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Biomedical subjects

T Kawase

Publications and source records attributed to T Kawase.

At least 217 records · Page 12Linked to original sources

Aluminofluoride- and epidermal growth factor-stimulated DNA synthesis in MOB 3-4-F2 cells.

In attempt to study the mechanism of F(-)-induced, osteoblast-mediated bone formation, we tried to show the characteristics of Al-F complex-induced mitogenesis in osteoblastic cells. The MOB 3-4-F2 cell line, an osteoblast-like cell line derived from neonatal mouse calvaria, responded to F- (1-2 mM) combined with Al3+ and epidermal growth factor (EGF, 0.01-100 ng/ml) with increased DNA synthesis. Of the several types of Al-F complexes, AlF4- is thought to act as a mitogenic factor. On the other hand, NaF at high concentrations (greater than 2 mM) markedly decreased cell viability. The AlF(4-)-stimulated DNA synthesis at least with a delay of 48 hr, while EGF stimulated DNA synthesis within a few hours (4-6 hr). Both 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine, inhibitors of protein kinase C (PKC), further enhanced DNA synthesis in AlF(4-)-treated cells, whereas 12-O-tetradecanoyl-13-acetate (TPA), an activator of PKC, decreased the DNA synthesis. In EGF-treated cells, staurosporine and TPA, but not H-7, decreased DNA synthesis. In addition, indomethacin, an inhibitor of cyclooxygenase, partly inhibited the EGF-induced mitogenesis, which, however, was restored by addition of PGE2. AlF4-, as well as EGF, stimulated the release of arachidonic acid and its metabolites. Indomethacin failed to inhibit the AlF(4-)-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Strategy for the diagnosis of small acoustic neuromas.

Twenty small (extra-meatal size less than 15 mm) acoustic neuromas have been diagnosed since high-resolution (HR) magnetic resonance imaging (MRI) became available in our clinic. Among these tumors, 18 had sensorineural hearing loss and 16 enlarged internal auditory meatus in X-ray photo, but only 8 tumors out of 18 tested showed diminished caloric response. Auditory brainstem responses (ABR) has been believed as the most reliable test for the diagnosis of acoustic neuroma despite several reports of false-negatives. In our series, 4 tumors out of 18 tested had normal ABR. The false-negative rate was 22%, which is much higher than expected. In CT, only 11 tumors were recognized. Although the total number is not large, present results clearly suggest the limits of these examinations. At present, HR-MRI is the most reliable diagnostic method for acoustic neuromas with no false-negative reported; ordinary MRI may have false-negatives. For the effective use of MRI, the results of audiometry, X-ray photo, ABR and other examinations must be evaluated properly.

Audiometry↗

[Clinical study of vitamin E status in patients with chronic liver diseases].

Vitamin E status was evaluated in patients with chronic liver diseases (chronic hepatitis, CH; n = 27 and liver cirrhosis, LC; n = 32) by the ratio of plasma alpha-tocopherol to plasma lipids (P-toc/lipid) and red blood cell alpha-tocopherol (RBC-toc). P-toc/lipid and RBC-Toc were significantly reduced in LC patients compared to controls (n = 31). There was a significant correlation between P-Toc/lipid and RBC-Toc values. Low vitamin E status was found in 3 patients with CH (11.1%) and 12 patients with LC (37.5%), but their P-Toc values were not necessarily reduced. Serum beta-lipoprotein concentration (beta-lipo) did not differ significantly between the low vitamin E group and the normal vitamin E group, but the ratio of P-Toc to beta-lipo was significantly reduced in the low vitamin E group. No significant differences were found in the clinical features or liver functions tests including parameters of hepatic synthetic functions and cholestasis between the two groups. Factors other than a cholestasis or an impaired synthesis of carrier protein may also be responsible for the frequent occurrence of low vitamin E status in patients with LC.

Chronic Disease↗

[Antitumor effect of direct intra-tumor administration of OK-432 on malignant glioma: basic and clinical observations].

In this study, we tried to examine the efficacy of a cytotoxic factor which is induced by periodic, repeated local administration of OK-432 into the tumor cavity of malignant glioma patients. OK-432 was administered intratumorally via a tube to 4 malignant glioma patients on Days 1, 3, 5, 7 and 12 in doses of 0.5 KE, 1 KE, 2 KE, and 3 KE, respectively. Cerebrospinal fluid (CSF) was collected several times during the 24-hour period beginning immediately after the administration on Day 12. The CSF was added to the culture medium of rat glioma cells (GA-1 and C-6) in order to observe the cytotoxic effect morphologically. The clinical efficacy in the patients was evaluated from the changes in tumor size observed by CT. CSF collected from the tumor cavity of 3 patients was bloody. By adding this bloody CSF, a significant morphological cytotoxic effect was observed on both the GA-1 and C-6 glioma cells in culture. The level of cytotoxicity was higher with the bloody fluid collected at 4 to 24 hours after the final administration than with the bloody fluid collected immediately after the final administration. The cytotoxic effect of this fluid was stronger than that of rabbit TNF (tumor necrosis factor) serum induced with P. acnes and LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anterior transpetrosal-transtentorial approach for sphenopetroclival meningiomas: surgical method and results in 10 patients.

This report presents a new surgical method and the results in 10 patients with petroclival meningiomas extending into the parasellar region (sphenopetroclival meningiomas). Minimal but effective extradural resection of the anterior petrous bone via a middle fossa craniotomy offered a direct view of the clival area with preservation of the temporal bridging veins and cochlear organs. The dural incision was extended anteriorly to Meckel's cave, and in cases with invasion of the cavernous sinus, Parkinson's triangle was enlarged by mobilization of the trigeminal nerve. This approach offered an excellent view from the mid-clivus to the cavernous sinus. Extra-as well as intradural tumor masses and dural attachments could be cleared under direct view of the pontine surface. The risk of injury to the lower cranial nerve and of retraction damage to the temporal lobe and brain stem were kept minimal by this approach. Total tumor resection was achieved in 7 patients, with no resultant mortality. Eight patients had a satisfactory postsurgical course, extraocular paresis being their main complaint. The extent of tumor resection depended on the degree of tumor adhesion to the carotid artery, and operative morbidity on the degree of tumor invasion of the brain stem. Of the 3 patients in whom subtotal tumor removal was achieved, only one experienced regrowth of the tumor and underwent a second operation during the follow-up period (6 months-6 years).

Adult↗

Role of endotoxin-responsive macrophages in hepatic injury.

Although administration of 100 mg galactosamine caused severe hepatic injury in C3H/HeN mice, splenectomy reduced the grade of this hepatotoxicity. However, this hepatic injury was scarcely detected in the endotoxin-resistant C3H/HeJ mice. In addition, in contrast to high lethality in C3H/HeN mice with a combined administration of galactosamine and endotoxin, splenectomy rendered C3H/HeN mice slightly resistant to this treatment. Further resistance was demonstrated in C3H/HeJ mice. In an attempt to clarify the role of endotoxin-responsive spleen cells in the pathogenesis of hepatic injury, we investigated galactosamine-induced hepatic injury by transfer of lipopolysaccharide-treated C3H/HeN or C3H/HeJ spleen cells. Both oxygen-derived free radical production and the proportion of macrophages in spleen cells were markedly enhanced in C3H/HeN mice after an intraperitoneal injection of lipopolysaccharide. Further increase in oxidative free radical production was found in the dish-adherent cells (macrophages). These enhancements were not demonstrated in lipopolysaccharide-treated C3H/HeJ spleen cells. Although hepatic injury was not demonstrated in both C3H/HeN and C3H/HeJ mice treated with 35 mg galactosamine alone, severe hepatotoxicity was found in these galactosamine-treated mice when they received lipopolysaccharide-activated C3H/HeN spleen cells, especially macrophages. Simultaneous administration of superoxide dismutase with the activated spleen cells reduced the grade of hepatic injury. On the other hand, hepatic injury was not demonstrated in the galactosamine-treated C3H/HeN or C3H/HeJ mice when they received lipopolysaccharide-treated C3H/HeJ spleen cells, although 3H-galactosamine incorporation into hepatocytes was nearly identical in both C3H/HeN and C3H/HeJ mice. These results suggest that oxidative free radicals of lipopolysaccharide-responsive macrophages could contribute to the pathogenesis of galactosamine-induced hepatic injury.

Alanine Transaminase↗

Thermodynamic study of phase transfer of precipitates on SiC whisker reinforced glass ceramics.

Physiochemical properties of glass ceramics in weakly buffered, supersaturated, metastable calcium and phosphate solution were studied. Formations of calcium phosphate precipitates were also analyzed thermodynamically. All biomaterials examined here showed primarily dissolution process and subsequent nucleation. Dissolution was enhanced in those which contained Na2O and/or SiC. The dissolution of calcium and phosphate ions from biomaterials and subsequent nucleation of calcium phosphate salts after induction time resulted in a stable equilibrium having solubility characteristics similar to octacalcium phosphate (OCP). The most soluble material, CPSN-SiC, showed an initial transient equilibrium with amorphous calcium phosphate (ACP). From above results, calcium phosphate ceramics had certain driving force of its own which kept the equilibrium of solution to OCP thermodynamically for 7 days. Despite the favorable solubility equilibrium attained, there still remain problems for clinical application.

Biocompatible Materials↗

In vivo measurement of intra- and extracellular space of brain tissue by electrical impedance method.

An impedance method was applied to evaluate transcellular fluid shifts in ischaemic brain oedema. The admittances (apparent electrical conductivities) of tissues were measured at varied frequencies based on a simple model of an electrical equivalent circuit for tissues, which consisted of Re (resistivity of extracellular fluid), Ri (resistivity of intracellular fluid) and Cm (capacitance of cell membrane). Calculated were Re, Ri, Rinf (resistivity of total fluid), Re/Ri and alpha (Cole-Cole distribution index) of brain tissue by Cole-Cole an arc of a circle. During ischaemia induced by cat middle cerebral artery occlusion (MCAO), the parameters were examined continuously. After MCAO, cerebral blood flow (CBF) decreased to under 10 ml/100 g/min. Then Re and Re/Ri increased, but Ri decreased. These results indicated that fluid shift from extracellular (EC) to intracellular (IC) space occurred after ischaemic insult. Rinf showed no changes during ischaemia of 30 min, which demonstrated no changes of total fluid volume. Using this impedance technique, fluid accumulation and shift may be examined by changes of Re, Ri, Re/Ri and Rinf in various types of brain oedema in vivo.

Animals↗

The effects of pressure on cochlear microphonics in experimentally induced hydropic ears in the guinea pig.

The effect of perilymphatic pressure on the cochlear microphonics (CM) threshold was examined in guinea pigs with experimentally induced hydrops. When a pressure of 300 mm H2O was applied to the scala tympani of the basal turn, the 500 Hz CM threshold shifts in ears during the 1st week following obliteration of the endolymphatic sac and duct were significantly smaller when compared with shifts in normal ears. Larger threshold shifts were then regained at 4-12 weeks after surgery. When acetazolamide was administered to hydropic animals, the effect of the increase of perilymphatic pressure on the CM threshold was also investigated. During the 1st postoperative week (4-7 days after surgery), CM threshold shifts were larger when compared to changes in hydropic animals without medication. The CM depression as the result of pressure is probably due to a mechanical effect on the intracochlear partition.

Acetazolamide↗

Impaired regulation of natural killer cells in immunoglobulin synthesis by peripheral blood mononuclear cells from patients with ulcerative colitis.

Immunoglobulin (Ig) synthesis, natural killer (NK) cell activity, and lymphokine production by peripheral blood mononuclear cells (PBMC) were studied in 34 patients with ulcerative colitis (UC). Levels of Ig produced by PBMC were significantly higher in patients with active UC as compared to controls. However, there were no significant differences in Ig-synthesis between patients with inactive UC and controls. NK cell activity was significantly decreased in patients with active UC as compared to controls, and a significant negative correlation was observed between the level of IgA and NK cell activity in patients with UC. Reconstitution experiments demonstrated that CD56+ cells from controls suppressed the levels of IgA, when added to the culture containing a constant number of B cells and CD4+ cells. In contrast, CD56+ cells from patients with active UC completely lacked the capacity to suppress IgA production. In addition, the activities of interleukin-2 and interferon-gamma were significantly decreased in patients with active UC. The present study suggests that immunoregulatory abnormality of NK cells exists in patients with UC and impaired NK cell activity may be related to increased Ig-synthesis observed in these patients.

Adult↗

Interleukin 2 and interferon-gamma activities of mononuclear cells from regional lymph nodes in patients with gastric cancer.

The interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) activities of regional lymph node mononuclear cells (LNMC) were studied in 22 patients with gastric cancer. Regional LNMC could produce high levels of IL-2 and IFN-gamma independent of the disease extension or the location of the lymph nodes. The activities of peripheral blood mononuclear cells (PBMC) from cancer patients were decreased especially in advanced disease compared to controls. The lymph node CD4+ cells were responsible for the bulk of IL-2 activity, whereas both CD4+ and CD8+ cells were equally capable of producing IFN-gamma. The proportion of T cells in LNMC was similar to that seen in PBMC, however, CD4+ cells predominated over CD8+ cells in the lymph nodes, contributing to higher activities of IL-2 and IFN-gamma in LNMC. Furthermore, significant cytotoxic activity could be induced from PBMC using the culture supernatant derived from autologous LNMC in cancer patients. This study suggests that regional lymph nodes are strategically located near the tumor and the local cells are capable of producing high levels of IL-2 and IFN-gamma.

CD4-Positive T-Lymphocytes↗

Role of xanthine oxidase in ethanol-induced lipid peroxidation in rats.

To investigate a possible role of free radical production by xanthine oxidase in the pathogenesis of ethanol-induced hepatic lipid peroxidation, chow-fed rats were given ethanol (5 g/kg) and placed at 32 degrees C for 6 h, which resulted in increased hepatic malondialdehyde levels. Pretreatment with allopurinol in amounts that effectively inhibited xanthine metabolism also significantly decreased ethanol-induced lipid peroxidation, suggesting participation of free radicals produced by xanthine oxidase in the peroxidative process. Both acetaldehyde and purine can serve as substrates for xanthine oxidase. Pretreatment with cyanamide increased hepatic acetaldehyde levels 5-fold, yet this was associated with a decrease in lipid peroxidation, indicating that acetaldehyde is not the xanthine oxidase substrate involved. By contrast, ethanol increased hepatic contents of hypoxanthine and xanthine and enhanced urinary output of allantoin (a final product of xanthine metabolism), incriminating increased metabolism of purines. Ethanol administration also enhanced hepatic nicotinamide adenine dinucleotide (reduced form). A corresponding rise of nicotinamide adenine dinucleotide (reduced form) in vitro inhibited xanthine dehydrogenase activity by 60%-76%. Increased purine degradation, possibly associated with a shift from the dehydrogenase to the xanthine oxidase pathway (secondary to nicotinamide adenine dinucleotide [reduced form]-mediated inhibition of xanthine dehydrogenase activity) is proposed as a possible mechanism for ethanol-stimulated free radical production. Because allopurinol attenuates the associated lipid peroxidation, this agent might be considered for possible therapeutic use in alcohol-induced liver damage.

Allopurinol↗

Leukotriene inhibitors modulate hepatic injury induced by lipopolysaccharide-activated macrophages.

In an attempt to elucidate the effect of lipoxygenase inhibitors on hepatic injury, we investigated D-galactosamine (GalN)-treated C57BL/6 mice receiving an intravenous (i.v.) injection of lipopolysaccharide (LPS)-activated autologous spleen cells. As compared with control spleen cells, the number of monocytes in the spleen cells isolated from LPS-treated mice and their oxidative free radical production increased markedly. Oxygen radical production by the dish-adherent cells (macrophage-rich population) was enhanced a further 4-fold. Although hepatotoxicity was not demonstrated in mice treated with 20 mg GalN alone, marked hepatic injury was found in the GalN-treated mice with a supplementation of LPS-activated spleen cells. The dish-adherent cells aggravated this hepatic injury, in contrast to minor hepatotoxicity by the nonadherent cells. Oxygen radical production by LPS-activated spleen cells was markedly reduced by the lipoxygenase inhibitors (azelastine, ketotifen and AA861). Hepatotoxicity was scarcely detected in the GalN-treated mice with a supplementation of the LPS-activated spleen cells which had been previously treated with lipoxygenase inhibitors. From these results, LPS-activated spleen macrophages contributed to hepatic injury induced by GalN, and lipoxygenase inhibitors which reduced oxygen radical production by the activated cells, protected against macrophage-induced hepatic injury in mice.

Alanine Transaminase↗

Initial responses of a clonal osteoblast-like cell line, MOB 3-4, to phosphatidic acid in vitro.

A number of studies have shown membrane phospholipid metabolism to have an important role in biological mineralization. We considered the effects of exogenously applied phosphatidic acid (PA), a minor component of membrane phospholipids, on an osteoblast-like cell line, MOB 3-4. Exogenous PA (10-40 micrograms/ml) raised the level of cytoplasmic free Ca2+ [( Ca2+]i), independent of the level of extracellular Ca2+, in a dose-dependent fashion, and this Ca2+ response to PA gradually fell on serial application of PA. In a dose-dependent manner, exogenous PA also increased inositol 1,4,5-trisphosphate (IP3) accumulation and cytoplasmic pH, but decreased basal cAMP level. This cytoplasmic alkalinization was inhibited by pretreatment with nonspecific protein kinase C (PKC) inhibitors, such as sphingosine or H-7. A long-term incubation with PA increased alkaline phosphatase (ALP) activity and cell proliferation. Exogenous PA thus appeared to increase IP3 accumulation by activating phospholipase C, raise [Ca2+] by releasing Ca2+ from intracellular stores, induce cytoplasmic alkalinization via a PKC-dependent mechanism, and simultaneously decrease basal cAMP level. We suggest that these initial responses may be responsible for the increase in ALP activity and the proliferation of PA-treated MOB 3-4 cells.

Alkaline Phosphatase↗

A clonal prostaglandin-responsive cell line (RDP 4-1) derived from rat dental pulp.

The RDP 4-1 cell line was established from isolated rat dental pulp and cloned with limiting dilution in 96-multiwell plates. Despite their fibroblast-like appearance, RDP 4-1 cells required more than 5% (v/v) heat-inactivated fetal calf serum to maintain the cell growth and function. Type I collagen, but not type II and type III collagen, was immunocytochemically detected in the cells in subconfluent cultures. Prostaglandin E2 (PGE2, 5 ng/ml-5 micrograms/ml) dose-dependently increased cAMP accumulation, while prostaglandin F2 alpha (PGF2 alpha, 5 micrograms/ml) slightly increased it, in the presence of 0.1 mM isobutylmethyl xanthine. PGE2 (5 ng/ml-5 micrograms/ml) also stimulated phosphoinositide hydrolysis to produce inositol phosphates (IPs) in a time- and dose-dependent manner in the presence of 10 mM LiCl. PGF2 alpha was a more potent stimulator of phosphoinositide hydrolysis. Both prostaglandins increased cytoplasmic free calcium, independent of the level of extracellular calcium. Prolonged exposure (48 h) of the cells to PGE2 at higher concentrations (greater than or equal to 0.5 micrograms/ml) increased DNA synthesis. In these RDP 4-1 cells, thus, PGE2 receptors appeared to be associated with both cAMP and IPs-Ca2+ signaling systems, and that PGF2 alpha receptors are poor stimulators of the former but more potent ones of the latter. Our results suggest that both prostaglandins have some roles in regulating dental pulp metabolism.

Animals↗

Isolation and partial characterization of bovine periodontal ligament alkaline phosphatase.

An alkaline phosphatase which binds to hyaluronate with a high affinity has been extracted from the bovine periodontal ligament and purified. The procedure consisted of extraction with a 10 mM Tris/Mg buffer containing 0.1% Nonidet P40, chromatography on a hyaluronate-conjugated Affi-Gel 15, and fast protein liquid chromatography. The hyaluronate-binding alkaline phosphatase has an apparent molecular weight of 110,000, contained sialic acid and was more stable to heat treatment than were two other species (Mr = 120,000 and 130,000) extracted from PDL. The heat stability and influence of inhibitors on its activity show that the hyaluronate-binding alkaline phosphatase of periodontal ligament was similar to the bone alkaline phosphatase.

Alkaline Phosphatase↗