Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 523 records · Page 29Linked to original sources

PubMed1998

Hepatic clearance of ONO-5046, a novel neutrophil elastase inhibitor, in rats and in the rat perfused liver.

The hepatic clearance of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)phenylsulphonylamino]benz oyl]aminoacetic acid), a low-molecular-weight neutrophil elastase inhibitor, has been investigated in rats and in the rat perfused liver. This ester was easily hydrolysed to its inactive metabolite EI-601 (N-[2-[(4-hydroxyphenyl)sulphonylamino]benzoyl]aminoacetic acid) in liver homogenate and in erythrocytes suspension in-vitro. On the other hand, it was stable in biological media such as plasma and whole blood, which contain plasma proteins. Scatchard plot analysis of ONO-5046 binding to bovine serum albumin (BSA) in-vitro indicated that the association constant (K) and number of binding sites (n) were 6.91 x 10(4) (M(-1)) and 4.33, respectively. Thus, ONO-5046 (100 microM) would bind to plasma proteins to an extent >99% at physiological plasma-protein concentrations. The total plasma clearance of ONO-5046 in rats was constant (approximately 9 mL min(-1) kg(-1)) under different steady-state plasma concentrations (5-50 microM) a value equivalent to the hepatic clearance. In the rat perfused liver, the hepatic extraction ratio of ONO-5046 was significantly reduced by adding BSA to the dosing solution. Thus, the relatively low hepatic clearance of ONO-5046, which has an ester linkage in its structure and is naturally susceptible to enzymatic hydrolysis, was found to be because of the extremely high protein-binding of the compound.

Animals↗

PubMed1998

In-vivo calibration of microdialysis probe by use of endogenous glucose as an internal recovery marker: measurement of skin distribution of tranilast in rats.

To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxy-cinnamoyl)anthranic acid), an anti-allergic agent, in rats. This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.

Animals↗

PubMed1998

Focal hepatic lesion detection: comparison of four T2-weighted MR imaging pulse sequences.

PURPOSE: To evaluate T2-weighted magnetic resonance (MR) imaging with conventional spin-echo, breath-hold fast spin-echo, respiratory-triggered fast spin-echo, and breath-hold multishot spin-echo echo-planar sequences for detection of focal hepatic lesions. MATERIALS AND METHODS: T2-weighted MR images obtained with the four sequences in 56 patients with 107 solid and 124 nonsolid lesions were retrospectively analyzed. Image review was conducted on a liver segment-by-segment basis; a total of 408 liver segments were reviewed separately and independently for solid and nonsolid lesions by three radiologists. Diagnostic accuracy was evaluated with receiver operating characteristic analysis. RESULTS: Lesion-to-liver contrast-to-noise ratio was highest with multishot echo-planar images of both solid and nonsolid lesions. Diagnostic accuracy for solid lesions was statistically significantly better with conventional spin-echo images than with any other type of image (P < .0001). Diagnostic accuracy for nonsolid lesions was statistically significantly better with respiratory-triggered fast spin-echo images than with any other type of image (P < .0001). Image quality was best with breath-hold fast spin-echo images. CONCLUSION: Conventional spin-echo MR imaging should not be replaced with breath-hold fast spin-echo or multishot spin-echo echo-planar imaging, despite the shorter acquisition times that are possible with the latter two sequences.

Female↗

PubMed1998

Preoperative staging of endometrial carcinoma: diagnostic effect of T2-weighted fast spin-echo MR imaging.

PURPOSE: To evaluate the usefulness of T2-weighted fast spin-echo magnetic resonance (MR) imaging with a 512 x 256 matrix for assessment of the preoperative stage of endometrial carcinoma. MATERIALS AND METHODS: Twenty-eight women with histopathologically proved endometrial carcinoma underwent preoperative T2-weighted fast spin-echo, dynamic T1-weighted fast spin-echo, and postcontrast T1-weighted spin-echo MR imaging with a phased-array surface coil. The uterine long-axis planes in each sequence were reviewed at separate sessions by three radiologists blinded to the histopathologic data. RESULTS: For the diagnosis of myometrial invasion, no statistically significant differences were found among T2-weighted imaging, dynamic imaging, and postcontrast T1-weighted imaging. For the diagnosis of deep myometrial invasion, T2-weighted and dynamic images showed higher specificity than postcontrast T1-weighted images (T2-weighted, 89%; dynamic, 88%; and postcontrast T1-weighted, 80%). For cervical invasion, T2-weighted and dynamic images showed larger areas under receiver operating characteristic curves than did postcontrast T1-weighted images (T2-weighted, 0.78; dynamic, 0.71; and postcontrast T1-weighted, 0.67). CONCLUSION: T2-weighted imaging is useful for identifying the stage of endometrial carcinoma.

Carcinoma↗

PubMed1998

KATP channels are common mediators of ischemic and calcium preconditioning in rabbits.

Calcium preconditioning (CPC), like ischemic preconditioning (IPC), reduces myocardial infarct size in dogs and rats. ATP-sensitive potassium (KATP) channels induce cardioprotection of IPC in these animals. To determine whether KATP channels mediate both IPC and CPC, pentobarbital sodium-anesthetized rabbits received 30 min of coronary artery occlusion followed by 180 min of reperfusion. IPC was elicited by 5 min of occlusion and 10 min of reperfusion, and CPC was elicited by two cycles of 5 min of calcium infusion with an interval period of 15 min. Infarct size expressed as a percentage of the area at risk was 38 +/- 3% (mean +/- SE) in controls. IPC, CPC, and pretreatment with a KATP channel opener, cromakalim, all reduced infarct size to 13 +/- 2, 17 +/- 2, and 12 +/- 3%, respectively (P < 0.01 vs. controls). Glibenclamide, a KATP channel blocker administered 45 min (but not 20 min) before sustained ischemia, attenuated the effects of IPC and CPC (31 +/- 4 and 41 +/- 6%, respectively). Thus KATP channel activation appears to contribute to these two types of cardioprotection in rabbits.

Adenosine Triphosphate↗

PubMed1998

Ulcerative porokeratosis.

A 54-year-old man presented with multiple annular plaques since infancy. During the intake of nifedipine and nitroglycerin over a period of 6 years, reddish, eruptive and ulcerative changes were seen in the pre-existing skin lesions on the penis, scrotum and legs. In addition to a typical cornoid lamella, histological examination revealed a band-like infiltration beneath the epidermis, liquefaction degeneration of the basal cell layer and subsequent coagulative necrosis of the keratinocytes. We review similar ulcerative types of porokeratosis in the literature and discuss the significance of our unusual case.

Histocytochemistry↗

PubMed1998

Altered proliferative and metastatic potential associated with increased expression of syndecan-1.

The process of metastasis involves a series of sequential steps in which malignant cells are released from the primary tumor and metastasize to distant sites. Syndecan-1 is a cell surface proteoglycan that mediates cell adhesion and undergoes changes upon cell transformation of some cells that may contribute to the process of metastasis. To investigate the possible role of syndecan-1 in cell proliferation and metastatic potential, we employed a highly metastatic cell line (KLN 205) derived from mouse lung squamous cell carcinoma that expressed moderate amounts of syndecan-1. At first, endogenous syndecan-1 production was inhibited by an antisense oligodeoxynucleotides (ODNs). Since antisense ODNs of syndecan-1 inhibited cell growth, we established stable transfectants of syndecan-1 in this cell line to examine a proliferative advantage with the level of syndecan-1 expression. Overexpresser cells grew at a significantly faster rate than the vector-transfected control and showed greater incidence of tumor formation when injected subcutaneously into nude mice. Surprisingly, overexpresser cells enhanced pulmonary metastasis when injected intravenously. These results indicate that syndecan-1 expression plays a role in the control of cell proliferation and suggest that syndecan-1 expression may be involved in facilitating distant metastasis of tumor cells once they managed to enter the bloodstream (after intravasation steps).

Animals↗

PubMed1998

Cardiac mitogen-activated protein kinase activities are chronically increased in stroke-prone hypertensive rats.

To examine chronic changes in mitogen-activated protein (MAP) kinases in cardiac hypertrophy, we determined the activities of two subfamilies of MAP kinases, including extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), in the heart of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) aged 5, 8, 14, and 24 weeks. MAP kinases were determined by using in-gel kinase assay. In both the left and right ventricles of WKY, the activities of ERKs (p44ERK and p42ERK) and JNKs (p46JNK and p55JNK) decreased significantly with age, indicating that aging remarkably downregulated cardiac MAP kinase activities. In SHRSP, left ventricular ERK and JNK activities were already significantly higher at the mild hypertensive phase than they were in the same age of WKY, and they remained higher until development of left ventricular hypertrophy. On the contrary, the right ventricle of SHRSP, which did not exhibit cardiac hypertrophy, had no significant increase in ERK or JNK activities compared with WKY, except for the slight increase in p55JNK in 24-week-old SHRSP. Antihypertensive treatment of SHRSP with imidapril, an angiotensin-converting enzyme inhibitor, decreased the left ventricular JNK activities (P<.01) but did not affect ERK activities, suggesting the contribution of hypertension or the renin-angiotensin system to the increase in JNKs. Our observations provide the first evidence that both ERK and JNK activities are higher in the left ventricle of SHRSP than WKY. However, further study is needed to elucidate the mechanism and the significance of the increased cardiac MAP kinases in SHRSP.

Aging↗

PubMed1998

Leptin affects pancreatic endocrine functions through the sympathetic nervous system.

The effects of leptin on the secretion of insulin and glucagon were examined. In an experiment involving insulin response to an i.v. glucose load in vagotomized rats, the plasma concentrations of insulin were significantly lower in the leptin (20 nmol/kg BW)-treated group than in a control group. However, in intact rats and rats that had undergone both vagotomy and chemical sympathectomy, this suppressive effect of leptin on insulin secretion was not detected. In an experiment involving a hypoglycemia-induced glucagon secretion test in intact rats, an i.v. injection of leptin (20 nmol/kg BW) augmented the plasma glucagon response to hypoglycemia. In the case of sympathectomized rats, however, this stimulative effect of leptin on glucagon secretion was not detected. In an experiment with perfused rat pancreas, the addition of leptin (20 nM) to the perfusate slightly suppressed insulin secretion, but had no effect on basal or glucopenia-induced glucagon secretion. In intact rats infused with leptin (0.31 micromol/day), the expression of uncoupling protein-1 messenger RNA in interscapular brown adipose tissue was increased, whereas no such effect of leptin on the uncoupling protein-1 messenger RNA expression was observed in brown adipose tissue in chemically sympathectomized rats. These findings suggest that leptin might indirectly affect pancreatic endocrine functions, probably through its stimulative effects on the sympathetic nervous system.

Adipose Tissue, Brown↗

PubMed1998

Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat.

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprotegerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect on serum calcium level remains to be determined. In this study we examined the acute effect of OCIF on thyroparathyroidectomized rats whose serum calcium concentrations were raised either by exogenous PTH or 1,25-(OH)2D3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was administered into rats with established hypercalcemia, it decreased serum calcium rapidly (within 2 hr) and dramatically. OCIF did not increase urinary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the formation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.

Animals↗

PubMed1998

Adaptive multimode lubrication in natural synovial joints and artificial joints.

To examine the lubrication mechanisms in both natural synovial joints and artificial joints with artificial cartilages, pendulum tests of pig shoulder joints and simulator tests of sliding pairs of a stainless steel spherical component and natural articular cartilage or artificial cartilage have been conducted. Firstly, it was shown in pendulum tests of pig shoulder joints that both concentration of hyaluronic acid or viscosity and adsorbed film formation of proteins and phospholipids exerted a significant effect on frictional behaviour in swinging motion immediately after a loading of 100 N. Under a high load of 1 kN, low friction was observed under wide-ranging viscosity conditions, since a high load similar to body weight probably enhanced the squeeze film effect due to improved congruity. Next, frictional behaviour of sliding pairs in knee joint models, consisting of a stainless steel spherical surface and either specimens of pig tibial cartilage or polyvinylalcohol (PVA) hydrogel, was examined during walking in simulator tests. In these tests, the influences of lubricant viscosity and addition of protein on frictional behaviour were evaluated. For both compliant materials, the appropriate addition of gamma-globulin to sodium hyaluronate (HA) solution maintained low friction and protected rubbing surfaces under thin film conditions. These phenomena are discussed from the viewpoint of adaptive multimode lubrication.

Animals↗

PubMed1998

Prediction of transient lubricating film thickness in knee prostheses with compliant layers.

The transient lubricating film thickness in knee prostheses using compliant layers has been predicted under simulated walking conditions based upon the elastohydrodynamic lubrication theory. Qualitative agreement has been found between the present theoretical predictions and the experimental measurements using an electric resistance technique reported earlier. It has been shown that the contact geometry plays an important role in the generation of fluid film lubrication in knee prostheses using compliant layers. The maximum lubricating film thickness is predicted for the maximized contact area of a transverse conjunction where the semi-minor contact radius lies in the direction of entraining. The additional advantage of the transverse contact conjunction is that the possibility of lubricant starvation due to small stroke length can be minimized. All these factors, together with the kinematic requirements in the natural knee joint, should be taken into consideration when designing artificial knee joint replacements.

Biocompatible Materials↗

PubMed1998

The lubricating ability of biomembrane models with dipalmitoyl phosphatidylcholine and gamma-globulin.

Two kinds of friction tests were conducted to investigate the lubricating effect of the injection of amphiphilies on the osteoarthritic joint. The effects of the addition of L alpha-dipalmitoyl phosphatidyl-choline (L alpha-DPPC) riposomes and gamma-globulin in a saline solution of sodium hyaluronate (HA) were evaluated through pendulum friction tests. The frictional characteristics of pig shoulder joints were confirmed to depend on the viscosity of the lubricants only in the physiologically low load condition and in the condition immediately after loading. Detergent (polyoxyethylene p-t-octylphenyl ether) was successfully used to remove adsorbed films from the articular surfaces. The friction coefficient of natural synovial joints was significantly increased in a mode of mixed lubrication with the HA solution of 0.2 g/dl by the treatment of the surface with the detergent. The addition of L alpha-DPPC riposomes or gamma-globulin significantly improved the boundary lubricating ability of the articular surfaces treated with the detergent, depending on the quantity of those additives. It appears that the L alpha-DPPC riposomes and gamma-globulin can form protective films on the articular surfaces like a biomembrane. Moreover, the reciprocating frictional behaviour in sliding pairs of pig articular cartilages and glass plates was studied in order to elucidate the tribological role of those constituents in the boundary lubricating film on the articular surface. Pig synovial fluid and water solutions of HA were used as lubricants. The synovial fluid had superior lubricating ability compared to the HA solution of equivalent viscosity under a physiologically high load condition. This fact seems to be responsible for the boundary lubricating ability of constituents other than hyaluronic acid. Langmuir-Blodgett (LB) films of L alpha-DPPC on the glass plate were kept at a low and stable friction coefficient, depending on the number of film layers. In conditions of mixed films with L alpha-DPPC and gamma-globulin, the frictional behaviour was improved by increasing the quantity of gamma-globulin. A model is proposed in which the effective adsorbed films are composed of proteins, phospholipids and other conjugated constituents on the articular surfaces to be accurate in describing the boundary lubricating mechanism. The mechanism is controlled by hydrophobic groups in those amphiphilies.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1998

Studies on Kochiae Fructus. V. Antipruritic effects of oleanolic acid glycosides and the structure-requirement.

We examined the antipruritic effects of various oleanolic acid glycosides from natural medicines such as Kochiae Fructus (the fruit of Kochia scoparia SCHRAD.) and Momordicae Radix (the roots of Momordica cochinchinensis SPRENG.) using a compound 48/80-induced pruritic model in mice. Oleanolic acid 3-O-monodesmosides showed an antipruritic effect, while oleanolic acid 3,28-O-bisdesmosides and their common sapogenol oleanolic acid lacked the activity. This evidence indicated that the 3-O-glycoside moiety and the 28-carboxyl group in oleanolic acid glycosides were essential for exhibiting the antipruritic effect. Furthermore, it was found that the 3-O-glucuronides showed more potent activity than the corresponding 3-O-glucosides.

Animals↗

PubMed1998

The effect of ethanolamine on acute carbon tetrachloride intoxication.

The effects of ethanolamine on injured liver were investigated by oral administration of ethanolamine to male ddY mice 24 h after carbon tetrachloride (CCl4) injection. The serum aminotransferase activities in mice with liver injury were reduced by ethanolamine treatment (10-30 mg/kg body weight). Drastically increased regenerative reaction of ethanolamine treated-CCl4 injured liver was also observed through an increase in 5-bromo-2'-deoxyuridine uptake. ATP concentration in liver tissue was recovered by administration of ethanolamine. These results suggest that oral administration of ethanolamine accelerates recovery from CCl4-induced liver injury.

Adenosine Triphosphate↗

PubMed1998

Medicinal foodstuffs. XIV. On the bioactive constituents of moroheiya. (2): New fatty acids, corchorifatty acids A, B, C, D, E, and F, from the leaves of Corchorus olitorius L. (Tiliaceae): structures and inhibitory effect on NO production in mouse peritoneal macrophages.

Following the characterization of the glycosidic constituents in a medical foodstuff "moroheiya," the leaves of Corchorus olitorius L., four higher fatty acids with a trienone function, corchorifatty acids, A, B, C, and D, an undecanoic acid, corchorifatty acid E, and a trihydroxyfatty acid, corchorifatty acid F, were isolated from the less polar fraction of "moroheiya". The structures and optical purity of corchorifatty acids were determined on the basis of chemical and physicochemical evidence. Corchorifatty acids A, B, and C showed an inhibitory effect on lipopolysaccharide-induced NO production in cultured mouse peritoneal macrophages.

Animals↗

PubMed1998

Kotalanol, a potent alpha-glucosidase inhibitor with thiosugar sulfonium sulfate structure, from antidiabetic ayurvedic medicine Salacia reticulata.

A potent natural alpha-glucosidase inhibitor called kotalanol has been isolated from an antidiabetic traditional Ayurvedic medicine, the roots and stems of Salacia reticulata Wight, through bioassay-guided separation. The structure of kotalanol was elucidated on the basis of chemical and physicochemical evidence to be the inner salt comprised of 1-deoxyheptosyl-3-sulfate anion and 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation. Kotalanol was found to show more potent inhibitory activity against sucrase than salacinol and acarbose.

Animals↗

PubMed1998

Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity.

We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.

Administration, Oral↗