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T Doi

Publications and source records attributed to T Doi.

At least 127 records · Page 7Linked to original sources

Gene transfer mediated by YKS-220 cationic particles: convenient and efficient gene delivery reagent.

A monocationic lipid, YKS-220, with a symmetrical and biodegradable structure can be used as an effective gene transfer vector in a cationic particle form (not a cationic liposome form), and is obtained by diluting an ethanol solution of YKS-220 and DOPE (1:5, molar ratio) with an aqueous medium. This preparation method is more convenient than that for cationic liposomes. YKS-220 cationic particles showed a heterogeneous large mean diameter of 4.4 microm. An obvious size change was not observed when plasmid DNA was added. The transfection activity of YKS-220 cationic particles was comparable to those of YKS-220 liposomes and DOSPA liposomes (LipofectAMINE), and even higher than that of DOGS (TRNSFECTAM). Interestingly, the YKS-220 cationic particle/DNA complexes were resistant to the neutralizing effect of serum. All of these findings indicate that YKS-220 cationic particles are a convenient and efficient gene delivery reagent.

Animals↗

White matter hyperintensities on MRI in a patient with corticobasal degeneration.

We describe a patient who presented with the clinicopathological features of corticobasal degeneration (CBD). Over the course of 8 years, the patient developed myoclonus, dystonia, and supranuclear gaze palsy associated with an akinetic-rigid syndrome. To our knowledge, no previous report of a patient with CBD has described clear-cut regional white matter changes as revealed by magnetic resonance imaging (MRI) scans. In our patient, a T2-weighted MR image of the brain showed focal atrophy of the bilateral frontal cortex and asymmetric regional hyperintensities of the subjacent white matter. These signal changes seemed to primarily reflect the progression of neuronal degeneration, especially the demyelination secondary to axonal loss or change.

Adult↗

Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.

Expression of the class A macrophage scavenger receptor (MSR) contributes to the uptake of modified low density lipoproteins (LDL) by macrophages and transformation of these cells into lipid-laden foam cells, which characterize atherosclerosis. Many environmental factors, in particular, proinflammatory cytokines and growth factors, can exert regulatory effects on MSR expression, whereas intracellular accumulation of cholesterol itself does not influence MSR levels to any considerable extent. In the present study, by using an in vitro model, we examined whether stimulation with interleukin-6 (IL-6), an immunoregulatory, multipotential cytokine, modulates the expression and activities of the MSR in macrophages. When treated with IL-6, macrophages derived from peripheral monocytes and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 monocytic cells showed significantly reduced uptake and/or binding of the MSR ligand, acetylated LDL. This effect was paralleled by a reduction in the expression of MSR protein and mRNA. Analysis of MSR promoter activity in THP-1 cells transfected with an MSR promoter-reporter gene construct demonstrated decreased activity of the MSR promoter in IL-6-treated THP-1 macrophages. Electrophoretic mobility gel shift assay also showed a reduction in the binding of a transcription factor to the MSR promoter AP-1/ets elements in IL-6-treated cells. Thus, exposure to IL-6 may inhibit expression of the class A MSR in differentiated macrophages at transcriptional levels. This result suggests that this cytokine may modulate foam cell formation during atherogenesis.

Carbocyanines↗

VXFD in the cytoplasmic domain of macrophage scavenger receptors mediates their efficient internalization and cell-surface expression.

We determined the endocytosis motif sequence of macrophage scavenger receptors by measuring the internalization of the ligand-bound cell-surface scavenger receptors at the early stage. Mutation experiments have indicated that the 28 amino acids at the N-terminal cytoplasmic domain are important for both efficient internalization and cell-surface expression of the receptor. The substitution of alanine for Val21, Phe23 or Asp24 reduced both the efficiency of internalization and the cell-surface expression of the receptors; in addition, that for Val28 reduced only the internalization efficiency and that for Lys22 reduced only the cell-surface expression of the receptors. Western blot experiments showed that the total levels of expression of the mutant receptors in the cells were approximately the same and all the mutants were identified in the membrane fraction. This suggests that the Val21, Lys22, Phe23 and Asp24 mutants are localized in membranes other than the cell-surface membrane by missorting. All our results indicate that VXFD is the motif sequence essential for not only the coated-pit-mediated endocytosis of macrophage scavenger receptors but also for the trafficking of the receptors to the cell surface.

Animals↗

Properties of cationic liposomes composed of cationic lipid YKS-220 having an ester linkage: adequate stability, high transfection efficiency, and low cytotoxicity.

Cationic lipid N-[3-[2-(1,3-dioleoyloxy)propoxy-carbonyl]propyl]-N,N,N-trimethyla mmonium iodide (YKS-220) having a symmetrical and biodegradable structure was employed for the preparation of cationic liposomes with dioleoylphosphatidylethanolamine (DOPE). The stability, transfection activity in several cell lines and cytotoxicity of YKS-220 cationic liposomes were studied. It was found the YKS-220 cationic liposomes were very stable and their transfection activity remained even after storage at 4 degrees C for 12 months. The transfection activity of these liposomes was assayed using CHO, COS, and HepG2 cells and found to be comparable with, or better than, that of other cationic liposomes, such as N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) liposome, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) liposome (Lipofectin), and 2,3-dioleyloxy-N-[2-(sperminecarboxamido)ethyl]-N,N-dimethyl -1-propanaminium trifluoroacetate (DOSPA) liposome (LipofectAMINE). In addition, the cytotoxicity of YKS-220 cationic liposomes was far lower than that of other cationic liposomes.

Animals↗

Mechanism of inhibitory effect of warfarin on mesangial cell proliferation.

Because proliferation of mesangial cells is a hallmark of glomerular diseases, understanding the regulatory mechanism of mesangial proliferation is important for the treatment. Warfarin has long been used to treat glomerular diseases, although its mechanism of effect on mesangial proliferation has remained unknown. Therefore, this study was conducted to examine whether warfarin can inhibit mouse mesangial cell proliferation by focusing on Gas6, which has been shown to be activated by vitamin K-dependent gamma-carboxylation. In mesangial cells, Gas6 and its receptor Axl were expressed. In addition, exogenous Gas6 phosphorylated Axl, activated extracellular signal-regulated kinase, and stimulated [3H]-thymidine incorporation in mouse mesangial cells. This study also examined whether endogenous Gas6 stimulates mesangial proliferation. Conditioned medium (CM) from serum-starved mesangial cells could stimulate [3H]-thymidine incorporation and phosphorylate extracellular signal-regulated kinase, whereas CM in the presence of warfarin could not. Simultaneous administration of vitamin K could cancel the inhibitory effect of warfarin. These results suggest that vitamin K-dependent growth factors in the CM are critical for mesangial proliferation. Addition of the extracellular domain of Axl to the CM inhibited its mitogenic effect on mesangial cells, suggesting that this vitamin K-dependent growth factor is Gas6. It is concluded that Gas6 is an endogenous mitogen in mesangial cells, and warfarin inhibits mesangial proliferation possibly by inhibiting gamma-carboxylation of Gas6. This study sheds light on the regulation of mesangial proliferation and may lead to a new therapeutic strategy for glomerular diseases.

Animals↗

[A decrease in urinary proteins in an elderly patient with refractory minimal change nephrotic syndrome administration of an angiotensin converting enzyme inhibitor in combination with steroids].

A 72-year-old woman had been treated for hypertension and hyperthyroidism by a local doctor. In May 1998, she came to this institution with a chief complaint of leg edema. Based on the clinical findings, she was diagnosed as having nephrotic syndrome with massive proteinurea, hypoproteinemia and hyperlipidemia. Renal biopsy findings showed minimal change nephrotic syndrome (MCNS). No substantial improvement was obtained by steroid therapy. We therefore additionally administered angiotensin-converting enzyme inhibitor (enalapril maleate). The urinary protein concentration significantly decreased. On decreasing the dose of steroids, the urinary protein concentration increased. Cyclophosphamide helped us to decrease the steroid dosage. This treatment resulted in type II incomplete remission. The final diagnosis was refractory MCNS. During steroid therapy, she developed hyperglycemia. She had no histology of diabetes mellitus. There is therefore a possibility that steroids can induce hyperglycemia even in patients without a history of diabetes mellitus. These results suggest that careful monitoring of plasma glucose is necessary during steroid therapy and that the administration of an angiotensin-converting enzyme inhibitor is effective in elderly patients with refractory primary nephrotic syndrome.

Aged↗

[A study of depressive state and background factors in community-dwelling older persons].

In order to maintain and improve the mental health of elderly people living in the community, a cross-sectional survey was conducted to elucidate their depressive state and its background factors. Subjects were elderly persons living in the community who were able to fill in the questionnaire themselves. The study used the self-recording questionnaire sheets used in the Kahoku Longitudinal Aging Study by Matsubayashi et al and the Zung Self-rating Depression Scale (SDS). Out of 2,379 elderly persons who were able to fill in the questionnaire by themselves in the community, 2,361 (99.2%) returned the questionnaire sheets. After removing inadequate responses, analysis was possible for 1,181 (49.6%) (542 males (average age 72.3 +/- 5.5) and 639 females (average age 73.0 +/- 6.3). Degree of depressive state as evaluated by SDS was normal for 731 persons (61.9%); mild, 240 (20.3%); moderate, 181 (15.3%); and severe, 29 (2.5%). The average age became higher as the SDS became high, of being indicating the seriousness of the depressive state (p = 0.0155), with the ratio women significantly higher (p = 0.0077). Among those with severe SDS, the ratio of single persons was high (p < 0.001) as well as those who were non-drinkers (p = 0.0015), without regular habit of walking (p < 0.001), or without work (p < 0.001). The ratio of those receiving medication regularly was also significantly high (p = 0.0022). As for the relation of SDS with various of the scores, the higher the SDS score became, the scores for ADL, information-related function, functional and emotional support network, family relationship, friendship, economic condition became significantly lower (p < 0.001, respectively). In logistic regression analysis using the background factors for SDS as explanatory variables, factors such as being women (odds ratio, 1.73; 95% confidence interval, 1.10-2.72). ADL (0.80; 0.69-0.93), emotional support network (0.88; 0.81-0.96), friendship (0.98; 0.96-0.99) were significant independent contributing factors. As for the relation between SDS and subjective senses, the more serious the SDS score became, the scores for feelings of healthiness and satisfaction became significantly smaller (both p < 0.001). For prevention and amelioration of the depressive state of elderly persons living in the community, attempts should be made to improve the background factors which were clarified by the present study by efficiently utilizing health, medical and welfare services and following the future course with a positive attitude.

Activities of Daily Living↗

[A case of pituitary apoplexy approving as severe headache and nausea].

The causes of pituitary apoplexy are unclear. We report a case of pituitary apoplexy presenting with headache and nausea. On June 17th, 1997 a 74-year-old woman had complained of retro-orbital headache, fever and vomiting. A cold was diagnosed for which she recurred medication. In addition to the previous symptoms she was getting to lose appetite. She was admitted to our hospital for further examination and treatment on June 21. On admission neurological examination showed left pupil mydriasis, the left eye had no light reflex and the right eye had only a slight response to the light. She could hardly move both eyeballs up. Laboratory data showed a normal white blood cell count and the CRP was 16.2 mg/dl. Lumbar puncture showed 97 mg/dl total protein and 82 cells per microliter, most of which were lymphocytes. We diagnosed viral infection based on the evidence of clinical symptoms and lumbar puncture data. The patient was treated with gamma-globulin and improved. From the 16th day of sickness we recognized symptoms of oculomotor paralysis and the syndrome of inappropriate antidiuretic hormone. On the 23rd day of sickness we strongly suspected pituitary apoplexy based on transaxial MR images. After absorption of intra-tumor hemorrhage, the oculomotor symptoms recurred. We finally reached a diagnosis of pituitary apoplexy based on pathological material, MR images, symptoms and laboratory data. We must think of pituitary apoplexy when we see an aged out-patient with severe headache, nausea, vomiting and oculomotor paralysis. It was difficult to diagnose this disease in the early time course of the disease.

Aged↗

[Happiness and background factors in community-dwelling older persons].

In order to maintain and improve mental health of elderly people living in the community, a cross sectional survey was conducted to elucidate their happiness and background factors. The subjects were elderly persons living in the community who were able to fill in the questionnaire themselves. The study employed the self-recording questionnaire forms used in Kahoku Longitudinal Aging Study by Matsubayashi et al. Happiness was assessed using a visual analogue scale. Out of 2,379 elderly persons who were able to fill in the questionnaire by themselves in 2,361 (99.2%) returned the questionnaire sheets. After removing inadequate responses, analysis was possible for 1,873 (78.7%) (860 men (average age 72.7 years) and 1,013 women (average age 72.8 years). Among those with greater happiness, the ratio of those living with others (p = 0.0051) was high as well as those with spouses (p = 0.0240), without a history of hypertension (p = 0.0096) and apoplexy (p = 0.0039), not receiving medication regularly (p = 0.0039), with regular habit of walking (p < 0.001), or with work (p < 0.001). As for the relationship between happiness and various scores, the higher the happiness scale became, the scores for ADL, information-related function, functional and emotional support network, healthy condition, appetite condition, sleep condition, memory condition, family relationships, friendship, economic condition became significantly higher (p < 0.001, respectively). On multiple regression analysis using the background factors for happiness as explanatory variables, factors such as functional support network (p < 0.001), emotional support network (p = 0.0254), healthy condition (p < 0.001), good memory condition (p = 0.0027), friendship (p < 0.001), good economic condition (p < 0.001) were significant independent contributing factors. As for the relation between SDS and happiness, the more serious the SDS score (higher score) became, the scores for the feeling of happiness became significantly smaller (p < 0.001). For amelioration of the happiness of elderly persons living in the community, attempts should be made to improve the background factors clarified by the present study by efficiently utilizing health, medical and welfare services.

Aged↗

Effect of meal timing after resistance exercise on hindlimb muscle mass and fat accumulation in trained rats.

To study the effect of meal timing after exercise on body composition, 20 male rats were assigned to either a group fed a meal right after exercise (R) or a group fed a meal 4 h after exercise (L). Resistance exercise (squatting) was conducted from 6:00 to 7:00, 3 d/wk for 10 wk. Meals were consumed from 7:00 to 8:00 and from 19:00 to 20:00 for R, and from 11:00 to 12:00 and from 19:00 to 20:00 for L. The room was lighted from 7:00 to 19:00. After 10 wk, the body weight was comparable between the groups. The hindlimb muscle weight was higher in R than in L by 6% (p < 0.05), whereas the sum of the weight of perirenal, epididymal, and mesenteric adipose tissues was lower in R than in L by 24% (p < 0.01). The soleus lipoprotein lipase (LPL) activity was higher in R than in L by 70% (p < 0.01), and the activity negatively correlated with the adipose tissue weight (r = -0.49, p < 0.05). These results suggest the possibility that ingesting a meal right after resistance exercise may contribute to an increase in the muscle mass and to a decrease in the adipose tissue compared to ingesting a meal several hours later.

Adipose Tissue↗

Effect of timing of meal intake after squat exercise training on bone formation in the rat hindlimb.

We hypothesized that bone acquisition was affected by the timing of meal intake after resistance exercise training. This was based on the following previous results: 1) Nutrient intake right after exercise resulted in an increase in muscle mass and a decrease in abdominal fat mass as well as muscle protein synthesis when compared to the intake of a meal later after the exercise; and 2) body composition has been proposed to be a good predictor of bone mass. To substantiate our hypothesis, 20 male rats were assigned to either a group fed a meal right after squat exercise (R) or a group fed a meal 4 h after the exercise (L). The 10-wk training program consisted of approximately 70% of one repetition maximum for each animal, 15 repetitions per set, 10 sets per day, 3 d per week. As a result, hindlimb muscle mass in the R group was greater (p < 0.05) than that in the L group and abdominal fat mass was less (p < 0.01) in the R group as compared to the L group, regardless of there being no significant difference in body weight between the groups. Bone volume in the tibia (p < 0.01) and femur (p < 0.05) were both significantly greater in the R group than in the L group. Bone mineral content index (BMCI) and bone mineral density index (BMDI) in the tibia of the R group were significantly (p < 0.05) greater than the corresponding values of the L group. The greater BMCI and BMDI in the tibia were positively and significantly (p < 0.05) related with hindlimb muscle mass, but not with abdominal fat mass. There was no significant difference in BMCI and BMDI in the femur between the groups. These results suggest that the R regimen may contribute to increased bone acquisition in the tibia as compared to the L regimen, and this effect is partly due to the enlargement of muscle mass in the R group as compared to the L group.

Adipose Tissue↗

[Evaluation of child-rearing environmental factors that affect the occurrence of sudden infant death syndrome: interview conducted by public health nurses].

PURPOSE: We examined the child-rearing environmental factors that affect the occurrence of sudden infant death syndrome (SIDS) by using a nation-wide survey. METHOD: Infants who died due to SIDS between January 1996 and June 1997 in Japan were identified from death certificates. Controls of the same sex, birthplace, and birth months as the corresponding SIDS were chosen from birth certificates. Interviews of both cases and controls were undergone in January and February 1998 by public health nurses. RESULTS: The following Child-rearing factors exhibited a significant relationship with the occurrence of SIDS: 1. Concerning the sleeping position, the prone position was associated with increased risk compared to the supine position, with an odds ratio of 3.02 (95% c.i. 2.07-4.65). 2. Regarding the feeding method, artificial feeding only demonstrated a higher risk than breast feeding only, with an odds ratio of 4.92 (95% c.i. 2.78-9.63). 3. With regard to smoking, infants with both parents who smoked exhibited a higher risk than infants where neither parents smoked, with an odds ratio of 3.50 (95% c.i. 1.74-8.32).

Child Rearing↗

Serum soluble Fas antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients.

We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25 (mean+/-SD) in the high grade malignant group (n=9) that demonstrated diffuse large cell (DL) components and 2.53+/-0.46 (mean+/-SD) in the low grade malignant group (n=12) that did not demonstrate DL components. Among 12 patients who underwent HP eradication therapy, the blood sFas antigen level lowered after eradication in 7 out of 10 patients who showed complete response or partial response, while sFas antigen level did not decrease in the 2 patients who showed no change or progression of the disease. In the high grade malignant group, 2 of 3 patients who underwent HP eradication treatment showed a mild decrease in the sFas antigen level as well as an improvement on endoscopic and histological examinations, but these sFas level were not normalized. The blood sFas antigen level tended to coincide with pathological activity and malignancy, suggesting that the sFas antigen level may be a prognostic indicator and useful index for the response of HP eradication treatment in gastric MALT lymphoma.

Apoptosis↗

[Giant testicular tumor: a case report].

We report a case of giant testicular tumor. A 30-year-old man visited our department complaining of a painless swelling of the right scrotal contents. In chest X-ray and abdominal computerized tomography (CT) there were no abnormal findings. Serum alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase levels were normal. Right high orchiectomy was performed. The size of the removed specimen was 13.5 x 8.5 x 7.5 cm, and weight 530 g. The pathological diagnosis was immature teratoma. The patient has received no further therapy. There has been no recurrence for 7 months postoperatively.

Adult↗