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Biomedical subjects

K Hayashi

Publications and source records attributed to K Hayashi.

At least 217 records · Page 12Linked to original sources
PubMed2001

Divergent renal vasodilator action of L- and T-type calcium antagonists in vivo.

OBJECTIVE: To assess the in-vivo action on the renal microvasculature of the calcium antagonists nifedipine (L-type blocker), efonidipine (L/T-type blocker), and mibefradil (predominant T-type blocker). DESIGN: An intravital needle-type charge-coupled device (CCD) camera videomicroscope was introduced to visualize the renal microcirculation directly in vivo. METHODS: In anesthetized mongrel dogs, nifedipine (0.01-1 mg/kg per min), efonidipine (0.033-0.33 mg/kg per min), or mibefradil (0.01-1 mg/kg per min) was infused intravenously after the insertion of a CCD probe into the kidney. Renal microvascular responses to calcium antagonists were directly evaluated, with concomitant observation of renal clearance. RESULTS: Each calcium antagonist caused modest vasodepressor action without affecting heart rate. Nifedipine (1 mg/kg per min, n = 9) increased renal plasma flow (RPF) (14 +/- 4%, P < 0.05) and glomerular filtration rate (GFR) (19 +/- 5%, P < 0.05), and tended to increase the filtration fraction (5 +/- 2% increment, P = 0.07). Efonidipine (0.33 mg/kg per min, n = 9), however, had no effect on filtration fraction, with 14 +/- 6% increments in RPF (P < 0.05) and 14 +/- 7% increments in GFR (P = 0.08). Rather, mibefradil (1 mg/kg per min, n = 9) elicited 6 +/- 2% decreases in filtration fraction (P < 0.05), with slight increments in RPF (6 +/- 3%) and no changes in GFR. In direct in-vivo microvasculature observations, nifedipine caused predominant (22 +/- 2%) dilatation of afferent arterioles (from 15.5 +/- 0.4 to 18.9 +/- 0.4 microm, n = 5), compared with that of efferent arterioles (10 +/- 2%; from 11.0 +/- 0.4 to 12.1 +/- 0.3 microm). In contrast, efonidipine caused a similar magnitude of vasodilatation (16 +/- 4%) compared with 18 +/- 2%; n = 6), and mibefradil caused greater dilatation of efferent arterioles (20 +/- 4%, n = 7) than that of afferent arterioles (13 +/- 4%). CONCLUSIONS: There exists marked heterogeneity in action of nifedipine, efonidipine and mibefradil on the renal microvascular in canine kidneys in vivo. Furthermore, our current observations suggest an important contribution of T-type calcium channel activity to efferent arteriolar tone in vivo.

Animals↗
PubMed2001

Increased uptake of 99Tcm-ethyl cysteinate dimer in patients with brain tumours.

We performed 229 99Tcm-ethyl cysteinate dimer (ECD) single photon emission tomography (SPET) studies in 185 patients with brain tumour. Increased uptake of the tracer was observed in 11 cases. In six of these 11 patients, focal intense activity was seen in the area surrounding the tumour. Five of these six patients had episodes of seizure, and ictal SPET showed further increased uptake in the area of hyperperfusion in one patient. Hyperperfusion surrounding the tumour might be related to seizure. In the remaining five patients, increased accumulation was seen in the tumour. Three of these five patients had a discrepancy between 99Tcm-ECD SPET and 201Tl SPET imaging. There could be some difference in the mechanism of accumulation in the tumour between 99Tcm-ECD and 201Tl.

Adolescent↗
PubMed2001

Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines.

Expression of retinoic acid receptor beta (RARbeta) is reported to be absent or down-regulated in oral squamous cell carcinomas. Recently, we found that the growth-inhibitory effect of 9-cis-retinoic acid (9CRA) on oral squamous cell carcinoma may depend on the expression levels of endogenous RARbeta. In order to clarify the role of RARbeta in growth and differentiation, we transfected RARbeta expression vector into oral squamous carcinoma cell lines, HSC-4 and Ho-1-N-1. Both RARbeta-transfected cell lines displayed growth inhibition. Moreover, RARbeta-transfected clones underwent morphological changes, and RARbeta-transfected HSC-4 clones underwent apoptosis even in the absence of 9CRA treatment. In contrast, RARbeta-transfected Ho-1-N-1 clones exhibited cell cycle arrest without undergoing apoptosis initially; however, apoptosis was induced in these cells after 6 days of 9CRA treatment. RARalpha and RARgamma expression was reduced at both the protein and mRNA levels in RARbeta transfectants, whereas the expression of retinoid X receptor alpha (RXRalpha) was not altered. RARb transfectants exhibited alterations in the levels of cell cycle-associated proteins, histone acetyltransferase (HAT) and apoptosis-associated proteins. After 6 days of 9CRA treatment, RARbeta transfectants overexpressed Waf1 / Cip1 / Sdi1 / p21, Kip1 / p27, chk1, p300 / CBP, BAX, Bak, Apaf 1, caspase 3 and caspase 9. Conversely, E2F1, cdc25B and HDAC1 were down-regulated in these transfectants. In addition, histone H4 acetylation was induced in RARb transfectants. These findings suggest that histone acetylation mediated by histone acetyltransferase and p300 / CBP may play a role in the growth arrest and apoptosis induced by RARbeta transfection in oral squamous cell carcinoma.

Alitretinoin↗
PubMed2001

Short-Term biomechanical adaptation of the rat carotid to acute hypertension: contribution of smooth muscle.

The biomechanical adaptation of the arterial wall to hypertension has been studied extensively in recent years; however, the exact biomechanical contribution of vascular smooth muscle cells (VSMCs) during the adaptation process in conduit vessels is not known. We induced hypertension in 8 wk old Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased from 92 +/- 2 (mean +/- SE) mm Hg to approximately 150 mmHg. Rats were sacrificed 2, 4, and 8 d after surgery and the left common carotid artery was excised for analysis. Wall thickness increased by 18% in 8 d and the opening angle by 32% in 4 d. The elastic properties were measured under normal VSMC tone (i.e., the amount of VSMC tone under normal conditions also called basal VSMC tone or normal resting VSMC tone), under maximally contracted VSMC (NE, 5 x 10(-7) mol/L) and under totally relaxed VSMC conditions (papaverine, 10(-4) mol/L). The most pronounced modifications were the changes in elastic properties related to normal VSMC tone. The functional contraction ratio at 100 mm Hg, defined as the relative contraction under normal conditions (normal VSMC tone), increased by 439% 4 d after the induction of hypertension. The total contraction capacity of the VSMC increased by 38% within 8 d. The changes in normal VSMC tone led to important changes in the mechanical properties of the arterial wall. Under normal VSMC conditions, compliance at mean pressure (148 mm Hg) increased by 159% within 8 d, whereas in the absence of VSMC tone, compliance did not increase significantly. We conclude that in conduit vessels, the VSMC, which is the sensing and effecting element of the adaptation process, is subjected to large-scale changes during the early phase of arterial adaptation to acute hypertension.

Adaptation, Physiological↗
PubMed2001

Anterior capsule contraction and intraocular lens decentration and tilt after hydrogel lens implantation.

AIM: To prospectively investigate changes in the area of the anterior capsule opening, and intraocular lens (IOL) decentration and tilt after implantation of a hydrogel IOL. METHODS: 100 patients underwent implantation of a hydrogel IOL in one eye and an acrylic IOL implantation in the opposite eye. The area of the anterior capsule opening, and the degree of IOL decentration and tilt were measured using the Scheimpflug videophotography system at 3 days, and at 1, 3, and 6 months postoperatively. RESULTS: The mean anterior capsule opening area decreased significantly in both groups. At 6 months postoperatively, the area in the hydrogel group was significantly smaller than that in the acrylic group. The mean percentage of the area reduction in the hydrogel group was also significantly greater than that in the acrylic group, being 16.9% in the hydrogel group and 8.8% in the acrylic group. In contrast, IOL decentration and tilt did not progress in either group. No significant differences were found in the degree of IOL decentration and tilt throughout the follow up period. CONCLUSIONS: Contraction of the anterior capsule opening was more extensive with the hydrogel IOL than with the acrylic IOL, but the degree of IOL decentration and tilt were similar for the two types of lenses studied.

Acrylic Resins↗
PubMed2001

Interferon responsiveness in patients infected with hepatitis C virus 1b differs depending on viral subtype.

BACKGROUND: Genotype 1b of hepatitis C virus (HCV) comprises mainly three subtypes, each named for its geographic prevalence (worldwide, W; Japan, J; and not in Japan, NJ). AIM: To characterise the newly identified subtypes of genotype 1b and to review factors associated with response to interferon (IFN) for each subtype. PATIENTS: Chronic hepatitis patients (80 men and 41 women; mean age 48.5 years, range 20.7--69.3) with HCV genotype 1b (W type, n=41; J type, n=38) or genotype 2a (n=42) were treated according to the same IFN protocol. Forty four patients (36.4%) negative for serum HCV RNA six months after cessation of treatment were considered complete responders. METHODS: Factors associated with complete response were investigated. RESULTS: Genotype 2a patients had lower viral loads (odds ratio 0.11 (95% confidence intervals (CI) 0.049--0.256)) and a better IFN response (odds ratio 0.25 (95% CI 0.117--0.552)) than genotype 1b patients whereas W type and J type patients had similar viral loads and responses to IFN. IFN response in W type patients was associated with female sex (odds ratio 0.23 (95% CI 0.055--0.983)) and low viral load (odds ratio 84.00 (95% CI 14.04--502.6)) whereas response in J type patients was related to transfusion history (odds ratio 7.20 (95% CI 1.443--35.91)), low viral load (odds ratio 117.0 (95% CI 17.82--768.3)), and genetic mutation in the interferon sensitivity determining region of the virus (odds ratio 0.08 (95% CI 0.013--0.553)). Multivariate analysis found low viral load (odds ratio 64.19 (95% CI 14.66--281.06)) to be the only significant independent factor associated with IFN response. CONCLUSIONS: Factors associated with IFN responsiveness in HCV infection differ with viral subtype.

Adult↗
PubMed2001

Model of geometrical and smooth muscle tone adaptation of carotid artery subject to step change in pressure.

Recent experimental studies have shown significant alterations of the vascular smooth muscle (VSM) tone when an artery is subjected to an elevation in pressure. Therefore, the VSM participates in the adaptation process not only by means of its synthetic activity (fibronectins and collagen) or proliferative activity (hypertrophy and hyperplasia) but also by adjusting its contractile properties and its tone level. In previous theoretical models describing the time evolution of the arterial wall adaptation in response to induced hypertension, the contribution of VSM tone has been neglected. In this study, we propose a new biomechanical model for the wall adaptation to induced hypertension, including changes in VSM tone. On the basis of Hill's model, total circumferential stress is separated into its passive and active components, the active part being the stress developed by the VSM. Adaptation rate equations describe the geometrical adaptation (wall thickening) and the adaptation of active stress (VSM tone). The evolution curves that are derived from the theoretical model fit well the experimental data describing the adaptation of the rat common carotid subjected to a step increase in pressure. This leads to the identification of the model parameters and time constants by characterizing the rapidity of the adaptation processes. The agreement between the results of this simple theoretical model and the experimental data suggests that the theoretical approach used here may appropriately account for the biomechanics underlying the arterial wall adaptation.

Adaptation, Physiological↗
PubMed2001

Effect of steroid-liposome on immunohistopathology of IgA nephropathy in ddY mice.

Immunopathological studies were performed to determine whether glomerular injuries in ddY mice, a spontaneous animal model for IgA nephropathy, are influenced by treatment with a newly developed liposome loaded with prednisolone phosphate (PSL-liposome). The newly synthesized novel cationic lipid 3,6-dipentadeciroxy-1-amizino-benzene (TRX-20) was employed to obtain selective affinity to the anionic cell surface and extracellular matrices in glomerular mesangial lesions. ddY mice were treated intravenously with 1.0 mg/kg of PSL-liposome once a week for 16 weeks (from 45 weeks to 61 weeks of age). ddY mice were also intravenously treated with 1.0 mg/kg of ordinary PSL once a week for the same duration. On immunofluorescence, depositions of IgA and C3 in the glomerular mesangial areas and capillary walls of PSL-liposome-treated ddY mice were markedly decreased as compared with those of ordinary PSL-treated and untreated control ddY mice. The mean intensity of IgA and C3 in glomeruli of PSL-liposome-treated ddY mice was decreased as compared with that in ordinary PSL-treated and untreated control ddY mice. Glomerular mesangial expansion in PSL-liposome-treated ddY mice was milder than that found in ordinary PSL-treated ddY mice or untreated control ddY mice. It appears that treatment with PSL-liposome is effective in improving glomerular IgA and C3 depositions and glomerular expansion in IgA nephropathy of ddY mice.

Animals↗
PubMed2001

Effect of the dose and duration of interferon-alpha therapy on the incidence of hepatocellular carcinoma in noncirrhotic patients with a nonsustained response to interferon for chronic hepatitis C.

OBJECTIVE: We evaluated the effect of dose and duration of treatment with interferon (IFN)-alpha on the incidence of hepatocellular carcinoma (HCC) after IFN treatment in patients with chronic hepatitis C. METHODS: A total of 291 noncirrhotic patients with chronic hepatitis C without hepatitis B virus coinfection in whom hepatitis C virus (HCV) was not eradicated by IFN-alpha therapy were retrospectively analyzed. The incidence of HCC after IFN therapy was compared according to the total dose or duration of treatment. RESULTS: Patients were followed up for 6-117 months after the end of IFN treatment. The duration of IFN treatment (< or =24 vs. >24 weeks) had no effect on the incidence of HCC. However, the incidence of HCC was significantly lower in patients who received >500 million units of IFN as a total dose than in patients who received < or =500 million units of IFN (p = 0.0480), and the total dose of IFN (>500 million units) was an independent factor affecting the incidence of HCC (p = 0.0405). In addition, when focusing on patients whose histology was F2 or F3 before IFN treatment, the suppressive effect of the total dose of IFN (>500 million units) was emphasized (p = 0.0049 in generalized Wilcoxon test and p = 0.0178 in multivariate analysis). CONCLUSIONS: Patients with chronic hepatitis C should receive more than 500 million units of IFN when IFN is used to decrease the incidence of subsequent HCC.

Adolescent↗
PubMed2001

Effect of T-type selective calcium antagonist on renal microcirculation: studies in the isolated perfused hydronephrotic kidney.

Although calcium antagonists exert preferential vasodilation of renal afferent arterioles, we have recently demonstrated that nilvadipine and efonidipine, possessing both L-type and T-type calcium channel blocking action, reverse the angiotensin (Ang) II-induced afferent and efferent arteriolar constriction. In the present study, we investigated the role of T-type calcium channels in mediating the Ang II-induced efferent arteriolar tone using the selective T-type calcium channel blocker mibefradil. Isolated perfused hydronephrotic rat kidneys were used for direct visualization of renal microcirculation. Administration of Ang II (0.3 nmol/L) caused marked constriction of afferent (from 13.5+/-0.6 to 9.2+/-0.6 microm, P<0.01, n=6) and efferent (from 11.5+/-1.0 to 7.4+/-0.7 microm, P<0.01, n=5) arterioles. Mibefradil (1 micromol/L) dilated both vessels, with 82+/-11% and 72+/-7% reversal of afferent and efferent arterioles, respectively. Similarly, nickel chloride (100 micromol/L) caused dilation of both arterioles, similar in magnitude in afferent (68+/-10%, n=7) and efferent (80+/-7%, n=7) arterioles. To eliminate the possibility that the mibefradil-induced dilation was mediated by L-type channel blockade, mibefradil was administered in the presence of nifedipine (1 micromol/L). Thus, nifedipine caused modest efferent arteriolar dilation (30+/-6% reversal, n=9), and subsequent addition of mibefradil elicited further dilation of this vessel (80+/-4%, P<0.01 versus nifedipine). Furthermore, mibefradil reversed the Ang II-induced efferent arteriolar constriction even in the presence of nifedipine and phentolamine. These findings demonstrate that T-type calcium antagonists markedly dilate the Ang II-induced efferent arteriolar constriction, but the action is not mediated by inhibition of catecholamine release. This potent activity would contribute to the efferent arteriolar response to nilvadipine and efonidipine and may offer benefit in light of glomerular hemodynamics.

Angiotensin II↗
PubMed2001

Characterization of inhibitory action of concanamycins against herpes simplex virus.

Concanamycins A (Conmy A) and B (Conmy B), well-known inhibitors of the vacuolar proton-ATPase, were isolated from the culture broth of Streptomyces sp. strain FK51 as antiherpetic agents. These compounds showed potent inhibition of herpes simplex virus type 1 (HSV-1) replication in an in vitro assay system, having antiviral activities with 50% inhibitory concentrations of 0.072 and 0.51 ng/ml for Conmy A and Conmy B, respectively. While the attachment of HSV-1 to Vero cells was not inhibited, both of the compounds blocked the penetration of virus into host cells. When added to the late stages of virus replication, the concanamycins also exerted marked inhibitory effects on the production of viruses. Release of progeny viruses was found to be suppressed by the agents. SDS-PAGE analysis of isotope-labelled HSV-specific proteins revealed that the synthesis of beta proteins was moderately inhibited and some of the glycoproteins were synthesized with reduced molecular weights. Western blot analysis using antibodies against two HSV-specific glycoproteins (gC and gD) showed differences in their syntheses between untreated and Conmy A-treated cells. Syncytium formation by HSV-1 strain HF was inhibited, and small plaques with rounded cells were formed in Conmy A-treated cell cultures. When wild-type HSV-1 was serially propagated under the selective pressure of Conmy A, and the resulting progeny viruses were grown in drug-free medium, their plaque morphology of syncytium and sensitivity to Conmy A were the same as those of parent virus. From these findings, antiherpetic activities of Conmy A and B might be mainly dependent on their activities as vacuolar proton-ATPase inhibitors with intracellular translocation of glycoproteins and the inhibition of the maturation of virus glycoproteins.

Adsorption↗
PubMed2001

Strategy for the treatment of inaccessible unruptured giant and large aneurysms of the internal carotid artery.

Our goal was to clarify the optimum management of the inaccessible unruptured giant and large aneurysms of the internal carotid artery (ICA). Since 1981, we have treated 18 patients with unclippable unruptured giant or large aneurysms of the ICA. Aneurysms were classified as either intracavernous or intradural. We performed proximal carotid occlusion in 12 patients and conservatively treated six patients. We retrospectively analyzed long-term outcomes in these patients. Four of seven patients with intradural aneurysm underwent proximal carotid occlusion, with good long-term outcomes. The three patients with intradural aneurysm, who were treated conservatively, died of subarachnoid hemorrhage. Eight of 11 patients with intracavernous aneurysm underwent proximal carotid occlusion, one dying of massive nasal bleeding 25 months after the procedure. In this case, the aneurysm was partially thrombosed, and residual lumen growth was revealed 22 months after proximal carotid occlusion. Cranial nerve paresis improved in five of the eight patients (63%), and two patients had a minor ischemic attack. Neurological problems failed to occur in the three patients with intracavernous aneurysm who were treated conservatively. The risk of rupture is relatively high in intradural giant and large aneurysms. Proximal carotid occlusion can effectively prevent bleeding from intradural aneurysms. Aggressive management is justified for intradural aneurysms with poor collateral circulation. Operative procedures in the management of an intracavernous aneurysm require careful consideration.

Aged↗
PubMed2001

N-acetylcysteine inhibited nuclear factor-kappaB expression and the intimal hyperplasia in rat carotid arterial injury.

Neointima formation associated with vascular restenosis is a complex local inflammatory process actively involving the vascular smooth muscle cell (SMC) proliferation. Nuclear factor-kappaB (NF-kappaB) is a transactivator of a diverse group of genes whose activation has been strongly associated with the cellular response to inflammation. Since anti-oxidant N-acetylcysteine (NAC) inhibit NF-kappaB activity in vascular SMC in vitro, we examined the in vivo effect of the NAC on balloon-induced neointimal formation in the carotid artery of rats. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. One group of these rats (n = 9) were treated with daily intraperitoneal injection of NAC (200 mg kg(-1)) for 14 consecutive days, whereas the control group (n = 9) was treated with saline. Fourteen days after the injury, the left carotid arteries were removed and analyzed under microscope. Several rats underwent the same treatment as above and were sacrificed three days after injury for immunohistochemistry and Western blot studies. A morphometric analysis revealed that there were significant differences in intima/media ratio between the two groups. Immunohistochemical and Western blotting studies demonstrated that NAC suppressed the injury-induced NF-kappaB activity in the medial SMC layer. Treatment with NAC suppresses vascular NF-kappaB activation and this inhibition reduced the pathological thickening of the arterial wall. The NF-kappaB pathway, therefore, represents an attractive therapeutic target for strategies to prevent vascular restenosis.

Acetylcysteine↗
PubMed2001

Social isolation stress impairs the resistance of mice to experimental liver metastasis of murine colon 26-L5 carcinoma cells.

Our previous study has demonstrated that the exposure of male BALB/c mice to social isolation stress caused a suppressed immune response and enhanced liver metastasis of colon 26-L5 carcinoma cells. To more precisely understand the influence of psychosocial factors on the metastatic process, here we have investigated the effect of social isolation stress on the vulnerability of the host to develop liver metastasis of colon 26-L5 cells, including the time span and incidence of metastatic formation, survival time and chemotherapy response. Isolation stress decreased the time period required for the metastasis formation relative to that in controls. On day 7 after the tumor injection, the 75% incidence of tumor metastasis in the stressed mice was 5 times the 15% incidence in the unstressed mice. When exposed to the challenge of lower cell numbers (0.025, 0.05, 0.1 x 10(4)/mouse) of colon 26-L5 cells, mice subjected to isolation stress developed an elevated incidence of metastasis (33.3, 66.6, and 100%, respectively) as compared with the controls (0, 33.3 and 50%, respectively). The survival time following the tumor inoculation was also shorter in the stressed mice (21.83 +/- 1.59d) than in the control mice (24.08 +/- 1.68 d). Furthermore, the response of liver metastasis to chemotherapy consisting of 2 mg/kg cisplatin (CDDP) was worse in the stressed mice than that in unstressed mice. These findings suggested that social isolation stress could significantly impair the resistance of mice to the development of metastasis.

Animals↗
PubMed2001

Effects of structural modification of calcium spirulan, a sulfated polysaccharide from Spirulina platensis, on antiviral activity.

Calcium ion binding with the anionic part of a molecule was replaced with various metal cations and their inhibitory effects on the replication of herpes simplex virus type 1 were evaluated. Replacement of calcium ion with sodium and potassium ions maintained the antiviral activity while divalent and trivalent metal cations reduced the activity. Depolymerization of sodium spirulan with hydrogen peroxide decreased in antiviral activity as its molecular weight decreased.

Antiviral Agents↗
PubMed2001

A novel antivirally active fucan sulfate derived from an edible brown alga, Sargassum horneri.

A novel fucan sulfate (Hor-1) was isolated from the hot water extract of an edible brown alga, Sargassum horneri (Turner) C. Agardh. The fucan sulfate was revealed to have sugar linkage types, sulfate content and uronic acid content different from those of sodium hornan (Na-HOR), another fucan sulfate isolated from this alga. However, it exhibited inhibitory activity against replication of herpes simplex virus type 1 with similar potency to Na-HOR.

Antiviral Agents↗