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Biomedical subjects

K Iwai

Publications and source records attributed to K Iwai.

At least 73 records · Page 4Linked to original sources

Field trials of a rapid test for G6PD deficiency in combination with a rapid diagnosis of malaria.

A rapid single-step screening method for detection of glucose-6-phosphate dehydrogenase (G6 PD) deficiency was evaluated on Halmahera Island, Maluku Province, Indonesia, and in Shan and Mon States, Myanmar, in combination with a rapid diagnosis of malaria by an acridine orange staining method. Severe deficiency was detected by the rapid test in 45 of 1126 volunteers in Indonesia and 54 of 1079 in Myanmar, but it was difficult to distinguish blood samples with mild deficiency from those with normal activity. 89 of 99 severely deficient cases were later confirmed by formazan ring method in the laboratory, but 5 with mild and 5 with no deficiency were misdiagnosed as severe. Of the samples diagnosed as mild and no deficiency on-site, none was found to be severely deficient by the formazan method. Malaria patients were simultaenously++ detected on-site in 273 samples on Halmahera island and 277 samples from Shan and Mon States. In Mon State, primaquine was prescribed safely to G6 PD-normal malaria patients infected with Plasmodium vivax and/or gametocytes of P. falciparum. The new rapid test for G6 PD deficiency may be useful for detecting severe cases under field conditions, and both rapid tests combined are can be useful in malaria-endemic areas, facilitating early diagnosis, prompt and radical treatment of malaria and suppression of malaria transmission.

Acridine Orange↗

Allyl-containing sulfides in garlic increase uncoupling protein content in brown adipose tissue, and noradrenaline and adrenaline secretion in rats.

The effects of garlic supplementation on triglyceride metabolism were investigated by measurements of the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretion in rats fed two types of dietary fat. In Experiment 1, rats were given isoenergetic high-fat diets containing either shortening or lard with or without garlic powder supplementation (8 g/kg of diet). After 28 d feeding, body weight, plasma triglyceride levels and the weights of perirenal adipose tissue and epididymal fat pad were significantly lower in rats fed diets supplemented with garlic powder than in those fed diets without garlic powder. The content of mitochondrial protein and uncoupling protein (UCP) in IBAT, and urinary noradrenaline and adrenaline excretion were significantly greater in rats fed a lard diet with garlic powder than in those fed the same diet without garlic. Other than adrenaline secretion, differences due to garlic were significant in rats fed shortening, also. In Experiment 2, the effects of various allyl-containing sulfides present in garlic on noradrenaline and adrenaline secretion were evaluated. Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations, whereas the administration of disulfides without allyl residues, diallylmonosulfide and S-allyl-L-cysteine did not increase adrenaline secretion. These results suggest that in rats, allyl-containing sulfides in garlic enhance thermogenesis by increasing UCP content in IBAT, and noradrenaline and adrenaline secretion.

Adipose Tissue, Brown↗

Detection of Man5GlcNAc and related free oligomannosides in the cytosol fraction of hen oviduct.

The presence of free oligomannosides in cytosol has been demonstrated by metabolic radiolabeling, and Manalpha1-2Manalpha1-2Manalpha1-3(Manalpha1-6)++ +Manbeta1-4GlcNAc was detected as the main free oligomannoside in Chinese hamster ovary cells [Kmiécik, D., Herman, V., Stroop, C.J.M., Michalski, J.C., Mir, A.M., Labiau, O., Verbert, A., and Cacan, R. (1995) Glycobiology, 5, 483-494]. In the present paper, the isomeric structures and amounts of oligomannosides in the cytosol fraction of hen oviduct were analyzed by pyridylamination and exoglycosidase digestion. Hen oviduct was used since our group has already characterized the cytosolic neutral alpha-mannosidase and endo-beta-N-acetylglucosaminidase obtained from the same source. The amounts of Man2GlcNAc, Man3GlcNAc, Man4GlcNAc, and Man5GlcNAc were 0.6, 0.6, 0.5, and 0.8 nmol/g tissue, respectively, but Man6GlcNAc-Man9GlcNAc were not detected. The isomeric structures of the Man3GlcNAc-Man5GlcNAc found were (Manalpha1-2)0-2Manalpha1-3(Manalpha1-6)Manbeta1 -4GlcNAc, which were compatible with the substrate specificities of cytosolic endo-beta-N-acetylglucosaminidase and neutral alpha-mannosidase, indicating that these enzymes participate in the formation of the oligomannosides present in the cytosol.

Animals↗

Quantitation and isomeric structure analysis of free oligosaccharides present in the cytosol fraction of mouse liver: detection of a free disialobiantennary oligosaccharide and glucosylated oligomannosides.

The amounts and isomeric structures of free oligosaccharides derived from N-linked sugar chains present in the cytosol fraction of perfused mouse liver were analyzed by tagging the reducing end with 2-aminopyridine followed by 2-dimensional HPLC mapping with standard sugar chains. Sixteen pyridylaminated (PA-) oligomannosides terminating with a PA-GlcNAc residue (GN1-type), three glucose-containing oligomannosides, and four oligomannosides terminating with a PA-di-N-acetylchitobiose (GN2-type) were detected. The total contents of the GN1- and GN2-type oligomannosides were 3. 4 and 0.5 nmol, respectively, per gram of wet tissue. Maltooligosaccharides (dimer to pentamer) were also detected, the total content of which was 13 nmol per gram of wet tissue. Besides these oligosaccharides, a PA-disialobiantennary sugar chain-the sole complex-type sugar chain-was also detected. All the oligomannosides identified had partial structures of Glc(3)Man(9)GlNAc(2)-p-p-dolichol, revealing that they were metabolic degradation products. Manalpha1-2Manalpha1-2Manalpha1-3(Manalpha1-6)++ +Manbeta1-4GlcNAc (M5B') was the major oligomannoside, suggesting that cytosolic endo-beta-N-acetylglucosaminidase and neutral alpha-mannosidase participate in the degradation, because these enzymes have suitable substrate specificities for the production of M5B'. Degradation by these enzymes seems to be the main pathway by which oligomannosides are degraded in mouse cytosol; however, small amounts of Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4(GlcNAc)1-2 and related oligomannosides together with parts of their structures were also detected, suggesting that there is another minor route by which cytosolic free oligomannosides are produced.

Acetylglucosaminidase↗

[Clinical effect of arotinolol hydrochloride and its influence on renal function in elderly patients with essential hypertension].

Arotinolol hydrochloride with alpha-and beta-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96 mmHg. 10 men and 32 women, with a mean age of 77.5 year. The patients received 10 mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p < 0.05). However, no significant changes were found in blood urea nitrogen, serum creatinine, serum albumin, beta2-microglobuline, NAG or creatinine clearance during the 24 weeks of treatment. These results indicate that arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.

Adrenergic alpha-Antagonists↗

Allylthiamindisulfide and related compounds enhance thermogenesis with increasing noradrenaline and adrenaline secretion in rats.

The effects of allylthiamindisulfide, an allyl derivative of thiamin, and related compounds on thermogenesis were investigated by measuring noradrenaline and adrenaline secretion and the temperatures of interscapular brown adipose tissue (IBAT) and rectum in rats. In Experiment 1, the effects of the administrations of allylthiamindisulfide and related compounds on noradrenaline and adrenaline secretion were evaluated as compared to thiamin in anesthetized rats. The administration of allylthiamindisulfide significantly increased the plasma concentrations of noradrenaline and adrenaline. These increases were dose dependent, while that of thiamin was not. Four synthetic compounds related to allylthiamindisulfide also increased the plasma adrenaline and noradrenaline concentrations. In Experiment 2, the effects of allylthiamindisulfide on thermogenesis were investigated by the direct measurement of temperatures in the IBAT and rectum in anesthetized rats, and compared to the effects induced by thiamin and diallyldisulfide. The temperatures in the IBAT and rectum were significantly increased by the administration of allylthiamindisulfide and diallyldisulfide, while there was no significant increase as the result of thiamin administration. These results suggest that allylthiamindisulfide and related compounds enhance thermogenesis by increasing noradrenaline and adrenaline secretion in rats.

Adipose Tissue, Brown↗

Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography.

BACKGROUND: Multiple investigations both in experimental models and in middle-aged patients with essential hypertension have demonstrated impaired endothelium-dependent vasodilation. OBJECTIVE: To determine whether hypertension exerts an additional negative effect on endothelial function of large arteries in hypertensive elderly patients who may already be affected by endothelial dysfunction due to aging. PATIENTS AND METHODS: Thirteen elderly patients with hypertension (69 9 years of age [mean SD]) were compared with 13 matched healthy elderly subjects (72 6 years of age). High resolution vascular ultrasound was used to measure brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and to sublingual nitroglycerine (causing endothelium-independent dilation). RESULTS: Flow-mediated diameter (FMD) was significantly impaired in the hypertensive elderly group (6.7 3.3% versus 13.3 3.8% in the control group, P<0.05). No significant difference could be found in nitroglycerine-induced dilation between the elderly control group (12.1 4.9%) and the hypertensive elderly (10.2 6.8%). On simple linear analysis, FMD was inversely correlated with age (r=-0.60, P=0. 03) in the healthy elderly group. FMD in the hypertensive elderly was inversely related to age (r=-0.41, P=0.04) and mean blood pressure (r=-0.67, P=0.01). CONCLUSIONS: This study showed decreased FMD with aging even in the healthy elderly, with a further decline in hypertensive elderly compared with healthy elderly subjects. This impairment of FMD in the hypertensive elderly group was related to age and mean blood pressure, indicating that aging and hypertension may impair endothelial function in the brachial artery of elderly patients with hypertension.

Age Factors↗

Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins.

The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity in cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitination in vitro. A regulatory pathway is described in which excess iron is sensed by its ability to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequently is degraded by the proteasome. Selective targeting and removal of oxidatively modified proteins may contribute to the turnover of many proteins that are degraded by the proteasome.

Animals↗

Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of steroid hormone receptors in endometrial carcinoma using immunohistochemical staining for progesterone receptor (PR) and estrogen receptor (ER). METHODS: We evaluated the correlation between PR/ER immunohistochemistry and age, clinical stage, tumor grade, myometrial tumor invasion, and disease-free survival in a series of 92 cases of endometrioid adenocarcinoma. RESULTS: Fifty (54.4%) endometrial carcinomas were PR-positive and 44 (47.8%) were ER-positive. PR immunohistochemistry of endometrial carcinoma was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (I, II vs III, IV, P = 0.001), FIGO grade (G1 vs G2 vs G3, P = 0.007), the depth of myometrial tumor invasion (< or = 1/2 vs > 1/2, P = 0.006), and disease-free survival (living vs dead, P = 0.0025). In contrast, ER immunohistochemistry had significant correlations with the depth of myometrial tumor invasion (P = 0.026) and disease-free survival (P = 0.032). Multivariate analysis of PR/ER immunohistochemistry, stage, grade, and myometrial invasion showed that the PR immunohistochemistry was a significant prognostic factor for survival (P = 0.026). CONCLUSION: PR/ER immunohistochemistry was significantly related to survival and PR immunohistochemistry appeared to be the most reliable means for predicting survival in endometrioid adenocarcinoma of the endometrium, independent of other clinicopathological parameters.

Adult↗

Effects of mesenchyme on epithelial tissue architecture revealed by tissue recombination experiments between the submandibular gland and lung of embryonic mice.

Lung epithelium during morphogenesis maintains a sheet structure of polarized cells lining a lumen, in which E-cadherin, beta-catenin and tight junctional proteins are localized at the cell-cell contact sites. On the other hand, the submandibular gland epithelium at early stages of development forms a non-cavitated mass of cells where E-cadherin/beta-catenin are present on the entire cell surfaces and tight junctional proteins are almost absent or weakly scattered. In the present study, tissue recombination experiments were performed between the two organs to explore roles of mesenchyme in the architectural development of the epithelium. Homotypic recombinants of both submandibular gland and lung showed the tissue architecture as observed in the intact organs. In contrast, 11-day lung epithelium cultured with 13-day submandibular mesenchyme formed multilayers of cells with the lumen being less visible. It was accompanied by redistribution of E-cadherin/beta-catenin along the entire cell surfaces and by an irregular distribution of tight junctional proteins. A similar redistribution of these molecules was observed in 15-day lung epithelium cultured with the submandibular mesenchyme, although the epithelial sheet structure lining the lumen was formed. On the other hand, the tissue architecture of submandibular gland epithelium was little affected by lung mesenchyme, although the epithelium was flattened and showed branching morphogenesis.

Animals↗

[An elderly patient with an insulinoma who had prolonged dementia-like symptoms].

A 77-year-old woman had suffered from memory disturbance and disorientation for two years before she was admitted to the hospital because of confusion. Her score on the Hasegawa dementia scale revised (HDS-R) was 12 points at the time of the first medical examination. No other abnormalities could be found except for a blood glucose concentration of 34 mg/ dl. A Magnetic Resonance Image (MRI) of the brain showed some small lacunae on both sides in the frontal white matter and basal ganglia. After hospitalization, glucose was administered and the blood glucose concentration increased, but the dementia-like symptoms did not resolve. She was discharged because the symptoms were too difficult to control in the general hospital. Although dementia-like symptoms were present even after discharge, they did not necessarily appear during fasting. Six months later she was rehospitalized. The insulin-blood sugar ratio was at least 0.3 and abdominal echogram showed a 1-cm tumor at the tail of pancreas. The pancreas tail was removed and the tumor cells were reacted with anti-insulin-antibodies. One month after the operation, the dementia-like symptoms had resolved. The HDS-R score was improved to 27 points (normal range) 40 days after the operation. The amount of the slow waves in the electroencephalogram decreased 5 months after the operation. The dementia-like symptoms observed in this case could be regarded as the Durchgangssyndrom of Wieck. This syndrome is observed transiently at the time of recovery of deterioration of disturbances of consciousness. But it is treatable. This patient was an interesting case that showed Durchgangssyndrom mimiking dementia associated with insulinoma.

Aged↗

Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2. Segregate expression profiles from a rap1GAP gene product.

Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation. Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA encodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regions and rap1GAP-related domain followed by a coiled-coil stretch. Baculovirally expressed p130(SPA-1) exhibited GTPase-activating protein (GAP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Rac, and Ran, with comparable specific activity to the rap1GAP gene product (p85/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2. Expression of SPA-1 and rap1GAP genes tended to be segregate in various tissues, lymphoid tissues expressing abundant SPA-1 transcript without rap1GAP, while those such as brain, kidney, and pancreas exhibiting rap1GAP mRNA with little SPA-1. Promyelocytic HL-60 cells, which expressed p130(SPA-1) with little p85/95(rap1GAP) in uninduced state, showed progressive decline in p130(SPA-1) and conversely drastic increase in p85/95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results suggested that products of SPA-1 and rap1GAP genes, albeit comparable GAP activity for Rap1 and Rap2, functioned in the distinct contexts depending on cell types and/or states.

Amino Acid Sequence↗

Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils.

Apoptosis is well known to be mediated by oxidative stress. To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-Fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-Fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway.

Apoptosis↗