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Biomedical subjects

N Shida

Publications and source records attributed to N Shida.

At least 19 recordsLinked to original sources

Morphologic and molecular analysis of estrogen-induced pituitary tumorigenesis in targeted disruption of transforming growth factor-beta receptor type II and/or p27 mice.

The critical genes and products involved in estrogen-induced tumorigenesis of the pituitary gland were investigated in heterozygous transforming growth factor-beta (TGF-beta) receptor type II and p27 knockout mouse models. Tgfbr2(+/-), p27(+/-); Tgfbr2(+/-), and p27(+/-) mice and C57BL/6J wild-type mice received sc implantation of estrogen or placebo pellets for 16 or 25 wk, after which the mice were sacrificed and their pituitary glands removed for examination. The bromodeoxyuridine labeling indexes in tissue from both the anterior and intermediate pituitary lobes from p27 (+/-) and Tgfbr2(+/-); p27(+/-) mice were significantly higher than those from wild-type and Tgfbr2(+/-) mice after treatment with estrogen for 16 wk. Pituitary tumorigenesis was significantly accelerated in Tgfbr2(+/-), p27(+/-), and Tgfbr2(+/-); p27(+/-) mice compared with wild-type mice after treatment with estrogen for 16 wk. Pituitary tumorigenesis was not accelerated in Tgfbr2(+/-); p27(+/-) mice compared with Tgfbr2(+/-) or p27(+/-) mice. Expression of TGF-beta receptor type II mRNA was lower in the pituitary gland of Tgfbr2(+/-) mice than in wild-type mice before estrogen treatment and was significantly reduced after treatment. Pituitary tumorigenesis is accelerated in mice with severe TGF-beta resistance, and greatly accelerated in mice with TGF-beta resistance combined with decreased p27 expression compared with wild-type mice. Both the TGF-beta receptor type II gene and p27 gene and their products are involved in estrogen-induced tumorigenesis.

Animals↗

Increased cerebrospinal fluid levels of substance P in patients with amyotrophic lateral sclerosis. Short communication.

To clarify the mechanism of brain and spinal cord impairment in amyotrophic lateral sclerosis (ALS), we measured the cerebrospinal fluid (CSF) levels of substance P (SP) in 11 patients with sporadic ALS. Findings were compared with those obtained in controls and diseased controls. The CSF SP levels of patients with ALS, and particularly in patients with a disease duration of less than 2.5 years, were significantly higher than those in controls. These findings strongly suggested that SP may play an important role in the pathophysiology of ALS.

Adult↗

Estrogen-induced tumorigenesis in the pituitary gland of TGF-beta(+/-) knockout mice.

Transforming growth factor (TGF)-beta receptor type II gene (Tgfbr2) knockout and wild type mice underwent chronic estrogen exposure using estradiol pellets. Histological examination of the pituitary glands found 38 adenomas in 14 Tgfbr2(+/-) mice but only one tumor in ten wild type mice. Pituitary tumorigenesis is greatly accelerated in Tgfbr2(+/-) mice by estrogen treatment.

Adenoma↗

Symptomatic vessel narrowing caused by spontaneous rupture of craniopharyngioma cyst--case report.

A 36-year-old female presented with cerebral infarction due to severe vessel stenosis after spontaneous rupture of a craniopharyngioma, manifesting as aphasia and drowsiness. Neuroimaging showed the suprasellar cystic tumor with wall enhancement and cerebral infarction in the left temporoparietal region, and also enhancement of the left sylvian fissure and prepontine cistern. Angiography showed severe narrowing at the C1 portion of the left internal carotid artery (ICA) and the M1 portion of the left middle cerebral artery (MCA). The tumor was subtotally removed via a bifrontal craniotomy. There was accumulated milky-white debris around the left ICA and MCA. She became alert within a few days postoperatively. Repeat angiography 1 month after surgery demonstrated slight improvement of vessel narrowing. The neuroimaging and intraoperative findings suggested that the stenosis was due to vasospasm induced by chemical meningitis resulting from cyst rupture.

Adult↗

Molecular analysis of p21 and p27 genes in human pituitary adenomas.

Pituitary tumours develop at a high frequency in p27-knockout mice and retinoblastoma gene-knockout mice, which suggests that cell cycle regulatory genes, such as cyclin-dependent kinase inhibitor genes, are involved in the tumorigenesis of pituitary adenoma. Analysis of p21 and p27 gene abnormalities in human pituitary adenoma was performed in 28 pituitary adenomas by polymerase chain reaction-single-strand conformational polymorphism. No point mutations were detected in these genes. As no abnormalities of the p21 and p27genes were observed, and if these genes are indeed inactivated, it is likely to be via transcriptional or translational defects.

Adenoma↗

Hirudin suppresses the invasion of inflammatory cells and the appearance of vimentin-positive astrocytes in the rat cerebral ablation model.

Hirudin is a specific and direct-acting thrombin inhibitor superior to heparin as an anticoagulant. Thrombin is a multifunctional molecule that acts as a serine protease locally generated from prothrombin during blood coagulation related to injury and/or inflammation. We previously reported that thrombin might be involved in the inflammatory response, glial reaction, and scar formation that occurred in central nervous system (CNS). Here we studied the suppressive effects of hirudin on the inflammation, vimentin-positive astrocytes, and glial fibrillary acidic protein (GFAP)-positive astrocytes using rat cerebral ablation models. Hirudin and vehicle solution soaked in Gelform were administered to the cavity of the traumatic brain defect. Brains were examined by conventional histologic and immunohistologic technique. Antibodies for monocytes/macrophages, GFAP, and vimentin were used to assess the infiltration of inflammatory cells and reaction of astrocytes. The number of the inflammatory cells, vimentin-positive astrocytes, and GFAP-positive astrocytes were quantitatively analyzed. Hirudin suppressed the infiltration of inflammatory cells and the increase in vimentin-positive astrocytes, but had no effects on the increase in GFAP-positive astrocytes. These data suggest that thrombin may play an important role in inflammatory and glial responses to CNS injury, and that hirudin can be a candidate for the therapeutic agent that minimizes the secondary brain damage following the inflammation, and the glial reaction mediated by vimentin-positive astrocytes near the lesion site.

Animals↗

Thrombin and TGF-beta promote human leptomeningeal cell proliferation in vitro.

Some disorders of the central nervous system, such as trauma, meningitis, or subarachnoid hemorrhage (SAH), result in inflammation and fibrosis of the arachnoid membranes followed by hydrocephalus. To clarify the role of growth factors in the pathophysiology of arachnoid fibrosis, we investigated the response of leptomeningeal (LM) cells to growth factors elevated in the cerebrospinal fluid (CSF) of patients with subarachnoidal inflammation. We examined the proliferative responses of LM cells to thrombin, transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), platelet derived growth factor (PDGF), tumor necrosis factor-beta (TNF-beta) and interleukin 1-beta (IL1-beta). Thrombin, TGF-beta, EGF, aFGF and PDGF promoted LM cell proliferation. TGF-beta enhanced the proliferative effect of thrombin and EGF on LM cells. These findings suggest that thrombin and TGF-beta, which may be elevated in CSF following SAH, may cause subarachnoid fibrosis and subsequent hydrocephalus.

Animals↗

Distribution of extravasated serum protein after cryoinjury in neonatal and adult rat brains.

The sequelae of cryoinjury to unilateral cerebral cortex were compared in neonatal and adult rats. In neonatal rats, immunostaining for autologous albumin disclosed a wide spread of extravasated albumin in both hemispheres on day 1 and rapid clearance from the tissue by day 7, whereas in adults rats, the distribution of albumin had progressively increased by day 7 and was then restricted to the injury site by day 14. Horseradish peroxidase tracing revealed a leakage of serum proteins by day 3 in neonates and by day 7 in adults. The rapid clearance of serum proteins from the neonatal brain tissue appeared to be promoted by vimentin-positive radial glia in the subpial and periventricular regions. A possible causal relationship between the rapid clearance of serum proteins and unique outcome of the cryoinjury in the neonatal brain is discussed.

Animals↗

Subarachnoid haemorrhage induced proliferation of leptomeningeal cells and deposition of extracellular matrices in the arachnoid granulations and subarachnoid space. Immunhistochemical study.

Subarachnoid haemorrhage (SAH) often leads to subarachnoid fibrosis and resultant normal pressure hydrocephalus; however, how subarachnoid fibrosis occurs is unknown. We examined the changes within arachnoid granulations (AGs) and the subarachnoid space (SAS) chronologically at the parasagittal region obtained from patients with SAH at autopsy and made comparison with controls by immunostaining for cytokeratin, specific marker for leptomeningeal cells and by the elastica Masson-Goldner methods. Within a week some AGs were torn, and many inflammatory cells filled the AGs and SAS. Cytokeratin positive cells were scarce. During the next two weeks cytokeratin positive cells increased. After three weeks, AGs and SAS were filled by dense deposits of extracellular matrices surrounded by multiple layers of leptomeningeal cells.

Arachnoid↗

[Ipsilateral coexistence of AVM and meningioma: a case report].

The authors encountered a rare case of sphenoidal ridge meningioma associated with an arteriovenous malformation in the same cerebral hemisphere. A 65-year-old female was admitted to our service because of headache. X-ray computed tomography (X-CT) and magnetic resonance image (MRI) disclosed a huge mass with peripheral edema, diagnosed as a sphenoidal ridge meningioma. An associated small mass was also noted in the right parahippocampal gyrus. This was confirmed by angiography as an arteriovenous malformation (AVM). During the waiting period for surgical treatment she had fallen into coma abruptly. Emergency X-CT revealed intracerebral and intraventricular hematomas. Both lesions were resected successfully in a one stage operation. Postoperative course was uneventful. In general, AVM located in the medial temporal lobe is difficult to approach. However, in this case, the resultant large cavity obtained after removal of meningioma afforded us easy access to the AVM.

Aged↗

Primary culture of human leptomeningeal cells in serum-free medium.

Human leptomeningeal (LM) cells were grown in serum-free medium supplemented with insulin, transferrin and bovine serum albumin. The cultured cells maintained the polygonal morphology characteristic of leptomeningeal cells. Electronmicroscopic and immunofluorescence examinations revealed interdigitation of cell membranes, invagination of cytoplasm into the nucleus, specialized intercellular junctions and the presence of cytokeratin. These characteristics are consistent with previous reports characterizing LM cells. This serum-free culture system may facilitate the in vitro study of the leptomeninges.

Arachnoid↗

Differences in wound healing pattern between mature and immature brain behavior of extravasated serum protein.

To clarify the fate of extravasated serum protein and tissue reaction following blood brain-barrier breakdown in mature and immature brain, we produced cryogenic injury in the cortices of adult and post natal day 2 rats, and immunohistochemical examination with GFAP, vimentin and albumin, endogenous tracer of serum proteins, antibodies. Mature and immature brain showed the same histological changes by day 3. However, fibrotic scar, cyst formation and GFAP, vimentin-positive astrocytosis were main features in mature brain, fusion of adjoining cortical plate without scar and astrocytosis was typical in the immature brain. In adult rats, presence of albumin was observed near the lesion on day 1, evidently extending to the contralateral hemisphere on day 7 and localized again around scar and cyst on day 14. In the P2 rats, albumin was present in both hemispheres on day 1, but was localized to molecular layer periventricular region and choroid plexus on day 7. No albumin was detected on day 14. These results suggest that rapid spreading and clearance of extravasted serum proteins may take place in the immature brain and this may be deeply involved in the characteristic wound healing pattern.

Animals↗

New chlorine-containing prenylated C6-C3 compounds increasing choline acetyltransferase (ChAT) activity in culture of postnatal rat septal neurons from Illicium tashiroi.

The structures of two new chlorine-containing C6-C3 compounds isolated from the woods of Illicium tashiroi have been established as 2(R)-12-chloro-2,3-dihydroillicinone E (1) and 12-chloroillicinone E (2) by X-ray crystallographic analysis and spectroscopic data, respectively. Compound 1 has been found to significantly increase ChAT activity in culture of P10 rat septal neurons.

Animals↗

[A family with MELAS whose main manifestations are maternally-transmitted deafness and diabetes mellitus].

A family with maternally-transmitted deafness and diabetes mellitus is described. Although the proband clinically exhibited MELAS-like symptoms such as sudden-onset cerebellar ataxia and weakness of the proximal portion of the limbs in addition to deafness and diabetes mellitus, the other three members of the family had only deafness and diabetes mellitus and no neurological manifestations. The analysis of mitochondrial DNA of the two members revealed an A-->G mutation of tRNA(leu(UUR)), a mutation commonly seen in patients with MELAS. According to the clinical histories and endocrinological investigations, the type of the diabetes mellitus in this family was considered to be IDDM, which may be attributed to the dysfunction of mitochondrial of the pancreas islet cells, resulting from the mutation of the mitochondrial DNA.

Adult↗

High-performance affinity chromatography system for the rapid, efficient assay of glycated albumin.

A high-performance affinity chromatographic system was constructed and shown to permit highly reproducible, rapid, automatic assays of serum glycated albumin (GA) by separation of albumin (Alb) on an anion-exchange column (Asahipak ES-502N) packed with a vinyl alcohol copolymer bearing diethylamino groups and consecutive separation of GA on a column packed with a vinyl alcohol copolymer bearing boronate groups. The first column selectively retained Alb free of other serum proteins and permitted at least a 95% recovery of sample Alb. The purity of the Alb peak was confirmed by two-dimensional electrophoresis. Chromatographic analyses of human serum Alb incubated with glucose on the second column showed that the peak area for GA increased in accordance with the incubation time and suggested selective adsorption of GA on the second column. Optimization of the conditions for the two-column system reduced the analysis time to 10 min. Analyses of human sera with the present system showed GA to be 16.1 +/- 1.1% (mean +/- S.D.) of total Alb in non-diabetic children and 39.9 +/- 9.1% (mean +/- S.D.) in diabetic children (0-17 years old).

Adolescent↗

Hyperprolactinemia in multiple sclerosis.

In order to clarify endocrine abnormalities due to hypothalamic involvement in multiple sclerosis (MS), serum prolactin levels were measured in 27 patients with MS and 22 healthy subjects. The presence of hypothalamic lesions was also studied by magnetic resonance imaging (MRI). Serum prolactin levels were found to be significantly higher in MS patients than in healthy controls in both sexes. Although only one patient had galactorrhea, one-third of the MS patients had mild to moderate hyperprolactinemia, which was a 4-13-fold increase over the mean value of healthy subjects. The results of thyrotropin-releasing hormone, sulpiride, L-DOPA and bromocriptine loading tests suggested a hypothalamic dysfunction, rather than pituitary prolactinoma in MS patients. Four of eight patients with hyperprolactinema had diencephalic hypothalamic lesion(s) contiguous with the third ventricle on the brain MRI, while none of the normoprolactinemic patients had any lesions in the diencephalon. All relapsing-remitting patients with hyperprolactinemia showed a rise in prolactin levels in the acute stage of the relapse and a decrease during the recovering stage and the following remission phase. Our findings suggest that latent hyperprolactinemia due to hypothalamic dysfunction occurs frequently in MS patients in relapse. The increase of serum prolactin is considered to be a sensitive indicator for hypothalamic lesions in MS.

Adult↗