Biomedical subjects

S Takashima

Publications and source records attributed to S Takashima.

At least 55 records · Page 3Linked to original sources

PubMed2001

Cerebrovascular damage in young rabbits after intravenous administration of Shiga toxin 2.

Acute encephalopathy associated with Shiga toxin-producing Escherichia coli (STEC) primarily affects children. To elucidate the age-dependent vulnerability of the central nervous system (CNS), we injected Shiga toxin 2 (Stx2) intravenously to young rabbits and examined the clinical and pathological effects on the CNS. Although neurological disorders caused by Stx2 were similar between young and adult rabbits, the dose required to produce them in the young was one third of that required for the adults. Vascular lesions appeared as early as 24 h after injection in the young, but not at all in the adult. Arteriolar changes, such as hydropic swelling of the endothelial cells and karyorrhexis of the medial cells, were specific to the CNS of young animals. Evidence for apoptosis of vascular cells was scarce because DNA strand breaks and activation of caspases-3 and -9 were absent in the vast majority. Given our results, we conclude that the cerebral blood vessels of immature brains are more vulnerable to Stx2 than those of adults in the rabbit.

Acute Disease↗

PubMed2001

A case of pulmonary hypoplasia associated with intrauterine brainstem necrosis.

UNLABELLED: An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. CONCLUSION: These findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.

Adolescent↗

PubMed2001

Pancreatitis induced by valproic acid: report of a case.

A 22-year-old woman with intellectual impairment, who had been taking valproic acid continuously for 19 years since being diagnosed with epiloia at the age of 3 years, presented to our hospital following the sudden development of epigastric pain. An abdominal computed tomography scan revealed acute exacerbation of chronic pancreatitis. Conservative treatment was initiated, despite which the pancreatitis became exacerbated, necessitating resection of the pancreatic head and duodenum. Histological examination of the resected specimens revealed a large number of pancreatic calculi in the main pancreatic duct, suggesting chronic pancreatitis with fibrosis at the periphery. The incidence of pancreatitis developing in association with valproic acid is unclear; however, only 40 such cases have been reported in the English literature. Most of the patients previously described presented with acute pancreatitis in the initial stage. However, the clinical course of our patient, with acute exacerbation following a relatively chronic course, was different from those previously described, suggesting the presence of chronic pancreatitis related to valproic acid.

Adult↗

PubMed2001

Multicentric occurrence of esophageal cancer after gastrectomy: a preliminary report.

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated, focusing on its multicentric occurrence. We retrospectively evaluated 28 patients who underwent subtotal esophagectomy for intrathoracic esophageal cancer between 1985 and 1999. They were divided into two groups according to whether or not they had previously undergone a gastrectomy: group 1, comprising 7 patients who had undergone gastrectomy and group 2, comprising 21 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer than in those who had undergone gastrectomy for a peptic ulcer, and also in the patients for whom anastomosis had been performed by Billroth I compared with Billroth II. The patients in group 1 were significantly younger than those in group 2. The multiple occurrence of esophageal cancer was found in 4 of 5 patients (80%) in group 1, and in 2 of 18 patients (11%) in group 2, with significantly higher frequency being seen in group 1. More than two coexisting cancer lesions apart from the primary tumor were detected in all four patients. Histological examination of all the coexisting cancer lesions showed well-differentiated squamous cell carcinoma confined within the superficial mucosal layer. No significant differences were noted in the location of the coexisting lesions between the oral and anal side of the primary tumors. Squamous dysplasia was randomly observed, especially around the cancer lesions. These findings suggest that gastrectomy precipitated subsequent chronic gastroesophageal reflux which in turn induced the development of squamous dysplasia and carcinoma at multiple locations in the esophagus.

Aged↗

PubMed2001

Primary subclavian venous thrombosis which developed after sleeping with the arm in an outstretched position: report of a case.

Primary subclavian venous thrombosis is more rare than secondary thrombosis. This type of thrombosis is called "effort thrombosis" or Paget-Schroetter syndrome, and develops after a strenuous effort of the superior limb. A day after a 55-year-old man got drunk and slept in the left lateral position in combination with an abducted and elevated position of the left superior limb, he became aware of swelling and an oppressive feeling in his left superior limb and was admitted 9 days later. Thrombus of the left axillary-subclavian vein was confirmed by venography, and thrombolytic therapy with urokinase was performed immediately. The left arm symptoms improved for the most part. Venography after the therapy revealed thrombolysis at the site of the axillary vein, while the subclavian vein enhanced the collateral vessel pathway. The patient was discharged on the seventh hospital day, and anticoagulant therapy with oral warfarin sodium has since been continued. This is considered to be a rare case of subclavian venous thrombosis caused by sleeping in an abnormal position with the arm outstretched.

Alcoholic Intoxication↗

PubMed2001

A spontaneously ruptured gastric stromal tumor presenting as generalized peritonitis: report of a case.

Among the diverse clinical presentations of gastrointestinal stromal tumor (GIST), spontaneous rupture with peritonitis is extremely rare. We report herein the unusual case of a 75-year-old man found to have a spontaneously ruptured gastric stromal tumor after presenting with generalized peritonitis. The patient was brought to the emergency department of our hospital by ambulance, with generalized severe abdominal pain. On examination, his abdomen was extensively distended with generalized severe rebound tenderness. Abdominal computed tomography scan showed a giant mass arising from the anterior gastric wall with an irregular internal low-density area and a small amount of ascites. An emergency laparotomy revealed a ruptured gastric tumor with dissemination of its necrotic tissue throughout the peritoneal cavity. The tumor was excised together with normal gastric tissue around its base. The tumor, which was 15 x 11 x 4.4cm in size, had a coarse laceration over its well-capsulated smooth serosal surface with massive necrosis and clotted blood inside. Immunohistochemical examination revealed positive reactivity to C-kit protein, which was consistent with the newly introduced diagnostic criteria of GIST. The patient had an uneventful postoperative course and remains well.

Aged↗

PubMed2001

A Japanese girl with leukoencephalopathy with vanishing white matter.

A Japanese girl with peculiar leukoencephalopathy was reported. Following normal development until 1 year of age, she showed progressive neurological deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement. Serial brain computed tomographies (CTs) revealed markedly low density and progressive volume loss in whole white matter. In extensive laboratory investigations, the level of glycine in the urine was elevated. She died at the age of 4 years, and the neuropathological findings were comprised of severe extensive changes in cerebral and cerebellar white matter, such as marked rarefaction or cystic degeneration with axonal loss. The pontine central tegmental tracts were also affected. Neuronal loss was seen in the cerebellar cortex. These features were compatible with leukoencephalopathy with vanishing white matter, which was recently established as a clinical entity. To our knowledge, this is the first report of a non-Caucasian patient with this new type of leukoencephalopathy.

Brain↗

PubMed2001

Development of lysosomal storage in mice with targeted disruption of the beta-galactosidase gene: a model of human G(M1)-gangliosidosis.

A deficiency of lysosomal acid beta-galactosidase leads to G(M1)-gangliosidosis in humans, which progressively and profoundly affects the brain and other organs mainly in the early infantile period. We report the pathology of mice with targeted disruption of the beta-galactosidase gene. In the central nervous system, vacuolated neurons appeared in the spinal cord 3 days after birth. The vacuolation extended to neurons in the brainstem, cerebral cortex, hippocampus and thalamus and ballooning neurons became prominent with age. The vacuolation also appeared in Purkinje cells without a marked ballooning change. Reactive astrogliosis in the entire brain was marked at the terminal stage of the disease. Immunohistochemical study using anti-ganglioside G(M1) and G(A1) antibodies revealed extensive accumulation of G(M1) and G(A1) in the cerebral neurons. In the liver, however, accumulation of G(M1) was localized in the cytoplasm of hepatocytes, whereas that of G(A1) was localized in foamy macrophages and Kupffer cells. There were no significant abnormalities in the bone, bone marrow, or cornea at any stage. Although there are some phenotypic and biochemical differences between this knockout mouse and human GM1 gangliosidosis, the mouse will be a useful model for therapeutic trials for the human disease.

Animals↗

PubMed2001

Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits.

We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a significant decrease in HbO2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.

Animals↗

PubMed2001

Neuropathology of early-infantile epileptic encephalopathy with suppression-bursts; comparison with those of early myoclonic encephalopathy and West syndrome.

For the critical lesions and pathomechanism of early-infantile epileptic encephalopathy (EIEE) with suppression-bursts, we investigated the brains of EIEE, early myoclonic encephalopathy (EME), and West syndrome (WS) patients using immunohistochemical technique and neuropathological examination. We could compare with the results of these diseases. The EIEE patients had the most severe lesions, which were in the putamen, thalamus, hippocampus as well as the tegmentum of the brainstem. Among the syndromes, EIEE brains showed the most expanded lesions. Tyrosine hydroxylase-immunopositive cells and fibers were not demonstrated in EIEE, but were detected in WS. Reduced tyrosine hydroxylase immunoexpression in the EIEE brains was in the putamen, globus pallidus, and substantia nigra. Tryptophan hydroxylase immunoreactivity was reduced in the three epileptic syndromes, but especially in EIEE. Reduced expression of tyrosine hydroxylase and tryptophan hydroxylase may demonstrate dysfunction of the catecholaminergic and serotonergic neurons. From this study, the lesions in EIEE were widespread, including in the lower brainstem and cerebellum, compared with in EME and WS. Dysfunction of the catecholaminergic and serotonergic systems could be suggested. These characteristic changes may lead to the pathophysiology of EIEE.

Atrophy↗

PubMed2001

Neuropathology of tuberous sclerosis.

In the cerebrum of patients with tuberous sclerosis (TSC), there are three types of nodular lesions: cortical tubers, subcortical heterotopic nodules and subependymal giant cell astrocytomas. Histologically, these hamartias and hamartomas contain abnormal giant cells that show evidence of abnormal differentiation of immature neural cells. Recent identification of the TSC1 and TSC2 genes has facilitated studies of the molecular pathology of TSC. The expression of their protein products, hamartin and tuberin, is altered in various TSC lesions. However, the molecular mechanism by which cortical tubers develop remains to be elucidated. The Eker rat, a naturally occurring animal model of TSC, will provide a powerful tool for future investigations of TSC.

Animals↗

PubMed2001

Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome.

We immunohistochemically examined neurotransmitter systems, which function in the brainstem and are involved in neuronal organization of respiration, in an autopsy brain from a patient with Rett syndrome (RS). Immunoreactivity (IR) for tyrosine hydroxylase, a functional marker for catecholaminergic neurons, was severely reduced in the locus ceruleus, while that for tryptophan hydroxylase involved in serotonin synthesis was spared in the raphe nuclei. In the brainstem, IR for substance P (SP) was reduced in the parabrachial complex and that for methionine-enkephalin (met-enk) was affected in the parabrachial, hypoglossal, dorsal vagal and solitary nuclei. In addition, expressions of these neuropeptides were also disturbed in the basal ganglia. A widespread altered expression of antagonistic neuropeptides, SP and met-enk, may be involved in the pathogenesis of RS, especially in its respiratory manifestation.

Adolescent↗

PubMed2001

MR imaging of primary leiomyosarcoma of the thyroid gland.

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.

Aged↗

PubMed2001

Characteristic neuropathology and plasticity in periventricular leukomalacia.

The brains of extremely low-birth-weight infants with periventricular leukomalacia, who survived for more than 30 days, were examined by means of neuropathologic and immunohistochemical methods. The characteristic neuropathology of the brain is comprised of spongy changes with astrogliosis, a widespread distribution (i.e., in the deep to intermediate white matter), and a diffuse distribution of associated recent lesions. Also, these lesions, both remote and recent, are located in the frontal to occipital lobes. Regarding the correlation between the lesions and transneuronal connecting fibers, the lesions involved fibers of the motor, sensory, visual, and higher cerebral functions. This involvement may cause motor and intellectual disabilities. Furthermore, immunohistochemistry demonstrated nestin-positive astrocytes, and neurons increased around the lesions, suggesting the plasticity of the brains.

Age Factors↗

PubMed2001

Development of GABAergic neurons and their transporter in human temporal cortex.

The gamma-aminobutyric acid (GABA) system plays an important role in the early development of the hippocampal formation. The immunohistochemical expression of gamma-aminobutyric acid transporter-1, GAT-1, in the human developing temporal cortex was examined, and the distribution of GAT-1 was compared with that of the 67-kDa isoform of glutamic acid decarboxylase as a marker of GABAergic neurons. Four postmortem tissue specimens from young patients with hippocampal sclerosis were also examined. GAT-1 immunoreactivity was present, with a few puncta, in the neuropil of the stratum oriens and in the molecular layer of the dentate gyrus from 21-22 weeks of gestation, and in the stratum lacunosum-moleculare from 26 weeks of gestation. The peak expression of GAT-1 was seen in early infancy and that of glutamic acid decarboxylase in the perinatal period. These findings may reflect the development of GABAergic inhibitory systems, and may be related to the seizure susceptibility in infancy and early childhood. In the temporal lobes with hippocampal sclerosis, GAT-1 immunoreactivity of the neuropil was preserved in the vicinity of the neuronal loss of the hippocampus. This finding may result from the neurotrophic function of GAT-1 and may be related to its ability of neuronal repair and plasticity in childhood.

Adolescent↗

PubMed2001

Regulation of pattern formation in the Drosophila hindgut by wg, hh, dpp, and en.

The hindgut of the Drosophila embryo is subdivided into three major domains, the small intestine, large intestine, and rectum, each of which is characterized by specific gene expression. Here we show that the expression of wingless (wg), hedgehog (hh), decapentaplegic (dpp), and engrailed (en) corresponds to the generation or growth of particular domains of the hindgut. wg, expressed in the prospective anal pads, is necessary for activation of hh in the adjacent prospective rectum. hh is expressed in the prospective rectum, which forms anteriorly to the anal pads, and necessary for the expression of dpp at the posterior end of the adjacent large intestine. wg and hh are also necessary for the development of their own expression domains, anal pads, and rectum, respectively. dpp, in turn, causes the growth of the large intestine, promoting DNA replication. en defines the dorsal domain of the large intestine, repressing dpp in this domain. A one-cell-wide domain, which delineates the anterior and posterior borders of the large intestine and its internal border between the dorsal and ventral domains, is induced by the activity of en. We propose a model for the gene regulatory pathways leading to the subdivision of the hindgut into domains.

Animals↗

PubMed2001

Heterogeneity of hepatic parenchymal enhancement on computed tomography during arterial portography: quantitative analysis of correlation with severity of hepatic fibrosis.

Background/Aims: In patients with chronic liver disease, heterogeneous enhancement of liver parenchyma is often noted on computed tomography during arterial portography (CTAP). We investigated the factors contributing to the heterogeneous enhancement and its relationship with postoperative histopathological findings. Methodology: Eighty-seven patients who had undergone a right lobectomy for liver tumor after CTAP were evaluated. The heterogeneity of hepatic parenchymal enhancement on CTAP was assessed quantitatively using standard deviation of mean CT numbers for five ROIs (S.D.) set in the right hepatic lobe, and comparatively evaluated among three histological groups (liver cirrhosis (LC, n=41), chronic hepatitis (CH, n=33), and normal liver (Normal, n=13)). Severity of fibrosis and degree of splenomegaly (Sp) were taken up as factors contributory to the heterogeneity, and were assessed for correlation with the S.D. Results: The range (mean) of S.D. was LC, 3.07-17.64 (9.10); CH, 1.83-11.12 (6.77); and Normal, 2.06-8.89 (5.64) (Scheffe's F-test: LC vs CH, P<0.0005; LC vs Normal, P<0.0002). The higher fibrosis group exhibited significantly greater S.D. values as compared with the lower fibrosis group (Scheffe's F-test: P<0.00003). Coefficient of correlation between the S.D. and the Sp was 0.295 (P<0.005). Conclusion: There was a fair possibility of LC in patients with heterogeneous enhancement of liver parenchyma on CTAP. The severity of liver fibrosis and the degree of splenomegaly were considered to be factors contributing to the heterogeneous enhancement.

Journal Article↗

PubMed2001

cDNA array hybridization reveals cardiac gene expression in acute ischemic murine hearts.

PURPOSE: Although cDNA array technique has recently become available in the cardiovascular field, it has not yet been established what kind of genes in the myocardium are expressed by acute ischemia. Since many substances contribute to the pathophysiology of acute ischemic hearts, we investigated transcription responses of murine hearts to ischemia using cDNA array representing 18,376 genes. METHODS AND RESULTS: In 29 male mice, we ligated the proximal site of the left coronary artery for 60 min. In 14 mice, we performed the sham operation without the ligation of the left coronary artery. After 60 min, the hearts were excised to obtain mRNA, and we performed cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, 11 known genes were upregulated 5.0- to 9.9-fold, and 32 unknown genes were upregulated over 5.0-fold compared to sham-operated controls. In contrast, 11 known genes and 7 unknown genes were downregulated to levels below 0.2-fold. For 9 of the 13 known genes of which expression was increased as analyzed by cDNA array, subsequent Northern blot analysis also revealed an increase in expression. CONCLUSION: Using cDNA array analysis we found that cardiac expression of 24 known and 39 unknown genes was modulated by acute ischemic stress, and appeared to be related to the pathophysiology of ischemic hearts. These results show that cDNA array analysis may provide a new molecular insight to the pathophysiology of acute ischemic hearts.

Animals↗