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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 199 records · Page 11Linked to original sources
PubMed1997

Intracoronary administration of adenosine triphosphate increases myocardial adenosine levels and coronary blood flow in man.

Adenosine triphosphate (ATP) is reported to be released mainly from presynaptic vesicles and cardiomyocytes. The released ATP, which can be degraded to adenosine, may cause coronary vasodilation. However, there is no clear evidence that ATP is degraded to adenosine and causes coronary vasodilation in humans. The present study was undertaken to test whether intracoronary administration of ATP increases myocardial adenosine levels and coronary blood flow. In 11 patients, 3 doses of ATP (0.1, 0.2, and 0.4 mg) were injected into the left anterior descending coronary artery. The velocity of coronary blood flow was measured by Doppler flow probe, and the adenosine concentration in the coronary sinus blood was measured. We also continuously infused ATP (0.2 mg/min) for 1 min in another 10 patients. Coronary blood flow increased dose dependently soon after injection of ATP. Coronary arteriovenous differences in adenosine concentration increased [from 21 +/- 15 to 178 +/- 15 pmol/ml (p < 0.05) 10 sec after the injection of ATP (0.4 mg)] and there were marked reductions in both aortic blood pressure and heart rate. The adenosine levels returned to baseline 20 sec after the injection of ATP, and aortic blood pressure and heart rate also recovered, although coronary blood flow remained increased. Furthermore, continuous infusion of ATP for 1 min increased coronary blood flow velocity and coronary arteriovenous differences in adenosine concentration from 25 +/- 14 to 71 +/- 13 pmol/ml (p < 0.05) in 10 patients. These results indicate that intracoronary administration of ATP immediately increases coronary blood flow and the adenosine concentration of coronary venous blood, which returns to the baseline level thereafter. The differences in the time courses of increases in coronary venous adenosine levels and coronary blood flow after ATP injections suggest that vasodilatory mechanisms other than adenosine, eg, nitric oxide and prostaglandins, may also be involved in the ATP-induced coronary vasodilation. ATP may be used as a cardioprotective agent as well as adenosine.

Adenosine↗
PubMed1997

A histological investigation on tissue responses to titanium implants in cortical bone of the rat femur.

Implant materials are placed under various sites-including cortical bone, spongy bone, and bone marrow-at the same time according to the depth at implantation. Although cortical bone is an important site for the prognosis of implantation, detailed reports on tissue responses to implantation have been meager. The present study aims to reveal tissue responses to pure titanium implantation in rat femoris cortical bone. The rats received titanium bars surgically in their femurs and were sacrificed 1 day to 40 weeks post-implantation. The prepared tissue specimens were processed for light and transmission electron microscopy (TEM). Further histochemical detections were performed. One day post-implantation, empty osteocytic lacunae indicating degeneration of osteocytes were found in pre-existing cortical bone around the implant. Such pre-existing bone was replaced by new bone, but remained in part even 40 weeks post-implantation. Light microscopy showed that direct contact between the implant and new bone was identified 12 weeks post-implantation. Chronological and ultrastructural observation showed that new bone deposition appeared to proceed toward the implant, and that the intervening layer at the interface was derived from the degenerated debris of multinucleated giant cells and/or osteoblasts. Furthermore, it seemed that the width of intervening layer varied in relation to the distance from the blood vessels. The cells showing tartrate resistant acid phosphatase activity possessed cytological features of osteoclasts under TEM; they were frequently observed in perivascular sites near the implants even after osseointegration, suggesting that bone remodeling took place steadily around the implant.

Acid Phosphatase↗
PubMed1997

Efficient isolation of subacute sclerosing panencephalitis virus from patient brains by reference to magnetic resonance and computed tomographic images.

Subacute sclerosing panencephalitis virus has been isolated with difficulty from brains of infected patients. More strains are needed for the study of the pathogenesis of this virus. To make the isolation more efficient, we selected portions to be examined from the brains of three patients with reference to findings of repeated magnetic resonance and computed tomographic imaging. Three cell lines susceptible to measles virus field strains were used. In all three cases viruses were isolated most effectively from recent lesions and with Vero cells. Our results suggested that these imaging methods and Vero cells could be used for improvement in the efficiency of isolation of this virus from patient brains.

Adult↗
PubMed1997

[Proliferating character of inverted papilloma of the urinary bladder].

BACKGROUND: Inverted papilloma (IP) of the urinary bladder is generally considered to be a benign lesion by histological examination. In recent years, however, there have been several cases of IP simultaneously accompanied with transitional cell carcinoma (TCC), elsewhere in the bladder or combined as a single urothelial lesion. So we investigated proliferating character of IP by DNA ploidy analysis and immunohistostaining with proliferating cell nuclear antigen (PCNA). METHODS: Six cases of IP of the urinary bladder were analyzed and 12 cases of TCC of G1 and G3 grade were included in this study as a control. As DNA ploidy analysis, all specimens were feulgen stained using CAS DNA staining kit and examined by image cytometry (CAS 200R system). For the PCNA immunohistochemistry, all specimens were stained with anti-PCNA monoclonal antibody (Novocastra Lab.: PC10) according to ABC (avidin-biotin-complex) standard method. We determined that the DNA Index of the case under 1.20 was diploid and the others was aneuploid. PCNA staining were determined by only one pathologist as follows: negative (-) and positive (+), (2+) and (3+). RESULTS: As DNA ploidy, 5 of 6 cases of TCC G3 group as a control were aneuploid. But in spite of all cases of TCC G1 group were diploid, among IP cases, only 1 out of 6 was aneuploid. As PCNA staining, 2 of 6 in TCC G1 group and 5 of 6 in G3 group were positive. And it was noted examination was positive. CONCLUSION: There have been no recurrence since transurethral resection in all IP in the study including the case recognized as aneuploid and positive for PCNA staining. But the present results suggest that among IPs, considered generally as a benign tumor, the case which has high proliferating character exists.

Adult↗
PubMed1997

The Alternaria alternata Melanin Biosynthesis Gene Restores Appressorial Melanization and Penetration of Cellulose Membranes in the Melanin-Deficient Albino Mutant of Colletotrichum lagenarium

Colletotrichum lagenarium and Alternaria alternata produce a dark pigment, melanin. The C. lagenarium PKS1 and A. alternata ALM genes are involved in polyketide synthesis in the melanin biosynthesis pathway. PKS1 encodes a type I polyketide synthase. For functional comparison of the ALM gene with the PKS1 gene, we examined whether the A. alternata ALM gene could restore melanin synthesis in C. lagenarium albino mutant (Pks1(-)). The ALM gene transformed the albino mutant (Pks1(-)) to melanin-producing phenotypes, designated CAL transformants. The pigment intensity of both melanized colonies and appressoria of CAL transformants was weaker than that of the wild type. Ultrastructural studies of the cell walls of appressoria demonstrated that CAL transformants formed an outer melanized layer, as did the wild type. On the other hand, the thin inner and middle layers were less electron-dense than those of the wild type. CAL transformants were able to penetrate cellulose membranes as effectively as the wild type. By contrast, the penetration frequency of CAL transformants on cucumber cotyledons was remarkably reduced compared to that of the wild type. During conidial germination, the PKS1 transcript accumulated de novo in both the wild-type and CAL transformants after the start of conidial incubation. On the other hand, ALM transcript accumulated in conidia of CAL transformants before the start of conidial incubation.

Journal Article↗
PubMed1997

The Alternaria alternata melanin biosynthesis gene restores appressorial melanization and penetration of cellulose membranes in the melanin-deficient albino mutant of Colletotrichum lagenarium.

Colletotrichum lagenarium and Alternaria alternata produce a dark pigment, melanin. The C. lagenarium PKS1 and A. alternata ALM genes are involved in polyketide synthesis in the melanin biosynthesis pathway. PKS1 encodes a type 1 polyketide synthase. For functional comparison of the ALM gene with the PKS1 gene, we examined whether the A. alternata ALM gene could restore melanin synthesis in C. lagenarium albino mutant (Pks1-). The ALM gene transformed the albino mutant (Pks1-) to melanin-producing phenotypes, designated CAL transformants. The pigment intensity of both melanized colonies and appressoria of CAL transformants was weaker than that of the wild type. Ultrastructural studies of the cell walls of appressoria demonstrated that CAL transformants formed an outer melanized layer, as did the wild type. On the other hand, the thin inner and middle layers were less electron-dense than those of the wild type. CAL transformants were able to penetrate cellulose membranes as effectively as the wild type. By contrast, the penetration frequency of CAL transformants on cucumber cotyledons was remarkably reduced compared to that of the wild type. During conidial germination, the PKS1 transcript accumulated de novo in both the wild-type and CAL transformants after the start of conidial incubation. On the other hand, ALM transcript accumulated in conidia of CAL transformants before the start of conidial incubation.

Alternaria↗
PubMed1997

Prognostic value of Ki-67 for recurrence and progression of superficial bladder cancer.

PURPOSE: We retrospectively reviewed 104 cases of superficial bladder cancer to ascertain whether the Ki-67 labeling index predicts recurrence and progression. MATERIALS AND METHODS: Archival specimens from superficial bladder cancer cases were immunostained with Ki-67. RESULTS: The recurrence rate was significantly higher in cases with a Ki-67 labeling index of 5.35 or greater than in those with a value less than 5.35 (p < 0.001). The recurrence rate at 2 years was 70% in cases with a Ki-67 labeling index of 5.35 or greater and 22% in those with an index less than 5.35 (p < 0.001). Using multivariate analysis the index predicted recurrence of bladder cancer (p < 0.005). Median Ki-67 labeling index in cases with progression was significantly higher than in those without progression (p < 0.01). CONCLUSIONS: The Ki-67 labeling index is an independent predictive factor for recurrence of superficial bladder cancer.

Adult↗
PubMed1997

Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid.

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly, we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (> or = 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (> or = 0.01 mg/kg). Also, it was slightly uterotrophic (> or = 1 mg/kg) with very low binding affinity for oestrogen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

Animals↗
PubMed1997

[Hyperalgesia induced by intrathecal administration of nitroglycerin involves NMDA receptor activation in the spinal cord].

Spinal NMDA receptors are involved in hyperalgesia and chronic pain. The activation of spinal NMDA receptor results in the production of nitric oxide in the second order neurons in the spinal cord dorsal horn. We investigated the effects of intrathecally administered nitroglycerin (NTG) which releases nitric oxide in the cell. Formalin test which reflects phasic and tonic nociception was used as a nociceptive measure in rats with chronically implanted intrathecal catheters. Intrathecal injection of NTG resulted in the increase of flinching behavior induced by formalin injection to one paw in phase 1 (phasic) and phase 2 (tonic) responses in a dose-dependent manner. Intrathecally administered NMDA antagonist, MK-801 (MK) dose-dependently inhibited the effect of NTG but the effect was significant only in the phase 2 of the formalin test. MK given after formalin injection had significantly less effect on the phase 2 response. L-NAME (NOS inhibitor), MB (guanylate cyclase inhibitor) and HB (nitric oxide scavenger) significantly antagonized the hyperalgesic effect of NTG in the phase 2 of the formalin test. These results show that nitric oxide plays an important role in producing hyperalgesia in the spinal cord acting postsynaptically as well as pre-synaptically.

Animals↗
PubMed1996

Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular nucleus.

Studies were performed on the central antidiuretic actions via the tachykinin NK-3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections of the selective tachykinin NK-3 receptor agonist senktide (2-200 pmol) into the PVN resulted in prolonged inhibition of urine output in water-loaded rats, its effect being dose-dependent. The antidiuretic action of senktide was blocked by pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg, i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the magnocellular part of the PVN and the supraoptic nucleus (SON) of the hypothalamus as detected by in situ hybridization histochemistry. Moreover, [3H]senktide binding sites were also detected in the PVN and the SON by receptor autoradiography. These findings suggest that NK-3 receptors in the PVN may be involved in water regulation by stimulation of vasopressin secretion from the posterior pituitary gland, and that vasopressin caused water reabsorbtion via the kidney V2 receptor.

Angiotensin Receptor Antagonists↗
PubMed1996

Occurrence of amorphous and crystalline mineral deposits at the epithelial-mesenchymal interface of incisors in the calcium-loaded rat: implication of novel calcium binding domains.

BACKGROUND: In order to clarify the regulatory factors that promote precipitation of enamel crystals in mammalian tooth germs, possible calcium binding domains were visualized at the epithelial-mesenchymal interface of rat incisor teeth by means of electron microscopy and X-ray microanalysis. METHODS: Adult rats were loaded with calcium (30 mM Ca) by vascular perfusion and further loaded through fixation and dehydration in the presence of high doses of calcium. RESULTS: Electron microscopy of anhydrously prepared Epon sections of the calcium-loaded rat incisors revealed numerous electron-dense granular deposits, enriched with calcium and phosphorus, scattering in the fibrous mantle dentin matrix and the intercellular spaces of the inner enamel epithelium, but not in the pulp tissues including the odontoblastic cells layer. The electron-dense deposits were specific for the enamel-related portion and were never shown to occur in the cementum-related portion. Proceeding incisally, dense deposits in both the mantle dentin matrix and presecretory ameloblast layer gradually converted to fine needlelike figures resembling the early enamel crystallites. Mineral deposits in experimental rats disappeared concomitant with the onset of normal mineralization of mantle dentin. There was no spatial correlation between the dense deposits and either stippled material or matrix vesicles. CONCLUSIONS: These results indicate the presence of novel calcium-binding domains in the enamel-related portion of the epithelial-mesenchymal interface of rat incisors that form enamellike crystallites under calcium-loaded conditions. A contribution of these putative calcium-binding domains in the induction and spontaneous formation of enamel crystals is suggested.

Animals↗
PubMed1996

Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats.

Intermittent treatment with human parathyroid hormone (1-34) [hPTH(1-34)] stimulates bone formation and increases cancellous bone mass in ovariectomized (OVX) rats. But PTH-induced cancellous bone rapidly disappears upon cessation of treatment. The fate of cortical bone treated by PTH has not been well characterized. Incadronate disodium (disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) was expected to be antiresorptive without inhibiting bone formation. The purposes of this study were to determine (1) whether PTH treatment increases new cancellous and cortical bone mass and bone formation, (2) whether the new bone could be maintained by YM175 sequential treatment, and (3) whether the maintenance effect is persistent after YM175 withdrawal. Eighty-eight 11-week-old Sprague-Dawley rats were divided into sham operation and OVX groups. The OVX rats were treated for 8 weeks with the subcutaneous intermittent injection of 30 micrograms/kg of hPTH(1-34) three times a week beginning 4 weeks after surgery, then PTH treatment was withdrawn and YM175 (10 micrograms/kg) was injected subcutaneously three times a week for 4 weeks. YM175 treatment was withdrawn for the last 8 weeks of the protocol. The results of microstructural assessment in proximal tibial metaphysis and bone mineral density in distal and proximal femur demonstrated that PTH treatment for 8 weeks restored bone mass to the sham control level. However, after cessation of PTH treatment, the PTH-induced tibial cancellous bone mass showed a decrease at 4 weeks and almost totally disappeared after 12 weeks. Conversely, YM175 treatment maintained the PTH-induced tibial cancellous bone mass, and the bone continued to be maintained after 8 weeks of withdrawal of the YM175. Cortical bone was not lost during PTH treatment. YM175 maintained the PTH-induced new tibial cancellous bone in OVX rats by suppressing remodeling.

Animals↗
PubMed1996

Mineral anisotropy in mineralized tissues is similar among species and mineral growth occurs independently of collagen orientation in rats: results from acoustic velocity measurements.

It has been reported that the mineral crystals in long bones have their c-axis aligned with the bone axis, presumably because collagen fibrils in bone also align with the bone axis. However, the predominant collagen orientation in bone often does not appear to be aligned with the mineral crystals, especially in rat primary bone. We hypothesized that mineral orientation in bone is not necessarily related to collagen orientation. An acoustic microscope was used to measure elastic constants of mineralized tissues from rat, cow, monkey, and human bone, and mineralized turkey leg tendon (MTLT). Measurements were made before and after demineralization with 10% ethylenediaminetetraacetic acid (EDTA) or decollagenization with 7% sodium hypochlorite. The elastic anisotropy ratio (AR) was defined as the ratio of the elastic coefficient in the longitudinal direction to the elastic coefficient in the transverse direction. Anisotropy ratios of mineralized tissues were not affected by formalin fixation or plastic embedding. An evaluation of tissues from the different species showed that the AR after decollagenization was not significantly different (p > 0.4, analysis of variance) among the groups, while AR after demineralization varied from 1.04 (rat bone) to 1.51 (MTLT). There was no correlation between AR after demineralization and AR after decollagenization (r = 0.13, p = 0.5). This showed that the elastic anisotropy of collagen is more variable than mineral anisotropy in bone and MTLT. Another experiment showed that mineralization of turkey leg tendon changes the elasticity of the collagen matrix, making it less anisotropic. A final, prospective experiment was performed in which tibiae of rats were subjected to mechanical loading for 16 weeks. After 12 days, new periosteal woven bone was observed on the tibiae and, after 16 weeks, this new bone was consolidated and mineralized. Mineral in the newly formed woven bone was virtually isotropic (AR = 1.07) after 12 days of loading, then became more anisotropic (AR = 1.52) after 16 weeks of mechanical loading, as the mineral density of the new bone increased. This increase in anisotropy of bone mineral occurred even though the collagen matrix was woven and had no measureable fibril orientation. We conclude that (1) collagen anisotropy and mineral anisotropy are not necessarily correlated in mineralized tissues, (2) mineralization can affect the collagen matrix elasticity of mineralized tissues, and (3) an organized mineral structure can form in the absence of an organized collagen matrix.

Acoustics↗
PubMed1996

Bcl-2 expression and allelic loss of the p53 gene in gastric carcinomas.

In order to clarify the association between bcl-2 protein (Bcl-2) expression and genetic alteration, we investigated p53 and DCC (deleted in the colon carcinoma gene locus) gene abnormalities in Bcl-2-positive and -negative gastric carcinomas using a polymerase chain reaction/loss of heterozygosity (LOH) assay. Bcl-2 immunoreactivity was found in 25 of 178 (14%) gastric carcinoma cases. With these 25 positive cases, the proportion 18/87 (20.6%) of the total in early stages demonstrating invasion of the mucosa and/or submucosa was significantly greater (P = 0.013) than the 7/91 (7.7%) found for advanced tumors exhibiting invasion into or through the muscularis propria. However, there was no statistically significant variation between the proportions for differentiated (17/98 cases, 17.3%) and undifferentiated (8/80 cases, 10%) lesions. Sixteen Bcl-2-positive cases (9 cases were not studied because of insufficient specimen material to allow extraction of DNA) and 31 cases randomly selected from a Bcl-2-negative group were analyzed for the presence of p53-LOH or DCC-LOH and for p53 by immuno-histochemistry. The minority of the Bcl-2-positive group had p53-LOH and were immunopositive for p53 (P = 0.033, P = 0.028 respectively), while no association was found in the Bcl-2-negative category. In contrast, there was no correlation at all between Bcl-2 expression and DCC-LOH although the number of informative cases analyzed was too small to allow definite conclusions. These results indicate that Bcl-2 may be predominantly expressed at an early stage in gastric carcinomas, possibly in negative association with p53 gene abnormalities.

Alleles↗
PubMed1996

Apoptosis of colon cancer: comparison with Ki-67 proliferative activity and expression of p53.

The role of apoptosis in colon cancer was investigated in terms of control of growth and expression on p53, using the nick-ended-DNA labelling method and immunohistochemistry. The apoptotic labeling index was highest in the T1 stage (24 cases), as was the proliferative activity, assessed in terms of the Ki-67 labeling index. Both labeling indices demonstrated similar overall incidence curves for the total 95 colon cancer cases, and examination of individual cases revealed a statistically significant correlation (P=0.01). However, neither index had any relation to p53. The results thus suggest that apoptosis in colon cancers has a linkage with proliferative activity that can be assessed by Ki-67 labeling, but is not regulated by the p53 system. This might contribute to the diversity of colon cancer growth.

Apoptosis↗
PubMed1996

Three-dimensional arrangement of enamel prisms and their relation to the formation of Hunter-Schreger bands in dog tooth.

The three-dimensional architecture of enamel prisms and their relationship to Hunter-Schreger bands were examined in the developing enamel of several dog teeth by light and electron microscopy, and computer-assisted reconstruction. Sections were prepared from a single demineralized tooth germ. Longitudinal semithin sections parallel to the meridian of the tooth showed parazones and diazones of the Hunter-Schreger bands in alternate rows at equal intervals. On sections vertical to the tooth crown through the middle region of parazone or diazone, a row of parallel prisms were angulated with the largest tilting angle being 55 degrees to the enamel-dentin junction, running in opposite directions in the respective zones. Tangential sections parallel to the enamel-dentin junction showed numerous belt-like zones arranged perpendicular to the meridian of the tooth. Each belt-like zone consisted of a group of enamel prisms oriented in the same direction, those in the neighboring zones being oriented in an opposite direction. The densely stained boundaries between the adjacent belt-like zones corresponded to the interface between parazone and diazone. Computer-reconstructed enamel prisms in the adjacent two zones were oriented in the opposite sidewards direction with occasional confluence and divergence. Scanning electron-microscopic observation of the developing enamel surface exposed by dissolution of the enamel organ revealed band-like arrangements of groups of pits encasing the Tomes' processes of secretory ameloblasts. The secretory faces of the pits inclined uniformly in the same sidewards direction, with those in the neighboring groups, in the opposite direction.

Animals↗
PubMed1996

Bone mineral lies mainly outside collagen fibrils: predictions of a composite model for osteonal bone.

We propose that the elastic properties of osteonal bone can be modeled accurately as a simple fiber-reinforced composite, provided that accurate properties for the mineral and collagen phases of the ultrastructure are available. Off-axis stiffness coefficients were measured in anterior quadrant of canine femora at 10 degrees increments from longitudinal to transverse direction using an acoustic microscope. The resolution of these measurements was about 60 microns or less than the radius of one osteon. The bone specimens were subsequently demineralized and the off-axis measurements were repeated to determine the elasticity of bone collagen. Bone collagen fibrils were not principally aligned along the long axis of the bone, but demonstrated an alignment that was 30 degrees from the long axis. A simple composite model was developed based on the experimental data. The model that best fit experimental data assumed that (1) bone collagen was aligned 30 degrees from the long axis of the bone, (2) 75% of mineral crystals reside outside of collagen fibrils, and (3) mineral crystals outside of collagen fibrils have their c-axis in the longitudinal direction.

Acoustics↗