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Biomedical subjects

I Naruse

Publications and source records attributed to I Naruse.

At least 37 records · Page 2Linked to original sources
PubMed1996

Positional cues that are strictly localized in the telencephalon induce preferential growth of mitral cell axons.

In mice, mitral cells are the major efferent neurons of the main olfactory bulb and elongate axons into a very narrow part of the telencephalon to form a fiber bundle referred to as the lateral olfactory tract (LOT). To clarify the mechanisms responsible for guidance of mitral cell axons along this particular pathway, we co-cultured mouse embryo main olfactory bulbs with the telencephalons, and analyzed the pathways taken by mitral cell axons. Ingrowth of mitral cell axons into the telencephalon was observed in those co-cultures in which the olfactory bulbs had been exactly combined to their normal pathway (the LOT position) of the telencephalon. The axons grew preferentially along the LOT position, and formed a LOT-like fiber bundle. When the olfactory bulbs were grafted at positions apart from their normal pathway, however, no mitral cell axons grew into the telencephalon. Neocortical fragments combined with the telencephalon projected fibers into the telencephalon in random directions. These results suggest that the LOT position of the telencephalon offers a guiding pathway for mitral cell axons and that guiding cues for mitral cell axons are extremely localized.

Animals↗
PubMed1996

Phase I study of a carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

Cisplatin (CDDP)-containing chemotherapy has become the mainstay of clinical trials in unresectable non-small-cell lung cancer (NSCLC), but the role of chemotherapy in the routine management of NSCLC remains controversial. We conducted a phase I study with the combination carboplatin (CBDCA), CDDP, and etoposide (Etop) in unresectable NSCLC. CBDCA, at a starting dose of 80 mg/m2, on day 1, was combined with a fixed dose of CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3). Escalation was performed after four patients entered at each dose level. If no World Health Organization (WHO) grade 4 toxicity developed after the first cycle in more than half of the patients or WHO grade 3/4 toxicity in more than two thirds, the dose was escalated. The maximum tolerated dose was established at 300 mg/m2 for CBDCA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. No grade 3/4 nonhematologic toxicities were seen. The recommended dose of CBDCA to be combined with CDDP (80 mg/m2, day 1) and Etop (80 mg/m2, days 1-3) is 280 mg/m2. This trial suggests that our combination chemotherapy may be effective in patients with advanced NSCLC. A multicenter phase II study based on these findings is now under way.

Adult↗
PubMed1995

Distribution of a brain-specific proteoglycan, neurocan, and the corresponding mRNA during the formation of barrels in the rat somatosensory cortex.

Neurocan is a developmentally regulated chondroitin sulphate proteoglycan in the rat brain. In the present study, spatiotemporal patterns of expression of neurocan and the corresponding mRNA were examined in the developing cortical barrel field of the rat brain by using a monoclonal antibody that was highly specific to neurocan and a riboprobe for a portion of the mRNA. Immunohistochemical analysis revealed that neurocan was distributed throughout the cerebral cortex during early postnatal development but was excluded from the centres of cortical barrels at the time of entry and arborization of thalamocortical axons. At this developmental stage, expression of neurocan mRNA was shown by in situ hybridization to be down-regulated in the barrel centres. When a row of whisker follicles was laser-cauterized on postnatal day 1, the pattern of expression of neurocan was disturbed in the row of barrels that corresponded to the lesioned whisker follicles in the contralateral somatosensory cortex. From these observations, it appears that neuronal stimuli through early thalamocortical fibres from the sensory periphery cause reduced expression of neurocan mRNA in neurocan-producing cells in the presumptive barrel centres. Our findings also suggest that the pattern of distribution of neurocan in early postnatal barrel fields may be due mainly to the down-regulation of expression of neurocan mRNA.

Animals↗
PubMed1995

Apoptosis in the developing CNS.

In this review, apoptosis during normal development of the CNS and abnormal apoptosis inducing hydrocephaly and arhinencephaly will be discussed. As the prominent sites of apoptosis during normal development of the CNS, we focused on the area of fusion of the neural plate to form the neural tube, the developing rhombomeres, and neuronal loss in the CNS during embryogenesis and postnatal development. As examples of abnormal apoptosis inducing abnormal brain morphogenesis, we will discuss genetically induced arhinencephaly and hydrocephaly. It was suggested that apoptosis of the precursor mitral cells in the anlage of the olfactory bulb was induced by non-innervation of olfactory neurons, and apoptosis of the precursor neurons in the pyriform cortex was induced by the non-innervation caused by the death of mitral cells in the mutant arhinencephalic mouse brain (Pdn/Pdn). Thus, sequential apoptosis of the precursor neurons and sequential manifestation of the brain abnormalities were proposed in arhinencephalic mutant mouse embryos and also in the arhinencephalic brains induced experimentally by fetal laser surgery exo utero. Meanwhile, it was speculated that the Gli3 gene, mutation of which is responsible for the arhinencephaly in Pdn/Pdn mice, might play a role in mesenchymal programmed cell death during development.

Animals↗
PubMed1995

Effects of all-trans-retinoic acid on limb development in the genetic polydactyly mouse.

Pdn/+ female mice, mated with Pdn/+ males, were treated with 40 mg/kg body weight of all-trans-retinoic acid (RA) intraperitoneally on day 10 or 11 of gestation, and effects on the limb development were investigated. RA treatment induced the shortening of stylopodium and zygopodium. In the present experiment, we focused on the differences between genotypes in the shortening of stylopodium and zygopodium induced by RA. The effects of RA were milder in Pdn/Pdn than +/- (Pdn/+ and/or +/+) fetuses. The differences between genotypes in the effects of RA were more significant in the group treated on day 11 than on day 10 of gestation. Cartilage of stylopodium and zygopodium was longer in day-13 Pdn/Pdn embryos exposed to RA on day 11 of gestation than those in similarly treated +/- embryos. Many apoptotic cells were observed in the mesenchyme of the forelimb plates at 12 hr after injection of RA on day 11 of gestation. These results suggest that the Pdn gene might influence the apoptosis induced by RA in the mesenchymal cells of the limb, causing milder effects in the shortening of stylopodium and zygopodium in Pdn/Pdn fetuses.

Animals↗
PubMed1994

The arrest of luteinizing hormone-releasing hormone neuronal migration in the genetic arhinencephalic mouse embryo (Pdn/Pdn).

From previous observations, it was suggested that non-attachment of the olfactory nerve to the telencephalon blocked the induction of the olfactory bulbs in genetic arhinencephalic mouse embryos (Pdn/Pdn). The olfactory nerve ends in a tangle beneath the forebrain in these embryos. From these observations, we speculated that the migration of luteinizing hormone-releasing hormone (LHRH) neurons might be disturbed in the olfactory nerve. A mass of LHRH neurons was observed in the end of the olfactory nerve fibers, but LHRH neurons were found in the hypothalamus in Pdn/Pdn embryos on day 16 of gestation. Narrow by-paths were found between the olfactory nerve and the forebrain, and the migration of LHRH neurons through these by-paths was observed in Pdn/Pdn embryos on day 13 of gestation. From the reports that a gene deleted in the arhinencephalic syndrome (Kallmann's syndrome) shares homology with neural cell adhesion molecules (N-CAM), it was speculated that non-attachment of the olfactory nerve in the Pdn/Pdn embryo might be associated with abnormalities of N-CAM. The axon fibers of the olfactory nerve reacted specifically with anti-N-CAM IgG both in +/- (+/+ and/or Pdn/+) and Pdn/Pdn on day 11.5 and 12, but not on day 13 and 16 of gestation. The axon fibers of the olfactory nerve were positive to anti-N-CAM IgG specifically just during the developmental period that the olfactory nerve fibers attached to the telencephalon. It is still not clear whether non-attachment of the olfactory nerve may be associated with N-CAM or not from the present observations.

Animals↗
PubMed1994

Apoptotic degeneration in the arhinencephalic brain of the mouse mutant Pdn/Pdn.

The homozygotes of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) exhibit arhinencephaly and various brain malformations. In the present experiment, abnormal apoptotic degeneration in the arhinencephalic brain of Pdn/Pdn embryos and newborns was investigated immunohistochemically and by molecular genetic techniques. Polyclonal antibody against single-stranded DNA detected the nuclei of programmed dying cells (apoptotic cells) specifically in the interdigital necrotic zone of the normal mouse limb plate on day 14 of gestation. We used this antibody against single-stranded DNA to investigate the apoptotic degeneration in Pdn/Pdn brain. Abnormal apoptosis was observed in the infralimbic cortical plate, hypothalamus and periventricular thalamus on day 0 after birth in Pdn/Pdn brains. The TRPM-2 gene, which has been considered to mediate apoptosis, was expressed in the developing normal and Pdn/Pdn brains. TRPM-2 gene expressions in the brain stem and cerebellum of arhinencephalic Pdn/Pdn fetuses and newborns were higher than those of +/+ littermates. From these facts, it was suggested that the abnormal apoptosis caused a large amount of cell loss in the arhinencephalic mouse brain, and this cell loss induced the expansion of the ventricle, followed by the hydrocephaly.

Animals↗
PubMed1994

Neuro-glial neurotrophic interaction in the S-100 beta retarded mutant mouse (Polydactyly Nagoya). I. Immunocytochemical and neurochemical studies.

The homozygote of a mouse strain with genetic polydactyly (Polydactyly Nagoya; Pdn) shows several brain abnormalities, and significant decrease of S-100 beta in the brain. In order to clarify the effects of the retarded production of S-100 beta on the development of monoaminergic neuronal systems and supporting glial cells, immunocytochemical studies of tyrosine hydroxylase (TH), serotonin (5-HT), S-100 beta and glial fibrillary acidic protein (GFAP). In addition, high-performance liquid-chromatography (HPLC) measurements of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) of homozygote (Pdn/Pdn) mouse were examined, and the results were compared with those of other genotypes; heterozygote (Pdn/+) and wild type (+/+) mice. In all types of mice, S-100 beta positive cells and serotonergic fibers were widely distributed throughout the brains and serotonergic cell bodies were located in the brainstem. However, the hippocampus and caudo-dorsal cortex of Pdn/Pdn mouse were markedly reduced in S-100 beta positive cells and in serotonergic fibers. Furthermore, abnormal distribution of GFAP positive cells and fibers were observed in the neocortex and hippocampus of Pdn/Pdn brain. No differences were seen in the distribution of TH neurons or fibers distribution. In the HPLC study, the content of 5-HT and 5-HIAA of the hippocampus and cortex of Pdn/Pdn mouse was lower than those of Pdn/+ and +/+ mice. The present results suggest that the developmental defect of serotonergic fibers in the Pdn mutant mouse is correlate to the deficiency of S-100 beta in the astrocyte of this mutant.

Animals↗
PubMed1994

Antibody against single-stranded DNA detects both programmed cell death and drug-induced apoptosis.

Cyclophosphamide induced fragmented nuclei in mouse thymic epithelial cells. Agarose gel electrophoresis showed the fragmentation of the DNA extracted from mouse thymus exposed to cyclophosphamide. The cell death induced by cyclophosphamide was considered to be apoptotic. Polyclonal antibody against single-stranded DNA was used immunohistochemically to detect apoptotic cell death in thymic epithelial cells. This antibody also detected programmed cell death in the interdigital necrotic zone of the mouse limb plate on day 14 of gestation, and in the ganglion of the trigeminal nerve on day 13 of gestation. These results show that the antibody specific for single-stranded DNA detected both drug-induced apoptosis and programmed cell death during embryogenesis.

Animals↗
PubMed1993

Induction of agenesis of the corpus callosum by the destruction of anlage of the olfactory bulb using fetal laser surgery exo utero in mice.

It has long been discussed why some congenital anomalies were often involved with abnormalities in other organs, for example, brain anomalies accompanied by limb anomalies or cleft palate. The mechanism of combined abnormalities has been mysterious, and usually explained as pleiotropism. A combination between agenesis of the olfactory bulb and agenesis of the corpus callosum has been reported. In the present experiments, it has been suggested that non-attachment of the olfactory nerve to the rostro-ventral tip of the telencephalon blocked the induction of the olfactory bulbs from the telencephalon in genetic arhinencephalic mouse embryos. It was shown that the destruction of the olfactory bulb anlage using fetal laser surgery exo utero becomes a trigger of agenesis of the corpus callosum and irregular connection of the anterior commissure in later morphogenesis of the mouse brain. We believe that a fetal surgical experiment like this will make clear the morphogenetic mechanism of the combined abnormalities that have been previously explained as pleiotropism.

Abnormalities, Multiple↗
PubMed1993

Effects of methyl mercury in postnatal developing rats.

Rats on Postnatal Days 1 (PD 1), 14 (PD 14), and 35 (PD 35) were orally administered 0, 2.60, 3.64, 5.10, 7.14, and 10 mg/kg/day of methyl mercury chloride (MMC) for 10 consecutive days. Mercury (Hg) accumulation in the brain of the rats treated with 10 mg/kg/day of MMC for 10 consecutive days was highest in PD-14 rats, followed by PD-35 and PD-1 rats. Hg accumulations in the liver and kidney were lowest in PD-1 rats and increased markedly with development in postnatal phase. The effect of MMC treatment on body weight change was most severe in PD-35 rats. The body weight loss began on Day 5 in PD-35 rats and on Day 10 in PD-14 rats treated with 10 mg/kg/day of MMC, but not in PD-1 rates under the same treatment. The phenomenon of hindlimb-crossing was induced on Day 11 in PD-14 rats and on Day 14 in PD-35 rats treated with 10 mg/kg/day of MMC, but was not observed in PD-1 rats. The deficit of rotarod performance was apparent only at the dose of 7.14 mg/kg/day of MMC in PD-35 rats, whereas rotarod performance was dose-dependently inhibited by MMC treatment in PD-14 rats, and lowered even at the dose of 2.6 mg/kg/day of MMC. However, the performance was gradually restored to the control level by 1 month except in rats given 7.14 mg/kg/day of MMC. These findings indicated that the Hg distribution and the effects of MMC treatment on body weight gain and motor coordination were different among the rat postnatal developing phases.

Age Factors↗
PubMed1993

[Clinical study of intrapleural administration of pirarubicin (THP-ADM) in the treatment of malignant pleural effusion secondary to lung cancer].

The efficacy of intrathoracic administration of pirarubicin (THP-ADM), a derivative of adriamycin, was evaluated in 20 patients with malignant effusion due to lung cancer. All 20 patients had no previous intrapleural therapy. According to the criteria of ECOG, eight patients were at performance status 1 (P.S.1), nine were P.S.2, and three were P.S.3. Fourteen patients were clinical stage IIIB, and six stage IV. The effusions were first completely drained by thoracocentesis or tube thoracostomy drainage, and 30 mg/m2 THP-ADM was instilled. Overall response rate was 50.0%. The response rate for treatment with tube thoracostomy drainage was 69.2%, which was significantly higher than that for treatment with thoracocentesis (14.3%). Significant difference in survival was not seen between the tube thoracostomy drainage group and the thoracocentesis group. There were no severe side effects. In conclusion, intrapleural administration of THP-ADM with tube thoracostomy drainage was considered to be useful for the control of malignant pleural effusion due to lung cancer.

Adult↗
PubMed1993

Effects of methylmercury on the brain of infant rats reared artificially.

Fetal Minamata Disease leads to cerebral palsy, blindness, and deafness accompanying microcephaly. Fetal Minamata Disease has been considered to be exposed to methylmercury during mid and late gestation periods. Brain development in the late gestation in human seems to be equivalent to that in the postnatal stage in rats and mice. Artificial rearing systems for infant rats exclude the maternal and nutrient factors. We administered methylmercury to the infant rats in the artificial rearing system attempting to produce an animal model for Fetal Minamata Disease. Brain weight and brain weight/body weight ratio decreased, and pyknotic degeneration of the nerve cells in the inner granular layer of the cerebellum increased in the groups treated with methylmercury. But, we could not observe drastic degeneration in their brains which mimicked Fetal Minamata Disease in human.

Animals↗
PubMed1993

[A case of long-term survival in a patient with small cell lung carcinoma with syndrome of inappropriate secretion of anti-diuretic hormone].

A 73-year-old man was admitted on April 1984 because of an abnormal shadow on chest X-ray. He was diagnosed as having small cell lung carcinoma (oat cell type) with inappropriate secretion of antidiuretic hormone (SIADH). Initial chemotherapy with cyclophosphamide, ACNU, vincristine, adriamycin, cis-platinum and etoposide was administered. The mass subsequently disappeared, and the serum sodium level normalized. About 2 years later, the patient developed a relapse of the primary lesion with hyponatremia. The same regimen as the initial chemotherapy was initiated and a complete response was again obtained. Similar episodes were repeated four times, and he died in April 1991. This patient survived for about seven years after the initial treatment without maintenance chemotherapy.

Aged↗
PubMed1992

[A case of intractable status asthmaticus treated by isoflurane inhalational anesthesia and bronchial lavage].

A case of severe asthmatic attack treated by isoflurane inhalational anesthesia and bronchial lavage is reported. A 24-year-old woman was admitted to our hospital with severe asthmatic attack. Although she was treated by intravenous administration of aminophylline and corticosteroids, pulmonary function and consciousness deteriorated. Therefore, she was intubated nasally and mechanically ventilated by IPPV with administration of aminophylline, corticosteroids and epinephrine. Despite this treatment, she remained in status asthmaticus with high airway pressure and barotrauma causing pneumomediastinum and subcutaneous emphysema. On the 3rd hospital day, a system was arranged so that isoflurane could be given in an air and oxygen mixture, and administration was started with a concentration of isoflurane of 1.5%. In addition, bronchial lavage via bronchoscopy was performed in order to clear any mucous plugs. After 24 hours, there was marked improvement of wheezing, airway pressure and arterial blood gas level. Eventually, she was weaned from the ventilator on the 6th hospital day without significant side effects. The use of halothane inhalational anesthetic treatment for status asthmaticus is widely known, but it has serious side effects such as arrhythmia and liver injury. Isoflurane may be the inhalational anesthetic agent of choice in the treatment of status asthmaticus.

Adult↗
PubMed1990

Developmental brain abnormalities accompanied with the retarded production of S-100 beta protein in genetic polydactyly mice.

The homozygotes of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) exhibit various brain malformations including exencephaly in about 20%. In the present report, the brains of homozygotes (Pdn/Pdn) which were not exencephalic were examined morphologically and biochemically. Homozygous newborn brains showed hydrocephaly, some gyri on the cerebral hemisphere, absence of the corpus callosum, absence of the commissura anterior, absence of the fornix and commissura fornicis, protuberance of the cortical tissue from the brain surface, and abnormal architecture of the hippocampus. An irregular mass of olfactory nerve was observed on the cribriform plate, and the olfactory bulb was deficient. From these findings, we considered Pdn/Pdn as a kind of arhinencephalic mouse. Nervous tissue-related proteins, S-100 alpha, S-100 beta, creatine kinase B (CK-B), neuron-specific gamma-enolase, guanosine triphosphate binding proteins (Go alpha, Gi2 alpha and G beta) were immunoassayed in the cerebrum of Pdn/Pdn embryos and newborns. Among the protein analysed, only S-100 beta of Pdn/Pdn showed a significantly lower level than that of +/+ cerebrum during the observation period. The newborn brains were examined immunohistochemically using S-100 alpha, S-100 beta, CK-B, Go alpha and NSE antibodies. We could find no differences in the staining patterns among the Pdn/Pdn, Pdn/+ and +/+ brains.

Animals↗
PubMed1990

Fetal laser surgery in genetic polydactyly mice.

The first digital ray of the hindlimb plate in Slc:ICR mouse fetus was irradiated with 2 watts argon laser beam for 0.3 sec after releasing from the abdominal cavity and envelop of uterine myometrium on day 13 of gestation, and then the fetuses were allowed to develop in the abdominal cavity contacting with the uterus via the placenta exo utero until term. ICR mouse fetuses which received fetal laser surgery lost their first digits completely, resulting in 4-digit hindfoot on day 18 of gestation. The homozygous Polydactyly Nagoya (Pdn/Pdn) mice exhibit 1-3 extra digits both in the fore- and hindlimbs preaxially. The extra digital rays in the left hindlimbs of Pdn/Pdn fetuses were irradiated with 2 watts argon laser beam for 0.3 sec on day 13 of gestation exo utero. The left hindlimbs of the Pdn/Pdn fetuses which received fetal laser surgery lost their preaxial extra digits on day 18 of gestation, resulting in 5 digits, though their 1st digit was triphalangia. The combination of a laser instrument with the fetoscope and/or ultrasound scanner may promote the fetal surgery of congenital anomalies in humans.

Animals↗