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Biomedical subjects

J Ikeda

Publications and source records attributed to J Ikeda.

At least 55 records · Page 3Linked to original sources

Characterization of a granule-bound starch synthase isoform found in the pericarp of wheat.

Waxy wheat (Triticum aestivum L.) lacks the waxy protein, which is also known as granule-bound starch synthase I (GBSSI). The starch granules of waxy wheat endosperm and pollen do not contain amylose and therefore stain red-brown with iodine. However, we observed that starch from pericarp tissue of waxy wheat stained blue-black and contained amylose. Significantly higher starch synthase activity was detected in pericarp starch granules than in endosperm starch granules. A granule-bound protein that differed from GBSSI in molecular mass and isoelectric point was detected in the pericarp starch granules but not in granules from endosperm. This protein was designated GBSSII. The N-terminal amino acid sequence of GBSSII, although not identical to wheat GBSSI, showed strong homology to waxy proteins or GBSSIs of cereals and potato, and contained the motif KTGGL, which is the putative substrate-binding site of GBSSI of plants and of glycogen synthase of Escherichia coli. GBSSII cross-reacted specifically with antisera raised against potato and maize GBSSI. This study indicates that GBSSI and GBSSII are expressed in a tissue-specific manner in different organs, with GBSSII having an important function in amylose synthesis in the pericarp.

Amino Acid Sequence↗

Twenty-four hour rhythm of melatonin in patients with a history of pineal and/or hypothalamo-neurohypophyseal germinoma.

Melatonin deficiency after a pinealectomy has been investigated in animals; however, in humans, this status can be assessed solely by investigating patients with a tumor originating in the pineal gland. This study analyzes secretion of melatonin and pituitary hormones in 14 patients with germinoma originating in the pineal or the hypothalamic-neurohypophyseal region. Thirteen patients had been successfully treated prior to this study. One patient was included in this study before the initiation of treatments. Plasma sampling was performed every 2 hr for 24 hr and melatonin concentrations were measured by radioimmunoassay. Melatonin secretion was nearly absent in the patients with pineal germinoma regardless of treatment option, even in the patient who had been untreated. In contrast, melatonin secretion and its circadian rhythms were not affected in patients with a hypothalamo-neurohypophyseal germinoma. The circadian rhythms of growth hormone and adrenocorticotropic hormone were not dysregulated in patients with the melatonin deficiency. We conclude that germinoma cells originating the pineal gland impair the production of melatonin by pineocytes and consequently induce a permanent melatonin deficiency in those patients. Since melatonin exerts multiple physiological functions, once a clinical concept of "melatonin deficiency syndrome" is established, melatonin replacement therapy could be investigated in patients who have a pineal germinoma or who have undergone a neurosurgical pinealectomy.

Adolescent↗

Induction chemotherapy followed by reduced-volume radiation therapy for newly diagnosed central nervous system germinoma.

OBJECT: Although curative, radiation, which is conventionally administered for germinomas, causes significant neurological sequelae. This study aimed at reducing the volume and dose of radiation to a localized level of 24 Gy by pretreating the patient with chemotherapy. METHODS: Seventeen patients were divided into two risk groups based on serological findings and the extent of tumor. They were treated with chemotherapy prior to receiving localized radiation therapy. Six patients with solitary pure germinomas were treated with three or four cycles of cisplatin and etoposide (EP regimen) followed by 24-Gy local radiation therapy. Eleven patients with human chorionic gonadotropin (HCG)-secreting, multifocal, or disseminated germinomas received four to five cycles of ifosfamide, cisplatin, and etoposide (ICE regimen) followed by 24-Gy local radiation therapy. Craniospinal ports were used only in three cases of germinomas with dissemination. Gross-total resection was performed in three patients. Fourteen patients were able to be evaluated for their responses to chemotherapy. All patients achieved a complete response within three cycles. At a median follow-up duration of 24 months, 16 patients (94%) were alive without recurrence. One patient with an HCG-secreting germinoma experienced recurrence 38 months after surgery. That patient underwent successful salvage therapy using the same protocol. Thus, all 17 patients became free of disease with a 70 to 100% Karnofsky Performance Scale status. Toxicities associated with this study's chemotherapy regimen were mostly transient. No patient showed neurological or endocrinological deterioration during the follow-up period. CONCLUSIONS: The EP and ICE regimens were highly effective in treating the central nervous system germinomas and permitted dose and volume reduction of the radiotherapy. Localized 24-Gy irradiation was sufficient for disease control.

Adolescent↗

Teratomas of the central nervous system: treatment considerations based on 34 cases.

OBJECT: The optimum clinical management of central nervous system (CNS) teratomas, particularly postsurgical adjuvant therapy, is still unclear, partly as a result of the tumors' low incidence. In this study the authors analyze 34 cases of CNS teratomas so that they may adequately indicate management of these lesions. METHODS: The median age of the 34 patients was 13 years. Twenty-seven patients treated between 1970 and 1991 were retrospectively reviewed. Four of these 27 patients died as a result of radical surgery; each of them had a teratoma involving the hypothalamus. After initial treatment, which included radiation therapy, 20 patients (48%) had died. In all seven cases of mature teratomas there was no recurrence. In two cases of immature teratomas in which there was complete surgical resection there was recurrence; however, salvage therapies were effective. Seven of eight patients with highly malignant teratomas died; for these patients salvage therapies, including repeated radiation and chemotherapy, failed. Seven patients who presented with CNS teratomas between 1992 and 1996 received adjuvant chemotherapy and radiation therapy according to a prospective study protocol. All seven patients were free from recurrence with a 70 to 100% Karnofsky Performance Scale score at a median follow-up period of 41 months. Patients with CNS teratomas rarely responded completely to chemotherapy or radiation therapy; an effective adjuvant therapy produced a partial response at best. CONCLUSIONS: Because teratomas show various responses to adjuvant therapy, a misdiagnosis of their histological subtype will lead to inadequate therapy. A diverse therapeutic protocol based on histological diagnosis is necessary to plan appropriate management. Treatment recommendations are discussed in detail in the article.

Adolescent↗

[Dietary habits, lifestyle and physical condition of junior high school students].

Dietary habits, lifestyle and thirty subjective physical symptoms of all students at the first year level of junior high school were investigated by means of a specially designed questionnaire. After two years, the same questionnaire was again used on the same students who were now in their third year of junior high school. The students (305 boys and 319 girls totalling 624 students) who were included in both the first and the second surveys were used to analyze the relationship between physical conditions and lifestyle. The results were as follows: 1. The number of subjective symptoms increased significantly during the two years. 2. The students in their third year consumed less of a variety of foods than those in their first year. Dietary habits such as having a breakfast, lunch, or eating a meal with the family were worse at the third year level compared to the first year level. 3. In regard to lifestyle, recreational time or sleep time decreased while study time, dissatisfaction with life, or the rate of getting in or being in trouble increased during the two years surveyed. 4. Balance score and Dietary habits score decreased during the two years along with the increase in subjective symptoms. The survey suggests that better dietary habits and lifestyle are necessary in order to maintain good physical condition in junior high school students.

Adolescent↗

[Autoantibody to glutamate decarboxylase in a patient with spinocerebellar degeneration and Sjögren syndrome].

We report a 52-year-old woman with Sjögren syndrome from the age of 46, developed cerebellar ataxia, autonomic dysfunction and dysarthria at 50. She had no family history, and all known causes of cerebellar disease were excluded. Serum of the patient contained autoantibodies directed against glutamic acid decarboxylase (GAD) which was an enzyme involved in the biosynthesis of GABA. She also had autoantibodies that were specific with Sjögren syndrome (SS-A, anti-nuclear antibody). Anti-GAD antibody changed into negative after high dose intravenous and oral corticosteroid therapy, but symptoms did not improve. Western blot method revealed abnormal bands to human neuroblastoma cell line (10, 43, 49 kDa), considered relatively specific to nervous tissue. In this case cerebellar ataxia and atrophy were caused by autoimmune pathogenesis including cerebellar GABAergic system and central nerve cells.

Autoantibodies↗

[Effects of pregnancy and lifestyles including food intake on bone density of pregnant women].

Bone densities measured by ultrasound at the calcaneus, and urinary hydroxyproline (H.P) and calcium (Ca) concentrations adjusted for creatinine (Cre) were measured in 79 pregnant women, aged 20 to 38 years, at 5-40 weeks of gestation. Stiffness calculated from the combined value of speed of sound and broadband ultrasound attenuation was used as an index of bone density. The relationships between Stiffness and period of gestation, urinary H.P/Cre and Ca/Cre, and such lifestyles as current and past food intake frequency, physical activity and history of participating in sports obtained by questionnaire were examined using stepwise multiple regression analysis, including age and weight as independent variables. 1) The means of Stiffness in women with the gestation period of more than 20 weeks (primipara 79.6, multipara 83.4) are a little lower than those of non-pregnant and healthy women within the same age range. 2) Period of gestation showed a significant negative correlation to Stiffness. Significant positive correlations were found between urinary H.P/Cre and period of gestation. These results suggest that bone resorption increases with stage of gestation and causes bone loss in pregnant women. 3) Significant relationships with Stiffness was found only in frequency of cow's milk intake before pregnancy among various lifestyle factors. Stiffness of the subjects who took cow's milk every day before pregnancy was significantly higher than those who took less than 2-3 times per week or none. This result indicates that cow's milk and dairy products intake before pregnancy may be important for bone mineral maintenance during pregnancy.

Adult↗

[Evaluation of therapy for dilated cardiomyopathy with heart failure by iodine-123 metaiodobenzylguanidine imaging: comparison with heart rate variability power spectral analysis].

The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine (123I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data [left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)], plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data [mean low frequency (MLF) and high frequency power (MHF)] and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure.

3-Iodobenzylguanidine↗

Cloning and characterization of the nucleoredoxin gene that encodes a novel nuclear protein related to thioredoxin.

In a yeast artificial chromosome contig close to the nude locus on mouse chromosome 11, we identified a novel gene, nucleoredoxin, that encodes a protein with similarity to the active site of thioredoxins. Nucleoredoxin is conserved between mammalian species, and two homologous genes were found in Caenorhabditis elegans. The nucleoredoxin transcripts are expressed in all adult tissues examined, but restricted to the nervous system and the limb buds in Day 10.5-11.5 embryos. The nucleoredoxin protein is predominantly localized in the nucleus of cells transfected with the nucleoredoxin expression construct. Since the bacterially expressed protein of nucleoredoxin showed oxidoreductase activity of the insulin disulfide bonds with kinetics similar to that of thioredoxin, it may be a redox regulator of the nuclear proteins, such as transcription factors.

Amino Acid Sequence↗

Cloning and expression of cDNA encoding the human 150 kDa oxygen-regulated protein, ORP150.

We have cloned a cDNA encoding the human 150 kDa oxygen-regulated protein (ORP150) from hypoxia-treated astrocytoma U373 cDNA library. The deduced amino acid sequence of 999 residues contains a signal peptide and an ER retention-like signal at the N- and C-termini, respectively. It has a striking sequence similarity (91% identity) with Chinese hamster 170 kDa glucose-regulated protein (GRP170). The N-terminal half of ORP150 exhibits significant similarity to the ATPase domain of HSP70 family proteins with well-conserved ATP binding motifs. Northern blot analysis revealed that induction of ORP150 in U373 cells was not limited to hypoxia but also observed by 2-deoxyglucose or tunicamycin treatment. Furthermore, tissue specificity of expression of ORP150 was quite similar to that of GRP78. These findings suggest that ORP150 participates in quality control of proteins in the ER in response to diverse environmental stresses.

Adult↗

Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy.

We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.

Adult↗

[Interrelations of the calcium concentration in breast milk with maternal intake of cow's milk and milk products, bone resorption and bone mineral density during lactation].

The interrelations of the calcium (Ca) concentration in breast milk with maternal intake of cow's milk and milk products, 24-hour urinary hydroxyproline and Ca concentrations adjusted by creatinine (H.P/Cre, Ca/Cre) and bone mineral density measured by ultrasonic bone densitometry were examined to study the mechanism regulating the calcium concentration in breast milk. Subjects were 105 lactating women, aged 21 to 42 years, at 21.590 days postpartum. 1) The geometric means (logarithmically transformed calculated M +/- SD) of H.P/Cre were 40.7 (31-61) and 36.3 (28-47) mg/g in women lactating less than 150 days and 150 days or more, respectively. These values indicated increased bone resorption. 2) Intake of cow's milk and milk products significantly negatively correlated with urinary H.P/Cre. For women consuming less than 100ml per day of cow's milk, a significant positive correlation was found between the urinary H.P/Cre and Ca concentration in breast milk. These results suggest that the extent of bone resorption depends on maternal Ca intake and the Ca transfer from maternal bone to breast milk in women with a low Ca intake. 3) For women with a cow's milk intake of less than 100ml per day, a significant positive correlation was found between the Ca concentration in breast milk and bone mineral density, indicating that women with bone mineral loss are not able to compensate for the low Ca level in breast milk. 4) Urinary Ca/Cre significantly negatively affected the Ca concentration in breast milk. This result indicates that some amount of Ca in breast milk is due to renal conservation.

Adult↗

Full functional recovery after surgical repair of transected abducens nerve: case report.

OBJECTIVE AND IMPORTANCE: Results of surgical repair of the injured abducens nerve are rarely reported in the literature. A full functional recovery of a completely resected abducens root may be exceptional. We describe a patient who obtained normal ocular alignment and binocular vision after surgical reconstruction of a transected abducens nerve. CLINICAL PRESENTATION: A 56-year-old woman with a petroclival meningioma was presented. She underwent total removal of the tumor through a combined supra/infratentorial transpetrosal approach. The abducens nerve was tightly attenuated by the tumor and thickened dura. During dissection, the nerve was completely transected just behind the entrance to Dorello's canal. INTERVENTION: The abducens nerve was the single root type and inevitably required surgical repair. To obtain a sufficient length of the distal stump for trimming, part of the petrosphenoidal ligament was cut and the superior border of the petrous bone was exposed. The proximal stump of the nerve was also trimmed to obtain healthy tissue, and reconstruction was performed with five 10-0 nylon sutures. Five months later, esodeviation began to improve. Nine months after the surgery, the patient did not complain of diplopia and an objective assessment reported normal ocular alignment and estimated binocular function as "excellent" according to Biglan's system. Overcorrection of abduction did not occur. CONCLUSION: The result in our patient confirms the possibility of full functional recovery after surgical repair of a totally transected abducens nerve.

Abducens Nerve↗

Reappraisal of p53 mutations in human malignant astrocytic neoplasms by p53 functional assay: comparison with conventional structural analyses.

We previously reported clonal expansion of p53 mutations in malignant astrocytic tumors detected with a yeast p53 functional assay that measures mutant p53 alleles quantitatively and loss of p53 transcriptional competence qualitatively (Tada et al., Int J Cancer 67:447-450, 1996). This method selectively detects inactivating mutations and is relatively insensitive to contamination of tumor samples with normal tissue. To determine whether the mutation frequency and spectrum detected in this way differ from those seen with conventional techniques, 54 malignant astrocytomas were tested with the yeast assay, and the abnormalities detected were characterized by DNA sequencing. Inactivating p53 mutations were found in 67% of anaplastic astrocytomas and 41% of glioblastomas. Overall, mutations were found in 48% of tumors, compared with only 29% in previous studies (P < 0.005), a difference that probably reflects the greater sensitivity of the yeast assay than of conventional techniques. The frequency of mutations in anaplastic astrocytomas (in our study plus published studies) was significantly higher than in glioblastomas (39% vs 29%; P < 0.05). This suggests that acquisition of p53 mutations is not rate limiting for progression to glioblastoma and that many glioblastomas develop by p53-independent pathways. Sequencing of mutant p53 cDNAs rescued from yeast showed that the mutation spectrum for functionally inactive mutants was nearly identical to the spectra from previous studies on structural mutants, indicating that transcriptional activity is the critical biological target of p53 mutation in malignant astrocytomas.

Adult↗

Changes in bradykinin and prostaglandins plasma levels during dextran-sulfate low-density-lipoprotein apheresis.

The negative charges of dextran-sulfate (DS) used for low-density-lipoprotein (LDL) apheresis initiate the intrinsic coagulation pathway in which plasma kallikrein acts on the high-molecular-weight kininogen to produce large amounts of bradykinin. This study was undertaken to assess whether bradykinin generated during DS LDL apheresis has any physiologic effects in vivo. The plasma levels of bradykinin, prostaglandins and cyclic guanosine monophosphate (cGMP) were compared. when either of two anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the plasma levels of prostaglandin E2 (PGE2) increased significantly (5.6 +/- 1.2 (mean +/- SE, n = 4) pg/ml before apheresis and 33.4 +/- 13.2 after apheresis, p < 0.05) in association with an increase in bradykinin levels (17.9 +/- 2.6 pg/ml before apheresis and 470 +/- 135 after apheresis, p < 0.01). Interestingly, these changes were suppressed during apheresis using NM. There were no appreciable changes in cGMP during DS LDL apheresis with either of the anticoagulants. This finding suggests that bradykinin generated during apheresis has some pathophysiological effects via activation of the prostaglandin system. Our results support the view that in patients taking angiotensin-converting-enzyme inhibitors, the anaphylactoid reaction occurring during apheresis may be caused by an excessive rise in the bradykinin levels.

6-Ketoprostaglandin F1 alpha↗

150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.

The 150-kD oxygen-regulated protein (ORP150) was initially characterized based on its selective expression in astrocytes subjected to oxygen deprivation (Kuwabara, K., M. Matsumoto, J. Ikeda, O. Hori, S. Ogawa, Y. Maeda, K. Kitagawa, N. Imuta, K. Kinoshita, D.M. Stern, et al. 1996. J. Biol. Chem. 279:5025-5032). We have found that exposure of cultured human aortic smooth muscle cells and mononuclear phagocytes (MPs) to hypoxia (pO2 approximately 12-14 torr) induces ORP150 transcripts and production of the antigen, whereas incubation with either hydrogen peroxide, sodium arsenite, heat shock, or 2-deoxyglucose was without effect. Tissue extracts prepared from human atherosclerotic lesions demonstrated expression of ORP150 mRNA and antigen, vs lack of ORP150 in samples from nonatherosclerotic areas. In situ hybridization using ORP150 riboprobes showed the mRNA to be predominantly [correction of predominately] present in macrophages in in atherosclerotic plaques. Furthermore, autoantibody to ORP150 was demonstrated in the serum of patients with severe atherosclerosis, consistent with inducible in vivo expression of ORP150. Introduction of antisense oligonucleotide for ORP150 selectively diminished hypoxia-mediated induction of ORP150 antigen and reduced the viability of hypoxic MPs, especially in the presence of modified (oxidized/acetylated) LDL. In support of a role for ORP150 in the MPs' response to the microenvironment of an atheroma, the presence of oxidized LDL enhanced by approximately 10-fold ORP150 expression in hypoxic cultures. These data indicate that cells of the atherosclerotic vessel wall express ORP150 as part of a protective mechanism, potentially triggered by local hypoxia/hypoxemia and augmented by modified lipoproteins. The presence of antibody to ORP150 in sera of patients with severe atherosclerosis emphasizes the possibility that ORP150 may be a marker of vascular pathology.

Adolescent↗