferase from an alkalophilic Bacillus species and synthesis of glucosyl rhamnose.

Cyclodextrin glucanotransferase [1,4-alpha-D-glucan 4-alpha-D-(1,4-alpha-D-glucano)-transferase (cyclizing), EC 2. 4. 1. 19] from an alkalophilic Bacillus species A2-5a had a wider acceptor specificity than that from B. macerans, which was similar to those from B. stearothermophilus and B. circulans. Glucosyl rhamnose produced by the CGTase was identified as glucopyranosyl-alpha-1,4-rhamnopyranose by alpha- and beta-glucosidase treatments, and 1H- and 13C-NMR analyses.

Bacillus↗
PubMed1996

Synthesis of neohesperidin glycosides and naringin glycosides by cyclodextrin glucanotransferase from an alkalophilic Bacillus species.

Cyclodextrin glucanotransferase from an alkalophilic Bacillus species produced neohesperidin monoglucoside and a series of its maltooligoglucosides by transglycosylation with neohesperidin as an acceptor and soluble starch as a donor. As the reaction using beta-CD as a donor at an alkaline pH was very effective for solubilizing neohesperidin, the amount of glycosides formed was increased. As a result, its amount with beta-CD at pH 10 was about 7 times greater than that with soluble starch at pH 5. Neohesperidin monoglucoside was purified from the reaction mixture by glucoamylase and naringinase treatments, an Amberlite XAD-16 column, a Sephadex LH20 column, and HPLC on an ODS column. The structure of the purified monoglucoside was identified as 3G-alpha-D-glucopyranosyl neohesperidin by FAB-MS, methylation analysis, and 1H- and 13C-NMR. The solubility of neohesperidin monoglucoside in water was approximately 1500 times higher than that of neohesperidin, and the bitterness of the monoglucoside was about 10 times less than that of neophesperidin. In addition, naringin was also glycosylated by the same method as neohesperidin, and its monoglucoside was identified as 3G-alpha-D-glucopyranosyl naringin. The solubility of naringin monoglucoside in water was also at least 1000 times higher than that of naringin without altering its bitterness.

Alkalies↗
PubMed1996

Inhibitory effect of estrogens on the oxidative hemolysis induced by 2-amidinopropane hydrochloride, a free radical generator.

We investigated the effect of estrogens, 17 beta-estradiol, estradiol-3-benzoate and estrone, on 2-amidinopropane hydrochloride (AAPH)-provoked, free radical-dependent hemolysis in vitro. Incubation experiment was performed by mixing AAPH (400 mM) and washed human erythrocyte suspension with or without various sex hormones and radical scavengers. After 170 min of incubation, 50% hemolysis was detected in the control group (incubation without sex hormones or radical scavengers), whereas after the addition of estrogens (5 mM), hemolysis was nearly completely inhibited until 180 min of incubation. It was found that the inhibitory activities of estrogens on oxidative hemolysis were stronger than that of alpha-tocopherol and had nearly identical to that of N-acetyl-L-cysteine. Testosterone had no inhibitory effects. The elevation of thiobarbituric acid-reactive substances, a marker for lipid peroxidation, was also inhibited by estrogens. These results add further evidence that estrogens are strong radical scavengers in humans.

Acetylcysteine↗
PubMed1996

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Adult↗
PubMed1996

Induction of renal cell carcinoma in male Wistar rats treated with cupric nitrilotriacetate.

Systemic administration of copper, an essential trace metal in the human body, has never been reported to be carcinogenic in animals. We investigated the induction of tumors by the cupric complex of nitrilotriacetic acid (Cu-NTA) in male Wistar rats. Thirty-two animals received ip injections of Cu-NTA, 3 to 5 mg of copper/kg body weight 5 days a week for 12 weeks, and were kept under close observation. For comparison, 31 animals received ip injections of ferric nitrilotriacetate (Fe-NTA), 5 to 10 mg of iron/kg body weight, and 16 animals received nitrilotriacetic acid (NTA) alone at the molar dose equivalent to Cu-NTA for the same period of time. Sixteen animals were left untreated as controls. Fourteen animals in the Cu-NTA group died of hepatic failure during the treatment period, and renal cell carcinoma (RCC) was induced in eight animals (25%). Of these, four animals died of either pulmonary metastasis or intraperitoneal hemorrhage. A total of 12 RCC were obtained, of which six tumors were > or = 5 mm. The Cu-NTA group yielded fewer RCC and required a longer latent period for their incubation than the Fe-NTA group. Furthermore, the Cu-NTA group showed one hepatocellular carcinoma and one high-grade sarcoma of hepatic origin. No renal or hepatic tumor was observed in the NTA or control groups. The nontumorous part of the kidney treated with Cu-NTA presented hemosiderosis caused by copper-induced hemolytic anemia. This is the first report that systemic administration of copper compounds can induce malignant tumors in animals. Not only copper but also iron may play a role in the Cu-NTA-induced renal carcinogenesis model.

Animals↗
PubMed1996

Expression of full-length human dystrophin cDNA in mdx mouse muscle by HVJ-liposome injection.

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder which is caused by a defect of dystrophin, a 427-kDa muscle cell membrane protein. One of the possible means of DMD therapy is to express the dystrophin gene in patients' muscles. In this study, full length dystrophin cDNA was expressed in mdx (muscular dystrophy model) mouse muscle using the hemagglutinating virus of Japan (HVJ)-liposome method. With the HVJ-liposome method, the lacZ reporter genes were expressed in 50-80% of cultured mdx mouse myoblasts, which suggested its potential usefulness for an in vivo gene study. Three expression vectors containing human full length dystrophin cDNA driven by Rous sarcoma virus (RSV), mouse leukemia virus, or human dystrophin promoters, were used. HVJ-liposomes containing these plasmids were directly injected into mdx mouse quadriceps muscle. The highest efficiency of expression of dystrophin was in 26% of the muscle fibers at the injected site on day 3 after HVJ-liposome injection of the RSV-based vector. The expression was decreased on day 10. The study thus demonstrates the feasibility of full length human dystrophin cDNA transfer and dystrophin expression using HVJ-liposomes in vivo.

Animals↗
PubMed1996

[Outcome of initial treatment with high-dose vitamin B6, valproate sodium or clonazepam in West syndrome].

We reviewed the outcome (seizures and development) of 25 cases with West syndrome in which antiepileptic drugs (valproate sodium, clonazepam) or high doses of vitamin B6, instead of ACTH therapy, were administered for the initial treatment. Five of 9 cryptogenic cases (56%) and 4 of 16 symptomatic cases (25%) showed complete cessation of spasms. In cryptogenic cases, response to vitamin B6, valproate sodium or clonazepam was not predicted by clinical features (age of onset, seizure type, initial EEG finding or treatment lag). On the other hand, response to these drugs was correlated with some clinical findings in symptomatic cases; all infants with neurocutaneous syndrome (tuberous sclerosis, neurofibromatosis type 1) had controlled infantile spasms, while none of patients with severe neonatal asphyxia or with prior other seizures responded. Twenty of 25 patients have been followed-up. The average age at follow-up was 5 years and 8 months. Prognosis of both cryptogenic and symptomatic "responders" was favorable; all had seizures controlled, and 50% had normal psychomotor development or only mild impairment (DQ > 70). Symptomatic "nonresponders" had the worst prognosis. Our results suggest that choice of drug in the initial treatment of West syndrome should be determined by clinical features (especially etiology).

Anticonvulsants↗
PubMed1996

[3D contrast MR angiography of lower extremity : additional imaging with subtraction].

Immediately after pelvic contrast MRA, subtraction MRA with additional administration of contrast agent was performed for evaluation of the femoropopliteal artery. Mask images were taken with three- dimensional spoiled GRASS (24/6.9/40 degrees), followed by contrast images with 7.5 - 10 ml of Gd-DTPA. The subtracted images provided excellent depiction of the arteries without the disruption of overlapping from the venous system or surrounding tissues. Seven lesions of arterial occlusion or stenosis were pointed out by subtraction MRA in the nine lesions confirmed with IADSA. Subtraction MRA is feasible for long segment imaging of the lower extremities with Gd-DTPA.

Adult↗