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Biomedical subjects

K Torizuka

Publications and source records attributed to K Torizuka.

At least 127 records · Page 7Linked to original sources

Human calcitonin gene-related peptide possesses weak inhibitory potency of bone resorption in vitro.

Synthetic human calcitonin gene-related peptide (CGRP) was examined for the action on the bone in vitro. Human CGRP inhibited bone resorption stimulated by both human parathyroid hormone and basal. The mode of inhibitory action of human CGRP seemed to be similar to that of calcitonin and the relative potency of human CGRP to inhibit bone resorption is one five-hundredth of that of human calcitonin. Thus, a novel pharmacological action of CGRP was demonstrated.

Animals↗

Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism.

We examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1 alpha-hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6 +/- 37.6 pg/ml (mean +/- SD) in patients with primary hyperparathyroidism and 75.3 +/- 27.7 pg/ml (mean +/- SD) in normal volunteers after administration of 1 alpha-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5 +/- 16.5% (mean +/- SD) in patients with primary hyperparathyroidism and 34.1 +/- 5.1% (mean +/- SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism.

Adult↗

In the procurement of stable 99mTc labeled protein using bifunctional chelating agent.

Recently, technetium-99m (99mTc) labeling of proteins through the use of a bifunctional chelating agent (BCA) has been reported. In previous work, a BCA containing a di(N-methylthiosemicarbazone) (DTS) moiety for 99mTc has offered good potential; however, conjugation with bulky proteins has induced some steric interference in the 99mTc labeling step using the stannous chloride method. In order to minimize this effect, changes in the hydrocarbon chain length (spacer) between the DTS and the protein binding site (carboxyl group), as well as the chemical state of the reducing agent, stannous chloride, were considered of interest. DTS molecules with variable spacer length (n = 0, 2, 4) were synthesized, coupled with human serum albumin and labeled with 99mTc. Also, stannous chloride prepared in different media was evaluated. Validity of the present approach is tested and discussed.

Animals↗

Search for 99mTc labeled DTS bifunctional radiopharmaceutical: role of functional groups in myocardial accumulation.

Development of 99mTc-bifunctional radiopharmaceutical (BR) is attracting the interest of various research groups. In the present paper, various molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as the technetium chelating site, along with various functional groups (amino, carboxyl or isobutyl group with diverse charge) are tested for their chemical or biological functions. The study on the effect of those functional groups is carried out in vitro and in vivo. The validity of introducing an amino group along with the technetium chelating site DTS for myocardial accumulation is discussed.

Animals↗

Design of bifunctional radiopharmaceutical for the development of 99mTc complexes for myocardial imaging agents.

Several bifunctional radiopharmaceuticals (BR), molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as a chelating site, along with a functional amino group (primary tertiary and quaternary amino group) are tested for their chemical or biological functionalities as myocardial agents. Investigation of these amino compounds is carried out in vitro and in vivo. Mice (ddY) distribution studies show a high radioactivity distribution in heart with every tested derivative, but the highest heart to blood ratio of 2.92 (1 h) is achieved with the quaternary amino DTS. Also, this derivative displays low lung uptake inducing a proper target/non-target ratio for myocardial agent. The role conveyed by the various amino containing side chain in the biodistribution and validity of DTS derivative as BR are discussed.

Animals↗

Synthesis and evaluation of a new bifunctional chelating agent for 99mTc labeling proteins: p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone).

A new bifunctional chelating agent, p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), containing a di(N-methylthiosemicarbazone) as the technetium coordinating site and an aralkyl carboxylate site for the protein conjugation was synthesized. Coupling to human serum albumin (HSA), selected as a model protein was carried out by the phosphorylazide method using diphenylphosphoryl azide (DPPA). The conjugation level of CE-DTS to HSA played a critical role in its biological evaluation. A 99mTc-CE-DTS-HSA with high in vivo stability was obtained when CE-DTS was coupled to HSA at 1:1 molar ratio. This compound showed similar in vivo stability to 131I labeled HSA in mice and rabbits.

Animals↗

In the procurement of a neutral and compact monomeric complex of dithiosemicarbazone (DTS) derivative: 99mTc-KTS.

As a basic structure of a bifunctional radiopharmaceutical (BR), dithiosemicarbazone (DTS) enables the formation of a small conjugated chelating ring with divalent metals (Cu2+, Zn2+, Ni2+), yielding stable and compact complexes. In the development of a neutral and compact monomeric DTS complex of technetium (99mTc), a DTS containing ligand, kethoxal-bis(thiosemicarbazone) (KTS) was selected. A well known monomeric Cu-KTS complex (or 64Cu-KTS) is taken as a model compound, and in vitro (TLC, EP, HPLC) and in vivo (mice biodistribution) studies were compared. Using the stannous chloride method, under conditions to avoid the hydrolytic polynucleation of technetium, a good yield of 99mTc-KTS with characteristics resembling the non-charged, compact and stable Cu-KTS is obtained, in in vitro as well as in vivo studies. The importance of DTS as the constituent of a BR is discussed.

Animals↗

62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis.

As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post-administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases.

Animals↗

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA.

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.

Adult↗

SPECT with N-isopropyl-p iodoamphetamine in occlusive cerebrovascular diseases.

The role of SPECT imaging with N-isopropyl-p iodoamphetamine (I-123 IMP) in the detection of angiographically documented occlusive cerebrovascular diseases was evaluated in 24 patients, and the results of regional cerebral blood flow (rCBF) were compared with x-ray CT. Twelve patients had internal carotid occlusion, ten had intracranial occlusion beyond the circle of Willis, one had common carotid occlusion, and one had basilar artery occlusion. SPECT images were obtained with a gamma camera, which was rotated 360 degrees around the patient's head 30 minutes after an intravenous injection of 3 mCi of I-123 IMP. CT images in the transverse plane were obtained, and the regions of reduced attenuation were identified for comparison of topographic extension of the lesion with the regions of decreased rCBF seen on SPECT. In six cases, the lesions seen on the SPECT images were distinctly more extensive than those seen on CT. In the remaining 18 cases, the extent of the lesion was identical on both CT and SPECT images. Radiochemical and radionuclide impurities, the distance of the detector from the head, and the nature of the collimator affected the SPECT results. I-123 IMP SPECT imaging complements CT findings in detecting the ischemic zones beyond the regions identified on CT images, and may have a major rule in the management of patients with occlusive cerebrovascular diseases.

Amphetamines↗

Soft-tissue uptake of technetium-99m MDP in multiple myeloma.

Abnormal accumulation of Tc-99m MDP in the lungs and stomach was observed in a patient with multiple myeloma and refractory hypercalcemia. There was no roentgenographic evidence of calcification. At postmortem examination, the presence of amyloid deposits was confirmed in both organs, while the corresponding metastatic calcification was demonstrated only in the gastric mucosa. It seems likely that, in our case, soft-tissue localization of bone-seeking agent was attributable to the presence of amyloid deposits rather than metastatic calcification. No cases showing the combined occurrence of amyloid deposition and metastatic calcification in soft-tissues have previously been demonstrated to concentrate bone-seeking agent.

Amyloidosis↗

Bronchial venous plexus and its communication with pulmonary circulation.

This study was undertaken to clarify the microvascular anatomy of the normal human bronchial circulation, focusing on the bronchial venous system and its communication with the pulmonary circulation. Ten normal lungs obtained at autopsy were studied. Bronchial arteriography was performed in six lungs, pulmonary arteriography in two lungs, and pulmonary venography in another two. Using radiologic methods, including microradiography, and serial histologic sections, we found numerous bronchial venous plexuses around the airways and blood vessels into which the bronchial capillaries drained. Frequent communications of the venous plexuses with the pulmonary veins and neighboring alveolar capillaries were also demonstrated. The bronchial venous plexus and its close connection with the pulmonary circulation may be important in various pathologic conditions involving the interstitial space, such as interstitial pulmonary edema.

Adult↗

Changes in thyroid-stimulating and TSH-binding inhibitory activities in a patient who developed hyperthyroidism due to Graves' disease following primary hypothyroidism.

A 23-year-old female who developed thyrotoxic Graves' disease following primary hypothyroidism was reported. She presented with symptoms of hypothyroidism and slight exophthalmos. After primary hypothyroidism was confirmed, she was treated with T4 in a dose of 50 micrograms/d. Two months after delivery, 1 year after the initial diagnosis of hypothyroidism, hyperthyroidism developed while she was taking T4. Graves' disease was confirmed by persistent thyrotoxicosis, high 99mTc thyroidal uptake, negative T3 suppressibility and detection of TSH-receptor antibodies. During the hypothyroid phase, TSH-binding inhibitory immunoglobulins (TBII) could not be detected, while thyroid stimulating antibodies (TSAb) were positive showing between 5.8 and 9.0 fold increases in the amount of cAMP produced in cultured porcine thyroid cells. Her IgG did not inhibit TSH-induced cAMP increase in vitro. When she developed hyperthyroidism, TSAb activity became more potent (31.7 fold increase in cAMP) and TBII became positive (+61.3%).

Adult↗

Thalamic tumours invading the brain stem produce crossed cerebellar diaschisis demonstrated by PET.

Two cases of thalamic tumour, spreading through the midbrain into the pons ventrolaterally, showed suppression of cerebellar blood flow on the opposite side to the tumour, and also showed reduction of blood flow in the pons on the side of the tumour in positron emission tomographic studies. The pathophysiological mechanism of crossed cerebellar diaschisis may be due to functional suppression of the pontine nuclei by destruction of descending fibres from the cerebral cortex.

Adult↗

Ventilation imaging with positron emission tomography and nitrogen 13.

Ventilation imaging using positron emission tomography (PET) and highly insoluble nitrogen 13 (N-13) was performed in one healthy volunteer and ten patients. These PET studies showed the three-dimensional distribution of ventilation abnormalities, such as peripheral air trapping, which xenon 133 studies had not revealed. Therefore, PET with N-13 may help elucidate more precisely the distribution and nature of ventilation abnormalities in various diseases.

Humans↗

Sclerotic bone metastasis: radiologic-pathologic correlation.

Radiographic appearances were correlated with histologic findings in sclerotic bone metastases. For this purpose, undecalcified ground sections were made from lumbar vertebrae obtained at 12 autopsies. The primary tumor sites were the prostate gland in five cases, the breast in three, the lung in two, the stomach in one, and the urinary bladder in one. After Villanueva bone staining and methyl methacrylate embedding, 1-mm-thick ground sections were made for low-kilovoltage contact radiography. In sclerotic bone metastases, new bone is deposited on preexisting trabeculae and in the intertrabecular spaces, forming lacy networks. The radiographic indications of these histologic changes are trabecular thickening, marginal obscurity (the "silhouette" sign), and homogeneous dense sclerotic change. The silhouette sign in bone is a new concept, one that is helpful when the changes in density are not reliable.

Adult↗

Stripe sign in pulmonary perfusion scintigraphy: central pattern of pulmonary emphysema. Work in progress.

Morphologic changes and ventilation abnormalities in the lung that resulted in the peripheral perfusion stripe (the stripe sign) on pulmonary perfusion scintigrams were studied in six patients. Chest radiographs, computed tomography (CT) scans, and positron emission tomography (PET) scans obtained using N-13 were compared. Although there was no apparent correlation between the presence of the stripe sign and the findings on the chest radiographs, PET scans depicted ventilation abnormalities in all of 11 lung areas with the stripe sign in six patients. In addition, ventilation was affected more severely in the central part of the lung than in the subpleural region in ten of the 11 lung areas. CT scans demonstrated emphysematous changes, with low attenuation values located mainly in the central part of the lung in all four patients examined. The results suggest an intimate relationship between the stripe sign and the central pattern of pulmonary emphysema.

Aged↗