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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 325 records · Page 18Linked to original sources

Effect of cyclosporin A on human bone marrow granulocyte-macrophage progenitors with anti-cancer agents.

Cyclosporin A (CyA) overcomes P-glycoprotein (P-gp) associated multidrug resistance (MDR). P-gp expression is frequently observed among, not only various cancer cells, but also several normal tissues including bone marrow progenitor cells. These findings lead us to examine whether CyA enhances the myelotoxicity of anti-cancer agents. Bone marrow mononuclear cells were incubated with anti-cancer agents (vincristine, VCR; doxorubicin, ADM; etoposide, VP-16; cytarabine, Ara-C; methotrexate, MTX) and a concentration of CyA (0.5, 5.0 micrograms/mL). The methylcellulose assay for granulocyte-macrophage progenitors (CFU-GM) was conducted using the post-treated cells. There was no significant toxicity for marrow CFU-GM formation after 72 h incubation with CyA (84-108% of control). The inhibitory concentration that reduced colonies by 50% (IC50) was 12 nmol/L for VCR, 6 nmol/L for ADM, 220 nmol/L for VP-16, 15 nmol/L for Ara-C and 35 nmol/L for MTX, respectively. For VCR, ADM and VP-16, the number of CFU-GM was unchanged with the addition of CyA at 0.5 microgram/mL concentration. In contrast at 5 micrograms/mL CyA, the number of CFU-GM (% of control) was reduced significantly (P < 0.05 or P < 0.01). With MTX and Ara-C, the number of CFU-GM was unchanged after addition of CyA, even at 5 micrograms/mL concentration. We conclude CyA may therefore enhance cytotoxic drug sensitivity in MDR tumor cells at a clinically achievable concentration (0.5 microgram/mL) without marrow toxicity.

Antineoplastic Agents↗

[Experimental pneumonia with Pseudomonas aeruginosa in immunosuppressed guinea pigs as a model for biofilm-associated infection].

To establish a model where the role of bacterial biofilms in chronic pneumonia with Pseudomonas aeruginosa could be investigated, hydrocortisone-treated guinea pigs were given P. aeruginosa, strain 2126 by inhalation which were used throughout this study, in planktonic form. In these animals, the bacteria were recovered only from the lungs more than 4 weeks after infection. The persistence in bacterial colonization in the lungs coincided with the formation of glanulomatous lesions that surrounded spherical grains consisting of outer shell and inner bacterial colonies. The outer shell of grain was stained with ruthenium red and was presumed to be polyanionic and therefore to be a biofilm-like material. In normal animals without hydrocortisone-treatment, the number of neutrophils recovered from bronchoalveolar lavage fluid increased significantly from 3 hours after infection and subsequently the inhaled bacteria were eliminated from the lungs by day 3 of infection. This early influx of neutrophils into the lungs tended to be suppressed by treatment with hydrocortisone. The formation of grains did not take place in the lungs of normal animals, indicating the significant role of grain-formation in the initiation and the prolongation of bacterial colonization in the lungs. P. aeruginosa, strain 2126, incubated in saline formed thick biofilms on the surface of teflon piece. Levofloxacin (LVFX), a quinolone antibacterial, exhibited killing activity against the bacteria in in vitro-forming biofilms at MIC. In contrast, gentamicin (GM), an aminoglycosid antibiotic, and ceftazidime (CAZ), a beta-lactams antibiotic, showed no such killing activity at MIC. Treatment of this model with oral LVFX achieved complete eradication of the bacteria, whereas subcutaneous injection of GM or CAZ was hardly effective. The pharmacokinetic study on these antibacterials revealed that the doses used in this study were sufficient to obtain the pulmonary levels of these drugs far above MIC even in GM and CAZ. These data indicate that the outer shell of grains, a characteristic finding in the pulmonary lesions of this model, may be one of the forms of pseudomonal biofilms and that this model represents the significant role of biofilm mode of growth of P. aeruginosa in persistence in pulmonary colonization.

Animals↗

Perfusion lung scanning before and after percutaneous transvenous mitral commissurotomy--early estimation of lung congestion relief.

Percutaneous transvenous mitral commissurotomy (PTMC) has recently been used to treat mitral stenosis. The aim of this study was to evaluate the usefulness of radionuclide perfusion lung scanning in assessing the effect of PTMC on the relief of lung congestion. We studied 30 patients (7 males and 23 females, mean age 55 years). Perfusion lung scannings were performed within 1 week before and after PTMC. We calculated the ratio of activity in the upper quarter to that in the lower quarter of the right lung (U/L) as an index of lung congestion. After PTMC, the mean mitral valve area increased from 1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, the mean left atrial pressure decreased from 14.8 +/- 6.3 to 9.1 +/- 3.5 mmHg, the mean pulmonary artery pressure decreased from 22.7 +/- 8.6 to 17.4 +/- 6.3 mmHg, and the U/L ratio decreased significantly from 0.89 +/- 0.40 to 0.68 +/- 0.24 (p < 0.0001). The U/L ratio showed greater improvement (4.5%) in patients whose NYHA class improved (n = 19) than in those whose NYHA class did not improve after PTMC. The U/L ratio was closely related to mitral valve area, and left atrial and pulmonary artery pressures. The change in the U/L ration before and after PTMC also reflected symptomatic improvement. In conclusion, U/L ratios obtained from perfusion lung scannings before and after PTMC reflect mitral valve area and pressures, and can be used to assess lung congestion relief after PTMC.

Adult↗

Autophosphorylation of insulin receptor in a patient with Werner's syndrome associated with insulin resistant diabetes mellitus.

The tissue sensitivity to insulin was evaluated using the hyperinsulinemic euglycemic clamp technique in a 44-year old male with Werner's syndrome associated with diabetes mellitus. In addition, the autophosphorylation of insulin receptors and the number of autophosphorylated insulin receptors were measured in his erythrocytes by a new enzyme-linked immunosorbent assay. He had an increased serum insulin level (30.5 microU/ml) in addition to hyperglycemia (226 mg/dl), suggesting that he had insulin-resistant diabetes mellitus. A clamp study revealed that his insulin-stimulated glucose disposal rate (2.80 mg/kg/min) was comparable to that in noninsulin-dependent diabetes mellitus (4.14 +/- 1.94 (SD) mg/kg/min, n = 23). The number of autophosphorylated insulin receptors per 300 microliters of erythrocytes was also identical to that in normal control subjects. In addition, the autophosphorylation of insulin receptors determined at six different insulin concentrations was within the normal range, even when it was expressed as per 300 microliters of erythrocytes as well as per unit receptor. These results demonstrate that insulin resistance in the patient with Werner's syndrome is caused by a defect that cannot be detected by means employed in this study, and suggest that the defect is present at the steps distal to the autophosphorylation of tyrosine kinase of insulin receptors.

Adult↗

Long-term effects of dietary fiber supplementation on serum glucose and lipoprotein levels in diabetic rats fed a high cholesterol diet.

We have shown that cholesterol-fed diabetic rats developed atheromatous lesions in the aorta and coronary arteries, which were not observed in cholesterol-fed diabetic rats receiving concomitant supplementation with 15% glucomannan, a soluble dietary fiber concentrate. The present study was designed to examine the effects of the dietary fiber supplementation on serum levels of glucose and lipoproteins in cholesterol-fed diabetic rats. Feeding a diet containing 1.5% cholesterol (wt/wt) and 0.37% cholic acid for 18 weeks to rats made diabetic by streptozotocin (35 mg/kg body weight, iv) produced moderate hyperglycemia and moderate hypercholesterolemia, the latter being characterized by high concentrations not only of low density lipoproteins but also intermediate density lipoproteins and very low density lipoproteins. These changes in serum lipoproteins and hyperglycemia were substantially reduced by 18 weeks of supplementation with glucomannan but high density lipoprotein cholesterol and triglyceride levels did not change after feeding a cholesterol-rich diet in the presence or absence of glucomannan supplementation. These results suggest that amelioration in hyperlipoproteinemia and hyperglycemia induced by the dietary fiber supplementation may help retard or prevent the atheromatous formation found in cholesterol-fed diabetic rats.

Animals↗

Hypertrophic cardiomyopathy in patients with diabetes mellitus associated with mitochondrial tRNA(Leu)(UUR) gene mutation.

Left ventricular function and morphology were assessed using M-mode echocardiography in 3 patients with diabetes mellitus associated with mitochondrial tRNA(Leu)(UUR) gene mutation, who were free of clinical, electrocardiographic, or thallium scan evidence of ischemic heart disease. Echocardiograms revealed hypertrophic cardiomyopathy in all 3 patients. Hypertrophy of the interventricular septum was mild in Cases 1 and 3 (12 and 13 mm, respectively) and severe in Case 2 (22 mm) (normal 7-10 mm). When they had neither signs nor symptoms suggestive of congestive heart failure, percentage fractional shortening (%FS), an index of wall motion of the left ventricle (normal > 28%), was normal in Cases 2 and 3 (28 and 32%, respectively) whereas it was slightly decreased in Case 1 (22%). In Case 1 with mild hypertrophy, the development of congestive heart failure was associated with a marked decrease in %FS to 13%; this patient responded well to diuretics and captopril and %FS rose to 22%. However, a mild decrease in %FS to 21% caused congestive heart failure in Case 2 with severe hypertrophy. His response to treatment was marginal. The present study indicates that mitochondrial DNA analysis should be done in patients with diabetic cardiomyopathy, and that sequential echocardiography is invaluable for the detection of hypertrophic cardiomyopathy and the management of subsequent myocardial dysfunction in patients with mitochondrial diabetes mellitus and cardiomyopathy.

Adult↗

Vertebral slip in lumbar spondylolysis and spondylolisthesis. Long-term follow-up of 22 adult patients.

We studied the aetiology of vertebral slip in a long-term follow-up of 22 adult patients with isthmic spondylolysis or spondylolisthesis of L5. Of the 18 with spondylolysis without slip, 13 showed no slip after ten years, but five developed displacement of over 5%. All four patients with spondylolisthesis showed progression of the slip. We found that the vertical thickness of the transverse process of L5 was significantly greater (p < 0.01) in the 13 patients with no slip than in the other two groups. The relationship of vertebral slip to the shape of the transverse processes of L5 may be explained by differences in the bulk or physiological strength of the posterior bands of the iliolumbar ligament.

Adolescent↗

Effects of dietary vitamin D intake on plasma levels of parathyroid hormone and vitamin D metabolites in healthy Japanese.

To clarify the nutritional status of vitamin D in Japanese, effects of dietary intake of vitamin D on plasma levels of intact and highly sensitive parathyroid hormone (I-PTH and HS-PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium (Ca) and phosphorus (P(i)) in 79 healthy Japanese were investigated. The plasma levels of 25-OH-D in men were significantly higher than those in women, whereas those of HS-PTH in men were significantly lower than those in women. The levels of 25-OH-D in men were generally higher than those in women. Significant correlations were observed between the dietary vitamin D intake and the plasma 25-OH-D or HS-PTH levels. Correlations between the plasma 25-OH-D levels and the plasma HS-PTH levels were also significant. These results suggest that dietary intake of sufficient amounts of vitamin D is effective for improving the vitamin D nutritional status through normalizing PTH levels.

Adult↗

[Combination therapy of high dose 5'-DFUR+MMC for advanced or recurrent gastric cancer. 5'-DFUR Joint Research Group in the Osaka District for Gastric Cancer].

We conducted multi-center clinical trials of 'Treatment with high dose 5'-DFUR+MMC' in order to evaluate the effects, the possibility for outpatient treatment and the survival effects in patients with advanced or recurrent gastric cancer. The treatment schedule was as follow; 5'-DFUR 1,600 mg/body/day was given orally for five consecutive days every week and MMC 6 mg/m2 was injected intravenously once every four weeks. Forty-eight patients were enrolled and 34 cases were evaluated for anti-tumor responses. The overall response rate was 29.4% (10/34 cases). Side effects were mainly diarrhea, but outpatient treatment was possible in most cases. The median survival period was 249 days, which is longer than with other treatments. This result suggests that this combination chemotherapy is useful in patients with advanced or recurrent gastric cancers.

Adult↗

Detection of genomic variability among isolates of Campylobacter jejuni from chickens by crossed-field gel electrophoresis.

Digestion with Sal I facilitated the subclassification of 41 strains of Campylobacter jejuni into seven types, and digestion with Sma I enabled subclassification into twelve types. Sma I was potentially more useful for the detection of variability among the 41 strains, but both restriction enzymes seemed to be potentially useful for detecting variability among crossed-field gel electrophoresis profiles of the strains. The results clearly demonstrated that C. jejuni strains from different sources and with different routes of transmission had invaded the three farms investigated. At farms Sa and Ai, approximately 70% (23 strains) of isolates of C. jejuni (33 strains) were subclassified into the two major genotypes (I and II) on the basis of cleavage profiles with both Sal I and Sma I. These two major genotypes appeared to have invaded, expanded in and occupied the two chicken farms. All nine strains from farm Ai belonged genotype I.

Animals↗

[A case of renal cell carcinoma in a young adult].

Renal cell carcinoma in young adults under the age of forty is rare. A case of renal cell carcinoma in a 22-year-old female is presented. Microhematuria was pointed out in the patient by a health check up system and an ultrasonogram revealed a solid mass 5 cm in diameter in the lower pole of the right kidney. The patient was referred to our clinic in January, 1994. An abdominal CT showed a solid and well bordered mass in the right kidney. Renal tumor biopsy was revealed renal cell carcinoma. Right radical nephrectomy was performed on February 9, 1994. From 1986 to 1994, 4 cases of renal cell carcinoma in young adults, other than this case, have been treated in our clinic. All of them have been healthy for more than 6 years, suggesting a good prognosis.

Adult↗

Molecular subtyping of clinical isolates of Escherichia coli from patients with lower urinary tract infections in Japan.

Crossed-field gel electrophoresis was used to analyse the chromosomal genomic DNA from 41 clinical isolates of Escherichia coli serotypes O-2, O-4, O-6 and O-75 from patients with lower urinary tract infections after digestion of the DNA with Not I and Xba I, respectively. Not I generated 28 distinctly different genomic profiles after crossed-field gel electrophoresis (CFGE) from 34 strains and Xba I generated 35 distinctly different genomic profiles from 41 strains. Not I failed to cleave the genomic DNA from one strain of E. coli serotype O-6 and from all of six strains of serotype O-75. Both enzymes were shown to have equal potential utility for detection of variability in CFGE profiles among 34 strains because both classified 34 of the 41 strains into 28 profiles in a similar manner. No examples of essentially identical restriction profiles among strains of different serotypes were obtained.

Bacterial Typing Techniques↗

[Characteristics of regional sympathetic dysfunction in acutely ischemic myocardium assessed by 123I-metaiodobenzylguanidine imaging: impairment of myocardial norepinephrine uptake or retention].

To characterize regional cardiac sympathetic dysfunction due to myocardial ischemia, we examined 123I-metaiodobenzylguanidine (MIBG) myocardial distribution of initial 15-min and 4-hr delayed SPECT images in 14 patients with recent myocardial infarction (MI), 25 patients with vasospastic angina which was angiographically proven with elgonovine maleate (Gp VSAP) and 16 patients with chest pain syndrome and normal CAG findings (GpCP). In those with MI, the study was serially done at 2 weeks after (Gp MI-1) and at 3 months after the onset of MI (Gp MI-2). We estimated regional tracer uptake in 20 segments of tomographic images by using a 4-point scoring system (0 = normal, 1 = mild, 2 = moderate, 3 = severe reduction) and calculated the total defect score (IDS). In all patients with MI, the area of reduced MIBG uptake was more extensive than the 201Tl perfusion defect in the acute stage (Gp MI-1) indicating the presence of viable but denervated myocardial tissue. Also, the MIBG defect was persistently observed from initial (TDS: 24 +/- 13) to delayed imaging (TDS: 26 +/- 12). However, in the chronic stage (Gp MI-2), the initial MIBG uptake improved (TDS: 18 +/- 9) but the delayed uptake remained almost the same (TDS: 22 +/- 10) indicating high washout of MIBG from the ischemic myocardium. Fourteen in Gp VSAP and 14 in Gp CP showed the regional MIBG defect in the delayed image more extensively than in the initial image indicating high washout of MIBG in the involved myocardial regions. These results suggest that neuronal uptake of MIBG is impaired in the acute stage of MI although neuronal retention of MIBG is predominantly impaired in the chronic stage of MI or in Gps VSAP and CP.

3-Iodobenzylguanidine↗

Body fat and muscle thickness distributions in untrained young females.

Brightness-mode (B-mode) ultrasound was used to measure fat and muscle thicknesses on 44 untrained females (age = 18-29 yr, body density = 1.050 +/- 0.009 (SD)g.ml-1, %fat = 21.5 +/- 4.1%) at eight sites (triceps, biceps, forearm, subscapular, abdomen, quadriceps, hamstrings, and posterior calf). The correlation coefficients between fat and muscle thickness were not significant at any measurement site except for the triceps (r = -0.32, P < 0.05). Intercorrelation analyses among the eight sites were significant (P < 0.05) in almost all cases for fat thickness, while mainly between adjoining sites for muscle thickness. However, both tissues had a low degree of generality in thickness among sites. Fat thickness at all measurement sites was significantly correlated with body density except for the posterior calf; the best correlation was found with the quadriceps (r = -0.73). On the other hand, for muscle thickness, only the forearm and triceps were significantly correlated with body density. These results show 1) the extent of muscled and fat thicknesses are independent each of other within the same region, 2) fat and muscle thicknesses have a high degree of specificity in site distribution, and 3) fat thickness measurements determined from B-mode ultrasound may be of significant value assessing total body composition.

Adipose Tissue↗

[Relationship between 123I-BMIPP imaging and cardiac function in acute myocardial infarction].

We evaluated the relationship between free fatty acid metabolism using 123I beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and cardiac function in acute myocardial infarction. Twenty-five patients were examined with 123I-BMIPP and 201Tl dual SPECT. The 123I-BMIPP images were compared with the 201Tl images and the left ventricular wall motions. The 123I-BMIPP images showed a larger uptake defect than the 201Tl images. This was marked in the patients after revascularization therapy. The uptake decrease of 123I-BMIPP was in good agreement with the decrease in regional wall motion. The incidence of accordance was 79% of the wall segments. The correlation between 123I-BMIPP defect size and ejection fraction was higher (r = -0.54) than that of 201Tl (r = -0.44). Subtraction of ejection fractions four weeks and soon after infarction correlated well with the subtraction of 123I-BMIPP and 201Tl defect sizes (r = 0.55). In conclusion, 123I-BMIPP is more closely related to wall motion, than 201Tl and might be valuable in predicting the functional improvement of acute myocardial infarction.

Adult↗

[Detection of myocardial 123I-BMIPP distribution abnormality in patients with ischemic heart disease based on normal data file in bull's-eye polar map].

Visual interpretation of 123I-BMIPP (BMIPP) myocardial images has difficulties in detecting mild reduction in tracer uptake. We studied the significance of the objective assessment of myocardial BMIPP maldistributions at rest by using a Bull's-eye map and its normal data file for detecting ischemic heart disease. Twenty nine patients, 15 with prior myocardial infarction and 14 with effort angina were studied. The initial 15-min BMIPP image was evaluated by visual analysis and by generating the extent Bull's-eye map which exhibits regions with reduced % uptake under mean-2SD of 10 normal controls. The sensitivity for determining coronary lesions in non-infarcted myocardial regions with the extent map was superior to that with visual analysis (67% vs. 33%). In the regions supplied by the stenotic coronary artery, those which showed visually negative but positive in the map and which showed positive in both had higher incidence of wall motion abnormalities and severe coronary stenosis than those with normal findings in both. These results suggest that the objective assessment based on the normal data file in a Bull's-eye polar map is clinically important for improving the limitation of the visual interpretation in 123I-BMIPP imaging.

Adult↗