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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 109 records · Page 6Linked to original sources

Brain SPECT imaging using three different tracers in subacute cerebral infarction.

Two patients with subacute cerebral infarction underwent benzodiazepine receptor imaging using I-123-iomazenil and cerebral perfusion imaging with Tc-99m HMPAO and Tc-99m ECD. Iomazenil early images resembled HMPAO images, which demonstrated increased uptake in a part of the infarcted site. Iomazenil delayed images and ECD images showed reduced accumulation in the same area. Crossed cerebellar diaschisis was observed in HMPAO, ECD, and iomazenil early images, but it was not remarkable in iomazenil delayed images. These cases suggest that sequential iomazenil images visualized increased uptake with relatively impaired viability in the infarcted site and hypoperfusion with preserved viability in the contralateral cerebellar hemisphere, which could not be recognized without using both HMPAO and ECD in the subacute phase of cerebral infarction.

Adult↗

Increased excretion of urinary transforming growth factor beta 1 in patients with diabetic nephropathy.

The accumulation of extracellular matrix in the glomeruli of human and experimental models of diabetic nephropathy is associated with disease progression. Transforming growth factor beta 1 (TGF-beta1), which is a multifunctional peptide growth factor, plays a key role in the synthesis of extracellular matrix protein in vitro, and the expression of TGF-beta1 is elevated in human and rat diabetic nephropathy. In this study, we measured the urinary TGF-beta1 excretion in 57 patients with non-insulin-dependent diabetes mellitus and in 20 healthy volunteers to examine whether the determination of urinary TGF-beta1 excretion would facilitate the evaluation of the degree of mesangial expansion in patients with diabetic nephropathy. Both active and total TGF-beta1 levels in 24-hour urine samples collected from patients with diabetes mellitus and normal controls were measured using an enzyme-linked immunosorbent assay. We observed a higher excretion of urinary TGF-beta1 in patients with diabetes mellitus than in normal controls. In addition, the urinary TGF-beta1 excretion was elevated in patients with severe mesangial expansion. These results suggest that urinary TGF-beta1 may represent one parameter that can be used to evaluate the progression of diabetic nephropathy.

Biomarkers↗

Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy.

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3-9) as compared with the group with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.

Adrenomedullin↗

Plasma and urinary levels of adrenomedullin in chronic glomerulonephritis patients with proteinuria.

In this study, we measured levels of plasma and urinary adrenomedullin (AM) in 37 patients with chronic glomerulonephritis including minimal change nephrotic syndrome, focal segmental glomerulosclerosis or membranous nephropathy that can induce severe proteinuria. Thirty-nine healthy volunteers were enrolled as controls. Plasma and urinary AM levels were measured by an AM-specific radioimmunoassay. Plasma AM concentrations were higher and urinary AM levels were lower in patients with chronic glomerulonephritis than in healthy volunteers. Patients were divided into two groups according to urinary excretion of protein for 24 h (UPro, g/day) which reflects the disease activity or glomerular damage of the glomerulonephritis (group I: Upro < 1, group II: Upro >= 1). Plasma AM levels positively and urinary AM-levels negatively correlated with the degree of proteinuria. These results suggest that plasma and urinary AM levels in patients with chronic glomerulonephritis reflect the disease activity or glomerular damage represented by the degree of proteinuria.

Adrenomedullin↗

Abnormal regulation of transforming growth factor-beta receptors on vascular smooth muscle cells from spontaneously hypertensive rats by angiotensin II.

The effects of angiotensin II (Ang II) on the expression and characteristics of transforming growth factor-beta (TGF-beta) receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were investigated. TGF-beta-induced stimulation of DNA synthesis by VSMC from WKY rats was abolished with Ang II, whereas basal and TGF-beta-stimulated DNA synthesis by VSMC from SHR was increased with Ang II. Ang II stimulated DNA synthesis by VSMC from WKY rats in the presence but not in the absence of neutralizing antibody to TGF-beta1. Antibody to TGF-beta1 enhanced the stimulatory effect of Ang II on DNA synthesis by VSMC from SHR. Ang II increased the specific binding of TGF-beta to VSMC from WKY rats by increasing both the expression of the lower-affinity of TGF-beta receptors as well as the total number of TGF-beta binding sites. In contrast, VSMC from SHR showed a higher affinity and number of TGF-beta receptors in the absence of Ang II than did cells from WKY rats, and these parameters were not affected by Ang II. Ang II increased the expression of TGF-beta type I receptor mRNA in VSMC from WKY rats but had no effect of TGF-beta receptor type I or II mRNA in VSMC from SHR, which predominantly express the type II receptor. These results indicate that an increase in the expression of the TGF-beta type I receptor by Ang II may facilitate the ability of endogenous TGF-beta to counteract the stimulatory effect of Ang II on growth in VSMC from WKY rats, whereas endogenous TGF-beta induced by Ang II cannot counteract the growth-promoting action of Ang II in VSMC from SHR. The abnormal regulation of TGF-beta receptors by Ang II may be associated with the exaggerated growth of VSMC from SHR.

Angiotensin II↗

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

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65IU/ml (4.05, 6.8)) (P<0.01). Moreover, patients with the 11 genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II1 or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.

Adult↗

Single-photon emission computed tomography image of benzodiazepine receptors in a patient with Creutzfeldt-Jakob disease.

A 50-year-old woman presented with progressive visual disturbance, ataxia, and dementia. The cerebral cortex became atrophic, as the disease progressed, and electroencephalography showed periodic synchronous discharges. The patient's prion gene revealed a point mutation (232Met to Arg), and a diagnosis of Creutzfeldt-Jakob disease was made. Iomazenil single-photon emission computed tomography (SPECT) was performed to assess neuronal degeneration. Accumulation of the tracer in the late images was severely decreased diffusely spread throughout the cerebral cortex. Our experience with this case suggests that iomazenil SPECT is useful for detecting neuronal degeneration in Creutzfeldt-Jakob disease.

Brain↗

Changes in benzodiazepine receptor binding detected with SPECT in patients with cerebral infarction.

SPECT (single photon emission computed tomography) using iomazenil (IMZ) as a ligand for benzodiazepine receptors has recently been developed. Feasibility of the technique for detecting neuronal damage in the cerebral cortex was evaluated in 17 patients with cerebral infarction, specifically, patients with internal carotid artery (ICA) thrombosis (n = 6), middle cerebral artery (MCA) thrombosis (n = 5) and embolism (n = 6). IMZ SPECT was performed 5 to 17 days after stroke. Following the injection of 123I-IMZ 167 or 222 MBq intravenously, images were obtained at 15 minutes (early image) and 180 minutes (late image). In 11 cases, 99mTc-HM-PAO (hexamethyl-propylamine oxime) SPECT was also performed to measure cerebral blood flow (CBF). MRI was performed in all cases to elucidate areas of infarct. Early images from IMZ SPECT correlated well with those from HM-PAO, suggesting that early scans using IMZ SPECT reflect mainly CBF. In late images from IMZ SPECT, observed lesions were consistent with infarcted areas on MRI in most cases. However, in 3 cases of ICA thrombosis, 1 case of MCA thrombosis and 1 case of embolism, late IMZ SPECT imaging showed that the affected area was wider than apparent infarcts on MRI, indicating that the cerebral cortex, which was intact on MRI, was also involved. In these patients, clinical signs of cortical involvement were observed as well. These results suggest that moderately reduced CBF may affect cortical neurons without inducing apparent infarct, and such damage can be detected with IMZ SPECT.

Adult↗

[Relationship between cognitive function and discharge place among stroke patients after rehabilitation].

One hundred and ninety-nine elderly stroke patients, who received rehabilitation treatment, were examined, to clarify the relationship between cognitive function and discharge place. The patients who moved to long-term care facilities showed more severe disabilities of basic activities of daily living (ADL), more frequent incontinence, and lower functional impairments (Brunnstrom stage), compared with those discharged to their home. Multivariate regression analysis was done with discharge place as the dependent variable. Independent variables were age, sex, kind of stroke, rehabilitation period, level of ADL and IQ on Kohs test, or performance IQ on the Wechsler Adult Intelligence Scale. Older age, higher levels of ADLs, and higher scores on Kohs test IQ or Wechsler Adult Intelligence Scale Performance IQ were all significantly linked with home discharge. These results suggest that non-verbal cognitive dysfunction may affect discharge place in elderly stroke patients after rehabilitation therapy.

Activities of Daily Living↗

Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: distant metastasis and local recurrence.

One hundred and twenty-nine patients with NPC treated at the Department of Radiology, Chiba University Hospital and Keio University Hospital from 1980 through 1993 were selected for this study. Forty-four patients received cisplatin (CDDP)- or carboplatin-based chemotherapy, and 58 patients received adriamycin (ADM)- and/or 5-FU-based chemotherapy. The remaining 27 patients were treated with radiotherapy alone. The median radiation dose to the nasopharyngeal region was 64 Gy, and to the initially involved cervical node, 60 Gy. The 5 year survival rates for the CDDP, the ADM/5-FU and the radiation alone groups were 61%, 47% and 42%, respectively. The cumulative incidences of local control in the CDDP, the ADM/5-FU and the radiation alone groups were 77%, 49% and 53% respectively. The CDDP group achieved the significantly better local control (CDDP vs ADM: p=0.001). The overall incidence of distant metastases was 54% in the CDDP group. On the other hand, it was 24% in the ADM/5-FU group and 22% in the radiation alone group (CDDP vs ADM: p=0.048). While the locoregional control rate was significantly better in the CDDP given group, more distant metastases were seen in this group.

Adolescent↗

[Is medical linac suitable for high-precision stereotactic irradiation?: investigations in geometrical accuracies of gantry and couch].

Linac-based radiosurgery has many advantages over the gamma knife, including low initial cost and no need of source replacement. On the other hand, most of the medical linacs currently in use were not originally designed to be applied for radiosurgery, and, therefore, careful quality assurance programs are required. In the gantry-head of a linac, a small CCD video camera is mounted in a position optically identical to that of the x-ray source. The video signal from the camera was digitalized to be evaluated for geometrical errors. A metal ball fixed to the stereotactic base frame via XYZ-sliding rods was used as a simulated target. Displacements of the target from the isocenter were measured during rotation of the gantry. Displacements in the gantry-rotation plane were satisfactorily small, while those perpendicular to it were maximal at gantry position angles of 0 degree and 180 degrees. This error night be caused by gravitational vending of the heavy gantry head. Although other major errors of the linac were within one millimeter, the center of coach rotation around the isocenter did not coincide with the center of gantry rotation, probably owing to gravitational vending. Special care should be taken when very small collimators are employed.

Quality Control↗

[Some considerations on the avoidance of excess body burden in case of high dose 131I treatment: with special reference to the urination frequency].

In case of the treatment of metastatic thyroid cancer with radioiodine (131I), 3.7 GBq (100 mCi) or more is often repeatedly administered to the patient. Therefore, we must be aware of avoiding unnecessary exposure to the radioiodine except for the lesions to be treated. The administered radioiodine is excreted mainly through urinary system, resulting in an accumulation of the urine in the bladder for a certain period, which is highly concentrated with it. Based on this fact, we set one case having a particular pattern of the whole body retention curve. Then, two different modes of urination were considered; mode A indicates every 2 hour-urination x 6 times followed by every 6 hour-urination x 2 times, and mode B indicates every 6 hour-urination x 4 times. Focusing on the different amounts of urine in the bladder upon the different modes of urination, the radiation exposures from the urine to the neighboring organs, such as bladder wall, uterus, ovary and testis, and also to the whole body were calculated. As the results, it was found that the urination mode B would cause radiation exposure from the urine in the bladder twice as much as the urination mode A to the neighboring organs as well as to the whole body. This study will supply arguments for the necessity of frequent urination in the cases receiving radioiodine treatment for metastatic thyroid cancer.

Body Burden↗

[Radiobiological considerations for stereotactic irradiation].

Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a single high dose) was initially developed by Leksell for non-malignant brain lesions, but there has been increasing interest in using it to treat small primary brain tumors or metastases. In more recent years, stereotactic radiotherapy (SRT: fractionated STI) has been developed, but radiobiological factors have not been sufficiently evaluated in relation to these techniques. Larson classified potential STI targets into four categories according to whether the target tissue is early- or late-responding and whether it is embedded within or only surrounded by normal tissue. We have actually calculated biologically effective doses for these categories to determine the indications for SRS and SRT, and to be able to choose suitable SRT schedules. Based on our calculations, theoretically SRS would be recommended for AVMs and benign tumors having distinct margins separating them from surrounding normal tissue and SRT would be recommended for low or high grade astrocytomas without clearly defined boundaries and metastasis. Recommended SRT schedules would be 49 Gy/7 fractions, 52 Gy/8 fractions or 54.9 Gy/9 fractions completed within 2 weeks. However, clinically, these indications and SRT schedules should be modified according to the many other factors involved in individual cases, such as tumor size, presence of tumor necrosis, the patient's general condition, prognosis, and so on.

Brain↗

[Use of 99mTc-labeled myocardial perfusion agents in the Kanto-Koshinetsu area].

We sent out a questionnaire to investigate how the 99mTc-labeled myocardial perfusion agents are used in the Kanto-Koshinetsu area. Answers were obtained from 83 laboratories. Examinations using 99mTc-labeled agents were performed more frequently than those using 201T1 only in 10 of 83 laboratories. Main reasons for not using 99mTc-labeled agents were as follows: two injections required in the stress study, superiority of thallium-201 in the assessment of myocardial viability, a large amount of clinical data cumulated in thallium-201 imaging, and problems caused by abdominal uptake of 99mTc-labeled agents. Comparing purposes of the examinations using 201T1 and 99mTc-labeled agents, evaluation of myocardial viability was more common in 201Tl imaging, meanwhile, detection of myocardial ischemia was more common in imaging with 99mTc-labeled agents. It was pointed out that dual isotope imaging using 201Tl and 99mTc-labeled agents and simultaneous evaluation of myocardial perfusion and cardiac function are clinically feasible as new diagnostic procedures.

Heart↗

[Schedule of stereotactic radiotherapy: a study considering the factors of repair and cell proliferation].

Stereotactic radiosurgery (SRS: stereotactic irradiation [STI] delivered in a single high dose) was initially developed by Leksell for non-malignant brain lesions, but there has been increasing interest in using it to treat small primary brain tumors or metastases. Recently, stereotactic radiotherapy (SRT: fractionated STI) has been recommended on the basis of radiobiological considerations for tumors in which both normal glial cells and tumor cells reside within the tumor margin. Strangely, the factors 'repair' and 'cell proliferation' have been neglected in the radiobiological evaluations of STI reported so far, mainly because of the complexity of the calculations. 'Half-time repair' which is the key value in the 'repair' factor may be larger for nervous tissue than for many other normal tissues because nerve cells have decreased ability to recover from damage. 'Cell proliferation' should be an important factor when the total radiation period is extended by applying SRT. In this study, we created models based on estimated 'half-time repair' and 'cell doubling time' and attempted to determine optimal SRT schedules. When repair and cell proliferation factors are also taken into consideration, the recommended SRT schedules would be 7 Gy x 7 fractions every other day for malignant tumors and 3.5 Gy x 12 fractions every other day for benign tumors. However, clinically, these schedules should be modified according to factors in individual cases, e. g., tumor size, presence of tumor necrosis, the patient's general condition, prognosis, and so on.

Brain↗

[IS&C image viewing and conversion software for Macintosh computer].

Although standardized data-transmission protocols such as DICOM are very beneficial, on-line transmission on images is often difficult to establish because of cost or security concerns. On the other hand, media-based data exchange is simple and adequate for the private use of medical images. We developed a viewing software program for medical images stored in magneto-optical disks with IS&C standard format. It displays images with gray-scale tone and stores them in Macintosh PICT format. The software is available for personal use from the first author.

Diagnostic Imaging↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of hyperfunctioning parathyroid lesions in patients with hyperparathyroidism--a report of multicenter phase III clinical trials].

Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.

Female↗

[Evaluation of clinical utility of 99mTc-MIBI scintigraphy in the localization of thyroid, breast and lung/mediastinum tumors--a report of multicenter phase III clinical trials].

Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.

Adult↗