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Biomedical subjects

H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 73 records · Page 4Linked to original sources

Determination of trace amounts of total arsenic in environmental samples by hydride generation flow injection-AAS using a mixed acid as a pretreatment agent.

A method is described for the determination of total arsenic by hydride generation-atomic absorption spectrophotometry using a mixed acid as a pretreatment. Hydride generation is done by the flow-injection method. The authors investigated in detail the temperature and time of decomposition using inorganic, organic arsenic and environmental standard samples, pretreated with nitric-perchloric-sulfuric mixed acid. By using a mixed acid as a pretreatment agent at 220 degrees C, the decomposition time could be shortened and the blank value of arsenic from the reagents used was reduced. The mixed acid of nitric-perchloric-sulfuric was also found to be effective as a pretreatment agent for organic arsenic compounds in which a dimethylated compound, sodium cacodylate or biological samples, is known to be one of the indecomposables. The present approach was proved to be satisfactory as a pretreatment for the quantitative analysis of trace amounts of total arsenic in liquid or solid environmental samples, such as geothermal water, sediments and biological samples.

Acids↗

A kinetic method for the determination of nitrite by its catalytic effect on the oxidation of chlorpromazine with nitric acid.

A catalytic spectrophotometric method for the determination of trace amounts of nitrite is proposed. In acidic solution, chlorpromazine (CP) is oxidized by nitric acid to form a red compound, which is further oxidized to a colorless compound. The reaction is accelerated by trace amounts of nitrite and can be followed by measuring the absorbance at 525 nm: nitrite ion is regenerated and multiplied by nitric acid. The absorbance of the reaction increased with an increase in the reaction time, reached a maximum and decreased rapidly. Since the time required for the absorbance to reach the maximum decreased with increasing nitrite concentration, this value was used as the measured parameter for the nitrite determination. Under the optimum experimental conditions (2.3 M nitric acid, 1.2 x 10(-5) M CP, 40 degrees C), nitrite can be determined in the range 0-100 microg l(-1). The relative standard deviations (n = 6) are 4.7 and 1.8% for 40 and 100 microg l(-1) nitrite, respectively. The detection limit of this method (3sigma) is 1.2 microg l(-1). This method was successfully applied to a determination of nitrite in natural water samples.

Antipsychotic Agents↗

IgA nephropathy with complement deficiency.

We treated a female patient suffering from immunoglobulin A (IgA) nephropathy and congenital deficiency of the ninth component of the complement system (C9). She was admitted with hematuria and proteinuria, and the C9 deficiency was diagnosed based on the low hemolytic activity of 50 % of the hemolytic unit of the complements (CH50) and the normal C3 level in the plasma. Renal biopsy revealed mild mesangial proliferation, and immunofluorescence examination revealed mild mesangial deposits of IgA and C3 with the same distribution. We discuss the pathogenesis of IgA nephropathy and the role of the complements in its progression.

Adult↗

Enhanced in vitro production of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide.

UNLABELLED: Islet amyloid polypeptide (IAPP, "amylin") is the amyloid-fibril-forming polypeptide in the islets of Langerhans associated with type 2 diabetes mellitus. A missense mutation in the IAPP gene associated with early-onset type 2 diabetes has been identified in the Japanese population. This mutation results in a glycine for serine substitution at position 20 of the mature IAPP molecule. Whether or not formation of islet amyloid with resulting destruction of islet tissue is the cause of this diabetes is yet not known. The present in vitro study was performed in order to investigate any influence of the amino acid substitution on the fibril formation capacity. Synthetic full-length wild type (IAPPwt) and mutant (IAPPS20G) as well as corresponding truncated peptides (position 18-29) were dissolved in dimethylsulfoxide (DMSO) or in 10% acetic acid at a concentration of 10 mg/mL and their fibril forming capacity was checked by Congo red staining, electron microscopy, a Congo red affinity assay and Thioflavine Tfluorometric assay. It was found that full-length and truncated IAPPS20G both formed more amyloid-like fibrils and did this faster compared to IAPPwt. The fibril morphology differed slightly between the preparations. CONCLUSION: The amino acid substitution (S20G) is situated close to the region of the IAPP molecule implicated in the IAPP fibrillogenesis. The significantly increased formation of amyloid-like fibrils by IAPPS20G is highly interesting and may be associated with an increased islet amyloid formation in vivo and of fundamental importance in the pathogenesis of this specific form of diabetes.

Amyloid↗

Usefulness of endoscopic ultrasonographic analysis of variceal hemodynamics for the treatment of esophageal varices.

The correlation of between the endoscopic findings of esophageal varices and endoscopic ultrasound findings of the collaterals outside the esophageal wall in patients with portal hypertension remains unclear. We investigated the relationship between esophageal varices and the collaterals by endoscopy and endoscopic ultrasound. Moreover, we investigated the correlation between the collaterals around the esophagus and recurrence of esophageal varices in patients with portal hypertension who had undergone endoscopic injection sclerotherapy. The collaterals were divided into two groups: 1; those with peri-esophageal collateral veins (peri-ECVs) adjacent to the muscularis externa of the esophagus, and 2; those with para-esophageal collateral veins (para-ECVs) distal to the esophageal wall without contact with the muscularis externa. Peri- and para-ECVs were scored as mild or severe according to the stage of development. According to endoscopy, the varix form was significantly larger in severe peri-ECVs group than in mild peri-ECVs group. In contrast, the varix form did not differ significantly between the mild and severe para-ECVs group. The prevalence of perforating veins increased according to the varix form. With regard to variceal recurrence, in patients with variceal recurrences, EUS findings included a significantly higher incidence of severe-type peri-ECVs, a significantly larger number of perforating veins, and a significantly larger diameter of perforating veins compared with patients without recurrence. Moreover, when EUS found the abnormalities when no endoscopic recurrence was found, the results were the almost same as the findings when EUS was performed at the same time when endoscopic recurrence was found. In conclusion, the presence of severe peri-ECVs and large perforating veins in the esophageal wall strongly correlates with occurrence and recurrence of esophageal varices in patients with portal hypertension. An understanding of these EUS abnormalities on the basis of hemodynamics around the esophagus is thought to be important for management of esophageal varices in patients with portal hypertension.

Collateral Circulation↗

[Patient compliance and the quality of life are well maintained in weekly paclitaxel and carboplatin therapy for advanced gynecologic cancers in Japanese women].

OBJECTIVES: To assess patient compliance and efficacy of a combination chemotherapy consisting of weekly administration of paclitaxel and carboplatin for gynecologic malignancy in Japanese women. METHODS: Fourteen ovarian and three uterine cancer patients received 80 mg/m2 of paclitaxel (paclitaxel) and AUC 1.5 to 2.0 of carboplatin weekly. The toxicity was evaluated and patients' QOL was tested. RESULTS: Neutropenia higher than grade 3 were observed in 29.4%. Four patients received G-CSF support. Grade 1 neurotoxicity was seen in 76.5% of patients. Evaluation of QOL by EORTC-QLQC30 showed significantly better tolerance of a weekly than monthly regimen. Three out of four patients with lung metastasis showed complete disappearance of the lesions. One patient with stage IIIb cervical cancer underwent postchemotherapy-hysterectomy and a complete pathological response was confirmed. The overall response rate was 64.7% including patients previously treated with platinum based multidrug regimens. CONCLUSIONS: A weekly paclitaxel and carboplatin regimen was well tolerated by Japanese women. The regimen was active in over 60% of cases and it also appeared active in multidrug resistant cases.

Aged↗

[Effect of fluticasone propionate at half dose of beclomethasone dipropionate divided twice daily and once daily in asthmatics inhaling beclomethasone dipropionate 800 micrograms daily or more].

We conducted a 12 weeks' single-arm prospective study comparing beclomethasone dipropionate (BDP), 1/2 doses of fluticasone propionate (FP) twice daily and the same dose of FP once daily in 47 asthmatics who had been inhaling BDP 800 mcg daily or more. Peak expiratory flow (PEF), FEV1, a symptom score and a frequency of beta 2 agonist were all significantly better in FP twice daily phase than BDP phase (329 vs. 306 L/min, 1.87 vs. 1.76 L, 3.6 vs. 6.0/week and 2.7 vs. 4.5 puffs/day, respectively). There was no significant difference in these endpoints between FP twice daily phase and FP once daily phase. FP twice daily produced better plumonary function and symptom relief than the double doses of BDP. Furthermore, FP twice daily could, at least in a short-term basis, safely be changed into the same doses of FP once daily.

Administration, Inhalation↗

[A case of bronchioloalveolar carcinoma with multiple cystic shadows on chest CT].

A 68-year-old woman was admitted to our hospital in 1998 with shortness of breath on exertion. On the first admission, chest radiography revealed multiple nodular shadows and areas of ground-glass appearance mainly in the basal lung fields, and chest CT scans showed multiple thin-walled cystic lesions in both lung fields. Bronchioloalveolar carcinoma was diagnosed by transbronchial lung biopsy. The CA 19-9 level in the serum was abnormally high. The disease progressed, and the patient died 7 months after diagnosis. We report this case because CT scans showed multiple cystic lesions, which is very rare. The mechanism of cystic formation in this case of lung cancer may have involved disruption of the alveolar structure and enlargement of disrupted spaces or of the check valve mechanism.

Adenocarcinoma, Bronchiolo-Alveolar↗

Selective activation of apoptosis program by S-p-bromobenzylglutathione cyclopentyl diester in glyoxalase I-overexpressing human lung cancer cells.

PURPOSE: Glyoxalase I (GLO1) is an enzyme that plays a role in the detoxification of methylglyoxal, a side-product of glycolysis. We previously reported that GLO1 was a resistant factor to antitumor agent-induced apoptosis, and that S-p-bromobenzylglutathione cyclopentyl diester (BBGC), an effective inhibitor of GLO1, selectively sensitized to etoposide the drug-resistant human leukemia cells that overexpressed GLO1. In this study, we quantitatively measured GLO1 enzyme activity in various human solid tumor cells, and the antiproliferative effect of the GLO1 inhibitor was examined. EXPERIMENTAL DESIGN: BBGC-induced apoptosis was assessed by flow cytometry. To evaluate antitumor activity of BBGC in vivo, we developed human cancer xenografts in nude mice. RESULTS: We found that GLO1 enzyme activity was higher in all of the 38 human cancer cell lines that we examined than in the normal tissue samples. Moreover, GLO1 activity was frequently elevated in human lung carcinoma cells. Positive correlation between cellular GLO1 activity and BBGC sensitivity was observed in the lung cancer cell lines. Human lung cancer NCI-H522 and DMS114 cells, expressing higher GLO1 activity, underwent apoptosis when treated with BBGC, whereas A549 cells, expressing lower activity, did not. BBGC induced the activation of the stress-activated protein kinases c-Jun NH(2)-terminal kinase 1 (JNK1) and p38 mitogen-activated protein kinase (MAPK), which led to caspase activation in GLO1-overexpressing tumor cells. BBGC significantly inhibited the growth of xenografted DMS114 and human prostate cancer DU-145. CONCLUSIONS: Our present results indicate that GLO1 is a tumor-specific target enzyme especially in human lung carcinoma cells and that the GLO1 inhibitor is a potent chemotherapeutic agent to repress GLO1-overexpressing human tumors.

Animals↗

Simultaneous surgery for ischemic heart disease, type A aortic dissection and abdominal aneurysm.

The patient was a 72-year-old male with three-vessel coronary artery disease, chronic dissecting aneurysm of the ascending aorta with moderate aortic regurgitation, and abdominal aortic aneurysm 7 cm in diameter. Because staged procedure seemed to exacerbate the risk due to the remaining lesion, simultaneous procedures (double coronary artery bypass, aortic root remodeling, tube replacement of the ascending aorta and Y-graft replacement of the abdominal aneurysm) were performed. The patient recovered completely without any serious complication.

Aged↗

Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals.

OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation. METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique. RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen. CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals.

Animals↗

Purine-rich exon sequences are not necessarily splicing enhancer sequence in the dystrophin gene.

Purine-rich sequences within exons are proposed to promote proper splicing as splicing enhancers. In order to test this supposition in the dystrophin gene, which is characterized by the large size of its introns, purine-rich sequences from three exons (exons 43, 46 and 53) were examined for their splicing enhancer activity by using a Drosophila doublesex pre-mRNA. The most powerful activating effect on upstream intron splicing was seen with a sequence from exon 43. A sequence from exon 53 showed relatively low activity, whilst that from exon 46 had little effect. To characterize the splicing enhancer sequences in exons 53 and 46 further, entire exons were divided into 30nt fragments that were examined separately for their splicing enhancer activity. In exon 53, two fragments located at the 5' and 3' ends, respectively, had strong splicing enhancer activity, although they were not the most purine-rich regions of the exon. In contrast, all of the fragments derived from exon 46 had little activity. These results suggest that different exons in the dystrophin transcript are subject to different mechanisms of control by the splicing machinery.

Animals↗

[Clinical outcome for coronary artery bypass grafting in patients with severe carotid occlusive disease].

OBJECTIVES: To evaluate the management of coexisting severe carotid stenosis in candidates for coronary artery bypass grafting. METHODS: Twenty-six candidates for coronary artery bypass complicated with severe carotid stenosis > or = 70% were analyzed retrospectively. The prevalence of significant carotid stenosis was 6.4%. There were 21 males and 5 females with a mean age of 65.3 +/- 9.3 years. The hemodynamics of cerebral circulation, intervention for carotid stenosis, surgical mortality, morbidity, and long-term survival were analyzed retrospectively. RESULTS: The prevalence of bilateral carotid stenosis was 30.8% (8/26). Nine patients had total occlusion of the internal carotid artery, 10 had carotid stenosis of 90-99%, and 7 had carotid stenosis of 70-89%. Seven patients required mechanical support for cardiopulmonary insufficiency, including six patients requiring simultaneous artificial ventilation and intraaortic balloon pumping, and one requiring intraaortic balloon pumping. Concomitant carotid endarterectomy and coronary bypass grafting was performed in 10 patients, preceding carotid endarterectomy in 1, and preceding coronary bypass grafting with subsequent carotid endarterectomy in 7. Cardiopulmonary bypass was used in 22 patients. There was no surgical death. Although one patient undergoing concomitant carotid endarterectomy and coronary artery bypass grafting had perioperative stroke, the remaining patients recovered without any neurological complication (morbidity of stroke: 3.8%). The five-year survival rate was 71.9 +/- 11.7%. CONCLUSIONS: Coronary artery bypass grafting in candidates with carotid stenosis can be treated safely when appropriate preoperative evaluation and surgical strategies are utilized.

Adult↗

Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray.

Gene expression profiles were analyzed by using cDNA microarray for a cisplatin-sensitive cell line (KF), and three- and thirty-fold cisplatin-resistant ovarian cancer cell lines (KFr and KFrP200) both showing no p53 mutation within exon 5, 6, 7, 8 and no pglycoprotein overexpression. Expression of GST-pi mRNA increased as the level of resistance to cisplatin became high. Microarray analysis revealed that DNA repair associated genes, i.e., XRCC5, XRCC6, ERCC5, hMLH1 were over-expressed in three-fold cisplatin-resistant cell line, KFr as compared to cisplatin-sensitive parental cell line, KF. Apoptosis inhibitors, i.e., IGFR type I and II were over-expressed, and apoptosis inducer, i.e., caspase 3 and BAK were underexpressed in highly cisplatin-resistant cell line, KFrP200 as compared to KFr. As for clinical cases, cDNA microarray was used to compare gene expression profiles directly between two groups, i.e., the chemotherapy (CAP) sensitive group (n = 2) and the resistant group (n = 2). Six genes such as beta tubulin, high-mobility group (nonhistone chromosomal) protein 1, connective tissue growth factor, insulin-like growth factor binding protein 2, alpha tubulin, and RAS-related gene were overexpressed in CAP therapy resistance group, whereas seven genes such as CD9 antigen, alpha-2-macroglobulin, caveolin 2, interleukin 1 receptor antagonist, Rho GTPase activating protein 1, reticulon 3, cyclin-dependent kinase 10, keratin 7 were underexpressed in CAP therapy resistance group. By increasing clinical case number and gene number of microarray to be used in the analysis of expression profile of gene cluster affecting anticancer drug resistance and sensitivity of the ovarian cancer, it would be possible to apply microarray analysis to personalization of chemotherapy such as selection of effective chemotherapy protocol and prediction of therapeutic effect in the near future.

Cisplatin↗

The human genome and the human control of natural evolution.

Recent advances in research on the Human Genome are provoking many critical problems in the global policy regarding the future status of human beings as well as in that of the whole life system on the earth, and consequently, these advances provoke the serious bioethical and philosophical questions. Firstly, how can we comprehend that we are going to have the complete technology to manipulate the system of the human genome and other non-human genomes? Though no science and technology can be complete, we will, I believe, take possession of an almost complete gene technology in the early stage of the next Century. Gene technology will soon fall into the hands of human beings instead of rendering in the province of God. Secondly, which gene technologies will we actually realize and utilize in the early stages of the 21st Century? Most probably, we will adopt these technologies to health care to treat some apparent bodily diseases, for instance, cancer, hemophilia, ADA deficiency, and so forth, and sooner or later we will adopt gene therapy to germ lines, which, in the long run, suggests the possibility of a future "artificial evolution" instead of the "natural evolution" of the past. Thirdly, how is the new concept of "artificial evolution" justified ethically? I believe this kind of manmade evolution is the only way for human beings to survive into the future global environment. There cannot be any serious ethical objection against the idea of artificial evolution. Fourthly, what is the background philosophy for the concept of "artificial evolution"? I will discuss the nature of modern European humanism with individual dignity and fundamental human rights which has led the philosophy of modern culture and modern society, and I will conclude by suggesting that we should abolish an essential part of modern humanism and newly devise some alternative philosophy to fit the new Millennium.

Biological Evolution↗

Involvement of phospholipid hydroperoxide glutathione peroxidase in the modulation of prostaglandin D2 synthesis.

Antigenic cross-linking of the high affinity IgE receptors on mast cells induced the synthesis of prostaglandin D(2) (PGD(2)). The production of PGD(2) in L9 cells, which overexpressed non-mitochondrial phospholipid glutathione peroxidase (PHGPx), was only one-third that in the control line of cells (S1 cells). The reduction in the formation of PGD(2) in L9 cells was reversed upon inhibition of PHGPx activity by buthionine sulfoximine. Experiments with inhibitors demonstrated that prostaglandin H synthase-2 (PGHS-2) was the isozyme responsible for the production of PGD(2) upon cross-linking of IgE receptors. The conversion of radiolabeled arachidonic acid to prostaglandin H(2) (PGH(2)) was strongly inhibited in L9 cells, whereas the rate of conversion of PGH(2) to PGD(2) was the same in L9 cells and S1 cells, indicating that PGHS was inactivated in L9 cells. The PGHS activity in L9 cells was about half that in S1 cells. However, PGHS activity in L9 cells increased to the level in S1 cells upon the addition of the hydroperoxide 15-hydroperoxyeicosatetraenoic acid or of 3-chloroperoxybenzoic acid. These results suggest that non-mitochondrial PHGPx might be involved in the inactivation of PGHS-2 in nucleus and endoplasmic reticulum via reductions in levels of the hydroperoxides that are required for full activation of PGHS. Therefore, it appears that PHGPx might function as a modulator of the production of prostanoids, in addition to its role as an antioxidant enzyme.

Animals↗