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T Tominaga

Publications and source records attributed to T Tominaga.

At least 145 records · Page 8Linked to original sources
PubMed1997

Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells.

Nitric oxide (NO) exerts cytotoxic effects on various cells including neuronal cells. Glial NO production, mediated via induction of inducible NO synthase (iNOS), enhances neurotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor. The present study examined whether nicotinamide, an inhibitor of poly (ADP-ribose) synthetase, inhibits NO formation in primary culture of rat glial cells. Nicotinamide (5-20 mM) suppressed iNOS mRNA expression and subsequent NO formation, which were induced by the combination of interferon-gamma and lipopolysaccharide, in a dose dependent manner. In addition, high-concentration (20 mM) nicotinamide decreased mRNA of interferon regulatory factor-1, a transcription factor which plays a major role in iNOS mRNA induction. These results suggest that nicotinamide may have protective effect on glial NO-related pathologies by preventing iNOS mRNA induction.

Animals↗
PubMed1997

The origin of an EPR signal observed in dithiocarbamate-loaded tissues. Copper(II)-dithiocarbamate complexes account for the narrow hyperfine lines.

We examined the electron paramagnetic resonance spectra of some copper(II)-dithiocarbamate complexes in various media at liquid nitrogen temperature. It is demonstrated that Cu(II)-dithiocarbamate complexes exhibit atypical spectra with narrow hyperfine splitting, and that the dithocarbamates forming a water-insoluble Cu(II) complex are permeable in tissues, while those yielding water-soluble complexes are not.

Animals↗
PubMed1997

Maintenance of constant blood acetylcholine content before and after feeding in young chimpanzees.

We have shown that acetylcholine (ACh) is present in the blood of various species of mammals using a specific, sensitive radioimmunoassay. In the present study, the effect on blood and plasma ACh levels of feeding after overnight fasting was studied in one male and five female 4- to 7-year-old chimpanzees. The mean basal ACh concentrations of the blood and plasma were 3143 +/- 380 and 184 +/- 10 pg/ml (+/-SEM, n = 6), respectively. Feeding each chimpanzee 500 g boiled sweet potatoes as breakfast at 1000 h and tap water given ad libitum did not affect the ACh content of the blood and plasma, and constant values of the blood and plasma ACh contents were observed for 4 h after the feeding. Hematocrit and plasma acetylcholinesterase (AChE) activity were also insensitive to feeding. No correlation was observed between plasma AChE activity and either blood or plasma ACh content. The results of the present study indicate that the blood ACh of chimpanzees is distributed mainly in the blood cell fraction, and that the blood ACh content is not regulated directly by cholinergic nerve activity or by plasma AChE activity.

Acetylcholine↗
PubMed1997

Differential alteration of hippocampal synaptic strength induced by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38).

We investigated the effect of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on synaptic transmission in rat hippocampal slices using extracellular recordings. Brief bath application of PACAP-38 induced a long-lasting depression of transmission at the Schaffer collateral-CA1 synapse while at the same time causing enhancement of the perforant path-granule cell synapse in the dentate gyrus. Depression at the CA1 synapse was not occluded by low frequency-induced long-term depression (LTD), nor was enhancement at the granule cell synapse blocked by previous high frequency-induced long-term potentiation (LTP). Both actions of PACAP-38 could be elicited in the presence of an N-methyl-D-aspartate (NMDA) receptor antagonist, or in the presence of inhibitors of cyclic AMP- or Ca2+-dependent protein kinases, suggesting a novel mechanism of synaptic modulation.

Animals↗
PubMed1997

Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma.

BACKGROUND: The clinical outcome is generally positive for patients with node-negative breast carcinoma (i.e., those who do not have detectable metastases in the lymph nodes) who have been treated with surgery or surgery plus radiation therapy. In about 30% of the patients, however, the disease recurs, and they are at risk of death. Determination of valid new prognostic indicators would improve the ability to identify patients at high risk of recurrence. Breast cancer can entail substantial development of new blood vessels within the tumor tissue, and it is known that the growth and metastasis of solid tumors are dependent on such angiogenesis. The conversion of tumor cells to an angiogenic phenotype may be preceded by a change in the balance of angiogenic growth factors and angiogenesis inhibitors. PURPOSE: This study was conducted to determine if the levels of vascular endothelial growth factor (VEGF) protein, a potent endothelial growth factor and mediator of vascular permeability and angiogenesis, measured in the primary tumors of women with node-negative breast cancer are associated with known prognostic factors and patient survival. METHODS: By use of a selective enzymatic immunoassay, levels of VEGF protein were measured in cytosolic extracts of primary tumor tissue surgically obtained from 260 women with node-negative breast carcinoma who had been treated with surgery with or without radiation therapy but not with adjuvant therapy and who had been followed for a median time of 66 months. The relationships between VEGF concentrations and other prognostic dichotomous variables or clinical outcome were tested by the use of the Kolmogorov-Smirnov test and univariate and multivariate Cox analyses, respectively. The relationship between VEGF and hormone receptors (i.e., those for estrogen and progesterone) was examined by the use of Spearman's correlation analyses. All P values resulted from the use of two-sided statistical tests. RESULTS: Tumors from 247 (95%) of the 260 patients had detectable VEGF, ranging in concentration from 5.0 to 6523 pg/mg protein (median, 126.25 pg/mg protein). No statistically significant associations were found between VEGF and the other prognostic factors (e.g., age, menopausal status, histologic tumor type, tumor size, and hormone receptors) examined. Levels of VEGF were found to be prognostic for both relapse-free and overall survival in univariate and multivariate analyses (likelihood ratio tests; all four P values < .001). In the multivariate analysis, the first-order interaction term of VEGF and estrogen receptor was also prognostic for overall survival (likelihood ratio test; P = .05). CONCLUSIONS: The results show that cytosolic levels of VEGF in tumor tissue samples are indicative of prognosis for patients with node-negative breast carcinoma.

Adult↗
PubMed1997

Outcome of surgical resection for chest wall recurrence in breast cancer patients.

BACKGROUND: Although recurrent breast cancer is a systemic disease, there might be several exceptions where local treatment has a favorable outcome. METHODS: From 1989 to 1996, 15 patients underwent full thickness chest wall resection, supported by peri- and postoperative systemic treatments for patients with isolated chest wall recurrences, including soft tissue local recurrence and parasternal lymph node metastasis. RESULTS: The 5-year survival rate after surgical removal was 47%. Patients with > 5-year disease-free intervals (DFI) after mastectomy showed a long survival after chest wall resection. Local failures appeared in four cases whose surgical margins were positive. No serious complication except one pyothorax occurred after surgery. CONCLUSIONS: It is suggested that surgical treatment with a full thickness chest wall resection might have a favorable prognosis for selected patients with solitary lesion and long DFI.

Adult↗
PubMed1997

Multiple intracranial mixed germ cell tumors.

A case of sequential occurrence of multiple intracranial mixed germ cell tumors is presented. An 8-year-old boy with a cystic calcified tumor in the basal ganglia and an increased serum alpha-fetoprotein concentration was initially treated with radiotherapy. Six years later, a tumor composed of embryonal carcinoma and immature teratoma arose from the right temporo-parietal lobe. This tumor was treated successfully with surgery and radiochemotherapy. The possibility of multicentricity or intra-axial metastasis distant from the original site during the long-term course should be considered in treatment for intracranial germ cell tumors.

Brain↗
PubMed1997

Effect of TYB-2285 on passive cutaneous anaphylaxis in rats.

1. TYB-2285 (1-30 mg/kg p.o.) inhibited ovalbumin (OA)- and dinitrophenyl-Ascaris (DNPAs)-induced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. 2. The ED50 of TYB-2285 and ketotifen fumarate on OA-induced PCA were 0.5 and 3.9 mg/kg, respectively. The ED50 of TYP-2285 and amlexanox on DNP-As-induced PCA were 3.5 and 0.9 mg/ kg, respectively. 3. TYB-2285 (3-30 mg/kg p.o.) inhibited histamine consumption at the PCA site. 4. Unlike cyproheptadine or amlexanox, TYB-2285 (30 mg/kg p.o.) did not inhibit histamine-, serotonin-, ascites-, 48/80-, or A23187-induced capillary permeability. It inhibited dextran-induced capillary permeability slightly. 5. These results demonstrate that TYB-2285 inhibits PCA by inhibiting histamine release, although it does not inhibit capillary permeability.

Animals↗
PubMed1997

Effect of TYB-2285 on lung anaphylaxis in actively sensitized rats.

1. We examined the effect of TYB-2285 on the acute phase and the late phase of lung anaphylaxis in rats. 2. TYB-2285 (3-30 mg/kg PO) inhibited antigen-induced bronchoconstriction and TxB2 production during the acute phase of lung anaphylaxis in a dose-dependent manner. 3. Ketotifen fumarate (30 mg/kg p.o.) inhibited bronchoconstriction and TxB2 production less potently than TYB-2285. 4. TYB-2285 (30 mg/kg p.o.) inhibited the accumulation of neutrophils during the late phase of lung anaphylaxis significantly without a significant change in total cells. 5. Hydrocortisone acetate (100 mg/kg p.o.) inhibited the accumulation of total cells as potent as neutrophils.

Anaphylaxis↗
PubMed1997

Effects of TYB-2285 on the accumulation of eosinophils in the airway induced by antigen exposure in actively sensitized brown Norway rats.

1. The effect of TYB-2285 on the antigen-induced accumulation of eosinophils into the airway was investigated in two models (inhalant sensitization and noninhalant sensitization) using Brown Norway (BN) rats. 2. In the method of inhalant sensitization, BN rats were sensitized by weekly exposure to ovalbumin (OA). The accumulation of eosinophils was inhibited by the oral administration of TYB-2285 for the first 2 days of each sensitization in a dose-dependent manner. 3. With noninhalant sensitization, BN rats were sensitized by i.m. injection of OA and i.p. injection of killed Bordetella pertussis. The accumulation of eosinophils was inhibited by TYB-2285 in a dose-dependent manner, when TYB-2285 is given p.o. 5 mm before and 5 hr after the antigen exposure. Moreover, this accumulation of eosinophils was inhibited by a single administration of TYB-2285 5 hr after the antigen exposure, presumably when the mast cell degranulation was already finished. 4. In the method with noninhalant sensitization, the accumulation of eosinophils was not inhibited by mast cell stabilizers such as ketotifen, tranilast, or DSCG. 5. The present study demonstrates that TYB-2285, unlike other mast cell stabilizers, inhibits the antigen-induced accumulation of eosinophils into the airway. It also suggests that this drug might be effective in asthmatic patients.

Animals↗
PubMed1997

Effect of TYB-2285 on antigen-induced accumulation of eosinophils into the peritoneal cavity of rats sensitized with Ascaris suum extract.

1. The present study was carried out to investigate the effect of 3,5-bis-(acetoxyacetylamino)-4-chloro-benzonitrile (TYB-2285) on the accumulation of eosinophils in the peritoneal cavity of Wistar rats sensitized with Ascaris suum extract (Asc). 2. Rats were sensitized by IP injection of Asc on day 0 and were challenged by IP injection of Asc on day 7. Antigen challenge caused a specific, delayed infiltration of eosinophils into the peritoneal cavity that was inhibited by PO administration of TYB-2285, but not ketotifen fumarate, in a dose-dependent manner (3-30 mg/kg). 3. TYB-2285 inhibited the infiltration of eosinophils when during the induction phase, but not during the effector phase. The inhibitory effect of TYB-2285 when during the induction phase was stronger than any other antiallergic drugs, such as tranilast, azelastine, ibudilast, repirinast, tazanolast, oxatomide, or pemirolast. 4. Transfer of lymphocytes, but not serum, from sensitized rats to intact rats provoked a remarkable infiltration of eosinophils after the antigen challenge. In the experiment of adoptive transfer in rats, TYB-2285 was effective when given to donor rats. 5. These results demonstrate that TYB-2285 inhibits the accumulation of eosinophils presumably by inhibiting antigen recognition.

Adoptive Transfer↗
PubMed1997

The effects of TYB-2285 and its metabolites on lymphocyte responses in vitro.

1. We examined the effects of TYB-2285 and its metabolites (TC-286 and TC-326) on antigen-induced lymphocyte proliferation, allogeneic mixed lymphocyte reaction (MLR) and mitogen-induced lymphocyte proliferation. 2. Splenic lymphocytes from C57BL/6 strain mice sensitized with human serum albumin were cultured with the antigen in the presence of TYB-2285 or its metabolites (10(-7)-10(-4) M). The lymphocyte proliferation enhanced by antigen was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 3. Splenic lymphocytes collected from C57BL/6 and Balb/C strain mice were cocultured in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). Allogeneic MLR was inhibited by TYB-2285 and its metabolites in a dose-dependent manner. 4. Splenic lymphocytes from C47BL/6 strain mice were cultured with concanavalin A (Con A) in the presence of TYB-2285 and its metabolites (10(-7)-10(-4) M). TYB-2285 and its metabolites did not affect Con A-induced lymphocyte proliferation. Cyclosporin A showed an inhibitory effect on Con A-induced lymphocyte proliferation that was as strong as the inhibitory effect on antigen-induced lymphocyte proliferation and allogeneic MLR at a lower concentration.

Albumins↗
PubMed1997

Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: prognostic implications.

Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2-843.1), 0.22 ng/mg (range 0.0-41.65) and 33.80nmol/mg (range 4.20-216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p<0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p<0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.

Journal Article↗
PubMed1997

Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells.

Adrenomedullin is a potent vasodilator peptide that was originally isolated from pheochromocytoma. The production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells were studied by radioimmunoassay and northern blot hybridization. Choroid plexus carcinoma is a rare malignant tumor derived from the epithelium of the choroid plexus. Immunoreactive adrenomedullin was detected in the conditioned medium of choroid plexus carcinoma cells (40.8 +/- 7.5 fmol/10(5) cells/24 h; mean +/- SEM, n = 5). Reverse-phase HPLC of the conditioned medium showed one major peak of the immunoreactive peptide eluting in the position of synthetic human adrenomedullin and two smaller peaks eluting earlier. Addition of interleukin-1 beta (10 ng/ml) alone or in combination with three cytokines, interferon-gamma (100 U/ml), tumor necrosis factor-alpha (20 ng/ml), and interleukin-1 beta (10 ng/ml), caused significant increases in the immunoreactive adrenomedullin concentrations in the medium (approximately 175 and 293% of the control level, respectively). Northern blot analysis showed the expression of 1.6-kb adrenomedullin mRNA in the total RNA sample prepared from cultured choroid plexus carcinoma cells. Treatment with either interleukin-1 beta or the combination of three cytokines caused significant increases in levels of adrenomedullin mRNA in parallel with those in immunoreactive adrenomedullin concentrations in the conditioned medium. These findings raise a possibility that adrenomedullin is secreted from the choroid plexus and has physiological roles in the CNS via the CSF. In addition, adrenomedullin secreted from choroid plexus carcinoma may be related to the pathophysiology of the tumor.

Adrenomedullin↗
PubMed1997

A conserved arginine residue in the pore region of an inward rectifier K channel (IRK1) as an external barrier for cationic blockers.

The number, sign, and distribution of charged residues in the pore-forming H5 domain for inward-rectifying K channels (IRK1) are different from the otherwise homologous H5 domains of other voltage-gated K channels. We have mutated Arg148, which is perfectly conserved in all inward rectifiers, to His in the H5 of IRK1 (Kir2. 1). Channel activity was lost by the mutation, but coexpression of the mutant (R148H) along with the wild-type (WT) mRNA revealed populations of channels with reduced single-channel conductances. Long-lasting and flickery sublevels were detected exclusively for the coexpressed channels. These findings indicated that the mutant subunit formed hetero-oligomers with the WT subunit. The permeability ratio was altered by the mutation, while the selectivity sequence (K+ > Rb+ > NH4+ >> Na+) was preserved. The coexpression made the IRK1 channel more sensitive to extracellular block by Mg2+ and Ca2+, and turned this blockade from a voltage-independent to a -dependent process. The sensitivity of the mutant channels to Mg2+ was enhanced at higher pH and by an increased ratio of mutant:WT mRNA, suggesting that the charge on the Arg site controlled the sensitivity. The blocking rate of open channel blockers, such as Cs+ and Ba2+, was facilitated by coexpression without significant change in the steady state block. Evaluation of the electrical distance to the binding site for Mg2+ or Ca2+ and that to the barrier peak for block by Cs+ or Ba2+ suggest that Arg148 is located between the external blocking site for Mg2+ or Ca2+ and the deeper blocking site for Cs+ or Ba2+ in the IRK1 channel. It is concluded that Arg148 serves as a barrier to cationic blockers, keeping Mg2+ and Ca2+ out from the electric field of the membrane.

Animals↗
PubMed1997

International differences in approaches to 131I therapy for Graves' disease: case selection and restrictions recommended to patients in Japan, Korea, and China.

Members of the American Thyroid Association (ATA), European Thyroid Association (ETA), Japan Thyroid Association (JTA), Korean Thyroid Association (KTA), and Chinese Thyroid Association (CTA) were surveyed independently through an identical questionnaire on their management of Graves' disease. One of the major purposes of the survey was to determine how expert thyroidologists in different regions of the world use three different therapies available for a typical Graves' patient as well as for clinical variations provided. In this report, we summarized, contrasted, and interpreted the results of the surveys in three Asian countries by focusing on therapeutic preference of radioiodine. For the index patient with hyperthyroidism due to Graves' disease, radioiodine was the therapy of choice for 69% of ATA respondents but only 22%, 22%, 11%, and 11% of ETA, CTA, JTA, and KTA respondents, respectively. The goal of radioiodine therapy in Asian countries was to restore the euthyroid state. For the case of recurrence after surgery, there was consensus on choosing radioiodine among all countries surveyed. To interpret the reluctance to advocate radioiodine therapy for a typical Graves' patient in Japan, a new survey concerning the current trends in radioiodine therapy in Japan was conducted among clinical members of the JTA. The phobia of radiation and stringent safety rules for radioactive pharmaceuticals were the two major reasons found. Nevertheless, the percentage of JTA respondents who aim for the euthyroid of hypothyroid state by radioiodine therapy for typical Graves' significantly increased compared with respondents to the former survey in 1988. Moreover, a considerable number of JTA members believe that more radioiodine therapy should be applied for achievement of the rapid improvement of hyperthyroidism, for convenience, and for medical cost benefits.

Adult↗
PubMed1997

Cine magnetic resonance imaging of spinal intradural arachnoid cysts.

OBJECTIVE: The diagnostic value of cine magnetic resonance imaging (CMRI) that visualizes fluid and tissue movement was evaluated in patients with spinal intradural arachnoid cysts, a rare but increasingly detected cause of spinal cord dysfunction. METHODS: Four patients with thoracic spinal intradural arachnoid cysts were investigated with conventional T1- and T2-weighted and cardiac-gated CMRI. Four normal volunteers also underwent CMRI for comparison. RESULTS: Sagittal T1- and T2-weighted imaging showed lesions as an abnormal widening of the posterior spinal subarachnoid space, but mixed high- and low-signal intensities on T2-weighted imaging suggested cystic lesions. CMRI, using 16 to 20 sagittal gradient echo images during the cardiac cycle of normal volunteers, indicated synchronous signal changes along the subarachnoid space, suggesting a smooth cerebrospinal fluid flow. CMRI of patients detected that the caudal or cranial direction of the high-signal propagation suddenly reversed at some locations (as if rebounding) in an asynchronous fashion along the lesion (asynchronous rebound phenomenon), which was well demonstrated by the closed-loop video mode. Cystectomy revealed that the cysts consisted of multiple lobules and that the asynchronous rebound phenomenon corresponded with some boundaries of cyst lobules. CMRI also visualized dynamic spinal cord compression by the cyst. CONCLUSION: CMRI can demonstrate abnormal fluid flow and spinal cord compression caused by a spinal intradural arachnoid cyst.

Adult↗