Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 145 records · Page 8Linked to original sources

PubMed2000

Primary malignant lymphoma of the central nervous system presenting with ascites and pleural effusion.

A 70-year-old woman was admitted to our hospital owing to ascites and pleural effusion. Though malignant cells (B-cell type lymphoma) were detected in both the ascites and pleural effusion, neither lymph node swelling nor a tumor was detected upon chest, abdominal and pelvic computed tomography (CT). After weekly THP-COP therapy for 8 weeks, the ascites and pleural effusion completely disappeared. Two years after the first admission, she was re-admitted because of a disturbance of consciousness, and a brain tumor was detected on CT scan. The immunohistological and genetic data for the brain tumor were identical to those of the malignant cells in the pleural effusion and ascites detected 2 years previously. Whereas the symptoms at onset of a primary lymphoma of the central nervous system (CNS) are usually neurological ones, in this rare case of primary CNS lymphoma, the symptoms at onset were the ascites and pleural effusion without neurological symptoms.

Aged↗

PubMed2000

In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene, and its modifying effects on xenobiotic enzyme activities in mouse livers.

We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely occurring in citrus fruit, is a structurally novel type of effective cancer-preventive agent, as manifested in several rodent models. However, its bio-availability and metabolism in biological systems have yet to be investigated. In the present study, we examined the chemical stability of AUR at pH 1.57 and 37 degrees C (as a stomach digestion model) and observed its stoichiometric conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t1/2) = 15 h; 7-ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human colorectal adenocarcinoma cell line, were used as a small intestine model. ETC permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent manner; AUR slightly permeated the cells, but with an intracellular accumulation. Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9 mixture. ETC was also converted to UMB, but its t1/2 of two hours was much shorter than that of AUR (> 24 h). This suggests that AUR, bearing a geranyloxyl side chain, is a relatively metabolism-resistant substrate for cytochrome P-450 enzymes and, thus, is stable in the liver compared with ETC. Oral administration of AUR by gavage at 50-200 mg/kg body wt dose dependently induced glutathione S-transferase (GST) activity in mouse livers without affecting cytochrome P-450 activity. Using 10 coumarin-related compounds, we found that only those coumarins having a 7-alkyloxyl group induced GST, but not cytochrome P-450, activity. The present study presumes that AUR accumulates in the epithelial cells of the small intestine and then gradually permeates into the portal vein. Stable localizability of AUR in the colon and liver may be associated with the induction of GST activity, which is important as the action mechanism for suppression of rodent chemical carcinogenesis.

Absorption↗

PubMed2000

Effects of Aconitum alkaloid kobusine and pseudokobusine derivatives on cutaneous blood flow in mice; II.

Aconitum alkaloids of the C20-diterpenoid type, kobusine (1) and pseudokobusine (2), their anisoyl, veratroyl, p-nitrobenzoyl, nicotinoyl or pivaloyl derivatives, and dehydrokobusine and N,6-seco-6-dehydropseudokobusine derivatives were examined for their peripheral vaso-activities by laser-flowmetrical measurement of the cutaneous blood flow in the hind foot of mice after intravenous administration. Kobusine 15-anisoate (4), 11-veratroate (5), 15-veratroate (6), 11-pivaloate (9) and 15-pivaloate (10) were significantly effective at a low dose of 0.5 or 0.05 mg/kg. Pseudokobusine derivatives were all active at 1, 0.5 or 0.05 mg/kg, and the effects of pseudokobusine 15-anisoate (13), 15-veratroate (16) and 15-p-nitrobenzoate (19) at 0.1 mg/kg were remarkable. Yesoline (26) and alkaloid (28) were significantly effective at a low dose of 1 mg/kg, whereas yesonine (25) and N-acetyl-N,6-seco-6-dehydropseudokobusine (27) were inactive. Dehydrokobusine derivatives (29, 30) were significantly effective at a low dose of 0.5 or 0.1 mg/kg. It is thought that the hydroxyl groups of alkaloids, especially a free OH group of 2 at C-6, are important for action on the peripheral vasculature leading to dilatation, and the results indicated that esterification of the hydroxyl group at C-15 with either anisoate, veratroate orp-nitrobenzoate may contribute to enhancement of the activity of the parent alkaloids.

Animals↗

PubMed2000

Application of liquid chromatography-atmospheric pressure chemical ionization mass spectrometry to the differentiation of stereoisomeric diterpenoid alkaloids.

High-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI-MS) was successfully applied to seven stereoisomeric diterpenoid alkaloids at position 1 or 12. Comparison of the breakdown curves, observed by changing the potential difference between the first electrode and the second electrode of the APCI ion source, revealed stereochemical dependence of different fragmentations. The APCI spectra of alkaloids were predominantly the [M+H]+ ion and the major fragment ion, corresponding to the [M+H-H2O]+ ion or the [M+H-CH3COOH]+ ion, and comparison of the APCI spectra showed that the abundance of fragment ions was significantly higher for C-1 beta-form alkaloids than for C-1 alpha-form alkaloids, and for C-12 beta-form alkaloids than for C-12 alpha-form alkaloids. The characteristic fragment ions were formed due to the loss of an acetic acid or a water molecule at position 12. The fragmentation mechanisms depending on the stereochemistry of the precursor ion could be discerned by recording the spectra in a deuterated solvent system of 0.05 M ammonium acetate in D2O-acetonitrile-tetrahydrofuran. Loss of CH3COOD or D2O from the precursor ion gave the fragment ion. This result indicated that the proton of protonation was included in the leaving acetic acid and water molecule, respectively. The peak intensity ratio for R=[M+H]+/[M+ H-H2O]+ + [M + H-CH3COOH] + manifested the stereochemical differentiation of alkaloids at position 1 or 12.

Alkaloids↗

PubMed2000

Preparation and characterization of acrylic hydrogels neutralized by basic amino acids.

Basic amino acids were used as neutralizers in the gellation of Eudispert as an acrylic hydrogel. Arginine and lysine successfully neutralized Eudispert, as did sodium hydroxide, and formed hydrogels. A gentle rise of pH was observed as the dosage of the base increased when arginine and lysine were used, in contrast to the sharp rise of pH observed when sodium hydroxide was used. The rank of viscosity of the prepared hydrogels was as follows: lysine > arginine > NaOH. The release rate of model drugs (salicylic acid, theophylline, and bovine insulin) from the prepared hydrogels ranked as follows: NaOH>lysine>arginine, the sustained-release profile being observed with arginine. The rate of diffusion of the model drug from the hydrogel was inversely proportional to the molecular weight of the cationized neutralizer used. It is concluded that the strategy of neutralization of acidic polymers by basic amino acids has advantage with the respect to both the sustained-release characteristics of the gel and the biocompatibility of the basic amino acids themselves.

Amino Acids↗

PubMed2000

Quantitative evaluation of the bitterness of commercial medicines using a taste sensor.

The bitterness of 11 commercial medicines was evaluated both by a multichannel taste sensor and in human gustatory sensation tests with 15 volunteers. For basic drugs with amino groups in the molecule, such as quinine, there was a comparatively strong relative response electric potential (mV) of channels 1 or 2, those containing negatively charged membranes and the bitterness determined by human gustatory sensation tests. The suppression of the bitterness of quinine by sucrose and aspartame could be quantified using the artificial taste sensor and the results concurred with those from gustatory sensation tests. The usefulness of the sensor was thus confirmed for this type of compound. Anionic drugs, such as diclofenac sodium or salicylic acid gave rise in a negative response electric potential in channels 5 or 6, those containing positively charged membrane, seemed to be useful information even though their tastes are being sour rather than bitter. For drugs with both an amino (cationic) group and carboxylic acid (anionic) group in the molecule, such as theophylline, caffeine, and metronidazole, the relative response electric potential (mV) of channels containing negatively charged membranes was not increased, even though bitterness was observed in human gustatory sensation tests. Therefore, a different design of membrane component is required for more general evaluation of the bitterness of various medicines.

Aspartame↗

PubMed2000

Application of liquid chromatography-atmospheric pressure chemical ionization mass spectrometry to the differentiation of stereoisomeric C19-norditerpenoid alkaloids.

High-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI-MS) was successfully applied to stereoisomeric C19-norditerpenoid alkaloids at position 1. APCI-MS allowed the easy and precise control of the energy deposition by varying the drift voltage. Comparison of the breakdown curves, observed by changing the potential difference between the first electrode and the second electrode of the APCI ion source, revealed stereochemical dependence of different fragmentations. The APCI spectra of alkaloids were predominantly the [M+H]+ ion and major fragment ion, corresponding to the [M+H-H2O]+ ion or the [M+H-CH3COOH]+ ion, and comparison of the spectra showed that the abundance of fragment ions was significantly higher for C-1 beta-form alkaloids than for C-1 alpha-form alkaloids. The characteristic fragment ions were formed by the loss of a water, acetic acid or methanol molecule at position 8. The fragmentation mechanisms depending on the stereochemistry of the precursor ion could be discerned by recording the spectra in a deuterated solvent system of 0.05 M ammonium acetate in D2O-acetonitrile-tetrahydrofuran. Loss of D2O from the precursor ion gave the fragment ion. This result indicated that the proton of protonation was included in the leaving water molecule. The peak intensity ratio R=[M+H]+/[M+H-H2O]+ manifested the stereochemical differentiation of alkaloids at position 1.

Alkaloids↗

PubMed2000

Estrogen secreting adrenal adenocarcinoma in an 18-month-old boy: aromatase activity, protein expression, mRNA and utilization of gonadal type promoter.

We examined clinical, endocrinological and molecular biological aspects of an estrogen-secreting adrenal carcinoma in an 18-month-old male to clarify the pathogenesis of this condition. An 18-month-old boy was referred for evaluation of progressive bilateral gynecomastia and appearance of pubic hair. The patient had elevated plasma estradiol (349 pg/ml) and testosterone (260 ng/dl) levels that completely suppressed FSH and LH levels, and was subsequently diagnosed with an adrenal tumor on the right side. After removal of a 300-g adenocarcinoma, gynecomastia regressed and essentially normal hormone levels were restored. Aromatase activity in the tumor tissue determined by the 3H-water method was 71.0-104.4 pmol/min/mg protein. High levels of aromatase protein and mRNA in the tumor tissue were also demonstrated, while neither aromatase activity nor protein was detected in normal adrenal glands. To investigate the regulation of aromatase expression in the adrenal carcinoma, we examined the usage of alternate promoters responsible for aromatase gene transcription. In the present case, the amounts of aromatase mRNA utilizing gonadal types of exon 1c (1.3) and 1d (II) were significantly higher than those that using other exon 1s. This result suggested that the utilization of a gonadal-type exon 1 might be involved in the over-production of aromatase in estrogen-secreting adrenal carcinoma.

Adenocarcinoma↗

PubMed2000

Long-term outcome of endocrine function in patients with neurohypophyseal germinomas.

Since neurohypophyseal germinomas occur at the pituitary and hypothalamic axis in children and adolescents, the endocrinopathy is one of the common and critical QOL determinants. We carried out a retrospective study on the outcome of endocrine function in patients with neurohypophyseal germinoma, in order to improve or preserve pituitary function after treatment. Sixteen patients (7 men and 9 women), aged 6 to 26 years were admitted and followed up for 95.3 (14-197) months. DI was noted in 12 patients in pretreatment and 16 in posttreatment regardless of tumor size. We carried out the replacement of GH in all 8 patients, presenting the symptoms under 15 years of age. Gonadal or gonadotropic, thyroid and adrenal hormones were replaced in 9, 12 and 15 patients, respectively. Patients with large tumor compressing chiasm or hypothalamus needed hormonal replacement such as gonadal or gonadotropic and thyroid hormones more frequently (<0.01) than those with small one. In addition, two patients with a small tumor at the pituitary stalk and the 3rd ventricle floor showed the improvement of secretion pattern in gonadotropins and ACTH after chemotherapy, although they later needed radiation therapy to control the tumor. Based on our study and review of literature, the endocrinological studies before and after treatment demonstrated that pituitary dysfunction present before treatment persisted or worsened even after tumor remission, except for patients with small and localized ones. The poor endocrine results is considered to be largely radiation-related. Chemotherapy alone seems to be insufficient to obtain complete response (CR). To avoid radiation related pituitary injury, combination of 24 Gy or less dosage of radiation and appropriate chemotherapy is essential. The earlier diagnosis by repeatedly using neuroimaging and serum and CSF tumor markers and earlier initiation of treatment, before irreversible pituitary-hypothalamic damage occurs, contributes to improvement of the outcome of pituitary functions in patients with neurohypophyseal germinomas.

Adolescent↗

PubMed2000

Maternal hypothyroidism in autoimmune thyroiditis and the prognosis of infants.

We evaluated the developmental prognosis of 31 infants born to mothers with autoimmune thyroiditis. Four of the babies developed transient neonatal hypothyroidism. Their mothers all had low thyroid hormone concentrations during pregnancy. Neonatal thyroid function tended to correlate with maternal thyroid function at delivery in babies born to mothers with Graves'disease who were taking antithyroid drugs. Since severe fetal hypothyroidism sometimes results in neurological damage, it is important to maintain normal maternal thyroid function during pregnancy.

Antithyroid Agents↗

PubMed2000

Recurrence of sellar and suprasellar tumors in children treated with hGH--relation to immunohistochemical study on GH receptor.

PURPOSE: GH replacement therapy is required in the majority of children with GH deficiency after treatment of sellar and suprasellar tumors. Owing to the high cell proliferative ability of human GH (hGH), its influence on tumor recurrence has been debated. We retrospectively studied the immunohistochemical expression of the GH receptor in various tumor tissues, in order to investigate the relation between tumor recurrence and hGH replacement. METHODS: GH replacement therapy was performed in 25 patients (8 boys and 17 girls) after the treatment. Tumor recurrence was noted in 4 patients (craniopharyngioma: 2 patients, pilocytic astrocytoma and germinoma: 1 each). Immunohistochemical study of GH receptor in tumor tissue was carried out in those recurrent and recurrence-free cases, by using MAb 263 as a primary antibody. RESULTS: Two patients with recurrent craniopharyngioma were positive for MAb 263, but 1 recurrence-free patient was negative. Patients with pilocytic astrocytoma (recurrent and recurrence-free: 1 each) were all positive. Five patients with germinoma (1 with recurrence and 4 without recurrence) were all negative. CONCLUSION: In the patients with craniopharyngioma treated with GH, a positive immunohistochemical expression of GH receptor in tumor tissue may indicate a high probability of recurrence. In our cases, GH receptor was positive in astrocytomas and negative in germinomas, with or without recurrence. It is therefore speculated that each brain tumor may have its specificity in GH receptor expression.

Adolescent↗

PubMed2000

Bombesin-like peptides: studies on food intake and social behaviour with receptor knock-out mice.

Bombesin (BN)-like peptides and receptors for these peptides are widely distributed in mammalian peripheral tissues and the central nervous system. The physiological and behavioural functions of these peptides have been clarified by both in vivo and in vitro studies. In spite of intensive investigations, the functions of endogenous BN-like peptides remain unclear. In order to specify these functions, our group and another laboratory generated by gene targeting mutant mice that lack one of the three BN-like peptide receptors found in mammals, ie neuromedin B receptor (NMB-R; BB1), gastrin-releasing peptide receptor (GRP-R; BB2), or bombesin receptor subtype-3 (BRS-3; BB3). Using these mutant mouse, we have found unexpected phenotypes, such as hyperphagia and obesity in the BRS-3-deficient mouse, and abnormal social behaviour in the GRP-R-deficient mouse. In the present study, we present our most recent findings in addition to previous studies and discuss the functions of BN-like peptides related to feeding and social behaviour from the point of view of knock-out mice studies.

Animals↗

PubMed2000

Pretreatment with continuous-wave ultraviolet irradiation to prevent the development of delayed vasospasm in the rabbit common carotid artery model.

OBJECT: Ultraviolet (UV) light irradiation can lead to immunomodulation. The purpose of this study was to determine the preventive effect of UV light on cerebral vasospasm by using a rabbit common carotid artery (CCA) model. METHODS: Rabbit CCAs were constricted for a long period by application of autologous blood within a silicon sheath. Before immersion in blood, the CCAs were adventitiously exposed to UV light emitted from a helium-cadmium laser (wavelength 325 nm) yielding an irradiation energy of 10 mJ/mm2. The occurrence of vasospasm was evaluated using angiography 48 hours after blood exposure in this model. The UV light treatment significantly reduced the degree of vasospasm. Compared with luminal diameters measured on Day 0, prior to treatment, the luminal diameters of UV light-treated arteries (six animals) decreased by only 6%, whereas that of the sham-treated arteries (eight animals) significantly decreased by 26% (p<0.001). Histological examination of UV light-treated CCAs revealed no endothelial damage and extended smooth-muscle cells, in which some fragmented nuclei were confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Twenty-eight days after blood exposure, examination of UV light-treated CCAs revealed only myointimal proliferation, similar to that of the sham-treated CCAs. CONCLUSIONS: These results are the first to provide evidence of a prophylactic effect of UV light on vasospasm and are suggestive of involvement of apoptosis in the mechanism of this effect.

Animals↗

PubMed2000

[Suppressive effects of lanoconazole on arthus phenomenon in vivo and on production and functions of TNF in vitro].

The anti-inflammatory effect of lanoconazole (LCZ) was investigated in vivo and in vitro. The effect of LCZ was evaluated on the inflammatory reactions elicited by intradermal injection of ovalbumin to ovalbumin-immunized rabbits, as an Arthus phenomenon. A one or two % cream preparation of LCZ was topically applied on the lesion daily after challenging injection until the inflamation had diminished. By macroscopic observation and measuring the diameter of edema, erythema, hemorrhage and necrosis, the effects of LCZ on the reactions were compared with the reactions of the sites administered withcream vehicle as reference agent. Two % LCZ showed an anti-hemorrhagic effect. The in vitro effect of LCZ on production and functions of an inflammatory cytokine, TNF was also examined. LCZ suppressed the production of TNF by murine peritoneal macrophages at 20 micro g/ml and the adhesion of neutrophils at 100 micro g/ml. Moreover, LCZ significantly suppressed the growth inhibitory activity of TNF against L929 fibroblasts at 0.5 micro g/ml. A very low concentration of LCZ might protect the fibroblasts from immunological cytotoxicity in vivo. These findings suggest that LCZ has a suppressive activity to inflammatory responses and this suppressive action may be due to its protective activity to cells like fibroblasts.

Animals↗

PubMed2000

Recurrent cases of corticosteroid-induced mood disorder: clinical characteristics and treatment.

BACKGROUND: Corticosteroids often induce steroid psychosis, a collection of heterogeneous syndromes with different pathophysiologic mechanisms. To date, no study has focused specifically on recurrent corticosteroid-induced mood disorders and considered their long-term outcome and treatment strategies. METHOD: Nine patients whose initial clinical presentation met DSM-IV criteria for a substance-induced mood disorder were identified by a review of medical records. Their clinical characteristics and treatments were examined. RESULTS: All 9 corticosteroid-treated patients had a clinical course of bipolar disorder. Seven patients initially developed a manic or hypomanic state with subacute onset ranging from 1 to 3 months. Six patients had manic episodes accompanied by psychotic features. The proportion of manic episodes relative to total mood episodes of the 9 patients was 65.6%, suggesting manic predominance. Seven patients showed mood episodes that had no direct relationship to corticosteroid therapy and were preceded by various psychosocial stressors. Four of 5 patients who received steroid pulse therapy rapidly became manic or hypomanic. Antidepressants as well as mood stabilizers were useful for treatment of the present 9 patients. CONCLUSION: Recurrent cases of corticosteroid-induced mood disorder have interesting clinical features, such as subacute onset, manic predominance, frequent accompanying psychotic features, and similar recurrent episodes in association with psychosocial stressors and corticosteroid use. Management, including psychopharmacologic intervention, should be indicated by a consideration of the underlying illnesses and psychosocial stressors.

Adolescent↗

PubMed2000

[Proposal of a new lymph node mapping system for pancreatic head cancer].

The Japanese Pancreatic Society published the 4th edition of the general guidelines for the study of pancreatic cancer (JPS guidelines) in 1993. The current JPS guidelines differ from the UICC classification of lymph nodes. Thirty-five lymph node stations are divided into three groups in the JPS guidelines. Group 1 (n1) corresponds closely with the regional lymph nodes in the UICC classification. Group 2 (n2) and group 3 (n3) are distant metastases in the UICC classification. To clarify practical lymph node mapping, 2,449 resected tubular adenocarcinomas of the pancreas head registered with the JPS were analyzed. Lymph node involvement was observed most frequently in posterior pancreatoduodenal (PPD) and anterior pancreatoduodenal (APD) and then in paraaortic (n2) nodes. Fifty-six patients who achieved 5-year survival were registered, of whom 19 had lymph node involvement. The sites of lymph node involvement were limited to the PPD and/or APD nodes in 14 cases. PPD and APD nodes differ from the other n1 in terms of high incidence of metastasis and fair prognosis. In conclusion, we propose a new practical lymph node mapping system in which PPD and APD nodes are the first station and the other n1 are the second station.

Humans↗

PubMed2000

A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign familial neonatal convulsions.

At present, only one mutation of KCNQ3, a KCNQ potassium channel gene, has been identified as a cause of benign familial neonatal convulsions type 2 (BFNC2). We found a T to C substitution (c.925T-C) on one allele of affected individuals in a Japanese family with BFNC but not on 200 alleles from healthy subjects. c.925T-->C replaced Trp309, a conserved residue within the P-loop of the KCNQ potassium channel family that holds the channel pore open, with an Arg (W309R). We report c.925T-->C as the second mutation of KCNQ3 responsible for BFNC2.

Amino Acid Sequence↗

PubMed2000

Effect of lipoteichoic acid on dermal vascular permeability in mice.

Lipoteichoic acid (LTA), the cell wall component of Gram-positive bacteria, has been shown to cause inflammatory responses comparable to lipopolysaccharide (LPS) of Gram-negative bacteria. This study examined the activity of LTA to induce dermal microvascular permeability changes in mice. Vascular permeability was assessed by extravasation of Pontamine sky blue. Subcutaneous injection of LTA (200-400 microg/site) in mice that were preinjected i.v. with the dye increased local dye leakage in the skin at 1 to 3 h. The LTA-induced dye leakage was inhibited by indomethacin, valeryl salicylate, diphenhydramine, and a platelet-activating factor antagonist but not by inhibitors of nitric-oxide synthase, cyclooxygenase-2, or guanylate cyclase or by antibodies against tumor necrosis factor-alpha or interleukin-1alpha. LTA induced comparable increases in dye leakage in inducible nitric-oxide synthase-deficient mice and wild-type controls. Pretreatment of normal mice with i.v. LTA did not confer tolerance to LTA- or LPS-induced dye leakage. In contrast, systemic LPS administration induced tolerance against subsequent challenge with LPS but not LTA. Serum corticosterone levels, which were suggested to induce tolerance, were not increased by LTA pretreatment but were increased by LPS. Thus, LTA increases dermal microvascular permeability in mice. Among the inflammatory mediators, eicosanoids, platelet-activating factor, and histamine mediate the effect of both LTA and LPS, whereas nitric oxide, tumor necrosis factor-alpha, and interleukin-1alpha may not play a major role in LTA-induced dye leakage. The difference between LTA and LPS to stimulate corticosterone may partially explain the failure of LTA to induce tolerance against vascular dye leakage.

Animals↗