[Acute cell death of cultured rat hippocampal neurons due to mitochondrial disorders].
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Animals↗
Biomedical subjects
K Tsuboi
Publications and source records attributed to K Tsuboi.
Dumbbell-shaped trigeminal neurinoma in a child.
We experienced a case of solitary trigeminal neurinoma in a 10-year-old boy without stigmata of neurofibromatosis. This boy presented with progressive cerebellar ataxia, right abducens palsy and right hemiparesis. Magnetic resonance images (MRI) demonstrated a tumour extending into both the middle and posterior fossas forming a dumbbell-shaped mass lesion with a size of 35 x 30 x 45 mm. The tumour was successfully removed free of complications by a two-stage operation composed of right subtemporal and suboccipital retromastoid approaches. It is extremely rare for a solitary neurinoma to occur at this site in a child without neurofibromatosis. Surgical approaches in this type of tumour are discussed with a review of the literature.
Child↗
Microsatellite instability as a potential marker for poor prognosis in adult T cell leukemia/lymphoma.
Microsatellite instability (MSI) represents a replication error resulting from the dysfunction of mismatch repair gene products. In this study, MSI was analyzed in 18 patients with various subtypes of adult T cell leukemia/lymphoma (ATL/L). Using six different microsatellite loci, we defined MSI as positive when replication errors were observed in at least two loci. The MSI was positive in four cases (22.2%)with acute type ATL, who tended to show more prognostically unfavorable factors and shorter overall survival. These results suggest that genomic instability may be associated with tumor progression rather than the development of ATL/L itself. In addition, the presence of the MSI at initial presentation could appear to warrant consideration as an additional prognostically unfavorable factor.
Adult↗
Multiple myeloma preceding the development of chronic myelogenous leukemia.
A case of a 70-year-old man who first developed multiple myeloma and then chronic myelogenous leukemia (CML) within a 3-year period is documented. The patient, with monoclonal hypergammopathy, was diagnosed with smoldering myeloma with IgG-kappa and Bence Jones protein kappa paraproteinemia. No chemotherapy was given for the myeloma until progressive leukocytosis developed after approximately 3 years. This was found to be due to Philadelphia chromosome positive CML. A reverse transcription-polymerase chain reaction assay did not reveal BCR/ABL mRNAs when the myeloma was first diagnosed. The occurrence of 2 distinct hematologic malignancies in the same patient suggests either a different clonal evolution from a common pluripotent malignant stem cell since the CML stem cell also involves the B-lymphoid lineage, a coincident complication of the 2 hematological malignancies, or the coexistence of 2 distinct malignancies due to the same genetic background and/or exposure to similar carcinogenic agents. The literature provides support for the existence of a relationship between multiple myelomas and CML.
Aged↗
[Fundamental and clinical study of three-dimensional compensating filters and direct dose monitoring system for total body irradiation].
We devised 3D-compensating filters to improve dose distribution during total body irradiation (TBI). This study investigated the effect of these 3D-compensating filters and related complications in patients who had undergone bone marrow transplantation (BMT) followed by TBI. The 3D-compensating filters were fabricated by CT measurement of body thickness. The effectiveness of the 3D-compensating filters in producing a homogeneous dose distribution was checked by a thermoluminescent dosimeter (TLD) and semiconductor detectors in all patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average dose distribution to each site when the 3D-compensating filter was used was 93% to the head, 97% to the neck, 99% to the thorax, and 98% to the pelvis in TLD when the scheduled dose was taken as 100%. There was no significant difference between the TBI and non-TBI groups with regard to the frequency of lung toxicity. Clinical interstitial pneumonitis occurred in 22.7% of the patients, interstitial pneumonitis with CMV in 13.6%, and idiopathic pneumonitis in 6.1% without any virus infection. Only one patient was regarded as having radiation-induced pneumonitis. 3D-compensating filters can be conveniently produced within a short time following CT measurement, and they seem to be safe and useful for dose flattening during TBI.
Adolescent↗
Prosaposin prevents programmed cell death of rat cerebellar granule neurons in culture.
Prosaposin, the precursor of sphingolipid activator proteins (saposin A-D), has been reported to be a neurotrophic factor in vitro and in vivo. Prosaposin mRNA is transiently expressed at a high level in developing cerebellum during the period of granule cell proliferation and maturation, suggesting its significance during development of cerebellum. Here we investigated the neuroprotective effect of prosaposin on cerebellar granule neurons, exposing primary cerebellar granule cells to low K+ which induced programmed cell death. Prosaposin rescued mature cerebellar granule neurons in a bimodal manner. A similar neuroprotective effect was obtained using TX14(A), a 14-mer neurotrophic peptide derivative of prosaposin. An additive neuroprotective effect was observed between BDNF and TX14(A), but not between IGF-1 and TX14(A). Prosaposin rescued 60% of nifedipine sensitive cerebellar granule neurons as well as IGF-1, while BDNF did not. Furthermore, the neuroprotective action of prosaposin was inhibited by LY294002, a specific inhibitor of PI 3-kinase. These findings indicated that prosaposin had a trophic effect upon newborn cerebellar granule cells and that the neuroprotective action was similar to that of IGF-1 rather than BDNF. Prosaposin may play a role in cerebellar development during programmed cell death of cerebellar neurons.
Amino Acid Sequence↗
Detection of bcr/abl fusion transcripts by semiquantitative multiplex RT-PCR combined with a colormetric assay in Ph positive leukemia.
We studied the feasibility of the clinical application of a new bcr/abl analysis system, C-TRAK t(9;22), consisting of a multiplex RT-PCR and a colormetric assay. With this system, bcr/abl transcripts could be detected in all of 24 cytogenetic Philadelphia chromosome (Ph) positive leukemia patients and in none of eight Ph negative patients. Multiple bcr/abl transcripts could be detected in three of the 24 Ph positive patients, the fusion of bcr exon 1 to abl exon 2 (e1a2 junction) dominated that of bcr exon 13 to abl exon 2 (b2a2 junction) in two cases and that of bcr exon 14 to abl exon 2 (b3a2 junction) and b2a2 dominated e1a2 in one case. This system was sensitive enough to be able to detect even one bcr/abl transcript-producing cell in 50000 bcr/abl negative background cells, thus making it suitable for semiquantitative evaluation. Minimal residual disease (MRD) was monitored in one Ph positive leukemia patient who underwent allogenic bone marrow transplantation (allo-BMT). After allo-BMT, a weak positivity of the bcr/abl transcript continued with no clinical relapse; this result was consistent with that of a conventional nested PCR assay using ethidium bromide staining. Including all the procedures for RNA extraction, it took only about 10 h to detect the bcr/abl transcripts. Our findings indicate that this bcr/abl analysis system provides a quick and sensitive method for screening bcr/abl transcripts and possibly for monitoring MRD in Ph positive leukemia patients.
Acute Disease↗
Female reproduction in mice lacking the prostaglandin F receptor. Roles of prostaglandin and oxytocin receptors in parturition.
Female mice lacking the receptor for prostaglandin F2 alpha (FP) do not deliver fetuses at term, although these can be successfully rescued by cesarean section. No induction of oxytocin receptor mRNA is found in the uterus of these mice, and they show no uterine contraction on intravenous administration of oxytocin. Furthermore, a decline in serum progesterone levels during the periparturition period is not observed in these animals. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and caused successful delivery in these animals. These results indicate not only the essential role of luteolytic PGF 2 alpha action in natural parturition but also the importance of oxytocin receptor induction in this process.
Animals↗
Cell death induced by high-linear-energy transfer carbon beams in human glioblastoma cell lines.
The cytotoxic effect of high-linear-energy transfer (LET) carbon beams on two human glioblastoma cell lines (A172 and TK1) was analyzed, especially concerning cell death, including apoptosis. Gamma-ray radiation was used for comparison. The results of standard colony formation assay showed that the survival fraction of each cell line decreased in an LET-dependent manner. The results of other direct cytotoxic assays, dye exclusion test, and lactate dehydrogenase (LDH) release assay, also displayed a similar relationship between the cytotoxic effect of carbon beams and LET. The maximum values of the cell death index (CDI) were 50.2% in A172 and 37.5% in TK1, both obtained on day 7 after exposure to carbon beams of 80 keV/microm. Apoptosis was observed only on days 4 and 7 after carbon beam irradiation, with maximum values of 7% in A172 and 4.5% in TK1, and the induction of apoptosis after high-LET radiation could be p53-independent. This indicated that a combination of multiple assays to detect cell death was important in evaluating the radiosensitivity of tumor cells, because this approach could more precisely reflect the clinical effectiveness of radiotherapy.
Apoptosis↗
Prevention of hyperlipidemic acute pancreatitis during pregnancy with medium-chain triglyceride nutritional support.
CONCLUSION: A combination of diet therapy, nutritional support with medium-chain triglycerides (MCT), and well-planned preterm Cesarean delivery on demand is an effective measure to prevent gestational hyperlipidemic pancreatitis and leads to successful childbirth. BACKGROUND: Prevention and therapy of gestational hyperlipidemic pancreatitis are important, although difficult, because the condition carries a high maternal and fetal morbidity and mortality. RESULTS: We describe a 32-yr-old female with lipoprotein lipase-deficient familial hypertriglyceridemia who had recurrent episodes of acute pancreatitis. The third episode occurred with worsened hyperlipidemia 7 yr earlier at 32 wk of her first pregnancy and resulted in fetal death. The fourth and fifth episodes were also accompanied by marked hyperlipidemia probably caused by drug discontinuance and dietary noncompliance. She became pregnant. Serum triglyceride levels were controlled below 2000 mg/dL by strict monitoring with low-fat, low-calorie diet and MCT nutritional support. A premature but healthy infant was born by Cesarean delivery at 36 wk of gestation when the mother presented with mild abdominal pain and was found to have uterine contractions. The ensuing clinical course has been uneventful.
Acute Disease↗
Microsatellite instability is rare in the clinical course of myelodysplastic syndrome studied with DNA from fresh and paraffin-embedded tissues.
Microsatellite instability (MSI) has been reported to occur in various types of malignant neoplasms. We performed a polymerase-chain-reaction-based assay for MSI between the initial and the most recently available ("latest") samples from 23 patients with myelodysplastic syndrome (MDS). Of these patients, 15 were informative at more than three microsatellite loci. Seven patients showed an increase in leukemic cells while 8 patients did not during the interval between the two analyses. Only 1 of the patients, who had refractory anemia with excess blasts, which changed to acute myelogenous leukemia, showed microsatellite alteration at the analysis times. Among all 23 patients, two alterations were detected in the 42 informative paired samples that showed an increase in leukemic cells (4.8%), while none was detected in the 59 paired samples without such an increase. In total, therefore only two alterations were detected among 101 informative paired samples (2%). This indicates that MSI is rare in the clinical course of MDS irrespective of disease status, and is consequently not a critical genetic event for disease progression in most MDS patients.
Adult↗
Cytotoxic effect of accelerated carbon beams on glioblastoma cell lines with p53 mutation: clonogenic survival and cell-cycle analysis.
PURPOSE: The cytotoxic effect of high-LET carbon beams was analysed on p53 mutant and wild-type glioblastoma cell lines. MATERIALS AND METHODS: Three glioblastoma (U251MG, TK-1, A-172) cell lines, one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used. U251MG and TK-1 have mutated p53, A-172, ONS-76 and NB1RGB have wild-type p53. Gamma-ray and 290 MeV/u carbon mono-peak beams with average LET values of 20, 40, 81 and 105keV/microm were used. Cytotoxicity was measured by clonogenic survival assay and DNA histograms were analysed by flow cytometry. RESULTS: The RBE values for carbon beams at D10 ranged from approximately 1.5-1.7 (20keV) to 2.9-3.1 (105keV). Although p53 mutants were more resistant than wild-types for all radiation qualities, carbon beams yielded a higher RBE in p53 mutants than in wild-types. Alpha values were significantly smaller in p53 mutants than wild-types for gamma- and 20 keV/microm radiations, while no significant difference was noticed for LET greater than 40 keV/microm. A G1 block was noticed after irradiation with gamma-rays and carbon beams of 20 and 40keV/microm in p53 wild-types. A more pronounced G2 block occurred in p53 mutants than wild-types in proportion to LET up to 105 keV/microm. CONCLUSION: Accelerated carbon beams can yield higher RBE in gamma-resistant glioblastoma cell lines with p53 mutations. High-LET irradiation induces not only disappearance of the p53-dependent G1 block but also a greater G2 block in glioblastoma cell lines.
Cell Cycle↗
Granulocyte-macrophage colony-stimulating factor expressed in T cells mediates immunity against herpes simplex virus type 1 encephalitis.
A model of herpes simplex virus type 1 (HSV-1) infection was developed in rats to study systemic immune responses elicited by intravitreous inoculation of the virus. HSV-1 inoculation led to distinct granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing memory T cells, which did not develop in rats inoculated with either HSV-1 intraperitoneally or inactivated HSV-1 intravitreously. On subsequent intraperitoneal viral boosting, systemic GM-CSF production was elicited as a secondary immune response that caused neutroeosinophilia. To examine the role of GM-CSF in anti-herpetic immunity, cytokine-producing and -nonproducing rats were intravitreously challenged with HSV-1, which causes lethal encephalitis. Only intravitreously primed rats were protected upon production of GM-CSF. Furthermore, pretreatment with recombinant GM-CSF protected unimmunized rats against the encephalitis. It is thus strongly suggested that the production of GM-CSF leads to anti-HSV-1 immunity against the transneuronal spread of challenged HSV-1 within the visual system.
Adoptive Transfer↗
Interferon-alpha-induced thyroid dysfunction in patients with chronic active hepatitis C: a transient, reversible and self-limited dysfunction.
To survey the prognoses of interferon-alpha (IFNalpha)-induced thyroid dysfunction, a total of 100 patients (49 males and 51 females) with biopsy-proven chronic active hepatitis C were studied. Either during or after IFNalpha therapy, 29 patients (33.7%) revealed suppression/elevation of thyroid stimulating hormone (TSH) or both, transient thyrotoxicosis (TSH less than 0.1 microU/ml) or transient hypothyroidism (TSH 5.0-190.95 microU/ml). However, the thyroid function normalized without supplementation of the thyroid hormone in the follow-up period. In the same period, one of the 14 control patients (7.1%) developed thyroid dysfunction. Thyroid abnormalities developed significantly more in patients with IFNalpha therapy than in those without IFNalpha therapy. The findings suggest that the occult autoimmune disorder becomes overt with IFNalpha treatment in patients with pre-existent autoimmune thyroid disease. IFNalpha-induced thyroid dysfunction is transient, reversible and self-limited. It is not necessary to discontinue IFNalpha therapy when thyroid dysfunction develops.
Adult↗
[Total synthesis and conformational analysis of inhibitors].
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Animals↗
Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA-receptor function.
Animals vary in their sensitivity to ethanol, a trait at least partly determined by genetic factors. In order to identify possible responsible genes, mice lacking Fyn, a non-receptor type tyrosine kinase, were investigated. These mice were hypersensitive to the hypnotic effect of ethanol. The administration of ethanol enhanced tyrosine phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of control mice but not in Fyn-deficient mice. An acute tolerance to ethanol inhibition of NMDAR-mediated excitatory postsynaptic potentials in hippocampal slices developed in control mice but not in Fyn-deficient mice. These results indicate that Fyn affects behavioral, biochemical, and physiological responses to ethanol.
Animals↗
Failure of parturition in mice lacking the prostaglandin F receptor.
Mice lacking the gene encoding the receptor for prostaglandin F2alpha (FP) developed normally but were unable to deliver normal fetuses at term. Although these FP-deficient mice showed no abnormality in the estrous cycle, ovulation, fertilization, or implantation, they did not respond to exogenous oxytocin because of the lack of induction of oxytocin receptor (a proposed triggering event in parturition), and they did not show the normal decline of serum progesterone concentrations that precedes parturition. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and permitted successful delivery in the FP-deficient mice. These results indicate that parturition is initiated when prostaglandin F2alpha interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis.
Animals↗
Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line.
Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D37 values of 4.7Gy in OR-5 and 1.7Gy in OS-3. After gamma irradiation (8Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.
Caffeine↗