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Biomedical subjects

K Kusakabe

Publications and source records attributed to K Kusakabe.

At least 91 records · Page 5Linked to original sources

[Radionuclide assessment of cardiac involvement in patients with sarcoidosis].

This study was aimed to determine whether nuclear methods were useful for examining cardiac pathology and for making a decision of corticosteroid therapy in patients with sarcoidosis. Thirty six patients were divided into two groups; GpA consisted of 19 patients with cardiac sarcoidosis and abnormal ECG findings, and GpB of 17 patients with sarcoidosis without ECG abnormalities. Cardiac uptake of 67Ga-citrate in 2 and 99mTc-PYP in one of GpA was observed and steroid therapy resulted in the disappearance of the uptake. 201Tl-CL cardiac tomograms disclosed perfusion defects in 10 of 14 patients (71%) in GpA, including defects with redistribution in 8 of the 10 pts, but only one case in GpB. Radionuclide ventriculography using 99mTc-RBC revealed abnormal response of left ventricular (LV) function to exercise and LV dysfunction in GpA. These data suggest that nuclear study is a useful tool for diagnosing cardiac sarcoidosis, evaluating therapeutic effectiveness and long-term follow-up in patients with sarcoidosis.

Adult↗

[Long-term follow-up study of I-131 therapy for Graves' disease--index associated with late-onset hypothyroidism].

We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.

Adult↗

[The effects of diclofenac sodium on thyroid function tests in vivo and in vitro].

In order to investigate the effects of the non-steroidal antiinflammatory drug, diclofenac sodium on thyroid function, 8 male and 2 female volunteers were given single dose of 50 mg diclofenac sodium. Ninety minutes after the administration of the drug, the concentrations of total T 3, total T 4 and free T 4 were decreased significantly, but the concentrations of free T 3 and the levels of T 3 uptake, % free T 3 and % free T 4 were increased. When diclofenac sodium was added to serum in vitro, the levels of free T 3, free T 4 and T 3 uptake were increased. These results showed that diclofenac sodium inhibited the binding of T 3 and T 4 competitively to the binding protein. The apparent decline in the concentrations of total T 3 and total T 4 after diclofenac sodium administration suggested that the drug altered distribution and metabolism of T 3 and T 4 mainly by increasing their free forms.

Anti-Inflammatory Agents, Non-Steroidal↗

Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia.

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.

6-Ketoprostaglandin F1 alpha↗

Production of monoclonal antibody to thyroglobulin from malignant thyroid carcinoma.

In this study, the production of anti-human thyroglobulin (Tg) monoclonal antibodies was attempted to detect Tg levels in serum and to study the localization of thyroid metastases in patients with thyroid-gland ablation. As a result four clones of hybridoma cell lines were obtained. By means of enzyme immunoassay (EIA) and immunohistochemical method, it was found that one of them, 2G4, produced a monoclonal antibody recognizing a malignant structural change of Tg and other three clones produced monoclonal antibodies recognizing not only the normal human Tg but also the malignant Tg. Our monoclonal antibody, 2G4, will be a hopeful reagent for the diagnosis in thyroid carcinoma.

Antibodies, Monoclonal↗

[Estimation of regional myocardial sympathetic neuronal function with I-123 metaiodobenzylguanidine (MIBG) myocardial images in patients with cardiomyopathy].

I-123 Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic neuronal endings. Sympathetic neuronal function in 10 patients with cardiomyopathy under stable state were studied by using MIBG and Tl-201 (Tl) SPECT images with 50% cut off level. For myocardial imaging MIBG and Tl were simultaneously injected and collected (dual injection and dual collection mode; Dd mode). Four hours delayed images were also collected. Three types of abnormal findings were noted in MIBG images in combination with Tl images. 1) Enhancement of regional MIBG washout with otherwise normal MIBG and Tl uptake in infero-lateral wall were noted in 5 patients with history of congestive heart failure (Pathophysiologically acceleration of regional sympathetic neuronal function was suspected. Mean washout ratio is 63 +/- 7% vs. 45 +/- 10% in normal region). 2) In 3 patients with dilated cardiomyopathy increase of MIBG/Tl (M/T) ratio was noted in basal septal wall (Sympathetic neuronal function is abnormally accelerated in the region with depressed coronary perfusion. Exaltation of regional sympathetic neuronal function was suspected. Mean M/T ratio is 1.6. Tentative normal range is from 0.8 to 1.20). 3) In 2 patients with dilated cardiomyopathy under severe congestive heart failure defects of MIBG uptake with normal Tl uptake were noted (Sympathetic neuronal function was depleted in spite of normal coronary perfusion. Depletion of myocardial catecolamine was suspected. M/T ratio is 0.75 and 0.7 respectively). Heterogeneous abnormality of sympathetic neuronal function was noted in MIBG images. This findings corresponded to report about heterogeneous myocardial catecholamine concentrations in hearts of recipients of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

[Arterial perfusion study with 99mTc-MISA in monitoring intra-arterial chemotherapy of head and neck tumor].

RI-angiography with 99mTc microsphere albumin (MISA) was performed to evaluate the distribution during intra-arterial infusion chemotherapy from October 1985 to November 1987 at Tokyo Women's Medical College. Thirty studies were carried out in twenty-one patients with oropharyngeal (11), oral cavity (6), maxillary sinus (3) and laryngeal cancer (1). Six mCi of 99mTc-MISA was slowly injected through the intra-arterial catheter in 1-2 minutes. The evaluation of RI-distribution was classified into the following three categories: Excellent, all of the tumor are covered; Good, more than 50% of the tumor; Poor, less than 50% of the tumor. Good or excellent distribution was obtained in 18 of 21 cases (86%). Sequential perfusion studies were performed on 8 cases. Three cases had evidenced excellent or good distribution during the treatment. Five cases showed poor distribution in the first study. In three of these cases, distributions were improved after replacement of the catheter, RI-distribution at the internal carotid arterial area was seen in three patients, and in two of them, excellent or good distribution was obtained after replacement of the catheter. These data suggested that RI angiography with 99mTc-MISA was useful for evaluation of the drug distribution during intra-arterial infusion chemotherapy, especially for detection of abnormal distribution in the internal carotid arterial area.

Adult↗

A novel mechanism for the inhibition of adenylate cyclase via inhibitory GTP-binding proteins. Calmodulin-dependent inhibition of the cyclase catalyst by the beta gamma-subunits of GTP-binding proteins.

The adenylate cyclase catalytic protein partially purified from rat brain membranes was activated by the stimulatory GTP-binding protein (Gs), forskolin, and Ca2+-calmodulin. The Ca2+-calmodulin-stimulated activity was markedly, but the Gs- or forskolin-stimulated activity was essentially not, inhibited by low concentrations of the beta gamma-subunits of the inhibitory GTP-binding protein (Gi). The inhibition appeared to be competitive with calmodulin. On the other hand, the association of increasing amounts of beta gamma with the alpha of Gi, which was measured based on the ADP-ribosylation by islet-activating protein, pertussis toxin, was apparently competed by Ca2+-calmodulin. Furthermore, beta gamma bound to calmodulin-Sepharose in the presence of Ca2+, but not in its absence. Thus, the direct interaction of beta gamma with calmodulin is a likely mechanism involved in beta gamma-induced inhibition of the calmodulin-stimulated adenylate cyclase.

Adenylate Cyclase Toxin↗

A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin.

A new GTP-binding protein serving as the specific substrate of islet-activating protein (IAP), pertussis toxin, was purified from porcine brain membranes as an alpha beta gamma-heterotrimeric structure. The alpha-subunit of the purified protein (alpha 40 beta gamma) had a molecular mass of 40 kDa and differed from that of Gi (alpha 41 beta gamma) or Go (alpha 39 beta gamma) previously purified from brain tissues. The fragmentation patterns of limited tryptic digestion and immunological cross-reactivities among the three alpha were different from one another. However, the beta gamma-subunit resolved from the three IAP substrates similarly inhibited a membrane-bound adenylate cyclase and their beta-subunits were immunologically indistinguishable from one another. Thus, the alpha 40 beta gamma is a new IAP substrate protein different from Gi or Go, in the alpha-subunit only.

Adenylate Cyclase Toxin↗

Specific biodetection of B16 mouse melanoma in vivo by syngeneic monoclonal antibody.

The specific detection of tumors in vivo using a radiolabeled syngeneic monoclonal antibody made by fusion of P3U1 (BALB/c myeloma cells) and C57BL/6 spleen cells primed with syngeneic B16 melanoma cells was investigated by color imaging, autoradiography, and biodistribution. The radiolabeled antimelanoma antibody specifically accumulated only in the tumor lesions, whereas no radioactivity was observed in normal tissues or organs. The distribution patterns of the radioactive antibody in the tumor lesions depended on the sizes of the tumor. Almost the entire region of the small metastatic tumor in lymph nodes was labeled, whereas the radioactive antibody was irregularly localized mainly in the center of the medium-sized tumor. However, only the peripheral region of the large primary tumor was labeled. The highest uptake of radioactivity (tumor:blood ratio) was observed in the small lymph node metastatic tumor lesions rather than in the large primary tumor. Furthermore, high resolution color imaging of B16 melanoma was also obtained by using 125I-labeled monoclonal antibody. Tumor location was specifically visible without subtraction or enhancement methods 3-5 days after injection of the radiolabeled antibody.

Animals↗

Transient thyrotoxicosis associated with infarction of a large thyroid adenoma.

We report a 46-year-old male patient with a transient thyrotoxicosis that seems to have been caused by hemorrhagic infarction of a cold thyroid nodule. The serum level of triiodothyronine was markedly but transiently elevated, while the serum thyroxine level remained within the normal range. The resected nodule, measuring 8 x 7 x 5 cm, showed extensive degeneration and necrosis with viable follicles left only at the margin of the nodule. A transient thyrotoxicosis due to acute hemorrhagic infarction of autonomously functioning thyroid nodules has already been reported. This case showed that the phenomenon could occur even in cold thyroid nodules. Its implications were discussed in relation to the high incidence of impaired TSH response to TRH in patients with nodular goiter.

Adenoma↗