Self-induced vomiting in X-linked alpha-thalassemia/mental retardation syndrome.
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Adolescent↗
Biomedical subjects
J Ikeda
Publications and source records attributed to J Ikeda.
Comparison of the structural features of ubiquinone reduction sites between glucose dehydrogenase in Escherichia coli and bovine heart mitochondrial complex I.
To characterize the structural features of the ubiquinone reduction site of glucose dehydrogenase (GlcDH) in Escherichia coli, we performed structure/activity studies of a systematic set of synthetic ubiquinone analogues and specific inhibitors (synthetic capsaicins) of this site. Considering the proposed similarity of the quinone binding domain motif between GlcDH and one subunit of mitochondrial complex I [Friedrich, T., Strohdeicher, M., Hofhaus, G., Preis, D., Sahm, H. & Weiss, H. (1990) FEBS Lett. 265, 37-40], we compared the structure/activity profiles of the substrates and inhibitors for GlcDH with those for bovine heart mitochondrial complex i. With respect to GlcDH, replacement of one or both methoxy groups in the 2 and 3 positions of benzoquinone ring by ethoxy group(s) resulted in a drastic decrease in the electron accepting activity. The presence of a 5-methyl group and the conformational property of the 6-alkyl side chain did not significantly contribute to the activity. These results suggested that only half of the benzoquinone ring (the moiety corresponding to the 2 and 3 positions) is recognized by the quinone reduction site in a strict sense. In contrast, quinone analogues with structural modifications at all positions in the benzoquinone ring retained the activity with mitochondrial complex I. This finding indicated that the catalytic site of complex I is spacious enough to accommodate a variety of structurally different quinone derivatives. The correlation of the inhibitory potencies of a series of synthetic capsaicins between the two enzymes was very poor. These findings indicated that the binding environment of ubiquinone in GlcDH is very specific and differs from that in mitochondrial complex I.
Animals↗
Nuclear disintegration as a leading step of glutamate excitotoxicity in brain neurons.
Recent studies on ischemic brain disease in vivo and glutamate excitotoxicity in vitro suggest that apoptosis may play a role in excitotoxic neuronal death. To examine the possible involvement of apoptosis in glutamate excitotoxicity, we studied an early process of morphological changes in rat cortical neurons exposed to 1 mM glutamate. Observations under Nomarski optics combined with a digital image processor revealed a rapid change in the nucleus followed by a cellular swelling. The nucleus increased in granularity and swelled in 5 min, then became liquefied in 30 min. The cell body swelled slowly in 15-45 min. These changes could be prevented by treatment of the neuron with MK-801 (dizocilpine maleate), a blocker of N-methyl-D-aspartate (NMDA) receptor-coupled ion channel. However, treatment of the neurons with N(G)-nitro-L-arginine (N-NORG), a nitric oxide synthase inhibitor, had no significant effect. Use of the in situ end-labeling technique for the demonstration of free 3'-hydroxyl ends revealed that DNA fragmentation took place within 1 hr after glutamate exposure. A change in intracellular Ca(2+) concentration was examined with fluo-3 under a confocal laser microscope. Application of 1 mM glutamate induced rapid Ca transients in the nucleus as well as in the cytoplasm. Both of these Ca responses were blocked by MK-801. These results indicate that glutamate excitotoxicity in the brain neuron does not fulfill morphological criteria of apoptosis, but suggest that the nuclear disintegration associated with DNA fragmentation is involved as a leading step in glutamate excitotoxicity.
Animals↗
Purification and characterization of a novel stress protein, the 150-kDa oxygen-regulated protein (ORP150), from cultured rat astrocytes and its expression in ischemic mouse brain.
As the most abundant cell type in the central nervous system, astrocytes are positioned to nurture and sustain neurons, especially in response to cellular stresses, which occur in ischemic cerebrovascular disease. In a previous study (Hori, O., Matsumoto, M., Kuwabara, K., Maeda, M., Ueda, H., Ohtsuki, T., Kinoshita, T., Ogawa, S., Kamada, T., and Stern, D. (1996) J. Neurochem., in press), we identified five polypeptide bands on SDS-polyacrylamide gel electrophoresis, corresponding to molecular masses of about 28, 33, 78, 94, and 150 kDa, whose expression was induced/enhanced in astrocytes exposed to hypoxia or hypoxia followed by replacement into the ambient atmosphere (reoxygenation). In the current study, the approximately 150-kDa polypeptide has been characterized. Chromatography of lysates from cultured rat astrocytes on fast protein liquid chromatography Mono Q followed by preparative SDS-polyacrylamide gel electrophoresis led to isolation of a approximately 150-kDa band only observed in hypoxic cells and which had a unique N-terminal sequence of 15 amino acids. Antisera raised to either the purified approximately 150-kDa band in polyacrylamide gels or to a synthetic peptide comprising the N-terminal sequence detected the same polypeptide in extracts of cultured rat astrocytes exposed to hypoxia; expression was not observed in normoxia but was induced by hypoxia within 24 h, augmented further during early reoxygenation, and thereafter decreased to the base line by 24 h in normoxia. ORP150 expression in hypoxic astrocytes resulted from de novo protein synthesis, as shown by inhibition in the presence of cycloheximide. In contrast to hypoxia-mediated induction of the approximately 150-kDa polypeptide, neither heat shock nor a range of other stimuli, including hydrogen peroxide, cobalt chloride, 2-deoxyglucose, or tunicamycin, led to its expression, suggesting selectivity for production of ORP150 in response to oxygen deprivation, i.e. it was an oxygen-regulated protein (ORP150). Northern and nuclear run-off analysis confirmed the apparent selectivity for ORP150 mRNA induction in hypoxia. Subcellular localization studies showed ORP150 to be present intracellularly within endoplasmic reticulum and only in hypoxic astrocytes, not cultured microglia, endothelial cells, or neurons subject to hypoxia. Consistent with these in vitro results, induction of cerebral ischemia in mice resulted in expression of ORP150 (the latter was not observed in normoxic brain). These data suggest that astroglia respond to oxygen deprivation by redirection of protein synthesis with the appearance of a novel stress protein, ORP150. This polypeptide, selectively expressed by astrocytes, may contribute to their adaptive response to ischemic stress, thereby ultimately contributing to enhanced survival of neurons.
Aerobiosis↗
Phase II study of DTIC, ACNU, and vincristine combination chemotherapy for supratentorial malignant astrocytomas.
This phase II clinical study evaluated the use of 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) pretreatment to reduce cellular resistance and enhance the antitumor effects of chloroethyl nitrosoureas in 32 patients with supratentorial malignant gliomas, including 13 anaplastic astrocytoma and 19 glioblastoma multiforme. All patients received a total dose of 50-65 Gy radiation therapy after surgery. Chemotherapy consisted of DTIC (1 mg/kg) on days 1-5, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (2 mg/kg) on day 5, and vincristine (0.02 mg/kg) on days 1 and 15 every 5 weeks. One patient achieved complete response and 12 patients showed partial response. Median survival time was 18 months and median time-to-progression was 11 months. No significant toxicity was encountered. There was no significant benefit of this pretreatment to combination chemotherapy when compared with previous results. This study does not support a further role for DTIC as a depleter of O6-alkylguanine deoxyribonucleic acid alkyltransferase activity preceding chloroethyl nitrosourea-based chemotherapy.
Adolescent↗
Combined irradiation and chemotherapy using ifosfamide, cisplatin, and etoposide for children with medulloblastoma/posterior fossa primitive neuroectodermal tumor--results of a pilot study.
Ten children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor of the posterior fossa were treated with total surgical resection, radiation therapy, and ICE chemotherapy regimen with ifosfamide (900 mg/m2, days 1-5), cisplatin (20 mg/m2, days 1-5), and etoposide (60 mg/m2, days 1-5) every 4 weeks for eight cycles. Four children under 2 years old were at first treated with eight cycles of ICE chemotherapy, and then irradiated. The ICE regimen was well tolerated by all children, with no irreversible adverse effects. However, dose reductions during the eight cycles were inevitable mainly due to myelosuppression. Complete remissions were achieved in eight of 10 patients at 1 month after completion of the treatment. One child showed recurrence 21 months after complete remission. The disease-free survival rate was 70% with a mean observation period of 24 months after surgery. The ICE regimen is a useful treatment modality for children with medulloblastoma. Further study is warranted to clarify long-term outcome in a number of patients.
Antineoplastic Combined Chemotherapy Protocols↗
[Effects of lactation and lifestyles including food intake on bone density of lactating women].
Ultrasonic bone densities were measured in 131 lactating women, aged 21 to 42 years, at 6-590 days postpartum. STIFFNESS Calculated from the combined value of speed of sound and broadband ultrasound attenuation at the calcaneus was used as an index of bone density. The relationships of STIFFNESS with period of lactation, current and past consumption of cow's milk, various food intake frequency, history of participating in sports, daily physical activity, using calcium drugs and sun exposure were examined using stepwise multiple regression analysis, including age and weight as independent variables. 1) The mean (SD) of STIFFNESS was 79.8 (11.9). Thirty-three women (25% of subjects) showed STIFFNESS less than 70. 2) Period of lactation showed a significant negative effect on STIFFNESS (p < 0.05). However, no such effect appeared for women with cow's milk intake of less than 100 ml per day. This result suggests a protection of calcium levels in bone. 3) Current daily cow's milk intake showed significant positive effect on STIFFNESS (p < 0.05). For women lactating less than 150 days, this relation between cow's milk intake and STIFFNESS was clear (r = 0.44, p < 0.01). 4) Significant relation between STIFFNESS and food intake frequencies was found in milk and milk products only among various foods. This result indicates that cow's milk and milk products are important sources of calcium during lactation.
Adult↗
[Analysis factors associated with bone density in young women].
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Adult↗
[Cross sectional study of the relationship between bone density to diet and life style using ultrasound bone densitometry].
The relationship between bone density to diet and life style was investigated in pre- and postmenopausal women in Kyoto Prefecture in 1994 by a cross-sectional study. Bone densities of 453 women aged 30-86 years were measured by ultrasound bone densitometry. History of pregnancy and delivery, menstruation, medical history, bone and arthral symptoms, life style, food intake frequency, current and past intake of dairy products, and physical activity were examined by self-administered questionnaire. Analysis of covariance and multiple-regression analysis were performed to determine the relation between bone density and life style adjusted for age and obesity index among 151 premenopausal women (PRE), 244 postmenopausal but not sedentary (under 65 years of age) women (POST), and 58 sedentary (older than 65 years of age) women (SED). The results were as follows; 1) A marked age-related decline in bone density was observed at 45-55 years of age. The correlation coefficient between age and bone density was significant at -0.65 (p < 0.01). 2) Obesity index and bone density were positively correlated in each group. 3) Among the PRE group women, there was no relation between life style and bone density. Those who experienced bone fractures tended toward low bone density. Among the POST group, time since menopause, exercise, and current milk intake were significantly correlated with bone density. In the SED group, women with arthralgia showed significantly lower densities. 4) From multiple-regression analysis, age, obesity index, and milk intake during childhood were shown to be related to bone density in each group.
Adult↗
Towards the finer mapping of facioscapulohumeral muscular dystrophy at 4q35: construction of a laser microdissection library.
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder which has been mapped to the 4q35 region. In order to saturate this distal 4q region with DNA markers, a laser-based chromosomal microdissection and microcloning procedure was used to construct a genomic library from the distal 20% of chromosome 4, derived from a single human metaphase spread. Of the 100 microclones analyzed from this library, 94 clones contained inserts sized from 80-800 bp, with an average size of 340 bp. Less than 20% of these clones hybridized to human repeat sequences. Seventy-two single-copy clones were further characterized by Southern blot hybridization against a DNA panel of somatic cell hybrids, containing various regions of chromosome 4. Forty-two clones mapped to chromosome 4, of which 8 clones mapped into the relevant 4q35 region. Twenty of these chromosome 4-specific clones were screened against "zoo-blots"; 11 clones, of which 3 mapped to 4q35, identified conserved sequences. This is the first report to describe the isolation of potential expressed sequences derived from the FSHD region. These chromosome region-specific microclones will be useful in the construction of the physical map of the region, the positional cloning of potential disease-associated genes, and the identification of additional polymorphic markers from within the distal 4q region.
Biomarkers↗
Successful chemoradiation therapy for high-grade skull base chondrosarcoma in a child.
High-grade chondrosarcoma in the skull base has been known to be extremely refractory to adjuvant therapy. We report successful chemoradiation therapy for skull base chondrosarcoma in a child. The patient was a 6-year-old boy with an invasive skull base tumor. In spite of gross total removal of the tumor, it recurred 1 month after surgery. Following an intra-arterial injection of adriamycin (10 mg), the second gross total removal was carried out. At the end of the operation, cisplatin (20 mg) was locally injected into the surgical cavity. The patient was further given a total of six courses of systemic chemotherapy in combination with adriamycin (30 mg/m2) and cisplatin (100 mg/m2) and 55 Gy focal irradiation. One year after the most recent surgery, the patient is in complete remission. The efficacy of adjuvant therapy of this rare tumor is discussed.
Antineoplastic Combined Chemotherapy Protocols↗
SMA genes: deleted and duplicated.
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Gene Deletion↗
Magnetic resonance images reveal a high incidence of asymptomatic pineal cysts in young women.
MACROSCOPIC BENIGN PINEAL cysts, according to previous reports, may preferentially occur in the young population at the fourth decade; symptomatic pineal cysts have been found mainly in females. To confirm the relationship of age and sex to the incidence of pineal cysts, we reviewed 8623 consecutive magnetic resonance images in 6023 patients. Tiny and obscure cysts in the pineal gland were ignored; only the pineal cysts > 5 mm were examined. The cysts were encountered in 79 (1.3%) of 6023 patients evaluated. The cysts predominantly occurred in females; we found 29 cysts in 3008 males and 50 cysts in 3015 females (P < 0.05). Young adults had higher incidence of these cysts, with a peak incidence occurring between the ages of 21 and 30 years, then the incidence gradually decreased with age. We found no significant age distribution in males. However, among all groups, young women between the ages of 21 and 30 years had the highest frequency (5.82%). The incidence of pineal cysts among women between the ages of 21 and 30 years was significantly higher than in any other group (P < 0.001; 21-30 versus 51-60, 61-70, and 71-80). In females, when the incidence below the age of 41 was compared with that above or equal to 41, the z score was 4.98 (P < 0.001). The cystic expansion of the pineal gland in females appeared to begin at adolescence, and presumably the pineal gland decreases in size with aging. In this article, we will also speculate about the relationship of these changes to the secretory activity of the pineal glands.
Adolescent↗
[Validity of scores calculated from the results of a food frequency questionnaire].
To study the validity of three evaluative scores (Balance score, Vegetable score, Dietary habit score) calculated from the results of a food frequency questionnaire, the frequency of food selections from various food groups and other dietary habits were investigated in 308 female students aged 18-19 using a specially structured questionnaire. In addition, a quantitative nutrient survey with values indicated by weight was performed on each participant. (1) Balance score, Vegetable score and Dietary habits score appeared to be useful indicators for estimation of nutrient intake, vegetable intake and dietary habits, respectively. (2) Analysis showed that nutrient intake can be estimated more distinctly by the simultaneous use of balance score and dietary habits score.
Adult↗
Isolation and characterization of 21 novel expressed DNA sequences from the distal region of human chromosome 4p.
We have established an approach to the isolation of expressed DNA sequences from a defined region of the human chromosome. The method relies on the direct screening of cDNA libraries using pooled single-copy microclones generated by a laser chromosome micro-dissection in conjunction with a single unique primer polymerase chain reaction (SUP-PCR) procedure. We applied this method to the distal region of human chromosome 4p (4p15-4pter), which contains the Huntington disease (HD) and the Wolf-Hirschhorn syndrome (WHS) loci. Twenty-one nonoverlapping and region-specific cDNA clones encoding novel genes were isolated in this manner. Ten of 21 clones were subregionally assigned to 4p16.1-4pter, and the remainder mapped to the region proximal to 4p16.1. Northern blot and reverse transcription followed by the PCR (RT-PCR) analysis revealed that 16 of these 21 clones detected transcripts in total RNA from human tissues. Our method is applicable to other chromosomal regions and is a powerful approach to the isolation of region-specific cDNA clones.
Base Sequence↗
Low-field phase boundaries of bcc solid 3He.
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Journal Article↗
Involvement of nitric oxide and free radical (O2-) in neuronal injury induced by deprivation of oxygen and glucose in vitro.
Nitrix oxide (NO) is a free radical that has been recently proposed as a messenger molecule in the central nervous system. Since its involvement in glutamate neurotoxicity in vitro has been recently reported, using rat cortical cultures, we tested the hypothesis that NO also plays a role in neuronal injury induced by deprivation of oxygen and glucose. About 80-90% of neurons were killed in less than 12 h after a 4-6 h period of oxygen and glucose deprivation. N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxidase synthase (NOS), significantly ameliorated this neuronal injury in a dose dependent manner. Since it has been suggested that NO is inactivated in a short time period by interaction with superoxide anions (O2-), which are generated during ischemia-reperfusion in vivo, we further evaluated the effect of superoxide dismutase (SOD) on neuronal injury in this test system. SOD failed, however, to protect against neuronal death. Furthermore, concomitant addition of SOD and L-NNA rather reduced the beneficial effects of L-NNA. Our results suggest therefore that NO, at least in part, mediates neuronal injury secondary to deprivation of oxygen and glucose in vitro and that superoxide anions may have a protective role by inactivating NO.
Amino Acid Oxidoreductases↗
Coexpression of c-fos and hsp70 mRNAs in gerbil brain after ischemia: induction threshold, distribution and time course evaluated by in situ hybridization.
Levels of mRNAs encoding the proto-oncogene, c-fos, and the 70 kDa stress protein, hsp70, were evaluated in gerbil brain following transient cerebral ischemia of varied duration by in situ and blot hybridization techniques. Blots of total hippocampal RNA obtained after 5 min ischemic insults confirmed a characteristic, transient time course of c-fos expression with a striking elevation within 1 h and a return to control levels by 3 h recirculation. Hsp70 hybridization was significant at 1 h and continued to increase until 3-6 h after the insult. Striking accumulation of c-fos mRNA was detected within 15 min recirculation in dentate granule cells, persisting through 1 h, and a weaker signal was evident in CA1 and CA3 pyramidal neurons of hippocampus, as well as in prepiriform/entorhinal cortex and neocortical regions, during the same interval. Hsp70 hybridization showed an identical distribution at 1 h recirculation. Ischemic insults of 1 min duration resulted in no detectable increase of either mRNA, while 2 min ischemia resulted in changes comparable to those seen after 5 min insults. This common threshold corresponds to the ischemic interval required for energy depletion and resultant failure of intracellular ion homeostasis. In contrast, expression of hsp70 mRNA was not observed under conditions of brief depolarization accompanying cortical or hippocampal spreading depression that were shown to induce c-fos. A delayed component of c-fos mRNA expression was not detected in this model, while persistent hsp70 hybridization, restricted to hippocampal CA1 neurons, was evident at 48 h after either 2 min or 5 min ischemic insults. The parallels in c-fos and hsp70 mRNA expression during early recirculation suggest that overlapping mechanisms triggered following postischemic depolarization contribute to their induction after transient ischemia.
Animals↗