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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 541 records · Page 30Linked to original sources

Distribution of nitric oxide synthase-immunoreactive neurons in fetal rat brains at embryonic day 15 and day 19.

Although nitric oxide (NO) is hypothesized to play a role in the modelling of neuronal connections in the developing brain, no precise histological information has been reported on nitric oxide synthase immunoreactive (NOS-IR) structures in the embryonic brain. Thus, we examined the distribution of NOS-IR structures in the rat brain at embryonic day 15 (E15) and day 19 (E19), as a stage of early embryonic neurogenesis and active synaptogenesis, respectively. In the brain at E15, a few NOS-IR cell bodies were observed in the diencephalon near the 3rd ventricle and in the pons. By E19, the number of NOS-IR cells was greatly increased. Many NOS-IR cells were distributed throughout the forebrain and the medulla oblongata. NOS-IR cells of the neostriatum were located in its ventrolateral two-thirds. NOS-IR cells in the hypothalamus were distributed densely in the medial part while sparsely in the latero-ventral part, suggesting medio-lateroventral directions of NOS development. In the lower brainstem, on the other hand, NOS-IR cells were distributed in a similar pattern to that reported in adult rat, indicating earlier development of synaptic refinement in this area. The number of NOS-IR cells in the cerebral cortex and the cerebellum was very few.

Animals↗

Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation.

This study was conducted to investigate whether or not the antioxidation effect of ginseng extract directly inhibits decomposition of unsaturated fatty acid caused by iron and hydrogen peroxide-induced lipid peroxidation, and whether this effect involves a hydroxyl radical-scavenging mechanism. Thiobarbituric acid-reactive substances (TBARS), gas chromatography, and electron spin resonance (ESR) spectrometer were used to measure lipid peroxidation, unsaturated fatty acid, and hydroxyl radical. The results showed TBARS formed and the loss of arachidonic acid during lipid peroxidation, and that hydroxyl radical formed by the Fenton reaction were completely inhibited by ginseng extract. This antioxidant effect of ginseng may be responsible for its wide pharmacological actions in clinical practice by a free radical reaction-inhibition mechanism.

Arachidonic Acid↗

Magnetic resonance imaging and serum CA-125 in evaluating patients with endometriomas prior to medical therapy.

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) and serum levels of CA-125 can be used to evaluate patients with endometriomas before initiating medical treatment. DESIGN: Comparative study before and after medical treatment. SETTING: Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Eleven consecutive patients with at least one endometrioma > 10 mm in maximal diameter that was diagnosed by laparoscopy and treated with 900 micrograms/d buserelin acetate for 6 months. INTERVENTIONS: Magnetic resonance imaging and blood sampling was performed < 2 weeks before laparoscopy. MAIN OUTCOME MEASURES: Signal intensity of edometrioma/signal intensity of gluteus maximum muscle on T2-weighted image (T2SI:MSI); volume of endometrioma and serum CA-125. RESULTS: There was a positive linear correlation (r = 0.787) between T2SI:MSI before treatment and the extent of decrease in the volume of endometrioma. There was a negative linear relationship between serum CA-125 before treatment and the mean extent of decrease in the cyst volume (r = 0.678). The reduction in volume of endometrioma and T2SI:MSI before treatment related to the outcome of patients. CONCLUSION: The T2SI:MSI on MRI and serum CA-125 may be useful for estimating the outcome of patients with endometriomas before initiating medical treatment.

Adult↗

Lidocaine in bronchoalveolar lavage fluid (BALF) is an inhibitor of eosinophil-active cytokines.

Eosinophils and eosinophil granule proteins may play an important role in the pathogenesis of asthma. BALF from 40 patients with symptomatic asthma were analysed for cytokine activity by the eosinophil survival assay. BALF from 15 patients showed increased survival activity. Survival activities in BALF from four of these patients were almost completely blocked by anti-IL-5 MoAb, and the remaining activities were blocked by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-IL-3 antibody, or both. Surprisingly, BALF samples from the other 25 patients decreased eosinophil viabilities below the levels of medium control. The inhibitory factor in these BALF was of low molecular weight, was heat-stable, was largely overcome by excess exogenously added cytokines, and was positively correlated with the concentrations of lidocaine in the BALF. Lidocaine itself inhibited eosinophil survival at concentrations less than those present in the BALF. These findings indicate that lidocaine is an inhibitor of cytokines in the eosinophil survival assay, and they suggest the need for caution in analyses of BALF containing lidocaine or other local anaesthetics.

Adult↗

Molecular cloning and expression of cDNA for murine galactocerebrosidase and mutation analysis of the twitcher mouse, a model of Krabbe's disease.

The cDNA for a murine galactocerebrosidase was isolated from a murine testis cDNA library on the basis of its homology with the cDNA for human galactocerebrosidase and a PCR method was used to clone the 5' end. It has a 2,278-nucleotide sequence including a 2,004-nucleotide open reading frame, which encodes 668 amino acid residues. The identity between the human and murine amino acid sequences was very high, being calculated to be 84%. Sequencing of cDNA from liver of the twitcher mouse revealed a nonsense mutation at codon 339 (TGG-->TGA). The most abundant mRNA of the murine galactocerebrosidase gave a 3.6-kb band, which was not detected in twitcher mice. This suggests that the cDNA (2,278 bp) we characterized represents a minor species generated by an alternate poly(A) signal and that most of the mRNA has a much longer 3'-untranslated region. Genome analysis revealed that this mutation was homozygous in the twitcher and heterozygous in the carrier but was not present in normal mice. The normal mouse cDNA but not the mutant cDNA of the galactocerebrosidase transfected into COS1 cells gave rise to an increase in enzymatic activity. We concluded that this mutation results in the deficiency of galactocerebrosidase in the twitcher mouse.

Amino Acid Sequence↗

Activator protein-1 binding activities in discrete regions of rat brain after acute and chronic administration of methamphetamine.

The activator protein-1 (AP-1) binding activities increased in three brain regions (striatum, nucleus accumbens, and cingulate cortex) after a single methamphetamine (METH) injection to rats. Pretreatment with SCH 23390, but not (-)-eticlopride, significantly inhibited the enhanced AP-1 binding activities induced by acute METH administration. The magnitude of enhancement of AP-1 binding activities 3 h after the last dose of chronic METH administration (4 mg/kg once daily for 14 days) was significantly attenuated as compared with those 3 h after a single METH administration. The AP-1 binding activities after a 1-, but not 4-, week abstinence from chronic administration of METH were still significantly higher than those of the saline-treated controls. A METH challenge after a 4-week abstinence period induced significantly lower AP-1 binding activities in rats chronically injected with METH than in rats chronically injected with saline. The supershift assay revealed that the levels of Jun family protein, but not Fos-related antigen, increased significantly in the striatum and nucleus accumbens of chronically METH-treated rats after a 1-week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.

Animals↗

Oxidative damages by iron-chelate complexes depend on the interaction with the target molecules.

To elucidate that in iron-catalyzed oxidative damage the interaction of iron complex with the target molecules is important, the oxidative damage to plasmid DNA, protein and fatty acid has been compared using iron-chelate complexes with nitrilotriacetic acid (nta), citric acid, ethylenediamine-N,N'-diacetic acid (edda) and diethylenetriamine-N,N,N',N",N"-pentaacetic acid (dtpa). In the presence of hydrogen peroxide, plasmid pBR322 strand breaks occurred in the order of Fe-edda > Fe-citrate > Fe-nta > > Fe-dtpa. However, fragmentation of bovine serum albumin and diene conjugation of linoleic acid micelle occurred in the order of Fe-nta > Fe-edda > > Fe-citrate > Fe-dtpa = O, which were similar to hydroxyl radical production by these iron complexes and H2O2. Bleomycin-detectable free radical-promoting irons in these iron complexes were about 85% of iron in Fe-nta, Fe-citrate and Fe-edda, and only about 33% in Fe-dtpa. Not only hydroxyl radical productivity and free radical-promoting iron content in iron complex, but also the interaction of the complex with the target molecules determines the iron-catalyzed oxidative damage.

Animals↗

Exposure to dimethylarsinic acid, a main metabolite of inorganic arsenics, strongly promotes tumorigenesis initiated by 4-nitroquinoline 1-oxide in the lungs of mice.

The effect of dimethylarsenics on the pulmonary tumorigenesis initiated by 4-nitroquinoline 1-oxide (4NQO) in mice was examined. The exposure of mice to dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics in mammals, resulted in not only promotion but also progression of the tumorigenic process in the lungs of mice administered 4NQO. Furthermore, dimethylarsenics influenced the differentiation process in lung tumorigenesis by 4NQO. These results may pave the way for the elucidation of lung carcinogenesis caused by arsenics.

4-Nitroquinoline-1-oxide↗

Magnetic resonance relaxation time in evaluating the cyst fluid characteristics of endometrioma.

To determine whether the cyst fluid characteristics of endometrioma can be evaluated by magnetic resonance imaging (MRI), 36 endometriomas obtained from 24 patients (age range 21-43 years; mean 34 years) were studied. MRI was performed < 2 weeks before laparoscopy or laparotomy. Comparative studies of the density and concentration of iron in the endometrioma and the signal intensity (SI) of MRI [calculated relaxation time T1 value, calculated relaxation time T2 value, signal intensity on a T1-weighted image (T1SI) and on a T2-weighted image (T2SI) of the cyst; T1SI/signal intensity of the gluteus maximus muscle (MSI), and T2SI/MSI of the cyst] were performed. The density of the cyst fluid and its iron concentration were found to be directly proportional. There was a significant relationship between the concentration of iron and the T2SI, T2SI/MI and calculated T2 values. In particular, the concentration of iron and the ration of T2SI/ MSI were inversely proportional. Therefore, T2SI/MSI reflected the concentration of iron in endometriomas without recourse to measurement of the calculated T2 value, which suggests that the MRI and T2 signal intensity may be useful for evaluating the cyst fluid characteristics of endometriomas.

Adult↗

Prognostic application of magnetic resonance imaging in patients with endometriomas treated with gonadotrophin-releasing hormone analogue.

We evaluated the usefulness of magnetic resonance imaging (MRI) for assessing the response of patients with endometriomas to medical therapy. MRI was performed before and after treatment in 20 consecutive patients with at least one endometrioma with a maximal diameter >10 mm diagnosed by laparoscopy who received 900 microg of buserelin acetate daily for 6 months. Patients were categorized as good responders (group I, n = 13) and poor responders (group II, n = 7) depending on the results of a third-look laparoscopy performed 6 months after treatment. We determined the ratio of the signal intensity (SI) of the endometrioma to the SI of the gluteus maximus muscle on T2-weighted images [T2SI/M (muscle) SI] and the volume of the endometrium. The volume decreased by >50% in 61.5% of the good-response group and 57.1% of the poor-response group. There was no significant difference between the two groups. The T2SI/MSI decreased in 12 of 13 patients in group I but in only one of seven patients in group II, a significant difference (P < 0.05) between the two groups. In the good-response group, there was a positive linear correlation between the decrease in the volume of the endometrioma and the decrease in the T2SI/MSI after treatment (r = 0. 561, P < 0.05). Therefore, the T2SI/MSI determined from MR images may be useful in assessing the therapeutic response of patients with endometriomas.

Adult↗

Clinical response to systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in patients with advanced pancreatic cancer.

Pancreatic cancer shows high mortality and has a poor prognosis. Although the rate of response to all chemotherapeutic regimens is low, some patients have shown improvement of their symptoms after chemotherapy and/or radiotherapy without obvious tumor regression. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 21 patients with advanced cancer of the pancreas. The clinical response to FP therapy was evaluated using two parameters: pain (intensity of pain and consumption of morphine) and performance status. A patient was considered to be a clinical responder if one of two parameters was positive and the other was positive or stable. Four patients (19%) responded. Two of the responders achieved partial response according to the objective tumor response, and the remaining two showed no change. The survival period in responders was significant longer than in the other patients. The clinical response may be one parameter for evaluating the results of treatment for pancreatic cancer, and the longer survival period of the clinical responders in this study supports this notion.

Adenocarcinoma↗

Prognostic factors in patients with advanced pancreatic cancer treated with systemic chemotherapy.

The clinical features of 65 patients with advanced pancreatic cancer treated between 1984 and 1993 were analyzed retrospectively to identify the significant prognostic factors. All the patients had presented unresectable or metastatic disease on imaging diagnostic evaluation and had received systemic chemotherapy. The overall median survival time and 1-year survival rate were 3.9 months and 9.8%, respectively. The independent favorable prognostic factors identified by multivariate analysis using the Cox proportional hazards model were a performance status of 0-1, a serum carcinoembryonic antigen level of < 10 ng/ml, and an absence of distant metastasis. A prognostic index calculated from the regression coefficients for these three factors was used to classify the patients into three groups, with good, intermediate, and poor prognoses. The median survival time for these three groups was 7.4, 3.5, and 2.0 months, respectively (p < 0.001). The results of this study may be useful in the design and analysis of future clinical trials of systemic chemotherapy for advanced pancreatic cancer.

Adult↗

Immunoglobulins and their receptors on epidermal Langerhans cells in atopic dermatitis.

To elucidate the etiological role of immunoglobulin molecules on Langerhans cells (LCs) in atopic dermatitis, we conducted immuno-histochemical studies on the localization of immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA and IgM on epidermal LCs from 30 patients with atopic dermatitis (AD) and five non-atopic healthy volunteers. We also investigated the types of receptors for the immunoglobulins (Fc epsilon RI, Fc epsilon RII, Fc gamma RI, Fc gamma RII, and Fc gamma RIII) on epidermal LCs in the patients. IgE positive epidermal LCs were observed in 28 of 30 AD patients, and 46.7% of the epidermal LCs were positive for IgE. Both IgG1- and IgG2-positive epidermal LCs were observed in 70% of AD patients, and 21.8% and 28.7% of the total epidermal LCs were positive for IgG1 and IgG2, respectively. IgG3- or IgG4-positive LCs were present in only small proportions of AD patients. IgA-positive LCs were observed in 8 AD patients; our study suggested that the IgA bound on LCs was secretory IgA (S-IgA). These surface immunoglobulins were observed significantly more frequently on epidermal LCs in the involved skin of AD than in clinically uninvolved skin. No IgM-positive epidermal LCs were observed in the AD patients or healthy volunteers. In non-atopic healthy controls, no immunoglobulin-binding LCs were observed. In receptors for immunoglobulins, Fc epsilon RI and Fc gamma RII were exclusively expressed on nearly all epidermal LCs from all AD patients and all non-atopic controls. These results suggested that not only IgE but also IgG and IgA may play some etiological role in the pathogenesis of AD.

Adolescent↗

Effect of heavy alcohol intake on long-term results after curative resection of hepatitis C virus-related hepatocellular carcinoma.

We studied the effect of heavy alcohol intake (ethanol intake > or = 80 g/day for > or = 5 yr) on long-term results in 53 patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) who had undergone curative hepatic resection. Cell proliferative activity in the tumor and non-tumorous liver was also assessed by counting argyrophilic nucleolar organizer region-associated proteins (Ag-NOR) in the resected specimens. Twenty patients (20 males, 0 females) were positive for heavy alcohol intake [AI(+)] and 33 (28 males, 5 females) were not [AI(-)]. All patients were positive for HCV antibody and negative for hepatitis B surface antigen. Carcinoma recurred within 3 to 51 postoperative months in 42 (79.2%) of the 53 patients. The median disease-free survival time was 12.6 mo in the AI(+) group and 25.4 mo in the AI(-) group (P < 0.01). The AI(+) group also had significantly poorer survival than the AI(-) group (P < 0.05, 3-year survival rate: 66.7% vs. 93.5%). HCC tumor in the AI(+) group showed significantly increased proliferative activity compared with that in the AI(-) group (P < 0.05, Ag-NOR number: 2.3 +/- 0.8 vs. 1.9 +/- 0.4). However, there was no significant difference between the numbers of Ag-NORs in non-tumorous liver from these two groups (1.5 +/- 0.2 vs. 1.5 +/- 0.2). Patients with heavy alcohol intake should be followed particularly closely, even if they have received curative surgery, since heavy alcohol intake is closely related to a poor postoperative prognosis.

Carcinoma, Hepatocellular↗

Partial deletion of the long arm of chromosome 11: ten Japanese children.

The clinical features of partial deletion 11q were correlated with the size of the deleted region. Ten Japanese children with partial deletion of 11q were investigated. They were divided into three groups. Three patients in the first group had interstitial deletions and preserved subband q24.1. Six patients in the second group demonstrated terminal deletion of 11q including subband q24.1, with typical features of 11q- syndrome (Jacobsen syndrome). The third group included only one patient, who had terminal deletion of 11q without characteristics of typical 11q- syndrome. Prominent features of patients in the first group included severe mental and motor developmental delay, seizures, cleft lip and palate, and ophthalmological findings. Patients in the second group showed mild to moderate developmental delays without deterioration. Abnormalities in neuroimages, high intensity in the cerebral white matter in T2-weighted magnetic resonance (MR) images, and recurrent infections were not observed after the age of 7 years. The subject in the third group, with the smallest amount of deleted chromosome, did not show developmental delays, suggesting that some unknown genes related to developmental delays may be located adjacent to subband q24.1. Variation in the deleted parts of 11q resulted in different clinical features in each group.

Abnormalities, Multiple↗

Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals.

Oxygen is poisonous, but we cannot live without it. The high oxidizing potential of oxygen molecules (dioxygen) is a valuable source of energy for the organism and its reactivity is low; that is, spin forbidden. However, the dioxygen itself is a 'free radical' and, especially in the presence of transition metals, it is a major promoter of radical reactions in the cell. Humans survive only by virtue of their elaborate defense mechanisms against oxygen toxicity. Iron is the most abundant transition metal in the human body. Because iron shows wide variation in redox potential with different co-ordination ligands, it may be used as a redox intermediate in many biological mechanism. However, it is precisely this redox activeness that makes iron a key participant in free radical production. The current research on the relationship between iron and cancer is briefly reviewed. Research results are reported here which indicate that iron, when bound to certain ligands, can cause free-radical mediated tissue damage and become carcinogenic. The present study also suggests that iron may also have a significant role in spontaneous human cancer.

Animals↗

Cyclization reaction catalyzed by branching enzyme.

The action of branching enzyme (EC 2.4.l.l8) from Bacillus stearothermophilus on amylose was analyzed. The enzyme reduced the molecular size of amylose without increasing the reducing power. This result could not be explained by the normal branching reaction model. When the product was treated with glucoamylase (an exo++-type amylase), a resistant component remained. The glucoamylase-resistant component was easily digested by an endo-type alpha-amylase or by isoamylase plus glucoamylase. These results suggested that the glucoamylase-resistant component was a cyclic glucan composed of alpha-1,4- and alpha-l,6-glucosidic linkages. In other words, it was suggested that branching enzyme catalyzed cyclization of the alpha-l,4-glucan chain of the amylose molecule to form an alpha-l,6-glucosidic linkage, thereby forming two smaller molecules. Mass spectrometry also supported the cyclic nature of the product.

1,4-alpha-Glucan Branching Enzyme↗

Studies on the detection of small endometrial implants by magnetic resonance imaging using a fat saturation technique.

To assess the usefulness of fat-saturated magnetic resonance (MR) imaging in detecting small endometrial implants, 258 pigmented lesions of endometriosis from 80 consecutive patients with histopathologically diagnosed pelvic endometriosis were compared using fat-saturated and conventional MR imaging. MR imaging was performed with a 1.5-tesla superconducting magnet with spin echo T1-, T2-, and fat-saturated T1-weighted images. Both conventional MR images and fat-saturated MR images permitted identification of almost all endometriomas > 10 mm in diameter. With conventional MR imaging, 29 endometrial implants measuring < 10 mm in diameter were detected. One hundred and seven lesions were detected by fat-saturated MR imaging. However, conventional MR images demonstrated only 4 lesions among these 111 small endometrial implants that measured < 5 mm in diameter. The addition of fat-saturated MR imaging increased the detection rate to 55 of 111 lesions. Fat-saturated MR imaging can, therefore, be useful in detecting small endometrial implants.

Adult↗