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Y Takano

Publications and source records attributed to Y Takano.

At least 19 recordsLinked to original sources

Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.

The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.

Animals

The effect of intrathecally administered imiloxan and WB4101: possible role of alpha 2-adrenoceptor subtypes in the spinal cord.

To define the antagonist pharmacology of spinal antinociceptive effects of alpha 2-adrenoceptor agonists, the ability of WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane) and imiloxan to antagonize the effect of spinal ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline), clonidine and dexmedetomidine was examined. Antinociceptive effects of ST-91 were antagonized by WB4101 and imiloxan; clonidine only by WB4101; and, dexmedetomidine was not antagonized by either antagonist. It is hypothesized that the alpha 2 adrenoceptor subtype alpha 2A is involved in the antinociception of spinal clonidine and dexmedetomidine, and alpha 2B is involved in that of ST-91.

Adrenergic alpha-Agonists

Role of NK-1 receptor in central cardiovascular regulation in rats: studies on a novel non-peptide antagonist, CP-96,345, of substance P NK-1 receptor.

CP-96,345[(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)- methyl]-1-azabicyclo [2.2.2] octan-3-amine] was recently discovered to be a nonpeptide substance P (SP) antagonist. We examined the effects of CP-96,345 on the central cardiovascular responses to tachykinin peptides in anesthetized rats. CP-96,345 (200 nmol, i.c.v.) inhibited the pressor responses of the NK-1 receptor-selective agonist GR 73632 (0.5 nmol, i.c.v.) and SP (7 nmol, i.c.v.). It also inhibited the increase in blood pressure elicited by neurokinin A (7 nmol, i.c.v.). However, it had no effect on the earlier pressor response induced by neuropeptide gamma (l nmol, i.c.v.) or by a selective NK-3 agonist senktide (1 nmol, i.c.v.). These findings suggest that SP (i.c.v.) induces pressor responses via the NK-1 receptor, and that the pressor response to neurokinin A may also be mediated by the NK-1 receptor in the brain.

Animals

In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after short treatment with 15-deoxyspergualin.

15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent already used to inhibit acute rejection in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanisms underlying DSG-induced heart allograft acceptance were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third-party donors, respectively. Survival of ACI heart grafts in LEW recipients treated with a short course of DSG starting on day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per day, respectively. On day 20 after grafting, the mechanism of inducing allograft survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing the activation of spleen cells or serum in several assay systems. Spleen cells from DSG-treated rats with surviving heart allografts showed almost no proliferative response against donor strain stimulator cells compared with controls. The cytotoxic activity towards donor strain target cells of spleen cells from DSG-treated rats with surviving heart allografts was lower than that of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Argyrophilic nucleolar organizer regions in human adrenocortical neoplasms.

Argyrophilic nucleolar organizer regions (AgNOR) in human adrenocortical neoplasms, including five carcinomas and ten adenomas, were studied using a semi-automatic image analyzer. Both the number and total area of AgNOR per nucleus in the carcinomas were found to be statistically greater than in adenomas and control tissues. However, there were no statistically significant differences in total AgNOR area per nuclear area or in the mean area of individual AgNOR dots. The AgNOR of neoplastic and normal cells were of four morphological types: type 1 had a few dots at the periphery of the nucleus, type 2 a few dots at the center, type 3 a large round dot along with several small ones at the center, and type 4 numerous diffusely distributed polymorphic dots. Most type 3 and 4 cells were found in carcinoma cases. Type 1 cells decreased in proportion to the severity of biological malignancy. It follows from these findings that careful observation of AgNOR should facilitate the distinction of malignant from benign adrenocortical neoplasms.

Adenoma

Molecular-genetic analysis of ocular adnexal benign lymphoid hyperplasias by a two-step polymerase-chain-reaction.

Twelve biopsied ocular adnexal benign lymphoid hyperplasias (OABLH) satisfying benign histological criteria were investigated for clonal immunoglobulin (Ig) heavy-chain gene rearrangement by means of a two-step polymerase chain reaction (PCR) method using formalin-fixed and paraffin-embedded tissue. Of the 12, 4 (33%) demonstrated clear single bands of the rearranged gene for the Ig heavy-chain, of between 100 and 150 base pairs. The selected cases were all free of malignant lymphoma and all of the lesions were small (2 x 2-22 x 6 mm; median 4.5 x 3 mm). Histopathological and cytological features were not essentially different between monoclonal and non-monoclonal examples. Immunohistochemistry was of little benefit in separating the two. It is concluded that OABLH demonstrating a benign clinical course frequently contain monoclonal B cell populations suggesting a continuous progressive spectrum of lesions in B cell neoplasia. In addition, the significance of molecular-genetic analysis for OABLH and the utility of the two-step PCR method should be emphasized.

Adolescent

Calcium movement in vivo and in vitro in secretory-stage enamel of rat incisors.

The lower incisors of young rats were dissected, immersed in physiological saline containing 45Ca under various conditions, and processed for autoradiography. The data were compared with those from in vivo 45Ca autoradiography. In secretory-stage enamel, wiped free of the enamel organ and immediately immersed in radioactive saline, there was intense labelling in the surface layers. The labelled area expanded only gradually into the deeper layers at a rate similar to that observed in vivo. Labelling in the enamel was similar in pattern but much weaker in intensity when the incisor was identically treated in vitro with the enamel organ attached. Glutaraldehyde pretreatment of the exposed enamel abolished expansion of the labelled area, whereas a hypochlorite pretreatment allowed a rapid diffusion of the isotope into the deeper layers of the secretory-stage enamel. The findings confirm the role of the enamel organ as a diffusion barrier to the penetration of calcium from the extracellular fluid to the secretory-stage enamel, and suggest an intimate correlation between physicochemical properties of the organic enamel matrix and the rate of surface-to-interior diffusion of calcium within the secretory-stage enamel of rat incisors.

Animals

Clonal Ig-gene rearrangement in some cases of gastric RLH detected by PCR method.

Clonal immunoglobulin (Ig) heavy chain gene rearrangement in gastric reactive lymphoid hyperplasia (RLH) cases was investigated by means of the 'double' polymerase chain reaction (PCR) using formalin-fixed and paraffin-embedded tissue. Rearranged DNA sequences, formed by combinations of variable (VH) and joining (JH) regions, were amplified with oligomeric primers. One microgram of DNA extracted from formalin-fixed and paraffin-embedded tissue was applied as the 'first PCR' template and one ten-thousandth of the first PCR product was used as the 'second PCR' template. As a control study for the double PCR method, DNA isolated from frank B cell gastric malignant lymphomas was assessed. Clear single bands between 100 and 150 base pair markers in length were evident on agarose gel electrophoresis in 10 out of 13 cases (76.9%) of malignant lymphomas while 2 out of 22 cases (9%) of RLHs revealed clear single bands of the same length, suggesting malignant lymphomas; however, no histologic features of malignant lymphomas were present. It is concluded that even gastric RLH cases satisfying histopathologic criteria for benign lymphoid hyperplasia may contain occult monoclonal B cell populations suggesting a continuous and progressive spectrum of lesions contributing to B cell neoplasia.

Base Sequence

The in vitro immunosuppressive effect of deoxymethylspergualin in man as compared with FK506 and cyclosporine.

The effect of deoxymethylspergualin (MeDSG) on in vitro human lymphocyte response was assessed in comparison with FK506 and cyclosporine. Peripheral blood mononuclear cells from normal human volunteers were used for assay of mixed lymphocyte reaction, cell mediated lympholysis, and blastogenesis by PHA, IL-2, and OKT3. MeDSG suppressed only allogeneic stimulation (MLR and CML) and IL-2-induced blastogenesis, not PHA- or OKT3-induced blastogenesis, although the other immunosuppressive agents showed some suppressive effect for all assays. A kinetic study of MLR showed that the suppressive activity did not decrease even when MeDSG was added at day 3 or day 4. The other agents, however, showed a weak suppressive effect when added at a later phase of MLR.

Cyclosporine

FK506-induced kidney tubular cell injury.

Some renal changes associated with cyclosporine, such as tubular vacuolization and glomerular thrombosis, have also been reported with FK506. Furthermore, FK506 therapy is associated with a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. We studied the in vitro tubular cell sensitivity to FK506 in comparison with CsA, the ultrastructural changes induced by FK506 and CsA, and the effect of both drugs on tubular cell growth in vitro. We also investigated whether FK506 and CsA induced endothelin-1 (ET-1) secretion of cultured tubular cells and whether this stimulatory effect coincided with a change in the endothelin systemic synthesis. Exposure of tubular cells to high concentrations of FK506 or CsA (10, 50, 100 microM) induced a time- and dose-dependent cell injury in vitro. The damage induced by FK506 and CsA was characterized by a direct cytotoxic effect on tubular cells, as expressed by release of 3H thymidine from prelabeled cells, N-acetyl-beta-D-glucosaminidase release, and cell detachment. Ultrastructural changes (vacuolizations, swelling, and mitochondrial enlargement) and inhibition of the growth of cultured tubular cells were also observed at high concentrations of FK506 and CsA. Low concentrations of FK506 and CsA (1, 0.1, 0.01, 0.001 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. We demonstrated that FK506 (1, 0.1, 0.01 microM) time-dependently stimulated the secretion of endothelin by cultured tubular cells. CsA 10, 1, 0.1, 0.01 also exerted an enhancing effect on ET-1 secretion in cultured tubular cells. We observed that the concentration of CsA that induced the most important enhancing effect was 10 or 100 times higher than that required for FK506 to observe the same effect. The concentrations of FK506 or CsA that induced ET-1 secretion were not cytolytic for tubular cells in vitro. FK506- or CsA-treated rats showed an increase in serum level of ET-1 in comparison with the control. Through the stimulatory effect on endothelin secretion by tubular cells, FK506 and CsA may induce a perturbation of renal hemodynamics. Concentrations of FK506 and CsA, higher than established serum levels but close to those reached in tissues, are cytotoxic for tubular cells and induced ultrastructural changes and a significant delayed regeneration.

Acetylglucosaminidase

Histopathological and immunohistochemical study of atypical lymphoid hyperplasia and benign lymphoid hyperplasia of the stomach.

We propose dividing histologically reactive lymphoid hyperplasia (RLH) of the stomach into two categories: atypical lymphoid hyperplasia (ALH), characterized by abnormal follicular architecture and infiltration of atypical lymphoid cells, and benign lymphoid hyperplasia (BLH), where normal follicular patterns are preserved and no atypical cells are found. Using twenty RLH cases (10 ALHs and 10 BLHs), both categories were compared from histopathological and immunohistochemical aspects. Macroscopic division into superficial, thick-walled and nodular types revealed most ALH (80%) to be superficial in character whereas in BLH superficial and thick-walled types were almost equally represented. Lesion size tended to be larger in ALH (greater than 6.1 cm) than in BLH (6.0 cm greater than) cases. As for prognosis after gastrectomy, both categories were favorable. On immunohistochemistry, ALH tended to be strongly labeled by B lymphocyte markers as compared to BLH, where only a weakly positive reaction was expressed. Infiltration of cells labeled by T lymphocyte markers was less conspicuous in ALH than in BLH. From these data, we concluded that ALH and BLH are two distinctive categories of lesion and that ALH has characteristics similar to these demonstrated by malignant lymphoma.

Female

Isolation, identification and pharmacological studies on three toxic metabolites from a mushroom, Hebeloma spoliatum.

Three metabolites, tentatively named HS-A, -B and -C, were isolated from a mushroom, Hebeloma spoliatum, as the fatal toxic principles to mice. HS-A was identified as 3-acetyl-2-(3'-hydroxy-3'-methyl)glutarylcrustulinol, which has been isolated from Hebeloma crustuliniforme and H. sinapizans as a cytotoxic principle. HS-B and -C were deduced to be 3,21-diacetyl-2-(3'-hydroxy-3'-methyl)glutarylcrustulinol and 3-acetyl-2-(3'-hydroxy-3'-methyl)glutarylanhydrocrustulinol, respectively, from their chemical and spectral data. Intraperitoneal administration of HS-A, -B and -C at a dose of 100 mg/kg caused death after paralysis of the limbs in mice. The compounds caused relaxation of mouse small intestine contracted by acetylcholine chloride or barium chloride treatment in vitro. They appear to exhibit a papaverine-like relaxation effect.

Animals

Innervation of the periodontal ligament in the dog with special reference to the morphology of Ruffini endings.

The distribution and terminal formation of nerves in the periodontal ligament of dog incisors and canines were investigated by immunohistochemistry for neurofilament protein (NFP) and by electron microscopy. The NFP-immunoreactive nerve fibers were found to be densely distributed in the apical third of the periodontal ligament, while they were sparse in the coronal two thirds. Most of the nerve endings in the periodontal ligament showed a tree-like appearance and resembled those nerve endings demonstrated in the periodontal ligament of human and monkey under the category of free nerve endings. Presumable axon terminals of these were slightly thicker than preterminal portions, running along periodontal collagen fibers and tapering within them. In light microscopic images, at least, they differed from the Ruffini endings which are commonly seen in rodents, displaying a glove-like configuration with extremely expanded tips. Under the electron microscope, however, the tree-like endings of the dog appeared similar to the Ruffini endings of rodents: their terminals were filled with mitochondria, covered with a cytoplasmic process of a Schwann cell, and surrounded by collagen fibers. These ultrastructural findings, combined with the results of previous physiological studies suggest that the nerve endings demonstrated in the present study can be identified as Ruffini endings. It is even stressed that the dog-type of Ruffini ending can be regarded as a representative of the sensory receptors in the mammalian periodontal ligament. In addition to these endings, knobbed endings, corpuscular (lamellated and glomerular) endings, and free nerve endings were rarely encountered in the periodontal ligament of incisors and canines of the dog.

Animals

Histochemical and immunohistochemical demonstration of macrophages and dendritic cells in the lingual periodontal ligament of rat incisors.

The distribution of macrophages in the lingual periodontal ligament of rat incisors was surveyed by histochemical and immunohistochemical methods. Numerous macrophages showing intense ACPase reactions were located primarily in the shear zone of the periodontal ligament. Immunostaining with an ED1-monoclonal antibody that recognizes various subpopulations of macrophages revealed plentiful positive cells showing flamelike profiles throughout the periodontal ligament, in addition to regular macrophages associated with sinusoidal blood vessels. A similar distribution of flamelike cells expressing Ia antigens was demonstrable with immunostaining using an OX6-monoclonal antibody. A consecutive staining of sections for ACPase histochemistry followed by immunoreactions for Ia antigens revealed the presence of two types of the flamelike cells in the periodontal ligament: one with and the other without distinct ACPase activity, corresponding to the macrophage and the dendritic cell, respectively. Either type of flamelike cells was located in the bone-related and shear zones, whereas only dendritic cells without ACPase activity were restricted to the tooth-related zone. OX6-immunonegative cells showing ACPase reactions were also found in the periphery of the sinusoidal blood vessels. Our data are the first to demonstrate the abundance of macrophages and dendritic cells expressing Ia antigens throughout the lingual periodontal ligament of rat incisors. In addition to regular macrophages, an exclusive localization of macrophages with flamelike extensions has been demonstrated in the bone-related and shear zones of the ligament. The region-specific arrangement of macrophages and dendritic cells with various histochemical and immunological features suggests that the periodontal ligament of rat incisor is a useful model for analyzing the process of differentiation of antigen-presenting cells.

Acid Phosphatase

Immunoelectron microscopic observation of calcitonin gene-related peptide (CGRP)-positive nerves in the dental pulp of rat molars.

The ultrastructure of nerves containing immunoreactivity for calcitonin gene-related peptide (CGRP) was investigated in the dental pulp of rat molars. The immunoreactivity was recognized predominantly in unmyelinated nerve fibers, and sparsely in a few myelinated fibers. It was localized throughout the axoplasm, as well as in the large cored vesicles. Small clear vesicles and mitochondria were free of the immunoreaction. The CGRP-immunoreactive nerves were frequently observed to terminate, being devoid of Schwann cell investment, in the vicinity of blood vessels in the coronal pulp, suggesting that CGRP may be involved in the regulation of pulpal blood flow. Moreover, CGRP-immunoreactive axon terminals containing numerous small clear vesicles, a few large cored vesicles and mitochondria were recognized in contact with the cell bodies of odontoblasts and their processes in the dentinal tubules. Although specialized synaptic ultrastructures were not recognizable, a functional association of CGRP nerves and odontoblasts was suggested. Thus, CGRP in the dental pulp appears to have multiple functions, including vascular regulation and sensory transduction.

Animals

[The experience of administration of 15-deoxyspergualin on rejection in kidney transplant recipients].

We report here the favorable results of clinical application of 15-deoxyspergualin (DSG) as a rescue therapy for rejection episodes in kidney transplant recipients. DSG was discovered in Japan and was proved to be a novel immunosuppressant in various animal transplantation models. The immunosuppressive mechanism of DSG is unclear yet, but its point of action is supposed to be in the early immuno response to allogeneic stimulation without the regulation of cytokine production. We performed the administration of DSG in fifteen patients, who had rejection episodes, with a dosage of 3 mg/kg/day or 5 mg/kg/day for five days by drip infusion. In the group of recipients who had rejection episodes within six months after kidney transplantation, DSG proved effective on six out of seven acute rejection episodes and induced favorable remission. And in the group of recipients who had rejection episodes after six months since kidney transplantation, DSG proved effective on all of ten rejection episodes. There was not a difference of effectiveness in respect to the dosage of DSG. The side effect of DSG treatment was mainly leukopenia but in most cases these leukopenia was remitted just under careful observation. Some patients complained the sense of abdominal discomfort. But so far, we did not encounter serious or critical side effects and complications during all the time of progression. Another benefit was that DSG was able to reverse the rejection episode even in the patient who had already treated with anti lymphocyte globulin and/or anti CD3 monoclonal antibody OKT3. We concluded that the administration of DSG as a rescue therapy was not accompanied by the serious side effects and was most effective against acute rejection after kidney transplantation.

Adult

Histochemical demonstration and microanalysis of possible calcium binding sites in the enamel organ of rat incisors.

The rat incisors obtained from rats perfused with high-calcium solution containing 30 to 50 mM CaCl2 were processed for rapid freeze/freeze-substitution and embedded in epoxy resin. GBHA staining, a histochemical staining for calcium, or unhydrously prepared sections revealed a large number of granular Ca-GBHA reactions in the enamel organ, most of which being located along the lateral plasma membranes of the ameloblasts. In the ameloblast layer, the reaction was negative in the presecretory stage, became intense in concert with the onset of enamel matrix formation, and remained so by the end of the transitional stage where the reaction gradually diminished. In the maturation stage, similar GBHA reactions emerged only in association with the smooth-ended ameloblasts and were absent in the ruffle-ended ameloblasts. Some granular reactions of much smaller diameter were occasionally noted in other cells of the enamel organ at both the secretory and maturation stages. Electron microscopy confirmed large electron-dense granules, each showing distinct peaks for Ca and P by microanalysis, associated with the cytoplasmic aspect of lateral plasma membranes of secretory, transitional, and smooth-ended ameloblasts. The present study thus revealed a strong calcium-binding property of the cytoplasmic aspect of lateral plasma membranes of secretory ameloblasts and its fluctuation in the maturation ameloblasts under the given experimental conditions. A necessity for an extensive analysis of membrane constituents of the enamel organ was proposed for better understanding of cellular roles in calcium regulation during amelogenesis.

Ameloblasts