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Biomedical subjects

H Yamanouchi

Publications and source records attributed to H Yamanouchi.

At least 19 recordsLinked to original sources

Enhanced expression of microtubule-associated protein 2 in large neurons of cortical dysplasia.

To evaluate neuronal cytoarchitectural changes in cortical dysplasia, we examined microtubule-associated protein 2 (MAP2) expression in surgically resected specimens obtained from 20 patients (age range, 3 months to 10 years) treated for intractable epilepsy. Large neurons were investigated in the specimens from all patients and showed significantly strong immunoreactivity with antibodies against MAP2 in the perikaryon and proximal portion of their processes. In situ hybridization with MAP2 antitense riboprobe showed increased hybridization signal intensities in the large neurons, which correlated with the pattern of immunoreactivity for MAP2. We conclude that MAP2 is strongly expressed in the large neurons in cortical dysplasia. The results of preliminary immunoblotting in 1 patient with focal cortical dysplasia showed that the low-molecular-weight form of MAP2 (MAP2c) was strongly expressed in the dysplastic cortex, suggesting that MAP2c may be a major component contributing to the increased expression of MAP2 in the large neurons of cortical dysplasia. Since it has been suggested that MAP2 plays a crucial role in the branching and remodeling of neuronal processes, increased expression of MAP2 may reflect activated plasticity of the large neurons in cortical dysplasia.

Base Sequence

Susceptibility of fetal, virgin, pregnant and lactating rats for the induction of mammary tumors by gamma rays.

Pregnant Wistar-MS rats received a whole-body irradiation of 0-2.6 Gy gamma rays at day 20 of pregnancy. The mother rats were implanted with a diethylstilbestrol (DES) pellet 30 days after weaning, and the female pups delivered by the irradiated mother were treated with DES after maturation. Lactating rats were irradiated with gamma rays 21 days after parturition and then treated with DES. Virgin rats 70 days of age were also irradiated and then administered DES. The rats which received intrauterine irradiation did not develop mammary tumors at doses less than 2.1 Gy and showed a low incidence of tumors at 2.6 Gy. In virgin rats, the maximum tumor incidence was obtained with 1 Gy. The incidence of total mammary tumors in the mother rats and lactating rats increased in a dose-dependent manner with increasing doses of gamma rays up to 2.1 Gy. With 0.1-1 Gy, the incidence of adenocarcinoma in the mother rats was significantly lower than that observed in the lactating rats. However, the incidence in the mother rats irradiated with 1.0-1.5 Gy was significantly higher than that of virgin rats treated with the corresponding gamma-ray doses. These findings suggest that the susceptibility of the mammary glands to radiation depends upon the differentiation at the time of exposure.

Animals

Relationship between stages of mammary development and sensitivity to gamma-ray irradiation in mammary tumorigenesis in rats.

Mature Wistar-MS rats were ovariectomized and treated with estradiol benzoate and/or progesterone. Control animals were treated with olive oil. The rats were then exposed to gamma-rays and implanted with a pellet of diethylstilbestrol. The incidence of mammary tumors in rats treated with estradiol benzoate or with progesterone was significantly higher than in rats in the non-treated control group, whereas, in rats treated with both estradiol benzoate and progesterone, the incidence was not significantly different from that in the controls. Histological examination of the mammary tumors showed 2 types of neoplasm: adenocarcinoma and fibroadenoma. Interestingly, over half of all the tumors in the rats treated with estradiol benzoate were adenocarcinomas, while fibroadenomas were mainly induced in the rats treated with progesterone or with both estradiol benzoate and progesterone. The expression of estrogen and progesterone receptors in the tumor tissues showed some differences according to whether the groups were treated with estradiol benzoate or with progesterone. Morphologically, mammary glands at irradiation showed well-developed lobuloalveoli in both the estradiol-benzoate-treated rats and in those rats treated with both estradiol benzoate and progesterone. This was consistent with the higher incorporation of [3H]thymidine into the DNA in the mammary glands of rats in both of these groups. Our findings suggest that a more advanced developmental stage of the mammary glands, dependent upon ovarian hormones, is related to a higher incidence of mammary tumors induced by irradiation.

Animals

MRI in neurofibromatosis type I: using fluid-attenuated inversion recovery pulse sequences.

Cranial magnetic resonance imaging results of 14 patients with neurofibromatosis type I were examined with T2-weighted fluid-attenuated inversion recovery pulse sequences, as well as conventional T2-weighted spin-echo sequences. Definition was better in 62 of 79 lesions or groups of lesions on fluid-attenuated inversion recovery images than on T2-weighted spin-echo images. The lesions were demonstrated not only in the brainstem, cerebellum, globus pallidus, and cerebral white matter, but also in the hippocampus, pulvinar thalami, and splenium of the corpus callosum. The latter 3 lesions have not been demonstrated or emphasized in previous studies. It is concluded that fluid-attenuated inversion recovery imaging is more effective in detecting multiple lesions in patients with neurofibromatosis type I than conventional T2-weighted spin-echo imaging.

Adolescent

Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats.

When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day 20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet for an experimental period of 1 year under feeding of a control diet, a high incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.6% dehydroepiandrosterone (DHEA) together with DES implantation significantly decreased the incidence (35.0%) of mammary tumors. The first appearance of palpable tumors in the DHEA-fed group was 4.5 months later than that in the control group. For clarification of the mechanism of the chemopreventive action, we measured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats, the concentration of estradiol-17 beta exceeded, by approximately 6-fold, that in the control rats, while the levels of progesterone and prolactin were decreased by 30 and 45%, respectively. Interestingly, DHEA feeding prevented DES-induced hypertrophy of pituitary glands and DES-induced high level of prolactin in pituitary glands detected by immunohistochemical studies, but stimulated the development of mammary glands more than that in control rats treated with DES alone. These findings suggest that DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced mammary tumorigenesis. The mechanism of chemoprevention by change of endocrinological environment is discussed.

Animals

Estradiol-17 beta as an initiation modifier for radiation-induced mammary tumorigenesis of rats ovariectomized before puberty.

This investigation evaluated the roles of estradiol-17 beta, progesterone and prolactin in the initiation of mammary tumorigenesis by irradiation. Sixty day old Wistar-MS rats ovariectomized bilaterally at 23 days of age were injected daily with olive oil, estradiol-3-benzoate (E2B), progesterone or haloperidol for 14 days, and were then irradiated with gamma-rays (260 cGy) on the morning following the last injection. Diethylstilbestrol pellets were administered by implantation 30 days after the irradiation. Following treatment with E2B, the incidence of mammary tumors was increased 2.2-fold, in comparison with that in the corresponding control rats. Bilateral ovariectomy before puberty caused the mammary glands of adult rats to atrophy, and a low degree of differentiation with long narrow ducts was observed in whole mounts. The DNA synthesis in the mammary glands and serum prolactin level of E2B-treated rats were markedly increased and the terminal ducts showed distinctly increased differentiation into terminal end buds and alveolar buds with prolactin receptors. When progesterone, another ovarian hormone, or haloperidol, a dopamine antagonist in adenohypophysis, was injected into the rats under estrogen-free conditions, neither expression of prolactin receptors nor stimulation of DNA synthesis was observed in the mammary glands, and the incidence of mammary tumors induced by irradiation was lower than that observed in rats treated with E2B. Combined treatment with E2B and progesterone resulted in a reduction in the incidence of mammary tumors and in serum prolactin levels compared with those in E2B alone, in spite of the synergistic effects on prolactin receptor concentration and DNA synthesis by the two hormones. On the other hand, concurrent administration of haloperidol did not reduce the E2B-induced tumor incidence or prolactin concentration in serum. Many of the mammary tumors which developed in the ovariectomized rats were of the ER(-)PgR(-) type. The incidence of development of ER(+)PgR(+) tumors was increased by treatment with E2B before the irradiation, and no ER(-)PgR(-) tumors were observed in this group. Our results suggest that estrogen is a direct or indirect sensitizer for tumor initiation by radiation, and is also one of the regulatory factors for hormone dependence of radiation-induced mammary tumors.

Animals

[A case of closed head injury with diffuse axonal injury, and oculomotor nerve avulsion and midbrain infarction].

We report an autopsy case of 66-year-old woman with closed head injury due to a fall from stairs. She had recovered after a half day period of coma following the fall. Severe right peripheral oculomotor nerve palsy was noted from the beginning. MRI demonstrated lesions in the corpus callosum and right midbrain. She had died of suffocation due to sputum impaction after 50 hours after the fall. Autopsy examination revealed traumatic subarachnoidal hemorrhage, partial tearing and petechial hemorrhage of the corpus callosum, and many axonal retraction balls scattered in the cerebral white matter. Avulsion of the right oculomotor nerve root and fresh midbrain infarct with hemorrhage in the territory of right paramedian artery were observed. Axonal retraction balls were densely distributed in the periphery of midbrain infarct. The distribution pattern of axonal retraction balls in the cerebrum was similar to that of damage due to shear strain in Holbourn's gelatin model of closed head injury. The midbrain infarct and oculomotor nerve avulsion may be due to both mechanical and ischemic damage during and after the fall. All of the lesions described above may be closely related to the rotatory force from the right forehead.

Aged

Three short tandem repeat loci in Japanese population.

Allele frequencies of three short tandem repeat loci, vWF, TH and GCG, were examined for 210 unrelated Japanese individuals. Eight alleles were identified with PCR and gel electrophoresis for vWF, 7 for TH and 13 for GCG, indicating that these loci are highly polymorphic. Combined discrimination power of the 3 STRs was 0.995. These results imply that the loci are useful as probes for the identification of Japanese individuals. Thus, we applied the probes to the identification of a forensic specimen that was decomposed severely. The vWF and TH probes successfully gave clear bands in gel electrophoresis, but GCG failed to be typed because of a lot of shadow bands. The results suggests the usefulness of at least the former two probes in forensic studies.

Alleles

[Hemorrhagic cerebral infarction at the old age in a case with familial antithrombin III (ATIII) deficiency].

An old woman had stroke at age 67. Cerebral CT scan disclosed the low-density lesion with high-density area in the left temporal lobe, but no empty delta sign in the superior sagittal sinus. Thereafter, she had sometimes panic attacks. At the age of 70, she was admitted because of loss of consciousness probably caused by the same attack. On admission, Brain CT scan showed no fresh lesions. During the stay in the hospital, she had an episode of deep vein thrombosis of her left leg. The patient was found to have not only reduced biochemical activity but also low immunological level of AT III. Her nephew had also the low plasma AT III antigen concentration. Transesophageal echocardiography showed no abnormality, but atherosclerotic change at the aortic arch. We speculated that hemorrhagic cerebral infarction in the territory of the branch of middle cerebral artery could be induced by the arterial thrombus which was related to the hypercoagulable state associated with familial AT III deficiency, although the possibility of cardiogenic embolic infarction or of cerebral vein thrombosis could not be ruled out. Familial AT III deficiency is one of the causes of cerebral infarction even in the elderly.

Aged

[An advanced invasive thymoma that responded remarkably to neoadjuvant chemotherapy with carboplatin, adriamycin, and etoposide].

A 23-year-old man was admitted to the hospital with hoarseness caused by recurrent nerve palsy. The chest X-ray film and CT scan on admission showed a large mass in the antero-superior part of the mediastinum and a small round mediastinal mass adjacent to right inferior pericardium. Examination of a specimen aspirated from the mediastinal mass revealed thymoma. The tumor was considered to be inoperable because of the pericardial dissemination, and the patient was treated with carboplatin, Adriamycin, and etoposide. After 4 courses of chemotherapy, remarkable regression of both tumors was observed on a chest X-ray film. The patient underwent surgery, and no remaining tumor was found. A combination of carboplatin, Adriamycin, and etoposide may be useful as neoadjuvant chemotherapy for advanced invasive thymoma.

Adult

Susceptibility of lactating rat mammary glands to gamma-ray-irradiation-induced tumorigenesis.

Lactating rats of the Wistar-MS strain were irradiated with 260 cGy of gamma rays 21 days after parturition (day 21). Diethylstilbestrol (DES) pellets were implanted one month after termination of nursing and were allowed to remain for one year. A significantly higher incidence (96.4%) of mammary tumors was observed in these rats irradiated during late lactation than in virgin irradiated animals (30.4%). A control group of lactating animals irradiated during late lactation but not treated with DES was also observed for one year; the final incidence of mammary tumors in this group was 35.3%. The latency period was shortest in the DES-treated group irradiated during late lactation. Histological examination showed that the mammary glands of lactating rats were highly developed, with alveoli filled with milk. Five days after weaning, there was degeneration of alveolar tissue, concomitant with a marked decrease in the concentration of estrogen and prolactin receptors. A considerable amount of epithelial tissue remained in the mammary glands during the process of atrophy. When the rats were irradiated 5 days after weaning, and then were treated with DES for one year, the incidence of mammary tumors was 73.3%, significantly higher than that in virgin irradiated rats. However, this incidence was not significantly different from that in animals irradiated during late lactation. These results suggested that the induction of mammary tumors by gamma irradiation before or after weaning was more dependent upon the stage of differentiation in mammary glands than upon the proliferative activity of epithelial cells, and that DES is essential as a promoter for radiation-induced mammary tumorigenesis.

Animals

Krabbe's disease with giant lamellar bodies in Purkinje cells.

An autopsy case of Krabbe's disease in a child aged 6 years 7 months 1s reported. Histologically, globoid cells, loss of myelin, oligodendroglia and axons, and marked gliosis were observed in the white matter. In addition, there was severe neuronal loss in the thalamus, pontine nucleus, dentate nucleus and olivary nuclei. The cerebellar cortex showed extensive loss of granular cells and moderate loss of Purkinje cells. There were numerous eosinophilic inclusion bodies, ranging from 2 to 15 microns in diameter, in the dendrites of Purkinje cells. The ultrastructural findings for the inclusion bodies were consistent with those of giant lamellar bodies. In addition, smaller lamellar bodies were frequently observed in the perikarya and dendrites. Although loss of granular cells was more prominent in the hemispheres than in the vermis, the inclusion bodies were observed in hemispheres but were infrequently observed in the vermis. They were found in degenerated Purkinje cells which had lost afferent fibers. It is considered that these giant lamellar body inclusions are an unusual type of degenerative structure specific to Purkinje cells.

Brain

Developmental brain-stem pathology in sudden infant death syndrome.

The brain-stems of control and sudden infant death syndrome (SIDS) infants were examined developmentally with Golgi and immunohistochemical methods. The development of dendritic spines changed dramatically from the prenatal to postnatal period in the ventrolateral medulla as well as in the reticular formation and vagal nuclei in controls, but persisted in SIDS infants. These observations suggest a delay in maturation of the meduallary respiratory neurons and transneuronal connection between the central chemoreceptor and neural respiratory center in SIDS. In addition, substance P (SP)-positive nerve fibers were increased in the pons of SIDS infants. An increased activity in the afferent SP neurons in SIDS may be due to chronic hypoxia as in brain-stem gliosis, and may be involved in cardiorespiratory regulation.

Brain Stem

Mutation of the p53 gene in gallbladder cancer.

Genetic alteration of the p53 gene was examined in tissue specimens of primary gallbladder cancer (GBC) using PCR-single strand conformation polymorphism (SSCP) and direct sequencing analyses. The p53 gene mutation was detected in five of the 16 GBC cases examined (31%). All five cases showed single point mutations; four were mutations resulting in amino acid substitution and the other was one base-pair deletion. Of the five mutations detected, four occurred at evolutionarily conserved regions and the remaining one at a well conserved region among species. Our result is similar to those of previous reports for various human cancers in mutation scattering over four of the five conserved domains.

Adult

[Adult-onset dementia with abundant neurofibrillary tangles resembling progressive supranuclear palsy].

We described an autopsy case of 79-year-old woman with clinically unclassified senile dementia. The patient developed forgetfulness at the age of 73, and later, persecution mania, apathy and episodic stupor, but no extrapyramidal symptoms. Neuropathological examination revealed severe neuronal loss and gliosis of substantia nigra, moderate neuronal loss and marked grumose degeneration of dentate nucleus, and mild astrocytosis of subthalamic nucleus. Abundant neurofibrillary tangles (NFT) were observed in subthalamic nucleus, globus pallidus, substantia nigra, locus ceruleus, tegmentum of brain stem, pontine nucleus, inferior olive, and dentate nucleus. Gallyas silver impregnation method showed a wide distribution of argyrophilic grains and threads in cerebrum, brain stem and cerebellum. Although absence of clinical and neuropathological hallmarks excluded the diagnosis of progressive supranuclear palsy (PSP), the distribution of NFT and argyrophilic grains in this patient resembled PSP.

Age of Onset

Sex typing of forensic DNA samples using male- and female-specific probes.

Forensic DNA samples have been examined to ascertain the feasibility of a sex-typing procedure that we have recently developed. This uses two sets of primers complementary to the DXZ4 and SRY genes for polymerase chain reaction (PCR). PCR target in the DXZ4, an 80-bp sequence within the 130-bp fragment specific to females, is generated from inactive chromosome X by the DNA digestion with a methylation-sensitive restriction enzyme, HpaII. Therefore, the DXZ4 amplification and subsequent agarose gel electrophoresis detect the 80-bp fragment from female DNA. On the other hand, the SRY probe identifies a male-specific sequence on chromosome Y. Testing DNAs from fresh Turner's blood and from postmortem tissues exhibited band-signals confirming the sex identification. Degraded DNAs isolated from severely decomposed specimens were also identifiable when high-molecular-weight DNA was isolated before the assay. This demonstrates the usefulness of this method in forensic identification.

Base Sequence