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Biomedical subjects

K Takano

Publications and source records attributed to K Takano.

At least 127 records · Page 7Linked to original sources
PubMed1999

Impaired respiratory mechanics in pulmonary emphysema: evaluation with dynamic breathing MRI.

To evaluate impaired respiratory mechanics in pulmonary emphysema, dynamic breathing magnetic resonance imaging (BMRI) was acquired with fast-gradient echo pulse sequences at fixed thoracic planes over two to three slow, deep respiratory cycles in 6 controls and 28 patients with pulmonary emphysema including 9 patients undergoing lung volume reduction surgery (LVRS). Respiratory motions of the diaphragm and chest wall (D/CW) were assessed by a cine-loop view, a fusion display of maximal inspiratory and expiratory images, and the time-distance curves. By contrast with normal subjects with regular synchronous D/CW motions, the patients frequently showed reduced, irregular, or asynchronous motions, with significant decreases in the maximal amplitude of D/CW motions (MAD and MACW), and the length of apposition of the diaphragm (LAD) (P < 0.0001, P < 0.001, P < 0. 01, respectively). After LVRS, nine patients showed improvements in D/CW configuration and mobility, with significantly increased MAD, MACW, and LAD (P < 0.01, P < 0.0001, and P < 0.05, respectively). In 40 studies of 28 patients including the post-LVRS examinations, the normalized MAD and MACW significantly correlated with %FEV(1) (r = 0. 881 and r = 0.906; P < 0.0001, respectively). BMRI seems useful for noninvasively and directly assessing the impaired respiratory mechanics associated with abnormal ventilation in pulmonary emphysema, and also for monitoring the effects of LVRS. J. Magn. Reson. Imaging 1999;10:510-520.

Aged↗
PubMed1999

X-ray microanalysis of melanin granules of retinal pigment epithelium and choroid in hereditary copper deficient mice (macular mice).

The role of trace elements in vivo has not been completely clarified. Trace elements were studied in melanin granules in the retinal pigment epithelium (RPE) and choroid of hereditary copper-deficient macular mice as a model of Menkes' disease. The analysis of elements in these melanin granules was done by new methods: freeze-embedding and an energy dispersive X-ray microanalysis (EDX). We used 14-day- and 1-month-old male hemizygote macular mice for the experiments and normal litter-mates as controls. Melanin granules in RPE and choroid contained sulfur, chloride, calcium, iron, copper and zinc. Calcium and copper were especially abundant in 14-day-old hemizygote macular mice, although there were few melanin granules in their RPE. The fact that copper was most abundant in the melanin granules in the RPE of 14-day-old macular mice suggests that the synthesis of melanin granules in the RPE and choroid of the hemizygote macular mice cannot be completed because of the lower activity of copper-containing enzymes such as tyrosinase and the abnormal copper distribution in various organs. Therefore, the melanin granules in the RPE and choroid of hemizygote macular mice are irregular in shape and few in number. Large amounts of copper concentrated in melanin granules in the RPE and choroid of hemizygote macular mice might induce quantitative abnormalities of trace elements.

Aging↗
PubMed1999

Dynamic contrast-enhanced subtraction MR angiography in intracranial vascular abnormalities.

We present our clinical experience with dynamic contrast-enhanced MR angiography (MRA) with subtraction for assessing intracranial vascular abnormalities. Ten patients with various cerebrovascular disorders underwent dynamic contrast-enhanced MRA on a 1.0-T system. Thirty sections (2 mm) were acquired in 29-30 s. Maximum intensity projection images and subtracted source images were compared with those obtained by conventional angiography. In all cases, the presence or absence of abnormalities in the targeted vessels, as well as the morphology of the sagittal sinuses, was clearly visualized as in conventional angiography, without any obstructions such as hyperintense hematomas or thrombi, or intraluminal turbulence. Although the temporal and spatial resolutions with current hardware are insufficient, these preliminary results suggest that dynamic contrast-enhanced MRA with subtraction may be useful for assessing vascular lesions with hemorrhage or thrombus, and the dural sinuses.

Adolescent↗
PubMed1999

Severe stenosis of the internal carotid artery presenting as loss of consciousness due to the presence of a primitive hypoglossal artery: a case report.

BACKGROUND: Symptoms of ischemic attacks in the internal carotid system usually involve focal cerebral dysfunction, i.e., hemiparesis or aphasia. However, an ischemic attack in the vertebrobasilar artery system usually presents with combined symptoms. The variety of manifestations included in the vertebrobasilar profile makes the potential pattern of symptoms considerably more variable and complex than that in the carotid system. Manifestations can include syncope and also vertigo. METHOD AND RESULTS: A 42-year-old woman experienced frequent attacks of faintness with vertigo. Angiography demonstrated severe stenosis of the left internal carotid artery with a persistent primitive hypoglossal artery just distal to the stenosis. The right internal carotid artery was normal and cross circulation through the anterior communicating artery was not well developed. Both vertebral arteries were hypoplastic. The patient underwent carotid endarterectomy and, thereafter the episodes of syncope completely disappeared. CONCLUSION: It was supposed that global ischemia including the brain stem occurred because of stenosis of the left internal carotid artery attributable to the presence of a primitive hypoglossal artery.

Adult↗
PubMed1999

Rat macrophage inflammatory protein-1alpha, a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo.

Recombinant rat macrophage inflammatory protein-1alpha (rMIP-1alpha) at a concentration of 3x10(-8) M had strong neutrophil chemotactic activity, though the potency of rMIP-1alpha was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1alpha induced neutrophil chemotaxis in vivo when rMIP-1alpha was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1alpha-treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10(-8) M. Stimulation of neutrophils with rMIP-1alpha induced a transient increase in intracellular free [Ca2+] dose-dependently. rMIP-1alpha still induced an increase in the intracellular [Ca2+] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1alpha. Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1alpha and CINC-were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1alpha were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1alpha acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.

Animals↗
PubMed1999

Effect of foreign N-terminal residues on the conformational stability of human lysozyme.

To minutely understand the effect of foreign N-terminal residues on the conformational stability of human lysozyme, five mutant proteins were constructed: two had Met or Ala in place of the N-terminal Lys residue (K1M and K1A, respectively), and others had one additional residue, Met, Gly or Pro, to the N-terminal Lys residue (Met(-1), Gly(-1) and Pro(-1), respectively). The thermodynamic parameters for denaturation of these mutant proteins were examined by differential scanning calorimetry and were compared with that of the wild-type protein. Three mutants with the extra residue were significantly destabilized: the changes in unfolding Gibbs energy (DeltaDeltaG) were -9.1 to -12.2 kJ.mol-1. However, the stability of two single substitutions at the N-terminal slightly decreased; the DeltaDeltaG values were only -0.5 to -2.5 kJ.mol-1. The results indicate that human lysozyme is destabilized by an expanded N-terminal residue. The crystal structural analyses of K1M, K1A and Gly(-1) revealed that the introduction of a residue at the N-terminal of human lysozyme caused the destruction of hydrogen bond networks with ordered water molecules, resulting in the destabilization of the protein.

Alanine↗
PubMed1999

Contribution of amino acid substitutions at two different interior positions to the conformational stability of human lysozyme.

To elucidate correlative relationships between structural change and thermodynamic stability in proteins, a series of mutant human lysozymes modified at two buried positions (Ile56 and Ile59) were examined. Their thermodynamic parameters of denaturation and crystal structures were studied by calorimetry and X-ray crystallography. The mutants at positions 56 and 59 exhibited different responses to a series of amino acid substitutions. The changes in stability due to substitutions showed a linear correlation with changes in hydrophobicity of substituted residues, having different slopes at each mutation site. However, the stability of each mutant was found to be represented by a unique equation involving physical properties calculated from mutant structures. By fitting present and previous stability data for mutant human lysozymes substituted at various positions to the equation, the magnitudes of the hydrophobicity of a carbon atom and the hydrophobicity of nitrogen and neutral oxygen atoms were found to be 0.178 and -0.013 kJ/mol.A(2), respectively. It was also found that the contribution of a hydrogen bond with a length of 3.0 A to protein stability was 5.1 kJ/mol and the entropy loss of newly introduction of a water molecules was 7.8 kJ/mol.

Amino Acid Substitution↗
PubMed1999

Experimental verification of the 'stability profile of mutant protein' (SPMP) data using mutant human lysozymes.

The stability profile of mutant protein (SPMP) (Ota,M., Kanaya,S. and Nishikawa,K., 1995, J. Mol. Biol., 248, 733-738) estimates the changes in conformational stability due to single amino acid substitutions using a pseudo-energy potential developed for evaluating structure-sequence compatibility in the structure prediction method, the 3D-1D compatibility evaluation. Nine mutant human lysozymes expected to significantly increase in stability from SPMP were constructed, in order to experimentally verify the reliability of SPMP. The thermodynamic parameters for denaturation and crystal structures of these mutant proteins were determined. One mutant protein was stabilized as expected, compared with the wild-type protein. However, the others were not stabilized even though the structural changes were subtle, indicating that SPMP overestimates the increase in stability or underestimates negative effects due to substitution. The stability changes in the other mutant human lysozymes previously reported were also analyzed by SPMP. The correlation of the stability changes between the experiment and prediction depended on the types of substitution: there were some correlations for proline mutants and cavity-creating mutants, but no correlation for mutants related to side-chain hydrogen bonds. The present results may indicate some additional factors that should be considered in the calculation of SPMP, suggesting that SPMP can be refined further.

Amino Acid Substitution↗
PubMed1999

Second-line chemotherapy with weekly cisplatin and irinotecan in patients with refractory lung cancer.

Cisplatin and irinotecan are reported to act synergistically. The authors have conducted a phase II trial combining cisplatin and irinotecan in patients with refractory lung cancer to evaluate the activity and safety of the regimen. Twenty-one patients, who had not responded to prior platinum-based chemotherapy, were entered into the study. Both cisplatin (30 mg/m2) and irinotecan (60 mg/m2) were administrated on days 1, 8, and 15, and the regimen was repeated every 28 days. There were six partial responses, and the response rate was 29% (95% confidence interval, 11.3%-52.2%). The median survival time of all patients was 32 weeks, and 1-year and 2-year survival rates were 43% and 11%, respectively. Major toxicities were hematologic; leukopenia of grades 3 and 4 developed in 43% patients, anemia developed in 38%, and thrombocytopenia developed in 19%. One notable nonhematologic toxicity was diarrhea; which was grade 3 in 38%. The weekly chemotherapy combining cisplatin and irinotecan was active against lung cancer, which is refractory to platinum-based chemotherapy. However, skips of drug administration or dose reduction were necessary in 76% patients during two courses of planned administration, though the ratio of actual dose to scheduled dose was 81%. Dose modification would be necessary to yield better results by this weekly chemotherapy.

Adult↗
PubMed1999

Pharmacokinetic characteristics of minocycline in debilitated elderly patients.

A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.

Aged↗
PubMed1999

Expression of p53 and glutathione S-transferase-pi relates to clinical drug resistance in non-small cell lung cancer.

To determine the predictive value of the expression of p53 and glutathione S-transferase-pi (GST-pi) with respect to chemotherapy response, immunostaining was performed on transbronchial biopsy specimens from previously untreated patients with non-small cell lung cancer. Of the 54 patients, 34 patients (63%) and 37 patients (69%) were positive for p53 and GST-pi, respectively. The response rates in the p53-positive and p53-negative group were 15 and 45%, and those in GST-pi-positive and GST-pi-negative groups were 16 and 47%, respectively. A multiple logistic regression analysis revealed that positive immunostaining for GST-pi was a significant risk factor for clinical chemotherapy resistance. The combination of these two markers was the most important independent factor in predicting a response to chemotherapy in multiple logistic regression analysis. Immunohistochemical expression of p53 and GST-pi was independently related to clinical chemoresistance in patients with non-small cell lung cancer. Combined use of these two biomarkers may be a useful predictor of clinical chemoresistance.

Adult↗
PubMed1999

Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas.

BACKGROUND AND PURPOSE: It has been speculated that the same type of hypertensive small-artery disease can cause either intracerebral hemorrhages or ischemic lesions, depending on the circumstances. METHODS: To test this hypothesis, we examined the association between spontaneous intracerebral hematomas and both small chronic hemorrhages and ischemic lesions using echo planar and T2-weighted MRI. We considered a hypointense area to represent a hemorrhage and a hyperintense area to represent an ischemic lesion. RESULTS: We identified small hypointense lesions in 56.7% of 30 patients with intracerebral hematomas (mean age, 62.2 years; total number of lesions, 108) and in 25.4% of 59 patients without hematomas (mean age, 67.6 years; total lesions, 28). The incidence of hypertension was 88.3% in patients with intracerebral hematomas and 42.3% in those without. The hypointense lesions were found in 56.0% of 50 patients with hypertension, whereas they were found only in 10.3% of 39 patients without hypertension. The hypointense lesions were most common in the subcortex, followed by the putamen, pons, thalamus, and cerebellum. The hyperintense lesions were of a higher grade in patients with intracerebral hematomas than in those without. The hypointense lesions were commonly surrounded by hyperintense areas. Additionally, in 3 of 3 autopsied brains, we found hemosiderin deposits around arteriosclerotic microvessels and a surrounding small infarction in areas that had appeared as small hypointense lesions surrounded by hyperintensity on MRI. One specimen also had an organized miliary pseudoaneurysm. CONCLUSIONS: Our findings indicate that spontaneous intracerebral hematomas are frequently associated with small chronic hemorrhages, ischemic lesions, and hypertension. We speculate that hypertensive intracerebral hemorrhage may have the same microangiopathic basis as cerebral infarction.

Adult↗
PubMed1999

Heterozygous gsp mutation renders ion channels of human somatotroph adenoma cells unresponsive to growth hormone-releasing hormone.

Ionic mechanisms play an important role in the regulation of hormone secretion. The GHRH-induced GH release by human GH-secreting cells is transmitted through protein kinase A (PKA), which activates nonselective cation current (NSCC) and induces membrane depolarization, intracellular Ca2+ increase, and GH secretion. To evaluate whether ionic mechanisms have pathophysiological significance in GH oversecretion of GH-secreting pituitary adenomas, we examined four adenomas with constitutively active Gs alpha mutation (gsp mutation) and compared with three gsp-negative adenomas. In primary-cultured cells of gsp-positive adenomas, GHRH did not increase the NSCC under voltage-clamp experiments. Detailed examination showed that NSCC was maximally activated at the basal level and application of GHRH did not increase the current in these adenomas. Furthermore, by using single-cell RT-PCR method, we demonstrated for the first time at the single cell level that gsp mutation is heterozygous in GH-secreting pituitary adenomas. These indicate that heterozygous gsp mutation fully activates NSCC at the basal level, which may account for the GH oversecretion in gsp-positive GH-secreting pituitary adenomas.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan.

The Foundation for Growth Science in Japan has monitored the safety and efficacy of GH treatment in GH-deficient patients since 1975. Data were collected from more than 32,000 patients up to December 31, 1997. New leukemia was observed in 14 patients and myelodysplastic syndrome (MDS) in one patient. The types of leukemia were acute lymphocytic leukemia (n = 6; 40%), acute myelocytic leukemia or MDS (n = 7; 47%), and chronic myelocytic leukemia (n = 2; 13%). Leukemia developed in 9 patients during GH treatment and in 6 after the cessation of GH treatment. Six patients had known risk factors for leukemia, such as Fanconi's anemia and previous radiation or chemotherapy. Patient-years of GH therapy was defined as the time from the first dose of GH to the date of the last visit during GH therapy, and patient-years of risk was defined as the time from the first dose of GH to December 31, 1997. The incidence of leukemia of patient-years of GH therapy and patient-years of risk in GH-treated patients without risk factors was 3.0/100,000 and 3.9/100,000, respectively, a figure similar to the incidence in the general population aged 0-15 yr. We conclude that the incidence of leukemia in GH-treated patients without risk factors is not greater than that in the general population aged 0-15 yr, and a possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors.

Adolescent↗
PubMed1999

Decreased serum levels of acid-labile subunit in patients with anorexia nervosa.

One of the observations in malnutrition is that serum insulin-like growth factor (IGF)-I levels are decreased, and this decrease is associated with an altered profile of IGF binding proteins (IGFBPs). In human circulation, IGFs are mostly present as an approximately 150-kDa ternary protein complex consisting of IGFs, IGFBP-3, and acid-labile subunit (ALS). In the present study, to clarify the effect of nutrition on serum ALS levels, we investigated 33 patients with anorexia nervosa. Serum levels of ALS were measured by RIA. Furthermore, we measured serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in the patients. From these data, we investigated which was the best predictor of body mass index (BMI) as a nutritional status marker. In the patients with anorexia nervosa, the serum ALS levels ranged from 0.7-16.9, with a mean of 10.6 +/- 0.7 mg/L, and the levels were significantly lower than those of normal subjects (13.8 +/- 0.8 mg/L, P < 0.05). Serum ALS levels positively correlated with BMI (r = 0.41, P < 0.05), and the levels increased during treatment. The serum IGFBP-2 levels in the patients were increased (871 +/- 91 microg/L), and the levels inversely correlated with BMI (r = -0.52, P < 0.01). The serum IGF-I and IGFBP-3 levels were low (152 +/- 14 microg/L and 2.56 +/- 0.12 mg/L, respectively), and the levels positively correlated with BMI (r = 0.46, P < 0.01; and r = 0.39, P < 0.05, respectively). The serum IGFBP-2, IGF-I, and IGFBP-3 levels returned toward normal ranges as BMI in the patients improved during treatment. Serum IGF-II levels did not correlate with BMI (r = 0.24, P = 0.17). Stepwise regression analysis revealed that serum IGFBP-2 was the best marker of BMI among these variables. The present study suggested that ALS was regulated by nutritional status, the same as IGF-I, IGFBP-2 and IGFBP-3; but the serum IGFBP-2 was the best predictor of BMI as nutritional status marker among the parameters in patients with anorexia nervosa.

Adult↗
PubMed1999

Serum leptin levels and bioelectrical impedance assessment of body composition in patients with Graves' disease and hypothyroidism.

We investigated whether thyroid status modulates serum leptin concentrations and body composition as determined by bioelectric impedance analysis (BIA). The percent body fat mass (%FM) in male Graves' disease was significantly lower than that in age- and sex- matched normal subjects, at the levels of 11.4+/-6.4% (mean+/-SD) vs 19.9+/-9.2% for men (n=12, P<0.05) but not for women (22.6+/-7.6% vs 24.9+/-13.1%, n=28). In contrast, in female hypothyroidism (n=11) %FM was significantly higher than that in normal subjects (32.9+/-11.5%, P<0.01). Among other body composition parameters, the percentage of body water (%BW), and lean body mass (LBM) were significantly lower in hypothyroid patients, and the ECM (extracellular mass)/BCM (body cell mass) ratio was significantly (P<0.0001) increased in Graves' disease which was the result of marked depletion of BCM with concomitant expansion of ECM. The serum leptin levels were significantly decreased in male Graves' patients (2.3+/-0.7 ng/ml, P<0.05), whereas in female Graves' patients (8.8+/-5.9 ng/ml) and patients with hypothyroidism (9.5+/-7.6 ng/ml), the levels were not different from those of normal controls matched for BMI or %FM. There was a positive correlation between serum leptin levels and %FM in female Graves' patients (r=0.635, P=0.001) and in hypothyroid patients (r=0.801, P=0.014) but not in male Graves patients. There was no significant relationship between serum leptin levels and thyroid hormones, TRAb, or TSAb. In euthyroid obese subjects there was a positive relationship between serum leptin levels and serum TSH levels (r=0.37, P<0.01). These results suggest that hyperthyroidism is characterized by the decreased fat mass and serum leptin levels in men, but female patients appear to be resistant to the effect of thyroid hormones. Together with previous reports, thyroid status has a minor role in the regulation of serum leptin levels.

Adult↗
PubMed1999

Height responses in complete idiopathic growth hormone deficient children less than three years of age during growth hormone therapy. Executive Committee of the International Cooperative Growth Study in Japan.

To know the effect of the age factor on growth response to growth hormone (GH) therapy in patients less than three years of age with complete idiopathic growth hormone deficiency (GHD). One hundred thirty-seven prepubertal children with complete idiopathic GHD from the database of the International Growth Cooperative Study (ICGS) of Japan for more than two years were analyzed. The patients were divided into four groups according to age at the start of GH therapy; group 1, < or = three years, group 2, three to < or = six years, group 3, six to < or = nine years, group 4, >nine years. In group 1 the mean birth weight SDS of -0.17 was not the lowest. Patients in group 1 had the lowest HSDS (-4.53) at the start of the therapy (P<0.01). During two years of the treatment, the mean HSDS improved from -4.53 to -2.15 with an increase in mean SD score of 2.12 in group 1, but in group 4 it was only 0.92 (P<0.01). In group 1, the mean HSDS declined from -0.17 at birth to -4.53 progressively. Delta height SDS during the first year of treatment in Group 1 was 1.59 SD, which is the highest. The decrease in %overweight during the first year showed that in group 1, the reduction in adiposity was the greatest among the groups (P<0.05). Our data showed that in children with complete GHD less than three years of age, there was severe growth failure, and the onset was not in the prenatal period, but in the postnatal period. Early detection of GHD and therapy with GH is important because normalization of height may be achieved earlier than in older age groups.

Age Factors↗