Biomedical subjects

S Kodama

Publications and source records attributed to S Kodama.

At least 55 records · Page 3Linked to original sources

PubMed2000

The effect of calcium-sensing receptor gene polymorphisms on serum calcium levels: a familial hypocalciuric hypercalcemia family without mutation in the calcium-sensing receptor gene.

Familial hypocalciuric hypercalcemia (FHH) is a benign syndrome with elevated levels of serum calcium, relative hypocalciuria, and non-suppressed serum parathyroid hormone (PTH) levels. FHH usually occurs by a heterozygous mutation of the calcium sensing receptor (Casr), but some FHH patients show no mutations of the Casr. We encountered a unique FHH family in which the proband and her mother had many calcium deposits on their skin. The proband was medicated with Levothyroxine for hypothyroidism due to an iodine transport defect (ITD). We searched for mutation of the Casr, but found none. The only change distinguishing the proband and her mother from her father was at codon 990, reported to be a polymorphic site. We investigated the frequency of polymorphism at codon 990, but a significant relationship between the three genotypes and the serum calcium concentration was excluded. At the other polymorphic sites at codon 536, 926, 986, and 1011, polymorphisms were rare in Japanese, and we could not confirm a significant relationship. In conclusion, mutation in the Casr gene alone does not explain all cases of FHH. The other mechanisms should be identified.

Base Sequence↗

PubMed2000

Dose-dependent biphasic accumulation of TP53 protein in normal human embryo cells after X irradiation.

The effects of various doses of X radiation on the kinetics of accumulation of TP53 protein (formerly known as p53) were examined in normal human embryo cells. We found that the rate of accumulation of TP53 protein was biphasic at X-ray doses between 1 and 4 Gy, while monophasic accumulation was observed after X irradiation with doses higher than 6 Gy. The first phase of accumulation was detected within 1 h after irradiation, and a second phase of accumulation was detected between 6 and 12 h after irradiation. The induction of CDKN1A (formerly known as p21(WAF1/CIP1)) and MDM2 proteins was also biphasic after doses of 4 Gy or less, while monophasic accumulation was observed after 6 Gy or higher. We found that the proteasome inhibitor ALLN increased the constitutive level of TP53 protein, and no change was observed in the TP53 level after X irradiation when cells were treated with ALLN. These results indicate that the dose-dependent accumulation of TP53 is due to an inhibition of TP53 degradation, and that the induction of MDM2 might be responsible in part for the different kinetics of accumulation of TP53.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed2000

Hypoxia relieves X-ray-induced delayed effects in normal human embryo cells.

We studied the effect of hypoxia on X-ray-induced delayed effects in normal human embryo cells to elucidate the role of oxidative stress in the susceptibility of cells to induction of genetic instability by radiation. We examined X-ray-induced delayed cell death, giant cell formation, and chromosome aberrations under normally oxygenated (20%) and hypoxic (2%) conditions at 28-38 population doublings postirradiation. The results revealed that hypoxia reduced the X-ray-induced delayed effects, suggesting that radiation enhances cellular oxidative stress, which plays a significant role in determining the susceptibility of irradiated cells to genetic instability. The present study emphasizes the biological significance of epigenetic effects, such as oxygen tension, as well as direct DNA damage in the induction of genetic instability by radiation.

Cell Count↗

PubMed1999

Heat-induced G1 arrest is dependent on p53 function but not on RB dephosphorylation.

Normal human cells were heat shocked at 43 degrees C for 2 hr and recovered at 37 degrees C. The levels of p53 and p21 reached a maximum approximately 2 and 6 hr after the heat shock, respectively, and these levels were higher than the control level even at 24 hr. The fraction of S phase cells decreased significantly 8 hr after heat shock, and gradually thereafter. Heat-induced G1 arrest was not found in NCI-H1299 and HeLa cells, which are deficient in p53 function, indicating that p53 function is essential for G1 arrest after heat shock. We found little or no change in phosphorylation of retinoblastoma (RB) protein until 12 hr after heat shock, and a significant change at about 24 hr. No change in phosphorylation of RB at serine-780 and serine-795 occurred within 12 hr after heat shock. These results suggest that heat shock induces G1 arrest mediated by p53, but that G1 arrest within 12 hr after heat shock does not require RB dephosphorylation.

Cell Line↗

PubMed1999

Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy.

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.

Aspartic Acid↗

PubMed1999

Axin directly interacts with plakoglobin and regulates its stability.

Plakoglobin is homologous to beta-catenin. Axin, a Wnt signal negative regulator, enhances glycogen synthase kinase (GSK)-3beta-dependent phosphorylation of beta-catenin and stimulates the degradation of beta-catenin. Therefore, we examined the effect of Axin on plakoglobin stability. Axin formed a complex with plakoglobin in COS cells and SW480 cells. Axin directly bound to plakoglobin, and this binding was inhibited by beta-catenin. Axin promoted GSK-3beta-dependent phosphorylation of plakoglobin. Furthermore, overexpression of Axin down-regulated the level of plakoglobin in SW480 cells. These results suggest that Axin regulates the stability of plakoglobin by enhancing its phosphorylation by GSK-3beta and that Axin may act on beta-catenin and plakoglobin in similar manners.

Animals↗

PubMed1999

Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation.

The product of the ATM gene, which is mutated in ataxia telangiectasia, is a nuclear phosphoprotein, and it involves the activation of the p53 pathway after ionizing radiation. Here we show that the ATM protein is constitutively associated with double strand DNA and that the interaction increases when the DNA is exposed to ionizing radiation. The ATM protein also had affinity to restriction endonuclease PvuII-digested DNA, but not to UV-irradiated DNA nor X-irradiated single-stranded DNA. The immunoprecipitation experiment detected very weak association between ATM and DNA-PK proteins, and immunodepletion of DNA-PK showed little or no effect on the interaction of the ATM protein with damaged DNA, indicating that an interaction with DNA-PK might not be required for the recruitment of the ATM protein to damaged DNA. Furthermore, the association was also confirmed in xrs-5 and xrs-6e cells, which are Chinese hamster ovary mutant cell lines defective in Ku80 function. These results indicate that the ATM protein is recruited to the site of DNA damage and it recognizes double strand breaks by itself or through an association with other DNA-binding protein other than DNA-PK and Ku80 proteins.

Animals↗

PubMed1999

Capacity gradient anion chromatography with a borate complex as eluent.

Complex formation between borate compounds and vicinal diols is well recognized. Generally, in a chemically bonded anion-exchange resin, many hydroxyl groups are introduced on the surface of the resin in order to make the resin hydrophilic. The borate as an eluting reagent also reacts to these hydroxyl groups, and this complex formation decreases the apparent ion-exchange capacity of the column by being dissociated to the anion depending on the eluent pH. In the present work a method is described for the simultaneous determination of anions based on the capacity gradient for suppressed ion chromatography. A Tosoh IC-Anion-PW column and dihydroxyphenylborane-mannitol eluent system were used. To maintain baseline stability, it was helpful to keep the borate concentration constant during a gradient of 16 to 0 mM mannitol as a modifier to prevent the complex formation with the hydroxyl on the resin. The chemical composition of the eluents and gradient profiles are discussed and the application to the analysis of the condensed phosphates with widely varying retention times as food additives in a cheese sample is presented.

Anions↗

PubMed1999

A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia.

The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previous reports concerning exons 2 and 3.

Adolescent↗

PubMed1999

Reversibility of alendronate-induced contraction in human osteoclast-like cells formed from bone marrow cells in culture.

Alendronate is a powerful therapeutic agent for the treatment of hypercalcemia in malignancy and osteoporosis and has recently been developed as a treatment for hypercalcemia of malignancy. In this study, time-lapse cinemicrography was used to investigate the effects of this agent on the morphology and the motility of human osteoclast-like multinucleated cells (MNCs) from human bone marrow. Alendronate at 10(-5)M induced contraction of the cells starting 7.5 h after its addition. Contraction was markedly induced immediately after alendronate removal. However, contraction almost disappeared 18h after removal, and osteoclast-like MNCs recovered their original sizes and shape. There was only partial recovery from contraction after alendronate treatment at 10(-4)M. In contrast, untreated control cells did not change their morphology after washing with culture medium. Motility analysis showed that osteoclast-like MNCs treated with 10(-5)M alendronate moved actively after washing, but at 10(-4)M the motility locus was very narrow. At 10(-4)M, the actin ring in the cells began to break down, beginning 6h after addition. The effects of alendronate on human osteoclast-like MNCs morphology and motility were reversible at 10(-5)M, suggesting that alendronate dose not cause any cellular damages in human osteoclasts up to 10(-5)M, which is an effective dose for bone resorption.

Alendronate↗

PubMed1999

Haloperidol improves membrane phospholipid abnormalities in temporal lobes of schizophrenic patients.

Using 31P magnetic resonance spectroscopy, we examined changes in the levels of phosphorus metabolites in the temporal lobes of 13 schizophrenic patients before and 12 weeks after initiating haloperidol treatment. Spectra were obtained from a volume of interest positioned in each temporal lobe. Findings were compared with those in 13 age- and gender-matched healthy subjects. Prior to treatment the patients showed higher levels of phosphodiesters (PDE) in both temporal lobes than healthy subjects. Haloperidol administration significantly reduced the excess of PDE in the left temporal lobe, although the PDE concentration remained somewhat higher bilaterally than in controls. Treatment was associated with a decline in the total symptom score according to the Brief Psychiatric Rating Scale and the score for positive symptoms showed a relatively high correlation with reduction in PDE level in the left temporal lobe. These preliminary results suggest that haloperidol may partially normalize disturbed metabolism or abnormalities in components of membrane phospholipids in the left temporal lobe of untreated schizophrenic patients, paralleling symptom alleviation.

Adolescent↗

PubMed1999

Major degradation pathway of thiuram in tap water processed by oxidation with sodium hypochlorite.

Thiuram (3 microM), a fungicide, was incubated in deionized water by adding 0-100 mg/L free chlorine at 30 degrees C for 30 min, and the solution was analyzed by HPLC and IC. The byproducts were identified by LC/MS, EI-MS, infrared, and (13)C NMR spectra and a reduction technique using 2-mercaptoethanol. On the basis of these results, it was found that the oxidation of thiuram with sodium hypochlorite initially produced an intermediate dimethylthiocarbamoyl dimethylcarbamoyl disulfide, which was finally degraded to bis(dimethylcarbamoyl) disulfide, its trisulfide, and dimethylamine. Subsequently, it was suggested that monitoring of bis(dimethylcarbamoyl) disulfide, its trisulfide, and dimethylamine should be included for the management and control of thiuram in tap water processed by oxidation with sodium hypochlorite.

Chromatography, Liquid↗

PubMed1999

Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity.

To determine the efficacy of a mucosal vaccine against nontypeable Haemophilus influenzae (NTHi), mice were immunized nasally, orally, intratracheally, or intraperitoneally with NTHi antigen together with cholera toxin. Antigen-specific IgA antibody titers in nasal washes and the numbers of antigen-specific IgA-producing cells in nasal passages showed the greatest increases in mice immunized nasally. Cytokine analysis showed that interferon-gamma, interleukin (IL)-2, IL-5, IL-6, and IL-10 were induced by nasal immunization, suggesting that Th2- and Th1-type cells were generated. Furthermore, bacterial clearance of a homologous strain of NTHi from the nasal tract was significantly enhanced in the nasal immunization group. These findings suggest that nasal immunization is an effective vaccination regimen for the induction of antigen-specific mucosal immune responses, which reduce the colonization of NTHi in the nasal tract.

Animals↗

PubMed1999

Failure of high-dose chemotherapy with peripheral blood stem cell support for refractory placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease. The metastatic and refractory cases have a very poor prognosis. To our knowledge, this is the first report of the application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) for the treatment of refractory metastatic PSTT. A 36-year-old woman had a metastatic PSTT refractory to several lines of chemotherapy. She was treated with high dose of carboplatin and etoposide with autologous PBSCT. She showed only a temporary response to high-dose chemotherapy with PBSCT support and died of disease.

Adult↗

PubMed1999

Observations of high iron diamine-alcian blue stain in uterine cervical glandular lesions.

We studied epithelial glycoproteins in uterine cervical lesions, including glandular lesions, and investigated whether a more accurate diagnosis could be obtained using high iron diamine-alcian blue (HID-AB) stain and immunostaining with carcinoembryonic antigen (CEA). In addition, we examined the usefulness of preoperative diagnosis using biopsy specimens stained with HID-AB and CEA. Normal endocervical glands showed a predominance of sulfomucin, while adenocarcinoma predominantly showed sialomucin. CEA was highly detected in adenocarcinoma, but not in normal endocervix or in glandular dysplasia, suggesting that this stain has high specificity. The staining patterns of biopsy specimens and hysterectomy specimens were similar. Therefore HID-AB stain and CEA stain may be useful as a supplementary means of diagnosing uterine cervical lesions.

Adenocarcinoma↗

PubMed1999

Carcinoembryonic antigen and carbohydrate antigen 19-9-producing adenocarcinoma of the prostate: report of an autopsy case.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are well known as specific tumor markers of prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-producing adenocarcinoma originating in the prostate is rare. We report here a case of prostatic adenocarcinoma positive for these 4 tumor markers in a 50-year-old man who had initially complained about chest pain due to metastatic bone tumor. In spite of the extensive treatment involving hormone and radiation therapy, the patient died of rapid tumor extension only 4 months after initial diagnosis. Autopsy revealed multiple metastases to the bone, liver, lungs and lymph nodes. Histologically, two types of adenocarcinoma were involved in both primary prostate and metastatic sites: one was a poorly differentiated adenocarcinoma positive for PSA and PAP but not CEA or CA19-9, and the other one was a less differentiated adenocarcinoma partially positive for CEA and CA19-9 but not for PSA or PAP. Based on this case and previous cases by review of the literature, CEA- and CA19-9-producing adenocarcinoma of the prostate was suggested to rapidly progress with multiple metastases and to show poor prognosis with strong resistance to any treatment.

Acid Phosphatase↗

PubMed1999

Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients.

OBJECTIVE: The authors examined phospholipids and high-energy phosphorus metabolism in the temporal lobes of drug-naive schizophrenic patients. METHOD: In vivo 31P magnetic resonance spectroscopy was performed on 17 first-episode, drug-naive schizophrenic patients and 17 age- and gender-matched healthy subjects. RESULTS: Patients showed higher levels of phosphodiesters and lower levels of phosphomonoesters than the comparison group. Phosphocreatine levels were increased in the left temporal lobes of patients. CONCLUSIONS: The results suggest disturbed membrane phospholipid metabolism in both temporal lobes and decreased energy demands in the left temporal lobes of drug-naive schizophrenic patients.

Adult↗

PubMed1999

Effects of protein kinase inhibitors on the accumulation kinetics of p53 protein in normal human embryo cells following X-irradiation.

DNA-damaging agents induce phosphorylation of the p53 protein, resulting in its accumulation in the nucleus. To clarify the signal transduction pathway(s) involved in p53 protein accumulation in normal human embryo cells following X-irradiation, the effects of three protein kinase inhibitors were examined. Quercetin, an inhibitor of heat-shock response, dose dependently suppressed the p53 accumulation induced by X-rays at more than 100 microM. No suppression, however, was observed with calphostin-C, a specific inhibitor of protein kinase C, in the range of 0.05 to 0.25 microM. Wortmannin was the most potent inhibitor of p53 accumulation. Its suppressive effect appears within a few minutes of pretreatment with a dose of 25 microM, but posttreatment was less effective. Our findings suggest that PKC is not involved in X-ray-induced p53 accumulation in normal human embryo cells and that a wortmannin-sensitive pathway acts as a sensor of DNA damage.

Androstadienes↗