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Biomedical subjects

T Nishikawa

Publications and source records attributed to T Nishikawa.

At least 325 records · Page 18Linked to original sources

Urinary excretion of D-serine in human: comparison of different ages and species.

The urinary excretion of D-serine (D-Ser) in human, rat and dog of various ages was studied. Great amounts of D-Ser were consistently excreted in human urine throughout life. No age-dependent changes were observed in urinary D-Ser/total-Ser ratios from the newborn to the aged. D-Ser/creatinine ratios in adult human urine were found to be relatively constant in individuals. The constant excretion of D-Ser in human urine was confirmed by analyzing the consecutive 24 h urine of three volunteers. High concentrations of D-Ser and D-alanine (D-Ala) were found in adult dog urine. The urinary D-Ser concentration was high in young rats at unweaned and weaned periods, and then declined with increasing age. In contrast, the urinary D-Ala concentration was very low in suckling rats, and increased rapidly after the weaned state and then declined with increasing age. The species- and age-related excretion of D-Ser in mammalian urine is considered to be due to the differences in the renal handing of D-Ser, because plasma D-Ser concentrations among the groups were not so different. Although free D-Ser has been detected in animal foods and human colostrum, the amount is insufficient to explain the concentration of D-Ser found in urine. These results indicate that urinary D-Ser in mammals may be mainly of endogenous origin.

Adult↗

[Role of ryanodine receptors in hydrogen peroxide-induced DNA fragmentation and thymidine incorporation in cultured rat astrocytes].

In the CNS, reactive oxygen species (ROS) have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemia-reperfusion injury, Alzheimer disease, Parkinson disease and aging. However, the exact mechanism is unknown, and there is little information on possible roles of ROS in cell injury and the process on recovery of astrocytes, the most abundant glial cells in the brain. We examined hydrogen peroxide (H2O2)-induced DNA fragmentation and thymidine incorporation into cultured astrocytes as an indicator of the process of recovery from astrocytic DNA injury. Astrocytes were isolated from cerebral cortices of 0-day-old rats and treated with 1 mM dibutyryl cyclic AMP for 4 days. H2O2 of 100 microM stimulated thymidine incorporation into astrocytes. Caffeine, ryanodine, cyclic ADP-ribose (endogenous ryanodine receptor agonist) and beta-NAD+ (precursor of cyclic ADP-ribose) suppressed partially the stimulatory effect of H2O2. Ruthenium red (ryanodine receptor antagonist) facilitated further the stimulatory effect of H2O2. The facilitated effect of ruthenium red on H2O2-induced thymidine incorporation was suppressed by caffeine, ryanodine, cyclic ADP-ribose and beta-NAD+. H2O2-induced DNA fragmentation and astrocytic death were suppressed by ruthenium red. These findings suggest that the process of recovery from astrocytic DNA injury by H2O2 may be regulated by Ca2+ efflux from ryanodine-sensitive intracellular Ca2+ stores.

Adenosine Diphosphate Ribose↗

The relatively high frequency of p53 gene mutations in multiple and malignant phaeochromocytomas.

To explore the clinical significance of p53 in the pathogenesis of adrenal neoplasms, we investigated the incidence of p53 gene mutations in functioning human adrenal tumours using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to screen p53 exons 4 to 9. We examined 29 adrenocortical adenomas (primary aldosteronism, n=17; Cushing's syndrome, n=12, all benign), and 33 phaeochromocytomas (benign solitary, n=18; benign multiple, n=5; malignant, n=10) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary phaeochromocytoma tissues. In contrast, six phaeochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands revealed six cases with nine mutations or intronic sequence alterations: three cases contained sequence alterations within intronic regions, three cases with silent mutation (sequence alteration in codon without amino acid alteration), and three cases contained missense mutations (one case each in exons 5, 6 and 9). Immunohistochemical staining demonstrated that two of three cases with missense mutations and one case with an intronic sequence alteration over-expressed p53 protein in tumour cell nuclei. We observed no association between p53 gene mutation and p21/WAF1/Cip-1 expression. The relatively high incidence of p53 gene mutations or intronic sequence alteration in multiple and malignant phaeochromocytomas, but not in benign solitary cases, suggests that p53 mutation could play some role in the pathogenesis of multiple and/or malignant phaeochromocytomas.

Adenoma↗

Primary cardiac angiosarcoma of the right atrium undiagnosed by transvenous endocardial tumor biopsy.

A 50-year-old man was admitted with acute pericarditis. Echocardiography demonstrated a large mass on the right atrial free wall along with a pericardial effusion. We performed transvenous biopsy of this mass under transesophageal echocardiographic guidance. Though the biotome obtained the mass, the pathological findings were of organized thrombus. Two weeks later, a new precordial mass appeared around the left third rib and was suspected to be a metastasis. Incisional biopsy of this mass gave the diagnosis of angiosarcoma.

Acute Disease↗

Basic and clinical studies on ApoE gene typing by line probe assay (LiPA) as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.

The fundamental reagent capability and clinical significance of ApoE gene typing has been investigated. The result of each test shows that the reagent capability satisfied the expected standard. Four-hundred thirty-nine samples classified into three groups (Alzheimer's disease (AD), other types of dementia and nondementia) were measured to examine the clinical significance. The rate of epsilon 4 genotype of each group was 31.5%, 14.6%, 10.4%, respectively. The AD group had a higher rate than the other groups (p < 0.001). The measurement of ApoE genotype is suggested to be useful as one of the guidelines in the diagnosis of AD.

Age Factors↗

Pityriasis versicolor with a unique clinical appearance.

We experienced an atypical case of pityriasis versicolor with a unique clinical appearance and undescribed mycological features. Although Malassezia sp. was cultured from the keratotic material, the fungal elements observed in the material were not readily identified as Malassezia. The diagnosis was established with the aid of immunohistochemical and ultrastructural studies with the aetiological agent being identified as M. globosa.

Diagnosis, Differential↗

Characterization of platelet abnormalities of Tester Moriyama (TM) rats with storage pool deficiency.

Platelet abnormalities of Tester Moriyama (TM) rats, which have prolonged bleeding time with normal platelet count, were characterized by comparison with those of fawn-hooded (FH) rats with platelet storage pool deficiency (SPD). Morphologically, the dense granules were virtually lacking in platelets from TM and FH rats. Platelets from TM and FH rats aggregated in response to adenosine diphosphate (ADP), but failed to have secondary aggregation. In contrast, platelet aggregation was completely absent in response to 1 to 20 micrograms of collagen/ml, although partial aggregation was observed at the higher dosage of 50 micrograms/ml. Normal amounts of platelet membrane glycoproteins IIb/IIIa were expressed in TM and FH rats, but platelet adenosine triphosphate (ATP) and ADP contents were lower than those in platelets from control Wistar rats. Platelet ATP-to-ADP ratio of TM and FH rats was significantly higher than that of Wistar rats. Serotonin content in platelets from TM and FH rats was 20 to 25% that of Wistar rat platelets. These results suggested that platelet abnormalities of TM rats are a typical characteristic of platelet SPD and are similar to those of FH rats, which are genetically different from TM rats. Therefore, TM rats may serve as a useful animal model for the study of platelet SPD.

Adenosine Diphosphate↗

Morphologic and hematologic characteristics of storage pool deficiency in beige rats (Chédiak-Higashi syndrome of rats).

Characterization of beige rats as having a platelet storage pool deficiency (SPD) was undertaken. Platelets from beige rats, an animal model of Chédiak-Higashi syndrome (CHS), completely lacked the ability to aggregate when stimulated with high dosages of collagen (50 micrograms/ml), and lacked secondary aggregation induced by adenosine diphosphate (ADP). Concentrations of ADP, ATP, and serotonin in the platelets of beige rats were significantly lower than those of control rats. However, platelet count remained within normal values. Electron microscopy revealed that platelets had fewer dense granules, whereas other organelles had normal structure. This morphologic and functional evidence confirms that platelets of beige rats have the typical characteristics of SPD.

Adenosine Diphosphate↗

Comparison of fluorine-18-FDG PET and thallium-201 SPECT in evaluation of lung cancer.

UNLABELLED: We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases. METHODS: Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated. RESULTS: Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT. CONCLUSION: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.

Adenocarcinoma↗

[Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors].

In this report, we showed the efficacy of a new contrast agent (SH/TA-508, Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular invasion by cancer became to be easily evaluated. On the other hand, hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were increased in color Doppler signals of vessels by SH/TA-508. We concluded that SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as well as vascularity of hypervascular mass and solid component of cystic neoplasma.

Adenoma, Islet Cell↗

A new derivatizing agent, trimethylammoniopropyl methanethiosulphonate, is efficient for preparation of recombinant brain-derived neurotrophic factor from inclusion bodies.

Derivatization with trimethylammoniopropyl methanethiosulphonate (TAPS-sulphonate) enabled brain-derived neurotrophic factor (BDNF) to be prepared efficiently from Escherichia coli inclusion bodies. Reduced BDNF obtained from inclusion bodies solubilized by urea and reduced by dithiothreitol was suggested to form a complex with itself or with other compounds such as lipids. It could hardly be adsorbed on to cation-exchange resin for partial purification prior to a refolding reaction. Reversible derivatization of cysteine residues was tested as a method of dissociating BDNF from such complexes. However, even if a methyl or aminoethyl group was introduced, BDNF could not be dissociated readily. Derivatization with TAPS-sulphonate brought about good dissociation of BDNF, and more than 50% adsorbed on to the cation-exchange resin. BDNF derivatized with TAPS-sulphonate refolded well, and the refolded samples showed the same biological activity as purified BDNF. Derivatization with TAPS-sulphonate would increase the intermolecular repulsion of BDNF, due to the positively charged character of the quaternized amine, and inhibit complex formation. Thus, TAPS-sulphonate is effective for the preparation of BDNF under denatured conditions.

Brain-Derived Neurotrophic Factor↗

Uptake of D- and L-serine in C6 glioma cells.

Cultured C6 glioma cells were able to accumulate [3H]D- and [3H]L-serine in a temperature- and Na+-dependent and saturable manner. The kinetic analysis of these accumulation phenomena indicates that the D- or L-serine uptake into the glioma cells might occur by a single-component system with an apparent Km value around 2480 microM (for D-serine) or 110 microM (for L-serine) and a Vmax value around 7 nmol/min per mg protein. The ratio of the L- to D-serine uptake affinity was similar to that previously reported in the astrocytes of rat cerebrum. The inhibition profiles of D- and L-serine uptake by various amino acid and related compounds resembled each other and those of the ASCT-like neutral amino acid transporter. The present findings therefore suggest that C6 glioma cells may accumulate D- and L-serine through a common ASCT-like transporter and provide a useful model for the glial uptake of extracellular D- and L-serine in the brain.

Amino Acid Transport Systems↗

Developmental changes in distribution patterns of phencyclidine-induced c-Fos in rat forebrain.

In the forebrain of 56-day-old rats, histochemical studies revealed that the subcutaneous injection of a psychotomimetic phencyclidine (PCP; 1 and 10 mg/kg) induced a dose-related and dense nuclear c-Fos-like immunoreactivity in the pyriform cortex, layers IV-VI of the neocortex and septum, but a sparse c-Fos immunostaining in the olfactory tubercle and mid-lateral striatum. Infant rats at postnatal day 8 expressed much fewer and more confined c-Fos-positive cells in the neocortex than young adult rats following PCP injection. However, a similar expression pattern of PCP-induced c-Fos was observed in the pyriform cortex, mid-lateral striatum, olfactory tubercle and septum between the infant and adult periods. These developmental changes in the regional distribution of a neuronal activity marker, c-Fos, suggest that neuronal populations involved in PCP-induced abnormal behavior are influenced by postnatal development, at least, in the neocortex.

Animals↗

A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis.

Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.

Acid Phosphatase↗