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Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 235 records · Page 13Linked to original sources

Developmental and aging changes of Bak expression in the human brain.

The gene bak regulates apoptosis. To explore its role in the human central nervous system, we examined the distribution of its protein product, Bak, in the brains at various ages, by immunochemical and immunohistochemical means. Western blotting revealed that Bak expression in the cerebrum and cerebellum is high in the brains of the fetuses and elderly subjects, but low in those of young adults. Immunostaining of the cerebellum localized Bak immunoreactivity to Purkinje cells, which was strong in the fetal period and senescence, but undetectable from infancy to adolescence. These results suggest that bak regulates neuronal death associated with the development and aging of the central nervous system.

Adolescent↗

Thyroid metastasis from rectal carcinoma coexisting with Hashimoto's thyroiditis: gray-scale and power Doppler sonographic findings.

We present the gray-scale and power Doppler sonographic findings in a case of rectal carcinoma metastasis to the thyroid that mimicked a primary thyroid neoplasm and coexisted with Hashimoto's thyroiditis in a 67-year-old man. Gray-scale sonography revealed a hypoechoic mass with ill-defined borders in the left lobe of the thyroid; the mass extended through the isthmus to the right lobe. Sonography also showed multiple enlarged cervical lymph nodes. Power Doppler sonography showed increased flow in the nontumorous thyroid gland and decreased flow in the tumor. This contributed to the differentiation between the tumor and the remainder of the thyroid, which was involved with Hashimoto's thyroiditis.

Adenocarcinoma↗

DNA ploidy, proliferative activities, and immunophenotype of malignant lymphoma: application of flow cytometry.

BACKGROUND: To explore the flow cytometric diagnosis of malignant lymphoma, we examined the deoxyribonucleic acid (DNA) ploidy, proliferative activities, and immunophenotype of surgical biopsy- and fine-needle aspiration (FNA)-derived materials. Our goal was to determine the possibility of making a diagnosis of malignant lymphoma by flow cytometric analysis of FNA-derived materials. METHODS: The DNA ploidy and proliferative indices including the percentage of S-phase fraction (SPF), G2 + M fraction (G2M), and Ki-67-positive fraction (Ki-67) were analyzed on the fresh materials from 84 consecutive patients with suspected malignant lymphoma. Flow cytometric analysis of surface antigens was simultaneously performed. Fourteen of the patients underwent FNA and subsequent surgical biopsy of the same lymph nodes for flow cytometric analysis. RESULTS: The proliferative indices of intermediate-grade non-Hodgkin's lymphomas (NHL) (n = 28) and high-grade NHL (n = 23) were significantly higher than those of the reactive hyperplasia (n = 25). The total for SPF + G2M of 6% was a satisfactory threshold for differentiating these NHL from reactive hyperplasia (sensitivity of 84%, specificity of 88%, and accuracy of 86%). However, low-grade NHL (n = 3) and Hodgkin's lymphoma (HL, n = 5) could not be discriminated by employing this parameter. DNA aneuploidy was seen in 13 of the 28 intermediate-grade NHL and 8 of the 23 high-grade NHL, whereas it was not seen in 25 reactive hyperplasia, 3 low-grade NHL, and 5 HL. The percentage of CD19-positive cells in B-cell NHL or CD3-positive cells in T-cell NHL was significantly higher compared with those for reactive hyperplasia. The percentage of CD16 + CD56-positive cells in natural killer (NK) cell NHL was extremely high, with a mean of 91.8%. Flow cytometric results for FNA-derived materials showed excellent correlation with those for surgical biopsy-derived specimens. CONCLUSIONS: Analyses of DNA ploidy, proliferative activities, and immunophenotype by flow cytometry (FCM) are useful for diagnosing intermediate- and high-grade NHL. Fine-needle aspiration is a less invasive approach than surgical biopsy, and, when combined with FCM, it may have a place in the diagnosis of NHL.

Biopsy, Needle↗

Gastric cancer occurring in a patient with Plummer-Vinson syndrome: report of a case.

We report herein the unusual case of a 59-year-old woman with Plummer-Vinson syndrome who developed gastric cancer. The patient had a longstanding history of dysphagia and iron deficiency anemia, for which she had sporadically taken iron supplements that improved the dysphagia to some extent, but not completely. Owing to her tolerance of the dysphagia, she had not been taking iron supplements for the past 17 years. On admission, she was in fair nutritional condition and not anemic. Blood chemistry results were all normal, including the serum iron level. Gastrointestinal radiographic series demonstrated cervical esophageal webs and advanced gastric cancer. Her dysphagia was successfully treated by endoscopic bougienage through the webs, and a distal partial gastrectomy with nodal dissection was performed. Histology of the resected stomach revealed atrophic mucosal change and, by chance, an adenomatous lesion in addition to adenocarcinoma. Her postoperative course was uneventful and she is now well, without any signs of recurrence. Although Plummer-Vinson syndrome is known to be associated with upper alimentary tract cancers, gastric cancer is extremely rare. A discussion on the etiology of Plummer-Vinson syndrome and its link with potential carcinogenesis follows this case report.

Adenocarcinoma↗

Effects of inhaled nitric oxide in canine lung transplantation from non-heart-beating donor.

Nitric oxide (NO) is believed to be identical to endothelium-dependent-relaxing-factor, a potent vasodilator. In addition, NO has been founded to play a critical role in the maintenance of vascular permeability through its attenuation of polymorphonuclear neutrophils (PMN) and platelets. In the present study, we have evaluated the effects of inhaled NO at reperfusion in canine left single-lung allotransplantation from a non-heart-beating donor. Twelve weight-matched pairs of adult mongrel dogs were used. The donor dogs were sacrificed by an intravenous injection of potassium chloride without heparinization. They were left at room temperature for 3 hours. Then, the recipient dogs received a left single-lung allotransplantation. After implantation, the right bronchus and pulmonary artery were ligated. In Group 1 (n = 6), NO gas was administered continuously at a concentration of 40 parts per million throughout a 6-hour assessment period. In Group 2 (n = 6), nitrogen gas was administered in the same manner as NO, for control. The survival time in Group 1 was significantly longer than that in Group 2. The arterial oxygen tension in Group 1 was significantly higher than that in Group 2. The pulmonary vascular resistance was significantly lower in Group 1 than in Group 2. The aortic pressure and the cardiac output each did not differ significantly between the two groups. Myeloperoxidase activity was significantly lower in Group 1 than in Group 2. Inhaled NO at reperfusion is beneficial in lung transplantation from non-heart-beating donors because it attenuates ischemia-reperfusion injury by inhibiting PMN activation and vasodilating pulmonary vasculature.

Administration, Inhalation↗

Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia.

We report the enhanced expression of early forms of microtubule-associated proteins (MAPs) in cortical dysplasia in surgical resections from 17 children with intractable epilepsy. Large neurons, which represent one of the characteristic cellular features of cortical dysplasia, showed strong immunoreactivity for MAP1B, as well as the low-molecular-weight isoform of MAP2 (MAP2c). In situ hybridization with MAP1B antisense riboprobe showed markedly increased hybridization signal intensities in the large neurons, whereas neurons in the normal-appearing cortex and most of the normal-sized neurons in the dysplastic cortex had faint signals. Because MAP2c and MAP1B are early forms of MAPs, which are abundantly expressed in the developing brain and down-regulated in the adult, and are thought to be involved in neuronal outgrowth and plasticity, our results suggest that the structural remodeling of neuronal processes is activated in cortical dysplasia.

Adolescent↗

Expression of a 45K subunit of platelet-activating factor acetylhydrolase in the developing mouse cerebellum.

The 45K subunit of platelet-activating factor acetylhydrolase (PAFAH-45K) is the product of a candidate gene for Miller-Dieker lissencephaly. We studied the expression of this protein in the developing mouse cerebellar cortex by immunochemical and immunohistochemical methods. Western blotting studies indicated that PAFAH-45K is more abundant in the fetal than the postnatal period. Immunohistochemical studies revealed developmental changes in the localization of PAFAH-45K-immunoreactivity, which shifted from the somata of Purkinje cells to the neuropil of the molecular layer. Our findings indicate that PAFAH expression is developmentally regulated and suggest its role in histogenetic processes in the cerebellar cortex other than neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels.

We report a case of anomalous junction of the pancreaticobiliary duct (AJPBD) associated with gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. The patient was a 63-year-old woman who complained of right hypochondralgia. Ultrasound, computed tomography, percutaneous transhepatic cholangiography, and endoscopic retrograde cholangio-pancreatatography revealed dilation of the bile ducts, an elevated lesion of the gallbladder, and AJPBD. She underwent percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. However, the total bilirubin concentration remained high 7 days after PTCD. Her serum interleukin 6 level was 57,359 pg/ml before PTCD, and gradually decreased to 10 pg/ml after PTCD. Bile interleukin 6 level was 10 pg/ml before PTCD, 8997 pg/ ml 3 h after PTCD and gradually decreased there after. Serum and bile levels of tumor necrosis factor alpha and hepatocyte growth factor were high before and after PTCD. The patient underwent an extended cholecystectomy and resection of the extrahepatic bile duct. The resected specimen showed two elevated lesions of the gallbladder which, microscopically, revealed moderately differentiated tubular adenocarcinoma. These findings suggest that pre-existing inconspicuous inflammation of the biliary tract due to reflux of pancreatic juice is involved in elevation of serum and bile cytokines, and that cytokines may participate in gallbladder carcinogenesis associated with AJPBD.

Adenocarcinoma↗

Developmental characteristics of vessel density in the human fetal and infant brains.

We demonstrated the developmental characteristics of vessel density in the human brain, using an antibody against CD31, which specifically reacts with endothelium. In the cerebral cortex and subcortical white matter, the vessel density was low at 16-28 weeks of gestation (GW), and then increased after 36 GW. In the deep white matter, the vessel density was high in the middle fetal period (16-24 GW), and then transiently decreased at 28-36 GW, and increasing after 39 GW. In the putamen, the vessel density was high at 20-21 GW, remained high throughout the fetal period, and then rapidly increased after birth. In the basis pontis, the number of vessels increased after 28 GW, and after 32 GW was greater than in the pontine tegmentum. These alterations in vessel density may correlate with the pathogenesis of perinatal brain injury. Thus, the transient decrease of vessel density in the deep white matter may predispose to periventricular leukomalacia in cerebral hypoperfusion. Similarly, the well-developed vascularity in the basis pontis may predispose its relatively immature neurons to neuron necrosis produced by free radical injury.

Aging↗

Pre-operative assessment of metastatic parotid tumors.

Metastatic disease to the parotid gland is rare and its diagnosing procedures are not established. We assessed several parameters, including the prior history of malignancy, fine needle aspiration cytology (FNAC) and magnetic resonance (MR) imaging and determined the most useful combinations for diagnosing metastatic parotid tumors. The primary tumors were squamous cell carcinomas of the eyelid, larynx, tonsil and of unknown origin, malignant melanoma of the auricle and small cell lung carcinoma. In three of four patients with parotid lymph node metastasis who underwent MR imaging, rim enhancement of the tumor was observed on gadolinium (Gd)-enhanced fat-suppressed T1-weighted MR images (sensitivity 75%). In the histopathologic examinations, the tumor was encapsulated and massive infiltration of normal lymphocytes was found peripheral to the capsule. These were not seen in the patients with metastasis to the parotid parenchyma via hematogeneous dissemination or with advanced-stage parotid node metastasis. The FNAC diagnosis accorded with the tumor histology in five of six patients (sensitivity 83%). Three of the six patients had a prior history of malignancy in other sites (sensitivity 50%). The triad of FNAC, prior history of malignancy and enhanced MR images was identified as the combination most useful in the diagnosis of metastatic parotid tumors (sensitivity 100%).

Aged↗

Decreased expression of microtubule-associated protein 5 (MAP5) in the molecular layer of cerebellum in preterm infants with olivocerebellar lesions.

The changes in microtubule-associated protein 5 (MAP5) expression in the cerebellum with olivocerebellar degeneration (OCD) were investigated by means of immunohistochemical method, compared with gestational age-matched controls. In controls of 24-33 postmenstrual weeks, the molecular layer was diffusely immunoreactive. However, in cases of olivocerebellar degeneration (25-35 postmenstrual weeks), MAP5 immunoreactivity was reduced in the inner half of the molecular layer, especially in a portion where Purkinje cells were absent. The ratio of the density in the outer half of the molecular layer to that in the inner half was also determined with an image analyzer, and increased significantly in Purkinje cell-negative areas. Because MAP5 was believed to be expressed mainly on growing axons in the early fetal period, the reduction of MAP5 immunoreactivity in OCD cases suggested that normal interaction of Purkinje cells and climbing fibers is vulnerable to ischemia and hypoxia in developing stage and that retrograde transynaptic degeneration of the inferior olivary nuclei is secondarily induced.

Brain Diseases↗

Neuropathological characteristics and alteration of the dopamine D2 receptor in hypoxic-ischemic basal ganglia necrosis.

The neuropathological characteristics and alteration of the dopamine D2 receptor (D2R) were investigated in 27 cases of hypoxic-ischemic basal ganglia necrosis (BGN) by means of neuropathological and immunohistochemical methods. Perinatal hypoxic-ischemic BGN manifested neuronal karyorrhexis as well as eosinophilia, karyorrhexis being more predominant in preterm infants and eosinophilia more predominant in full-term infants. Immunoreactivity to D2R was detected in the cytoplasm and dendrites of small and large neurons in the basal ganglia, and increased with neuronal maturation during the late gestational period in normal human basal ganglia. The number of D2R-positive neurons was smaller in all cases of acute BGN than that in controls, the areas of decreased D2R-positive neurons corresponding to the damaged regions observed on HE staining. Furthermore, neurons showed high expression of D2R in a few cases of remote BGN, suggesting some plasticity as to the recovery of D2R. Thus, the neuropathological characteristics of perinatal hypoxic-ischemic BGN may be related to neuronal maturation during different developmental stages in each region, and D2R development may play a role in the basal ganglia vulnerability to hypoxic-ischemia.

Basal Ganglia↗

Three siblings of fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microcephaly.

We report three male siblings born with fatal encephalopathy comprising microcephaly, myoclonus and muscle hypertonia. All three patients died during infancy. Postmortem examination on the brain revealed that all infants had neuronal loss in the cerebellar cortex, inferior olivary and pontine nuclei, which were more pronounced in the older subject than the younger ones. In addition, they were associated with polymicrogyria in the cerebral cortex of the insula, olivary and dentate nuclear dysplasia, and a hypoplastic corticospinal tract. The clinical and neuropathological findings in our cases were identical to those in fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microencephaly [Albrecht et al., Acta Neuropathol 1993;85:394-399], but an association of malformations suggests a new genetic factor in pathogenesis of olivopontocerebellar hypoplasia.

Abnormalities, Multiple↗

Study of the maturation of the child's brain using 31P-MRS.

The maturation of human cerebrum and cerebellum in 37 normal children aged 4 months to 13 years 8 months was evaluated by 31P-magnetic resonance spectroscopy using two different conditions of repetition time (TR) (TR = 3 seconds and 15 seconds) in each region. The results were as follows. First, the PME/PDE, PCr/gamma-ATP and Pi/PCr ratios differed between the cerebrum and the cerebellum. The PME/PDE and PCr/gamma-ATP ratios were greater in the cerebellum than in the cerebrum. However, the Pi/PCr ratio was smaller in the cerebellum than in the cerebrum. At TR = 3 seconds, the ratio of (PME/PDE ratio in the cerebellum)/(PME/PDE ratio in the cerebrum) and the ratio of (PCr/gamma-ATP ratio in the cerebellum)/(PCr/gamma-ATP ratio in the cerebrum) manifested a nearly constant value independent of age. Second, the phosphomonoester peak in the cerebrum contained a substance with a longer relaxation time than 3 seconds; this substance was present in large amounts in the early period, then gradually decreased during maturation.

Adenosine Triphosphate↗

Loss of neurofibromin in the leptomeningeal astroglial heterotopia of NF-1.

Neurofibromin, the protein product of the neurofibromatosis type 1 (NF-1) gene, has important roles in tumor suppression or normal embryogenesis. Cerebellar leptomeningeal astroglial heterotopia (LAH) is a proliferation of heterotopic astroglial cells and fibers in the cerebellar leptomeninges, which is characteristically demonstrated in the NF-1 patients. In this study, neurofibromin expression was investigated in NF-1 and non-NF-1 human tissues, especially in the cerebellum of NF-1 patients. Neurofibromin was found by immunoblotting in the CNS but not in the heart, liver, and kidney. Immunohistochemistry in the normal areas of the brains with NF-1 demonstrated neurofibromin immunoreactivity as did the brains of unaffected controls. Cerebellar LAH showed no neurofibromin immunoreactivity. The results of this study suggest that neurofibromin expression remains unchanged in the nonproliferated region of the CNS of the NF-1 patient but changes occur in the abnormally proliferated region, resulting in cerebellar LAH. Loss of neurofibromin may result in the excessive migration and growth of astrocytes in the early fetal period.

Adolescent↗

In utero brain lesions in SIDS.

Serial examination of the cerebral hemispheres of 20 sudden infant death syndrome victims revealed high incidence of leukomalacia (40%), leptomeningeal glioneuronal heterotopias (70%) at the base of the cerebrum, and astrogliosis (65%) in the white matter and medulla reticular formation compared with 20 age-matched controls. These results suggest that an antepartum insult may become an important predisposing risk factor in some patients for sudden infant death syndrome.

Brain↗

Vascular endothelial growth factor in brains with periventricular leukomalacia.

Vascular development was studied by means of immunohistochemistry, using a vascular endothelial growth factor (VEGF) antibody in human normal and periventricular leukomalacia brains. In the cerebral cortex, VEGF was expressed transiently in the endothelial cells of vessels in the leptomeninges, cortex, deep white matter, subependymal germinal layer, ependymal cells facing the lateral ventricles, and choroid plexus epithelia. In the leptomeninges, VEGF was expressed from 20 to 40 weeks gestation. In the cerebral cortex and deep white matter, VEGF was expressed from 17 weeks gestation, increased with maturation, was highest between 24 and 28 weeks gestation, and decreased gradually thereafter. In the subependymal germinal layer, VEGF was expressed the earliest at 9 weeks gestation, increased with maturation, was highest between 20 and 24 weeks gestation, and then decreased. In the ependymal cells and choroid plexus epithelia, VEGF was expressed between 22 and 40 weeks gestation and between 9 and 37 weeks gestation, respectively. VEGF may be transiently expressed in the vessels in the fetal and neonate periods in connection with vascular maturation and proliferation. In periventricular leukomalacia brains, VEGF was expressed in both astrocytes and endothelial cells in vessels that comprised neovascularization around foci of necrosis. VEGF plays important roles in embryonic angiogenesis and neovascularization around foci of necrosis.

Astrocytes↗