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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 901 records · Page 50Linked to original sources

[A Phase 1 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP)].

Phase 1 study of beta-methyl-p-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), a new radiopharmaceutical developed for the evaluation of myocardial fatty acid metabolism, was performed in six normal volunteers to evaluate its biodistribution and safety. After intravenous injection of 111 MBq of 123I-BMIPP, the agent accumulated to the myocardium rapidly (5.4 +/- 0.6% at 1.5 hr after injection) and was washed-out slowly (5.1 +/- 0.4% at 3.0hr). 123I-BMIPP demonstrated no significant accumulation to any specific organs other than myocardium, liver and muscle. Myocardium was clearly visualized in the planar and SPECT images obtained 30 min and 3 hrs after injection. The absorption doses from 123I-BMIPP estimated by MIRD method were lower than those from 201Tl in all organs. Neither adverse reactions nor abnormal clinical laboratory findings were found in the safety evaluation. These results suggest 123I-BMIPP is a promising agent for evaluating myocardial fatty acid metabolism.

Adult↗

[Assessment of denervated but viable myocardium in patients with myocardial infarction--by myocardial imaging with 201Tl and 123I-MIBG].

The present study assessed sympathetic function in viable infarcted areas of the myocardium following the onset of myocardial infarction. The subjects were 19 patients with myocardial infarction. After exercise on a bicycle ergometer, simultaneous SPECT with Tl-201 and I-123 MIBG was performed. The behavior of MIBG following exercise remains to be clarified, but in the present study MIBG provided images different from those obtained with Tl. While the redistribution of Tl in the infarcted area was observed in 8 of 19 patients, MIBG was absent in the infarcted area in both the initial and delayed scans. In the patient undergoing CABG, the infarcted area showed no MIBG despite the normal perfusion of Tl. The previous proposal that the redistribution of Tl indicates myocardial viability to some extent suggests that the sympathetic function of the area of the myocardium showing the redistribution of Tl decreases even though the area is viable. These findings indicate that after the onset of myocardial infarction, there is a denervated but viable area in the myocardium, despite the viability demonstrated by Tl imaging. They also indicate that concurrent myocardial imaging with MIBG is useful for the detection of such a myocardium.

3-Iodobenzylguanidine↗

Unusual mucoid impaction in a case of bronchogenic carcinoma. A case report on mucoid impaction caused by carcinomatous lymphangitis of the bronchial wall distant from the primary lesion.

An unusual mucoid impaction in a case of bronchogenic carcinoma is presented. While mucoid impaction occurred in the upper lobe of the bronchus, the primary site of the adenocarcinoma was found in the lower lobe at autopsy. Mucoid impaction was caused by marked carcinomatous lymphangitis of bronchial wall far distant from the primary lesion. The development of mucoid impaction in the case presented is the first report to the best of our knowledge.

Bronchi↗

[Perfusion lung scintigraphy in primary pulmonary hypertension].

Fifteen cases with primary pulmonary hypertension (PPH) were classified into two groups by using the perfusion lung scan pattern. Eight cases had multiple, small, ill-defined defects (mottled pattern), and remaining seven cases had no mottled pattern. These two groups were compared with mean pulmonary arterial pressure (mean PAP), right ventricular ejection fraction (RVEF), blood gas at room air (PaO2), and alveolar-arterial O2 difference (A-aDo2). The cases with mottled pattern showed a significant increase in mean PAP. There were no significant differences in RVEF, PaO2, and A-aDo2, between the groups. The survival rate of the patients with mottled pattern was significantly lower than that without mottled pattern (p less than 0.05). We concluded that perfusion lung scan is very useful for evaluation of the prognosis in primary pulmonary hypertension.

Adolescent↗

Assessment of myocardial damage in dilated-phase hypertrophic cardiomyopathy by using indium-111-antimyosin Fab myocardial scintigraphy.

For the detection of myocardial cell damage, an 111In-antimyosin Fab study was carried out on seven patients (Group A) in the dilated phase of hypertrophic cardiomyopathy, seven patients (Group B) with dilated cardiomyopathy, and eight control patients (Group C). Imaging was done 48 hr after intravenous injection of 74 MBq of 111In-antimyosin Fab. Myocardial antimyosin uptake was visually graded as 0, +1, +2 or +3. A score of +2 or +3 was considered positive. The heart/lung ratio of antimyosin uptake (antimyosin index) also was determined. Antimyosin uptake was positive in seven (100%), nine (90%) and no (0%) patients in Groups A, B, and C, respectively. The antimyosin index in Groups A and B was 2.46 +/- 0.49 and 2.04 +/- 0.24, respectively, findings were significantly higher than that in Group C (1.51 +/- 0.13) (p less than 0.01). Positive biopsy findings were noted in only two patients in Group A. Thus, antimyosin uptake was increased in dilated phase hypertrophic cardiomyopathy and dilated cardiomyopathy, which suggests ongoing necrotic changes in these patients.

Adult↗

Thymic stromal cell clone with nursing activity supports the growth and differentiation of murine CD4+8+ thymocytes in vitro.

Thymic stromal cell clone, TNC-R3.1 cell, was established from spontaneous AKR/J mouse thymoma. TNC-R3.1 cell, which has the similar properties to thymic nurse cells, formed a unique complex with normal thymocyte subpopulations. Flow cytometry analysis demonstrated that CD4+8+ and CD4-8- immature thymocytes preferentially interacted with TNC-R3.1 stromal cell clone. CD4+8+ thymocytes, which interacted with TNC-R3.1 stromal cell clone, contained a higher proportion of large size and cycling T cells than did noninteracting CD4+8+ thymocytes. As is generally accepted, CD4+8+ thymocytes did not respond to any stimulation such as IL-2, anti-CD3 mAb (2C11), or IL-2 plus 2C11. However, culture of isolated CD4+8+ thymocytes on TNC-R3.1 stromal cell monolayer in the presence of suboptimal dose of IL-2 induced a significant cell growth. Moreover, the addition of 2C11 and IL-2 into this coculture system resulted in a dramatic increase of the proliferative response of thymocytes. Flow cytometry analysis showed the proliferating cells on TNC-R3.1, which originated from CD4+8+ thymocytes, were mostly TCR-alpha beta+ CD3+CD4-8+ T cells. These results provide in vitro evidence that CD4+8+ thymocytes are at an intermediate stage of T cell maturation and TNC-R3.1 stromal cell clone induces the growth and differentiation of CD4+8+ thymocytes into CD4-8+ T cells.

Animals↗

[Radiation therapy of CNS lymphoma].

A retrospective analysis of 22 patients with central nervous system (CNS) non-Hodgkin's lymphomas seen from 1978 to 1989 at Hamamatsu University Hospital was carried out. These were corresponding to 16% (22/137) of non-Hodgkin's lymphomas treated by irradiation during the same period. Six patients had primary intracranial involvement, six had secondary one, five had leptomeningeal involvement and five had spinal cord compression. Median survival of these groups 29 months, 7 months, 6 months and 4 months, respectively. On the case primary intracranial involvement, neurological signs and symptoms and performance status (PS) were improved in most patients. Whole brain irradiation with a dose of 45 Gy to 50 Gy followed by systemic chemotherapy was considered as effective treatment modalities. On the other hands, for the secondary intracranial lymphomas, clinical symptoms and PS were excellently improved by radiation therapy, however these were not reflected to survival. The conditions having primary site on gastrointestinal tract and relapse as systemic dissemination were considerable risk factors for the control of CNS involvement. For these patients, prophylactic chemotherapy should be necessary. Improvement of PS on patients with leptomeningeal lymphomas was obtained in only 3 of 5 cases. These were treated by irradiation on whole spine or neuroaxis and intrathecal MTX injection. We observed 2 cases dying from cerebrovascular accident and one case from leukoencephalopathy. This showed that such combination therapy should be carefully attempted. Five patients having spinal cord compression suffered from paraplegia and none of them had been improved on their symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of intensity of illumination during the light period on diurnal variations of pineal indoles in rats and mice.

The diurnal variations of pineal indoles in New-Zealand Black (NZB) mice and Wistar rats were determined by HPLC fluorometry. Pineal N-acetylserotonin (NAc5HT) in NZB mice showed a marked diurnal variation, but no melatonin (MLT) was detected at any time of day or night. The night-time increases of NAc5HT in NZB mice and MLT in Wistar rats were delayed about one hour in animals kept under illumination of high intensity (2000 lux) during the light period (12 h) compared with those in animals kept under illumination of low intensity (10 lux). These results suggest that the intensity of illumination during the light period affects the diurnal rhythms of pineal indoles in experimental animals.

Animals↗

[Insufficiency fracture of the pelvis after the radiotherapy for carcinoma of the uterine cervix].

Bone injury after the radiotherapy for carcinoma of the uterine cervix has been reported since early days of this century. Recently, the concept of insufficiency fracture has been confirmed. Insufficiency fracture is one of the stress fractures and occurs when the elastic resistance of bone is inadequate to withstand normal or physiological stress. In the American and European studies, radiotherapy is known as a cause of insufficiency fracture. There are no reports on insufficiency fracture in the Japanese literatures. Four cases of carcinomas of the uterine cervix presented pelvic insufficiency fractures following radiotherapy. In the public bone, a vertical para-symphyseal fracture with mixed lytic and sclerotic changes of surrounding tissue is characteristic. Sacral insufficiency fracture shows a vertical or horizontal line with lytic and sclerotic appearance. Bone scintigraphy is a sensitive modality for the early detection. H-shaped configuration is diagnostic for sacral insufficiency fracture. CT is an accurate technique demonstrating a vertical fracture and excluding the malignant bony lesion. Although radiological findings of insufficiency fracture are similar to bone malignancy, differential diagnosis from malignant lesions is possible. Bony symptoms of all patients disappeared without specific treatments. In the follow-up study of patients with carcinomas of the uterine cervix after radiotherapy, it is important to have the consideration on insufficiency fracture.

Aged↗

Effect of phosphorylation on 68 KDa neurofilament subunit protein assembly by the cyclic AMP dependent protein kinase in vitro.

The effect of phosphorylation by cyclic AMP dependent protein kinase on the assembly of the core-forming 68 KDa neurofilament subunit protein (NF-L) was studied in vitro by fluorescence energy transfer and electron microscopy. Phosphorylation of unassembled NF-L in a low ionic strength buffer by cyclic AMP dependent protein kinase led to the incorporation of 1-2 phosphate groups/mole protein. Assembly of this phosphorylated NF-L was inhibited significantly; compared to non-phosphorylated NF-L, the critical concentration of phosphorylated NF-L was raised by greater than 30-fold. Assembled NF-L filaments could also be phosphorylated by cyclic AMP dependent protein kinase indicating that the sites were accessible. Phosphorylation of NF-L in the filamentous state induced their disassembly. The results suggest that phosphorylation by cyclic AMP dependent protein kinase is a possible means to modulate the assembly state of NF-L.

Animals↗

The mechanism of antifungal action of (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI-331: the inhibition of homoserine dehydrogenase in Saccharomyces cerevisiae.

We have explored the mechanism by which an antifungal antibiotic, (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI-331, preferentially inhibits protein biosynthesis in Saccharomyces cerevisiae, by inhibiting the biosynthesis of the aspartate family of amino acids, methionine, isoleucine and threonine. This inhibition was effected by inhibiting the biosynthesis of their common intermediate precursor homoserine. The target enzyme of RI-331 was homoserine dehydrogenase (EC.1.1.1.3) which is involved in converting aspartate semialdehyde to homoserine in the pathway from aspartate to homoserine. The enzyme is lacking in animals. So the antibiotic is selectively toxic to prototrophic fungi.

Alcohol Oxidoreductases↗

Does the washout phenomenon of Tc-99m HM-PAO correlate to the "filling-in" phenomenon of I-123 IMP with brain SPECT?

Using SPECT, the time course of brain uptake was compared between N-isopropyl-p-[I-123]-iodoamphetamine (I-123 IMP) and Tc-99m d,l hexamethyl-propyleneamine oxime (Tc-99m HM-PAO). Of 14 patients with cerebrovascular disease showing areas of the "filling-in phenomenon" (i.e. delayed uptake) with I-123 IMP brain SPECT, 7 exhibited persistent defects with Tc-99m HM-PAO (Group I), and 7 showed early washout after the initial uptake (Group II). The filling-in of I-123 IMP did not always correlate to the washout region of Tc-99m HM-PAO. The temporal changes were also confirmed by semiquantitative analysis. While the filling-in of I-123 IMP was affected by many factors, the washout of Tc-99m HM-PAO was attributed to significant reduction of Tc-99m HM-PAO in the plasma. Delayed imaging of the brain with Tc-99m HM-PAO using SPECT may give a more accurate estimate of regional cerebral blood flow in cerebrovascular disease, because it should be lees effected by cerebral blood volume.

Aged↗

Prediction of ACNU plasma concentration-time profiles in humans by animal scale-up.

Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Log-log plots of body weight (W; kg) vs total plasma clearance (CLtot,p; ml/min) and steady-state distribution volume (Vd,ss; l) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was greater than 97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CLtot,p = 50.6 W0.957; Vd, ss = 1.29 W1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CLutot,p and Vd,uss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CLutot,p = 71.7 W0.891; Vd,uss = 1.82 W0.966) were also high (r greater than or equal to 0.991). The extrapolated values vs those observed in a 70-kg human were the following: CLutot,p, 3,160 vs 2,290 ml/min; Vd,uss, 110 vs 106 l. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation.

Animals↗

Abnormal 67Ga uptake in a fibrosarcoma of the pericardium with malignant transformation.

A 31-year-old woman presented with general malaise, back pain, and edema of the lower extremities. A chest X-ray film showed an enlarged cardiac shadow and clear lung fields. A pericardial lesion with decreased activity on blood pool imaging and increased uptake on gallium citrate imaging displaced the heart upwards and to the left. The pericardial mass showed an inhomogeneous signal intensity on MRI and was large enough to obstruct the venous return by compressing the heart. At operation, the mass was found to originate from the pericardium and was histologically identified as a malignant fibrosarcoma. Twelve years previously, the patient had undergone an operation for the removal of a pericardial tumor which was histologically identified as a benign hemangioma. In view of the rarity of pericardial tumors, the present tumor is suspected to have undergone a transformation from benign hemangioma to malignant fibrosarcoma.

Adult↗

Scintigraphic determination of severity in pulmonary parenchymal damage in patients with atrial septal defect.

According to the pattern observed on a lung perfusion scan, patients with atrial septal defect (ASD) were classified into three stages: stage I, normal perfusion (n = 15); stage II, apical prone perfusion (n = 22); and stage III, mottled perfusion (n = 23). These stages were compared with hemodynamic data obtained from cardiac catheterization and with the right ventricular ejection fraction (RVEF). Staging from I to III correlated well with pulmonary arterial pressure, and patients in stage III showed a significant increase in pulmonary arteriolar resistance and a significant decrease in Qp/Qs. There was no significant difference in RVEF between the stages. We concluded that the scintigraphic severity determined by lung perfusion scan could be valid for evaluating the extent of pulmonary parenchymal damage in patients with ASD.

Cardiac Catheterization↗

Exercise thallium scintigraphy in aortitis syndrome (Takayasu's arteritis).

It is important for patient management to evaluate coronary arterial involvement in aortitis syndrome. Twenty one cases of aortitis syndrome who experienced chest pain were examined using exercise thallium scintigraphy. The patients were divided into four groups according to the angiographic findings. There were: five patients with left main coronary arterial involvement (group A), four with left or right coronary arterial involvement (group B), nine with aortic regurgitation (group C), and three with pulmonary arterial involvement (group D). In group A and B, all patients had positive ECGs and thallium perfusion defects. Group A patients showed extensive anterolateral perfusion defects, which were compatible with left main coronary arterial involvement. Group C and D patients, who had normal coronary arteries, showed no remarkable perfusion defects although five had positive ECG findings. Thus, the sensitivity and specificity of exercise scintigraphy for detection of myocardial ischemia were 9/9 and 12/12, while those of stress ECG were 9/9 and 7/12 (58%), respectively. It is recommended that exercise thallium scintigraphy be used for detecting clinically occult but significant coronary arterial involvement in aortitis syndrome with chest pain.

Adult↗

Papilloma of renal pelvis in childhood.

A papilloma in the renal pelvis of a five-year-old girl is reported. The transitional cell tumors of the renal pelvis in the pediatric age group are reviewed, and this is found to be the first case of a benign papilloma in childhood. We believe this pathologic entity should be included in the differential diagnosis of hematuria in a child.

Child, Preschool↗