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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 91 records · Page 5Linked to original sources

[Comparison of interviews and review of patient chart in evaluating falls among geriatric patients].

This study compared the reliability of interviewing and reviewing medical records to determine falls experienced by elderly patient admitted to a geriatric hospital. Subjects were 130 consecutive patients (mean age 76 years) who received physical therapy. They were divided into two different age groups: those aged below 75 years and those aged 75 years and over. In reviewing medical records, it was difficult for researchers to find out about falls based on information by patients and families, if no injury occurred. This tendency remarkable in patients aged below 75 years. Because of it, the rate of falls was significantly lower and that of injuries was higher than in the interviews. We conclude that review of medical records involves problems concerning the accuracy of information about falls. Hip fractures due to falls were seen only in patients aged 75 years and over, so we recognized that it is important to prevent falls especially in this group.

Accidental Falls↗

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of lupus nephritis.

BACKGROUND: Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis has not been fully understood; however, immunological abnormalities have been considered in the development and activity of lupus nephritis. As angiotensin-converting enzyme (ACE) is implicated in various immunological phenomena, we investigated the correlation between insertion (I)/ deletion (D) polymorphism of the ACE gene and the activity of lupus nephritis. PATIENTS AND METHODS: Eighty-four patients with SLE and 100 healthy subjects were enrolled in this study. Following the extraction of genomic DNA from the peripheral blood, the ACE genotype was determined by the polymerase chain reaction. The patients were classified by the histological findings according to the WHO classification. In addition, the activity index and chronicity index were used to assess the severity of renal involvement. RESULTS: Individuals with II genotype showed a significantly increased activity of lupus nephritis. The allelic frequency was I/D = 0.84/0.16 in patients with WHO class IV renal lesions, and I/D = 0.36/0.64 in those with WHO class I lesions and 0.61/0.39 in patients with WHO class I or WHO class II. The difference in the allelic frequency between patients with WHO class IV and those with WHO class I or WHO class I + WHO class II was statistically significant (p = 0.00016 or p = 0.027, respectively). Moreover, lupus nephritis patients with II genotype showed significantly higher activity index than those with DD genotype (p = 0.0009). CONCLUSION: These results suggest that the insertion polymorphism of the ACE gene may correlate with the activity of lupus nephritis.

Adult↗

[Evaluation of parathyroid imaging methods with 99mTc-MIBI--the comparison of planar images obtained using a pinhole collimator and a parallel-hole collimator].

Parathyroid scintigraphy with 99mTc-MIBI was performed using two kinds of collimators, namely, a pinhole one and a parallel-hole one, to evaluate which one was more suitable for the detection of hyperfunctioning parathyroid lesions. In the studies using 99mTc source, the pinhole collimator showed better efficiency and spatial resolution in the distance where the parathyroid scan are actually performed. In the phantom study, the nodular activities modeling parathyroid lesions were visualized better on the images obtained using the pinhole collimator. In clinical studies for 30 patients suspicious of hyperparathyroidism, hyperfunctioning parathyroid nodules were better detected when the pinhole collimator was used. In conclusion, the pinhole collimator was thought to be more suitable for parathyroid scintigraphy with 99mTc-MIBI than the parallel-hole collimator.

Aged↗

[Hard-copy (film) versus soft-copy (CRT) reading performance between compressed and uncompressed images: SOLs in abdominal CT images].

The objective of this study was to examine the feasibility of soft-copy (CRT) reading and suitable compression. Forty abdominal CT images with a space-occupying lesion (SOL) in liver and 40 normal images were selected for receiver-operating-curve (ROC) analysis. Each image was compressed by JPEG extended mode into 1/10 its original capacity, and then an expanded image was printed on film. Ten radiologists evaluated the presence of liver SOLs (primary and secondary tumors) on soft-copy (CRT) and hard-copy (film) images. Each radiologist reviewed four types of images (original and compressed hard-copy and original and compressed soft-copy images). Values of the area under the curve in the various ROC analyses were 0.858 (FILM) and 0.842 (CRT) for original images and 0.879 (FILM) and 0.846 (CRT) for compressed images. The results of ROC analysis showed better reading performance with hard-copy than soft-copy images, but the difference was not statistically significant. Compressed images showed a higher value (0.879) than original images (0.858), a difference that was statistically significant (p < 0.029) by the paired t-test but not by the jackknife method. The results indicate that soft-copy reading is a clinically acceptable alternative to hard-copy reading. We have had no difficulty in reading abdominal CT images compressed to 1/10 of the original size by the JPEG method. This study was supported in part by a grant from the Japanese Ministry of Health and Welfare.

Humans↗

[Phase 2 clinical study of 123I-IBF, a dopamine D2 receptor imaging agent, to evaluate clinical efficacy and safety in Parkinson's disease and Parkinson syndromes].

A Phase 2 multicenter trial of 123I-IBF, (S)-5-iodo-7-N-[(1-ethyl-2- pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, was conducted to evaluate its clinical efficacy and safety in 158 patients with Parkinson's disease (PD) or Parkinson syndromes (PS). SPECT data were acquired at two hours (2H-SPECT), after intravenous injection of 123I-IBF (167 MBq). Additional SPECT scan at three hours (3H-SPECT) and dynamic SPECT scan at most until one hour were performed when possible. No severe side effects due to 123I-IBF injection were observed. The sensitivity, specificity and accuracy for discriminating PS from PD using the striatal specific binding count-to-frontal cortex count ratio (St/Fc-1) in 3H-SPECT were 72.7%, 81.0% and 78.1% in 64 clinically definite cases (i.e., typical cases), respectively. The putamen-to-caudate ratios were significantly lower in striatonigral degeneration compared with those in PD. The contralateral-to-ipsilateral ratios against the symptomatic side of tremor and/or rigidity in the patients with PD (Hoehn & Yahr I) were significantly higher than the left-to-right ratios in the normal controls. St/Fc-1 in 3H-SPECT was significantly lower in the patients showing a poor response to levodopa than in those showing a good response. The dopamine D2 receptor binding potential (k3/k4), obtained by dynamic SPECT based on compartment model analysis, correlated well with the striatal specific binding count-to-occipital cortex count ratio. These results suggest that 123I-IBF is a promising agent for differential diagnosis and pathophysiological evaluation of PD and PS.

Adult↗

The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4.

Loss of p16 functional activity leading to disruption of the p16/cyclin-dependent kinase (CDK) 4:cyclin D/retinoblastoma pathway is the most common event in human tumorigenesis, suggesting that compounds with CDK4 kinase inhibitory activity may be useful to regulate cancer cell growth. To identify such inhibitors, the 60 cancer cell lines of the National Cancer Institute drug screen panel were examined for p16 alterations (biallelic deletion, intragenic mutations, or absent p16 protein), and the growth-inhibitory activity of more than 50,000 compounds against these 60 cell lines was compared with their p16 status. One compound, 3-amino thioacridone (3-ATA; NSC 680434), whose growth-inhibitory activity correlated with the p16 status of the cell lines had an IC50 of 3.1 microM in a CDK4 kinase assay. In addition, four compounds structurally related to 3-ATA inhibited CDK4 kinase with IC50s ranging from 0.2-2.0 microM. All five of these compounds were less potent inhibitors of cell division cycle 2 and CDK2 kinases, with IC50s 30- to 500-fold higher than that for CDK4. ATP competition experiments demonstrated a noncompetitive mode of inhibition for 3-ATA (K(i) = 5.5 microM) and a linear mixed mode for benzothiadiazine (NSC 645787; K(i) = 0.73 microM). We have successfully demonstrated a novel approach to identify specific CDK4 kinase inhibitors that may selectively induce growth inhibition of p16-altered tumors.

Antineoplastic Agents↗

Production of adrenomedullin in macrophage cell line and peritoneal macrophage.

We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7-fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-gamma, whereas IFN-gamma completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-beta dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor alpha (TNF-alpha) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-alpha and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.

Adrenomedullin↗

Adrenomedullin production is correlated with differentiation in human leukemia cell lines and peripheral blood monocytes.

We demonstrated that adrenomedullin (AM) is produced and secreted from human leukemia cell lines (THP-1 and HL-60) as well as peripheral blood granulocytes, lymphocytes, monocytes and monocyte-derived macrophages. Immunoreactive AM accumulated in the culture media of THP-1 and HL-60 cells increased according to their differentiation into macrophage-like cells. Retinoic acid exerted synergistic effects on AM secretion from THP-1 and HL-60 cells when administered with tumor necrosis factor-alpha, lipopolysaccharide or 12-O-tetradecanoyl phorbol-13-acetate. AM was shown to increase the scavenger receptor activity on THP-1 cells. Thus, monocytes/macrophages should be recognized as sources of AM, and the secreted AM may modulate the function of macrophages.

Adrenomedullin↗

Adrenomedullin stimulates interleukin-6 production in Swiss 3T3 cells.

Adrenomedullin (AM) has very recently been demonstrated to be produced and secreted from fibroblasts. The production of AM in the fibroblasts is augmented by inflammation-related substances, and Swiss 3T3 fibroblast cells express AM specific receptors coupled with adenylate cyclase. To assess the functions of AM secreted from fibroblasts, we measured the effect of AM on production in Swiss 3T3 cells of interleukin-6 (IL-6), a typical cytokine involved in the general inflammatory reactions. AM stimulated basal secretion of IL-6 5.5-fold, while other peptides elicited much weaker stimulatory effects. The effect of AM was inhibited with an AM receptor antagonist and a cAMP-dependent protein kinase (PKA) inhibitor. Furthermore, AM remarkably potentiated stimulatory effects of tumor necrosis factor-alpha, IL-1 beta and lipopolysaccharide on IL-6 production. This stimulatory effect of AM was induced through activation of gene transcription, which reached maximum within 30 min. These findings verify that AM is a rapid and extraordinarily potent regulator of IL-6 production in Swiss 3T3 cells acting through the cAMP-PKA pathway. The data thus obtained suggest that AM is a peptidergic regulator of inflammation.

3T3 Cells↗

New system for linear accelerator radiosurgery with a gantry-mounted video camera.

PURPOSE: We developed a positioning method that does not depend on the positioning mechanism originally annexed to the linac and investigated the positioning errors of the system. METHODS AND MATERIALS: A small video camera was placed at a location optically identical to the linac x-ray source. A target pointer comprising a convex lens and bull's eye was attached to the arc of the Leksell stereotactic system so that the lens would form a virtual image of the bull's eye (virtual target) at the position of the center of the arc. The linac gantry and target pointer were placed at the side and top to adjust the arc center to the isocenter by referring the virtual target. Coincidence of the target and the isocenter could be confirmed in any combination of the couch and gantry rotation. In order to evaluate the accuracy of the positioning, a tungsten ball was attached to the stereotactic frame as a simulated target, which was repeatedly localized and repositioned to estimate the magnitude of the error. The center of the circular field defined by the collimator was marked on the film. RESULTS: The differences between the marked centers of the circular field and the centers of the shadow of the simulated target were less than 0.3 mm.

Computer Terminals↗

The effect of bulk magnetic susceptibility on solid state NMR spectra of paramagnetic compounds

The effect of bulk magnetic susceptibility (BMS) on solid state NMR spectra of paramagnetic compounds was investigated theoretically and experimentally. The BMS shift was calculated for cylindrical and spherocylinderical containers with some ratios of the length L and the diameter D. The results show the best resolution can be obtained by using a long cylindrical sample container with L/D > 10 and by exciting only the region near the center of the container. The effect of the random orientations and distributions of crystallites in a powder sample was also calculated according to a model proposed by Schwerk et al. [J. Magn. Reson. A 119, 157 (1996)] with removing the Fermi contact term from their model. Static and the magic-angle spinning 13C NMR spectra were recorded on two paramagnetic compounds of Ln(C2D5SO4)3 . 8H2O where Ln = Pr, Yb. The modified theory predicts the BMS broadening of the experimental spectra very well. Copyright 1998 Academic Press.

Journal Article↗

Preoperative evaluation of the chemosensitivity of breast cancer by means of double phase 99mTc-MIBI scintimammography.

The chemosensitivity of breast cancer is important for its management, but it is difficult to evaluate preoperatively. Tc-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintimammography has been reported to indicate the expression of P-glycoprotein, which is one factor concerned with multidrug resistance. We developed a chemosensitivity assay by using surgical specimens to investigate whether 99mTc-MIBI scintimammography findings before the operation are related to chemosensitivity according to our assay. Fifteen patients with primary breast cancer were enrolled into the study. Early and delayed images were obtained at 10 and 120 minutes after intravenous injection of 99mTc-MIBI, respectively. Regions of interest were placed on the tumors and the contralateral healthy breasts in each patient to estimate 99mTc-MIBI uptake in the tumor, and retention indices were then calculated to assess the washout of 99mTc-MIBI. Chemosensitivity assay was performed by incubating surgical specimens with anticancer agents such as doxorubicin, epirubicin, pinorubicin, mitomycin C, cisplatin and 5-fluorouracil. 99mTc-MIBI washout on scintimammography was successfully related to inhibition ratios on chemosensitivity tests when compared with 99mTc-MIBI uptake by the tumor. In particular, high correlation coefficients were obtained between the retention index of 99mTc-MIBI and the inhibition ratios of doxorubicin (r = 0.75), epirubicin (r = 0.60) and pinorubicin (r = 0.62), but poor correlation was found for mitomycin C (r = 0.44) and cisplatin (r = 0.31). Our results indicate that the retention index of 99mTc-MIBI is closely correlated to chemosensitivity to anthracyclines, suggesting that double-phase scintimammography allows preoperative prediction of chemosensitivity of breast cancer.

Adult↗

Absent myocardial accumulation of two different radioiodinated pentadecanoic acids.

This article presents two cases with preserved myocardial 201Tl uptake and absent uptake of two kinds of radioiodinated fatty acids: iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and iodine-123-labeled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA). Although coronary angiography showed no stenotic lesion and left ventriculography revealed no wall motion abnormality, no myocardial uptake of BMIPP and 9MPA was observed in the first case. In the second case, no myocardial accumulation was recognized even in the initial phase of dynamic SPECT acquired soon after the injection of 9MPA. The results suggest that the non-visualized myocardium was not specific for BMIPP imaging and that rather than the early back diffusion of the tracers from the myocardium, abnormality of the myocardial cell membrane was a possible mechanism accounting for the phenomenon.

Biological Transport, Active↗

Application of transmission scan-based attenuation compensation to scatter-corrected thallium-201 myocardial single-photon emission tomographic images.

A practical method for scatter and attenuation compensation was employed in thallium-201 myocardial single-photon emission tomography (SPET or ECT) with the triple-energy-window (TEW) technique and an iterative attenuation correction method by using a measured attenuation map. The map was reconstructed from technetium-99m transmission CT (TCT) data. A dual-headed SPET gamma camera system equipped with parallel-hole collimators was used for ECT/TCT data acquisition and a new type of external source named "sheet line source" was designed for TCT data acquisition. This sheet line source was composed of a narrow long fluoroplastic tube embedded in a rectangular acrylic board. After injection of 99mTc solution into the tube by an automatic injector, the board was attached in front of the collimator surface of one of the two detectors. After acquiring emission and transmission data separately or simultaneously, we eliminated scattered photons in the transmission and emission data with the TEW method, and reconstructed both images. Then, the effect of attenuation in the scatter-corrected ECT images was compensated with Chang's iterative method by using measured attenuation maps. Our method was validated by several phantom studies and clinical cardiac studies. The method offered improved homogeneity in distribution of myocardial activity and accurate measurements of myocardial tracer uptake. We conclude that the above correction method is feasible because a new type of 99mTc external source may not produce truncation in TCT images and is cost-effective and easy to prepare in clinical situations.

Adult↗

Simultaneous acquisition of iodine-123 emission and technetium-99m transmission data for quantitative brain single-photon emission tomographic imaging.

The aim of this study was to obtain quantitative iodine-123 brain single-photon emission tomographic (SPET) images with scatter and attenuation correction. We used a triple-headed SPET gamma camera system equipped with fan-beam collimators with a technetium-99m line transmission source placed at one of the focal lines of the fan-beam collimators. Four energy windows were employed for data acquisition: (a) 126-132 keV, (b) 132-143 keV, (c) 143-175 keV and (d) 175-186 keV. A simultaneous transmission-emission computed tomography scan (TCT-ECT) was carried out for a brain phantom containing 123I solution. The triple energy window scatter correction was applied to the 123I ECT data measured by means of the windows (b), (c) and (d) acquired by two detectors. Attenuation maps were reconstructed from 99mTc TCT data measured by means of the windows (a), (b) and (c) acquired by one detector. Chang's iterative attenuation correction method using the attenuation maps was applied to the 123I ECT images. In the phantom study cross-calibrated SPET values obtained with the simultaneous mode were almost equal to those obtained with the sequential mode, and they were close to the true value, within an error range of 5.5%. In the human study corrected images showed a higher grey-to-white matter count ratio and relatively higher uptake in the cerebellum, basal ganglia and thalamus than uncorrected images. We conclude that this correction method provides improved quantification and quality of SPET images and that the method is clinically practical because it requires only a single scan with a 99mTc external source.

Algorithms↗

Significance of increased plasma adrenomedullin concentration in patients with cirrhosis.

BACKGROUND/AIMS: Adrenomedullin recently discovered in human pheochromocytoma is a potent vasodilatory peptide mainly derived from vascular endothelial and smooth muscle cells. Hyperdynamic circulation, ultimately leading to ascites formation, has been attributed to peripheral vasodilatation in liver cirrhosis. However, little is known about the role of adrenomedullin in this condition. METHODS: Plasma adrenomedullin concentrations were measured by radioimmunoassay after extraction and purification in 28 cirrhotic patients without ascites, 12 cirrhotic patients with ascites and 10 healthy subjects. RESULTS: Plasma adrenomedullin concentrations in cirrhotic patients with ascites (12.7+/-4.5 fmol/ml) were significantly higher than those in cirrhotic patients without ascites (8.2+/-2.3 fmol/ml, p<0.005) and healthy subjects (5.8+/-0.8 fmol/ml, p<0.005). Interestingly, plasma adrenomedullin concentrations were highest in patients with refractory ascites (n=5, 15.8+/-3.0 fmol/ml) and were positively correlated with the Child-Pugh score (r=0.44, p<0.01). Moreover, plasma adrenomedullin concentrations were positively correlated with plasma renin activity (r=0.63, p<0.0001), plasma aldosterone (r=0.60, p<0.0001) and plasma norepinephrine concentrations (r=0.60, p<0.0001), and negatively correlated with creatinine clearance (r=-0.61, p<0.0005) and urinary sodium excretion (r=-0.44, p<0.02). Stepwise multiple regression analysis using certain independent variables, including Pugh's score, vasoactive substances, renal function and hemodynamic parameters, showed that the adjusted R square was highest when plasma renin activity and creatinine clearance (standard coefficient=0.53, -0.49, respectively) were considered (adjusted R square=0.61, p<0.0001). CONCLUSIONS: Plasma adrenomedullin concentrations increased with the progression of liver cirrhosis and were highest in cirrhotic patients with refractory ascites. In addition, elevated adrenomedullin was associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and with functional renal impairment in cirrhosis. Considering the potent vasodilatory action of adrenomedullin, increased adrenomedullin may participate in the hyperdynamic circulation, ultimately leading to ascites formation, in patients with liver cirrhosis.

Adrenomedullin↗

Somatostatin-receptor-negative carcinoid tumour responsible for Cushing's syndrome.

A 30-year-old man presenting with Cushing's syndrome was admitted in 1995. A diagnosis of ectopically ACTH-secreting, primary-unknown abdominal carcinoid tumour was made. The patient's plasma ACTH and cortisol levels failed to decrease after short-term treatment with octreotide, and somatostatin-receptor scintigraphy did not show any accumulation in the tumour. The patient died 1 year after admission. This is a relatively rare somatostatin-receptor-negative case of this disease and it appears necessary to test for the presence of somatostatin receptors before treating with octreotide.

Abdominal Neoplasms↗

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage.

UNLABELLED: Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.

Adrenomedullin↗