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Biomedical subjects

H Tokuyama

Publications and source records attributed to H Tokuyama.

At least 37 records · Page 2Linked to original sources

Photocytotoxicity of water-soluble fullerene derivatives.

New water-soluble fullerene carboxylic acids (1 and 2) derived from C60 and C70 fullerenes, respectively, were examined for photocytotoxicity toward Raji cells (B lymphocyte). These compounds did not show any photocytotoxic effect even at 50 microM, while pheophorbide a showed significant photocytotoxicity at 0.5 microM. Therefore, fullerene derivatives derived from C60 and C70 would not be practical agents for photodynamic therapy.

B-Lymphocytes↗

Retinoids inhibit IL-4-dependent IgE and IgG1 production by LPS-stimulated murine splenic B cells.

The effects of retinoids (all-trans-retinoic acid (RA) and vitamin A) and hydrocortisone (HC) on the IL-4-dependent IgE and IgG1 response by mouse whole spleen cells and splenic B cells were studied. Whole spleen cells were cultured for 8 days in the presence of LPS and IL-4 and the supernatants were assayed for IgG1 and IgE. The levels of the two classes were enhanced about twofold by the addition of HC at 10 nM. The addition of retinoids to the above culture system within 1 day from the start strongly inhibited both IgG1 and IgE responses. The concentration inhibiting both of the reactions by 50% was about 3-10 nM for RA and 300 nM-1 microM for vitamin A. In the case of splenic B cells, HC also showed an enhancing effect on the IgG1 and IgE production at extremely low concentrations (20 pM-2 nM), but at higher concentrations (above 10 nM) it was inhibitory. IL-4-dependent IgG1 and IgE production of LPS-stimulated splenic B cells was also inhibited by retinoids. The concentration giving 50% inhibition was 0.2 nM for RA and 150 nM for vitamin A. Exogenous TGF-beta 1 also inhibited the IL-4-dependent IgG1 and IgE production by splenic B cells and the inhibition was reverted in the presence of the specific neutralizing antibody to TGF-beta 1. However, the inhibition by 1 nM RA could not be abolished by the excess antibodies to TGF-beta 1 and TGF-beta 2.

Animals↗

Endogenous cytokine expression profiles in retinoic acid-induced IgA production by LPS-stimulated murine splenocytes.

All-trans-retinoic acid (RA) enhances IgA production by LPS-stimulated murine splenocytes. After stimulation by RA and LPS, or by LPS alone, total RNA was extracted from cultured cells on Days 1 to 4, and the kinetics of expression of various cytokine mRNAs were analyzed by the RT-PCR method. RA induced the expression of IL-5 and TGF-beta 2 mRNAs in the LPS-stimulated cells. In addition, the expression of IL-6 and IL-2 mRNAs was more intensive in RA-stimulated cells than in unstimulated cells. TGF-beta 1 and TGF-beta 3 mRNAs were constitutively expressed in both culture groups. RA enhanced IgA production by LPS-stimulated spleen cells but not that by LPS-stimulated mu(+) naive splenic B-cells. For RA-induced IgA production, the B-cells required T-cells or the culture supernatant from RA-stimulated T-cells. Furthermore, exogenous IL-5 replaced the T-cell requirement, at least in part, in RA-induced IgA production by LPS-stimulated B-cells. This reaction was partially inhibited by anti-TGF-beta-neutralizing antibodies. These findings suggest that RA induces IgA production by (IL-5 + LPS)-stimulated B-cells in TGF-beta-independent and TGF-beta-dependent manners.

Adjuvants, Immunologic↗

In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity.

BACKGROUND: Water-soluble fullerenes have recently been shown to exhibit considerable in vitro biological activity including cytotoxicity, site-selective DNA cleavage and inhibition of HIV protease. To assess the potential of these compounds as drugs, studies on the in vivo behavior of fullerenes are needed. We therefore set out to synthesize a radiolabeled, water-soluble fullerene, in order to obtain data on the oral absorption, distribution and excretion of this class of compounds. RESULTS: We synthesized a 14C-labeled water-soluble [60]fullerene using dipolar trimethylenemethane, which undergoes cycloaddition to [60]fullerene. When administered orally to rats, this compound was not efficiently absorbed and was excreted primarily in the feces. When injected intravenously, however, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. The compound was also able to penetrate the blood-brain barrier. Acute toxicity of the water-miscible fullerene was found to be quite low. CONCLUSIONS: Although the water-soluble fullerenes (and possibly their simple metabolites) are not acutely toxic, they are retained in the body for long periods, raising concerns about chronic toxic effects. The fact that fullerenes distribute rapidly to many tissues suggests that they may eventually be useful to deliver highly polar drugs through membranes to a target tissue, however, and they may even have applications in the delivery of drugs to the brain. Recent advances in fullerene synthetic chemistry may also make it possible to control fullerene absorption/excretion profiles in the future.

Administration, Oral↗

Effects of occlusal splints on the asymmetry of masticatory muscle activity during maximal clenching.

The effects of stabilization splints on the electromyographic activity patterns of the masseter and anterior temporal muscles during maximal clenching in healthy subjects and subjects with different types of stomatognathic dysfunction syndrome were investigated. No marked effect of splints on the asymmetry of muscle activity during bilateral clenching was revealed immediately after splint insertion. During unilateral clenching in the intercuspal position (ICP), the relative asymmetry index (rAI) of the masseter muscles, detecting the imbalance of left and right muscular activity, was significantly increased. The use of splints suppressed the asymmetry of masseter muscle activity during unilateral clenching. This result suggests that the use of a splint is a method of suppressing clench-caused aggravation of stomatognathic dysfunction in the presence of an imbalance between left and right muscle activities.

Adult↗

Asymmetry of masticatory muscle activity during intercuspal maximal clenching in healthy subjects and subjects with stomatognathic dysfunction syndrome.

The present study investigated the asymmetry of masticatory muscle activity during maximal intercuspal clenching in healthy subjects and subjects with stomatognathic dysfunction syndrome. Stomatognathic dysfunction syndrome, unilateral mastication and the asymmetry of masticatory muscle activity appear to be related to each other. The asymmetry of masseter muscle activity was greater as stomatognathic dysfunction became increasingly severe. Because fatigue and pain are produced more quickly by unilateral clenching than bilateral clenching, clenching under conditions of left and right muscular imbalance can further aggravate stomatognathic dysfunction. It is suggested the asymmetry of masseter muscle activity during maximal clenching correlates with the onset of the stomatognathic dysfunction syndrome. Stomatognathic dysfunction syndrome is closely related to the asymmetry of masseter muscle activity and only slightly related to the asymmetry of temporal muscle activity. The asymmetry of anterior temporal muscle activity appears to have little clinical significance.

Adolescent↗

Retinoids enhance IgA production by lipopolysaccharide-stimulated murine spleen cells.

The effect of all-trans retinoic acid (RA) and vitamin A on IgA production by LPS-stimulated murine spleen cells was studied. Concentrations of immunoglobulins of six subclasses in the culture medium were determined. Only IgA level increased, RA dose dependently. In contrast, IgG1 level decreased and other subclasses (IgM, IgG2a, IgG2b, and IgG3) were not significantly affected by the treatment. IgA levels in LPS-stimulated spleen cells were usually between 10 and 100 ng/ml. When RA was added at the concentrations above 0.1 nM, the levels were increased dose dependently and peak response (8- to 20-fold) was observed from 0.1 to 1 microM. Enhancement of IgA secretion begins after 4 days culture and then increases linearly until Day 7. Vitamin A also showed IgA-enhancing activity, although its activity was about 1/170 of that of RA. TGF-beta activity in the culture medium was also determined, finding that RA rapidly stimulates secretion of biologically active TGF-beta, the elevation being evident after 1 day of culture. Specific neutralizing antibodies to TGF-beta 1 and TGF-beta 2 partially inhibited IgA enhancement caused by RA. These results suggest that retinoids at physiological concentrations may act as positive regulators for IgA production and the effect may be mediated, at least in part, via the induction of active TGF-beta.

Animals↗

Purification and identification of TGF-beta 2-related growth factor from bovine colostrum.

Bovine colostrum contains transforming growth factor (TGF)-beta-like activity. High levels of this activity are found in early colostrum (within 12 h after parturition); however, it decreases rapidly after 30 h. In this study, the activity in early colostrum was purified by a sequence of decaseination, DEAE-Sephacel chromatography, Sephadex G-100 gel filtration, precipitation at neutral pH, further gel filtration and reversed-phase FPLC. A homodimeric 23 kDa protein was identified that retained the TGF-beta-like activity. Its activity was completely neutralized by a specific anti-TGF-beta 2 antibody. These results indicate that the TGF-beta-like growth factor found in bovine colostrum is chemically and antigenically related to TGF-beta 2. The physiological roles of the TGF-beta 2-related growth factor are discussed.

Animals↗

[A study of methicillin-resistant Staphylococcus aureus (MRSA) infection in urological field].

Out of 110 strains of Staphylococcus aureus isolated from 1985 to 1990, isolation rate of methicillin-resistant S. aureus (MRSA) was investigated. Nineteen strains of 59 S. aureus from outpatients and 20 strains of 51 S. aureus from inpatients were determined as MRSA. Isolation frequency of MRSA from inpatients was increasing in the recent two years. Coagulase type, enterotoxin type and production of toxic shock syndrome toxin-1 (TSST-1) were examined in 22 strains of MRSA. Coagulase type II (86%), enterotoxin type C (68%) and TSST-1 positive strain was most dominant. Susceptibility of MRSA to 4 antimicrobial agents were measured, MRSA were sensitive to vancomycin (VCM), arbekacin (ABK) and minocycline, but resistant to flomoxef. Thirty-four patients from whom MRSA was isolated including 20 patients from urine, 13 from pus and 1 from blood, were analyzed clinically. Pyuria was not recognized in some cases in whom MRSA was isolated from their urine. Concomitant polymicrobial infection was frequently noted in those patients with MRSA in their urinary tract. These facts show that the pathogenic role of MRSA in the urinary tract infection was not significant. On the other hand, when MRSA was isolated from pus or blood, serious infections could be caused by MRSA, especially in compromised host. Regarding the treatment in these cases, administration of VCM or ABK was though to be necessary.

Aminoglycosides↗

Synthesis and biological activities of cyclopropenone antibiotic penitricin and congeners.

A number of derivatives of the cyclopropenone antibiotic penitricin have been synthesized by the reaction of metalated cyclopropenone acetals with electrophiles. Studies on the antimicrobial structure-activity relationships indicated that the penitricin skeleton, hydroxymethylcyclopropenone, is indispensable for antimicrobial activity. These compounds were also found to display cytotoxic activity.

Bacteria↗

A case of traumatic intramural hematoma of the duodenum effectively treated with ultrasonically guided aspiration drainage and endoscopic balloon catheter dilation.

A 52-year-old man was admitted on February 15, 1990, with hiccups and vomiting. He had been well until 13 days before admission when he stumbled and fell when intoxicated, striking his abdomen. A diagnosis of intramural hematoma was made with computerized tomography and sonography of the abdomen after admission, revealing a mass that was intimately related to the duodenum. Treatment of the intramural duodenal hematoma is controversial. However, this case illustrates the ideal situation where conservative management could be applied with total parenteral nutrition, percutaneous aspiration drainage, and endoscopic balloon catheter dilatation of the narrowed lumen of the duodenum. The patient's subsequent course supports the concept of planned conservative management.

Accidental Falls↗

Expression of placental alkaline phosphatase in gastric and colorectal cancers. An immunohistochemical study using the prepared monoclonal antibody.

The authors developed monoclonal antibodies (MoAb) against human placental alkaline phosphatase (PLAP). Four specific MoAb reacting only with PLAP and two nonspecific MoAb reacting equally with isozymes of alkaline phosphatase (hepatic, intestinal, and placental) were obtained. Immunohistochemical staining with the specific MoAb showed that the cell membrane and cytoplasm of cancer cells were stained in gastric and colorectal carcinoma. The incidence of PLAP positivity was 23% (25 of 107) of all gastric carcinomas. Among gastric carcinomas, the 42% (13 of 31) positivity of highly differentiated carcinoma (papillary adenocarcinoma and well-differentiated tubular adenocarcinoma) was a significantly higher rate than that found in poorly differentiated carcinoma (poorly differentiated adenocarcinoma and signet-ring cell carcinoma, five of 41, 12%). The incidence of PLAP positivity was 11% (four of 35) in colorectal carcinoma. In contrast, gastric adenoma, intestinal metaplasia, and noncancerous tissue adjacent to cancer did not show staining. These results indicated that expression of PLAP was apt to occur in more highly differentiated gastric carcinoma and was highly specific for carcinoma in the gastrointestinal tract, although its incidence was not high.

Alkaline Phosphatase↗

Isolation of two new proteins from bovine colostrum which stimulate epidermal growth factor-dependent colony formation of NRK-49F cells.

Defatted bovine colostrum and decaseinated whey contain biological activity similar to that of TGF-beta in that they stimulate the anchorage-independent growth of NRK-49F cells in the presence of EGF. Two new proteins with such activity, termed BC-1 and BC-2, were isolated from decaseinated colostrum by a sequence of DEAE-Sephacel chromatography, Sephadex G-100 gel filtration in 1 M acetic acid, Sephadex G-50 re-gelfiltration in 8 M urea-1 M acetic acid and reverse-phase FPLCs. The two proteins showed distinctly different molecular weight from that of TGF-beta 1. BC-1 was a small Mr peptide of 8.5 kD. BC-2 had molecular mass of 46 kD, which yielded peptides of 46,40, and 6 kD on reduction. In contrast to TGF-beta, both proteins did not lose their biological activity on reduction. Both BC-1 and BC-2 suppress DNA synthesis in concanavalin A-stimulated thymocytes. These results suggest that BC-1 and BC-2 belong to a new class of mitogen/inhibitors, though their biological activities resemble those of TGF-beta.

Animals↗

[Tissue free water tritium in pine needles around a nuclear power plant].

The elevation of the concentration of tissue free water tritium (TFWT) in pine needles was discernible in trees growing around a nuclear power plant. The values varied from 2.6 Bq/l to 6.1 Bq/l with a mean value of 3.8 Bq/l. Analysis of pine needles collected at Fukui City as control samples was done. The values averaged 1.7 Bq/l and fell within 1.5 B/l-1.8 Bq/l which was obtained nation-wide survey of TFWT in pine needles in Japan. The present study also revealed that reactor tritium incorporated into pine needles decreased rapidly with a half time of 6 days and then tissue free water tritium has a short retention time.

Japan↗