Biomedical subjects

T Kusunoki

Publications and source records attributed to T Kusunoki.

At least 37 records · Page 2Linked to original sources

PubMed1998

Malignancies of human thyroid tumors and dynamic magnetic resonance imaging (MRI).

Time intensity curves for gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), namely dynamic MRI, were determined for thyroid diseases and compared with findings of histopathologic examination. Time intensity curves for solid lesions were determined, excluding cases with secondary changes such as calcification, hemorrhage, necrosis and fibrosis. Three different patterns of time intensity curves were observed: rapid washout, delayed washout and no change. In our previous study, malignant grades of thyroid tumors were estimated immunohistochemically by epidermal growth factor receptor (EGFR) antibody. In most of malignant diseases and a few benign diseases that had marked cell proliferative activity with staining EGFR strongly, the time intensity curve displayed a delayed washout pattern, in which intensity was above 1/2-maximal value within 10 min after injection Gd-DTPA. Almost all benign diseases and a few well differentiated carcinomas displayed a rapid washout pastern, in which intensity was decreased to lower than 1/2 of peak grade within 10 min following injection and showed staining EGFR weakly. Benign diseases showing no change of time intensity curve, did not almost show aEGFR positive cell. These findings suggested that the time intensity curve obtained from dynamic MRI might indicate differentiated grades and cell proliferating activity of thyroid tumors.

Contrast Media↗

PubMed1998

[Re-evaluation of multi-allergen skin prick test for infants with atopic dermatitis--clinical relevance and evaluation by mothers].

We performed skin-prick tests (SPT) for 8 food and inhalant allergens on 55 infants (between 3 months and 2 years of age) with atopic dermatitis (AD) at their initial visit to our allergy clinic. SPT results were compared with those of radioallergosorbent tests (RAST) and the severity of AD symptoms. We also administered a questionnaire-based survey of 46 patients mothers to see how they evaluated SPT compared to blood tests. SPT for egg white had the highest positive rate (91%) and far exceeded that for other allergens. More than two allergens showed positive in more than half of the patients, and about 30% of them showed positive reactions to more than three allergens. Concordance rate between SPT and RAST was 78.6%. Patients showing positive reactions to multi-allergens tended to have more severe AD symptoms. Mothers appreciated the SPT test and felt that quick results for multi-allergens was the greatest advantage of SPT. More than 90% of the mothers wanted the allergic status of their next children to be evaluated with SPT. Especially, more than 30% of the mothers preferred SPT than RAST as initial screening test. As SPT is harmless, easy to administer even in infancy, and has different advantages for those of RAST, this method deserves further re-evaluation as a means of identifying allergic status especially among infants.

Child, Preschool↗

PubMed1997

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells.

Alterations in the superoxide dismutase (SOD) content of thyroid tissues occurring in association with thyroid dysfunction have been reported. In this study, the Mn-SOD content was found to increase in thyroid tissues of rats administered thyroid stimulating hormone (TSH) and in thyrocytes cultured in medium supplemented with TSH. Furthermore, in the thyroid glands of rats whose serum TSH level was elevated by inhibiting the synthesis of T3 and T4 by 6-methyl-2-thiouracil, the Mn-SOD increased as the TSH concentration increased. In the cultured thyrocytes, the increase in Mn-SOD induced by TSH was inhibited by the C-kinase inhibitor H7. These findings suggest the induction of Mn-SOD by TSH in thyroid cells and point to a role of C-kinase in this process, thereby indicating that a close relationship exists between the serum TSH level and the change in Mn-SOD content in thyrocytes with thyroid dysfunction.

Animals↗

PubMed1996

Chemical characteristics of Staphylococcus aureus molecules that have CD14-dependent cell-stimulating activity.

We have previously shown that Staphylococcus aureus contains molecules that bind CD14 and induce cellular responses. We have partially purified this activity and named the product active fraction (AF). Here, we further explore the chemical characteristics of AF. We show that 1) the activity is sensitive to base and hydrofluoric acid hydrolysis; 2) AF binds to Mono Q, indicating that it is negatively charged; 3) most activity in AF runs as a large species in aqueous buffer, but a small proportion runs with a size of <15 kDa by gel chromatography; and 4) native PAGE of AF yields a band of high apparent m.w., and SDS-PAGE yields a ladder of bands of lower apparent m.w. These data suggest that AF is a mixture of heterogeneous amphiphilic molecules that form tight micelles. These characteristics are shared by LPS, suggesting that AF has both functional and structural similarity to LPS. S. aureus cell wall has been shown to stimulate cells in a CD14-dependent fashion, and peptidoglycan (PGN) has thus been described as a ligand for membrane CD14. However, we found that the ability of S. aureus cell wall to stimulate CD14-bearing monocytes was enhanced by preincubation with soluble CD14 (sCD14). Upon treatment with sCD14, the cell-stimulating activity appeared predominantly in the supernatant, not in the insoluble PGN pellet. These findings are not consistent with a direct interaction of membrane CD14 with insoluble PGN. They suggest, rather, that the activity of cell wall may be caused by a sCD14-binding molecule that associates noncovalently with PGN.

Cell Line↗

PubMed1996

Ultrastructure of the crotaline snake infrared pit receptors: SEM confirmation of TEM findings.

BACKGROUND: Crotaline snakes possess a pair of infrared-sensing pit organs that aid the eyes in the detection and apprehension of prey. The morphology of the receptors in the pit organs has been studied by light and transmission electron microscopy, and the ultrastructure of the receptors has been inferred from the results of this work. But this theoretical reconstruction has never been confirmed by any kind of three-dimensional imaging. METHODS: We treated the receptor-containing membrane of the pit organs with potassium hydroxide to remove collagen and expose the receptors, which we then viewed by scanning electron microscopy. RESULTS: We were able to obtain three-dimensional views of all structures previously reported to exist within the receptor-containing membrane: terminal nerve masses formed from free nerve endings, supporting Schwann cells within the nerve masses, unmyelinated and myelinated nerve fibers, a capillary bed, and vacuole cells. CONCLUSIONS: By providing the first three-dimensional views of the infrared receptors, we have confirmed that previous theoretical reconstructions of the receptors were substantially correct and have provided new evidence of the spatial arrangement of the receptors in a monolayer array.

Agkistrodon↗

PubMed1996

Preparation of stable aqueous solution of keratins, and physiochemical and biodegradational properties of films.

A stable aqueous solution of reduced keratins was prepared by extracting the proteins from wool (Corriedale) with a mixture of urea, mercaptanol, surfactant, and water at 40-60 degrees C. Sodium dodecyl sulfate was especially effective as a surfactant, not only in promoting extraction but also in stabilizing the aqueous protein solution. The proteins had the following constants: MW, 52,000-69,000 daltons; cysteine content, 8-9 mol%; pl about 6.7. A clear film was readily prepared from a keratin solution containing glycerol. The film was insoluble in water and organic solvents including dimethyl sulfoxide. The keratin film was permeable to glucose, urea, and sodium chloride. The keratin film was degraded in vitro (by trypsin) and in vivo (by subcutaneous embedding in mice).

Animals↗

PubMed1996

Agents for the treatment of overactive detrusor. IX. Synthesis and pharmacological properties of metabolites of N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine (FK584) in human urine.

We synthesized the racemates of the five presumed metabolites (1b-f) of (S)-(--)-N-tert-butyl-4,4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(--)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate their inhibitory activity against detrusor contraction. (+/-)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxyphenyl)- and 4-phenyl-2-cyclopentenylamines (1b--e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass spectrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.

Amines↗

PubMed1996

General pharmacology of the new non-xanthine adenosine A1 receptor antagonist (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2- piperidine ethanol.

FK 453 ((+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-2-piperidine ethanol, CAS 121524-18-3) is a potent non-xanthine adenosine A1 receptor antagonist with diuretic and renal vasodilatory activity. The general pharmacology of FK 453 was investigated in mice, rats, guinea-pigs and dogs. In in vivo tests, FK 453 had little effect on the central nervous system (general behaviour, spontaneous motor activity, potentiation of barbiturate anesthesia, anticonvulsant activity, analgesic activity and body temperature), hematological system (bleeding time, coagulation time and recalcification time) and intestinal charcoal transit. FK 453 also did not show any cardiovascular (blood pressure, heart rate and femoral blood flow) or respiratory effects. In in vitro tests, although FK 453 had little effect on noradrenaline-induced contraction in rat vas deferens and histamine-induced contraction in guinea-pig trachea, FK 453 inhibited the acetylcholine-, histamine- and barium-induced contraction in isolated guinea-pig ileum and serotonin-induced contraction in isolated rat stomach. FK 453 also exerted significant inhibitory activity on collagen- and U 46619-induced platelet aggregation. However these effects of FK 453 on isolated tissue and platelet were observed only at high concentrations. These results suggest that FK 453 possesses a selective pharmacological profile, and one promising therapeutic site for this drug is in the kidney.

Analgesics↗

PubMed1995

Molecules from Staphylococcus aureus that bind CD14 and stimulate innate immune responses.

Mammals mount a rapid inflammatory response to gram-negative bacteria by recognizing lipopolysaccharide (LPS, endotoxin). LPS binds to CD14, and the resulting LPS-CD14 complex induces synthesis of cytokines and up-regulation of adhesion molecules in a variety of cell types. Gram-positive bacteria provoke a very similar inflammatory response, but the molecules that provoke innate responses to these bacteria have not been defined. Here we show that protein-free, phenol extracts of Staphylococcus aureus contain a minor component that stimulates adhesion of neutrophils and cytokine production in monocytes and in the astrocytoma cell line, U373. Responses to this component do not absolutely require CD14, but addition of soluble CD14 enhances sensitivity of U373 cells by up to 100-fold, and blocking CD14 on monocytes decreases sensitivity nearly 1,000-fold. Deletion of residues 57-64 of CD14, which are required for responses to LPS, also eliminates CD14-dependent responses to S. aureus molecules. The stimulatory component of S. aureus binds CD14 and blocks binding of radioactive LPS. Unlike LPS, the activity of S. aureus molecules was neither enhanced by LPS binding protein nor inhibited by bactericidal/permeability increasing protein. The active factor in extracts of S. aureus is also structurally and functionally distinct from the abundant species known as lipoteichoic acid (LTA). Cell-stimulating activity fractionates differently from LTA on a reverse-phase column, pure LTA fails to stimulate cells, and LTA antagonizes the action of LPS in assays of IL-6 production. These studies suggest that mammals may use CD14 in innate responses to both gram-negative and gram-positive bacteria, and that gram-positive bacteria may contain an apparently unique, CD14-binding species that initiates cellular responses.

Antigens, Bacterial↗

PubMed1995

A novel non-xanthine adenosine A1 receptor antagonist.

FK453, (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-alpha]pyridin-3-yl) acryloyl]-2-piperidine ethanol, was examined for adenosine receptor antagonistic activity using isolated guinea-pig atria and aorta and for affinity for adenosine receptors in the rat cerebral cortex and striatum in comparison with FR113452 (S enantiomer of FK453), PD116948 (1,3-dipropyl-8-cyclopentylxanthine), theophylline (1,3-dimethylxanthine) and CGS15943 ([1,2,4]triazolo[1,5-c]quinazolone). FK453 showed potent inhibition of the negative inotropic activity elicited by 10 microM adenosine with an IC50 of 560 pM in guinea-pig atria. However, FK453 was less potent in inhibiting the relaxation induced by 3.2 microM adenosine and had an IC50 of 1.18 microM in guinea-pig aorta. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 1.18 microM, 1.31 nM, 20.2 microM and 74.2 nM in atria and > 100 microM, 656 nM, 239 microM, 127 nM in aorta respectively. In the binding study, FK453 antagonized [3H]N6-cyclohexyladenosine binding to the rat cortical adenosine A1 receptor with an IC50 of 17.2 nM. The IC50 values for FR113452, PD116948, theophylline and CGS15943 were 10.1 microM, 4.7 nM, 67.7 microM and 241 nM respectively. FK453 inhibited [3H]5'-N-ethylcarboxamideadenosine binding to rat striatum adenosine A2 receptor with an IC50 of 11.3 microM. FK453 had no adenosine A1 receptor agonistic activity, since it had no negative inotropic activity up to 100 microM in isolated guinea-pig atria. These results demonstrate that FK453 is a novel non-xanthine adenosine receptor antagonist and is potent and selective for the adenosine A1 receptor subtype.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1995

Calcitonin gene-related peptide immunoreactivity in the trigeminal ganglion of Trimeresurus flavoviridis.

Crotaline snakes, which have infrared-sensitive pit organs, provide a good model for linking neuron morphology with sensory modality. In the trigeminal ganglion of the habu, Trimeresurus flavoviridis, cells positive for calcitonin gene-related peptide-like (CGRP) immunoreactivity were found to be of two types, darkly stained and lightly stained. They were pseudo-unipolar, having an axon divided into stem, peripheral branch, and central branch, all of which were 1 micron or less in diameter. Other, CGRP-negative cells in the ganglion were also pseudo-unipolar, but much larger. In configuration, some of the positive cells were similar to the neurons with A-delta fibers, and others to the neurons with C fibers that have been reported by other workers. On the basis of their distribution and density, and physiological studies by other workers, the CGRP-positive cells were judged to be not part of the infrared-receptive system, but to be involved in the transmission of nociception in small fibers.

Animals↗

PubMed1995

Somatosensory and visual correlation in the optic tectum of a python, Python regius: a horseradish peroxidase and Golgi study.

In snakes with infrared receptors the optic tectum receives infrared input in addition to visual and general somatosensory inputs. In order to observe their tectal termination patterns in ball pythons, Python regius, we injected horseradish peroxidase (HRP) into the nucleus of the lateral descending trigeminal tract (LTTD) which mediates infrared information, the optic nerve, and the nucleus of the trigeminal descending tract (TTD) which relays general somatosensory information. Fibers from LTTD were found in layers 5-13 of the contralateral optic tectum, and were especially dense in layers 7a-8. Optic nerve fibers terminated in layers 7a-13 of the contralateral tectum, and mainly in layers 12-13. TTD fibers were few, and could be seen in only the rostral half of the contralateral tectum. These fibers were found in layers 5-7b, but mainly in layers 6-7a. Among various types of neurons stained by the Golgi-Cox method, we focused on six types of neurons whose dendritic arborization overlapped with the distribution of the terminals of these sensory afferents described above. It is possible that these different sensory modalities converge on a single neuron of the various types.

Animals↗

PubMed1995

Productivity of thyroglobulin and thyroid hormone on human thyroid cell in collagen gel culture.

Thyroid cells obtained from 21 normal human thyroid tissue samples and 17 tissue samples from diseased thyroid, including one of Graves disease, 4 with follicular adenoma, 11 with papillary carcinoma, and 1 with follicular carcinoma, were cultured in collagen gel, and ability to produce thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4) was determined. Changes in morphological characteristics and production of Tg, T3, and T4 induced by addition of thyroid stimulating hormone (TSH) to medium in collagen gel culture were also determined. Twenty of all cases exhibited positive reaction for Tg. No relationship was found between rate of positivity for Tg and pathologic diagnosis. Three with carcinoma showed positive reaction for T3, and 4 with carcinoma showed positive reaction for T4. Only for normal thyroid cells did addition of TSH to medium induce increase the percentage of colonies producing Tg or T4 and morphological changes including an enlarged follicular lumen and increase in the height of columnar epithelium. These findings suggest that thyroid cells in collagen culture develop in an in vivo-like fashion. In conclusion, collagen has important effects on cellular differentiation when included in extracellular matrix.

Adenoma↗

PubMed1995

Study on cathepsin B activity in human thyroid tumors.

Cathepsin B activity was measured in human thyroid tissue obtained surgically from 2 patients with Grave's disease, 3 with follicular adenoma, 4 with papillary carcinoma, and 4 with follicular carcinoma. Three normal thyroid tissues were also studied. Comparisons were made between cathepsin B activity and clinical findings, including histopathological diagnosis and the presence or absence of extra-capsular invasion and metastasis. The abilities of original tumors to degrade type I and type IV collagen were also measured. Mean cathepsin B activities of both specimens with benign and those with malignant disease were significantly higher than those of normal thyroid. On cases of thyroid carcinoma, those with extra-capsular invasions and metastasis had the highest cathepsin B activities. Cases with high cathepsin B activities also tended to show high type I and IV collagen degrading abilities. These findings suggest that cathepsin B plays a role in the development of extra-capsular invasion and lymph node metastasis in human thyroid tumors.

Adenocarcinoma, Follicular↗

PubMed1995

[Study of type I and IV collagenase activity in human thyroid diseases].

The activity of type I and IV collagenase was measured in thyroid tissue obtained from 6 non-diseased thyroids, 4 patients with Graves' diseases, 5 with follicular adenoma, 6 with papillary carcinoma and 4 with follicular carcinomas. The relationship between these enzyme activities and invasion or metastasis of the original tumors was studied. The activity of type I collagenase in papillary carcinomas and follicular carcinomas was higher than in non-diseased thyroids, Graves' disease and follicular adenoma. Carcinoma tissue with invasion beyond the capsule in particular had higher type I collagenase activity. Type IV collagenase activity in carcinoma with lymph node metastasis was higher than in non-diseased thyroids, Graves' disease and follicular adenoma, and especially higher than carcinoma without lymph node metastasis. These findings suggest that increased type I collagenase activity plays an important role in local invasion in thyroid carcinoma, and that increased type IV collagenase activity plays an important role in lymph node metastasis.

Adenocarcinoma, Follicular↗

PubMed1995

[Clinical phase III study of tropisetron capsule in the treatment of nausea and vomiting induced by anti-cancer drug; a placebo-controlled, multicenter, double-blind comparative study].

A placebo-controlled, double-blind comparative study of tropisetron capsule was conducted to assess its clinical usefulness for nausea and vomiting induced by the anticancer drug, cisplatin, at a single dose of 50 mg/m2 or higher. Either 5mg tropisetron capsule or its placebo was given orally to patients 2 hours prior to cisplatin administration; the clinical efficacy was determined the severity of nausea and the number of emesis that occurred during 24 hours after cisplatin. Tropisetron significantly exceeded the placebo in the assessment of clinical efficacy. The ratings for the tropisetron group and the placebo group were 91.7% (22/24 cases) and 25.9% (7/27 cases), respectively. Adverse events observed were one case of headache in the tropisetron group and one diarrhea in the placebo group, while neither case was serious nor clinically problematic in particular. The above results reveal that tropisetron 5 mg capsule is significantly effective in the treatment of anticancer drug-induced nausea and vomiting. It has also been confirmed that tropisetron is a useful agent without any safety problems.

Administration, Oral↗

PubMed1995

[The brain of the Agnatha].

The brain of the Agnatha, especially of the hagfish, is discussed from the viewpoint of the telencephalon and the olfactory, visual, trigeminal, and vestibulolateral sensory systems. Myxiniformes and Petromyzontiformes, which were an independent group in the Ordovician, are thought to represent some parallels of ancestral vertebrate brains. It is interesting to study the brain of the Agnatha to investigate the process of the evolution of the vertebrate brain. In comparison with the lamprey, the hagfish has subcutaneous eyes under an unpigmented patch of skin, 4 paired tentacles at the rostral tip of the head, one semicircular canal on each side, a regressed ventricular system, a "primordium hippocampi" of unresolved homology in the telencephalon, no pineal body, fusion of the habenula of both sides, a tectum opticum with unclear laminations, no macroscopical cerebellum, and optic decussation within the hypothalamus. The arrangements of the trigeminal subnuclei of the descending tract are different from each other, unlike those of other gnathosomata. In the hagfish, the distribution of fibers carrying input of the vestibulum and lateral line system within the area vestibulo-lateralis differs from that of the lamprey, which resembles the teleosts and cartilaginous fish in this respect. These differences may be caused by an independent origin within the Agnatha. The basic organization of the brain of the Agnatha, such as the prosencephalon, mesencephalon, and rhombencephalon are common to the gnathostomata, although some variations in development are included in the sensory centers and higher centers of information processing. The sensory neurons within the brain are found in the medulla oblongata in the Agnatha, whereas in the gnathostomata the mesencephalic nucleus of the trigeminal nerve has been formed in connection with the development of the mandibula.

Animals↗

PubMed1994

Coexistence of galanin and substance P in the mouse nasal mucosa, including the vomeronasal organ.

Immunohistochemical fluorescent double labeling revealed the coexistence of galanin and substance P in nerve fibers in the mouse nasal mucosa. At the base of and in the epithelium, all galanin fibers also contained substance P, but around the blood vessels and glands, most of them did not. Since substance P fibers in the nasal mucosa originate from the trigeminal ganglion, these results suggest that galanin fibers in the submucosal region originate from ganglia other than the trigeminal.

Animals↗