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Biomedical subjects

S Kida

Publications and source records attributed to S Kida.

At least 19 recordsLinked to original sources

Tocopherol-associated protein is a ligand-dependent transcriptional activator.

Vitamin E is a term that encompasses a group of potent, lipid-soluble, chain-breaking antioxidants. Structural analysis reveals that molecules having vitamin E activity include four isomers (alpha, beta, gamma, and delta) of both tocopherols and tocotrienols. Alpha-tocopherol has been shown to have the highest biological vitamin E activity in mammalian tissues based on fetal resorption assays, and it reverses vitamin E deficiency symptoms. Although the molecular functions fulfilled specifically by alpha-tocopherol have yet to be fully described, it is unlikely that they are limited to general antioxidant functions. Here we show the functional characterization of alpha-tocopherol associated protein, TAP, which displays significant sequence similarity to the alpha-tocopherol transfer protein. Ligand competition analysis showed that recombinant TAP binds to alpha-tocopherol but not to other isomers of tocopherols. Using GFP fusion protein expression system, we observed that TAP translocates from cytosol to nuclei in alpha-tocopherol-dependent fashion. Transient transfection experiment showed that TAP activates transcription of the reporter gene in alpha-tocopherol-dependent manner. These results suggest that the biological function of alpha-tocopherol is not only as an antioxidant but also as a transcriptional regulator of gene expression via association with a transcription factor TAP.

Amino Acid Sequence↗

Improved cerebral perfusion and metabolism after stenting for basilar artery stenosis: technical case report.

OBJECTIVE: Recent advances in stent technology have allowed the introduction of more flexible stents that may be tracked more easily in the intracranial vessels. We present a patient with improved cerebral blood flow and metabolism as assessed by positron emission tomography after stent-assisted angioplasty for symptomatic basilar artery stenosis. CLINICAL PRESENTATION: A 62-year-old man, who had undergone left superficial temporal artery to middle cerebral artery bypass surgery for left internal carotid artery occlusion 10 years previously, presented with dizziness, blurred vision, and memory disturbance. Angiography revealed severe stenosis of the proximal basilar artery. Positron emission tomographic scans revealed decreased cerebral blood flow associated with increased oxygen extraction fraction in the entire brain, particularly in the posterior circulation and the left middle cerebral artery territory. Despite medical treatment, the patient experienced worsening visual disturbance and right-sided motor weakness. INTERVENTION: Ticlopidine and aspirin were used as antiplatelet agents. In addition, we used argatroban, which is a direct thrombin inhibitor, as an anticoagulant during the procedure. Predilation with a coronary artery balloon was performed, followed by placement of a GFX 3- by 8-mm stent (Arterial Vascular Engineering, Santa Rosa, CA), with excellent angiographic results. The patient made a good neurological recovery, and the postoperative positron emission tomographic scan demonstrated increases in both cerebral blood flow and cerebral metabolic rate of oxygen with a normalization of oxygen extraction fraction. CONCLUSION: Stent-assisted angioplasty can provide a favorable clinical course as well as improved cerebral perfusion and metabolism for a patient with basilar artery stenosis. Long-term follow-up data and additional clinical experience are required to assess the durability of this approach.

Brain↗

Cerebellar hemorrhage after coil embolization for a ruptured vertebral dissecting aneurysm.

BACKGROUND: We present a case of ruptured vertebral dissecting aneurysm that exhibited cerebellar hemorrhage after successful embolization of the vertebral artery including the dissected site. CASE PRESENTATION: A 59-year-old man suffered a sudden onset of severe occipital headache when he looked up. Computed tomography demonstrated subarachnoid hemorrhage. Angiography revealed a right vertebral dissecting aneurysm distal to the posterior inferior cerebellar artery. Endovascular embolization of the aneurysm was performed with preservation of the posterior inferior cerebellar artery. The next day, the patient suffered a cerebellar hemorrhage in the vermis. The intracranial pressure was controlled by external ventricular drainage. The patient was discharged with mild cerebellar ataxia and bilateral abducens nerve palsy. CONCLUSION: In a case of vertebral dissecting aneurysm distal to the posterior inferior cerebellar artery, blood circulation in the vertebral arterial system may change after embolization of the aneurysm. In our case, the preserved posterior inferior cerebellar artery might have been hemodynamically stressed postoperatively, resulting in cerebellar hemorrhage. Therefore, strict control of blood pressure is essential in the acute stage after occlusion of the aneurysm.

Aneurysm, Ruptured↗

Ruptured irregularly shaped aneurysms: pseudoaneurysm formation in a thrombus located at the rupture site.

OBJECT: The authors describe the clinical, radiological, and pathological findings of ruptured cerebral aneurysms with irregular configurations. METHODS: Eight patients with subarachnoid hemorrhage due to ruptured irregularly shaped aneurysms were examined. The preoperative radiological findings in these cases were compared with the pathological and operative findings of endovascular or open surgery. All of the aneurysms exhibited delayed opacification and delayed washout of contrast medium from the irregularly shaped portion of the aneurysm on digital subtraction angiography and/or helical computerized tomography scanning. Endovascular embolization with platinum coils was attempted in the first four patients who underwent treatment. In three of these patients the aneurysm ruptured again during the endovascular procedure. In the fourth patient an intraaneurysm thrombus was observed during the procedure and clipping was performed. In the subsequent four patients, three underwent clipping without complication and one underwent partial aneurysm embolization because of poor general status. A thrombus adjacent to the aneurysm dome was observed in the patients who underwent open surgery. Pathological examination of the operative specimens revealed a pseudoaneurysm-like cavity in the thrombus that was adherent to the aneurysm. CONCLUSIONS: Ruptured irregularly shaped aneurysms may be accompanied by fragile pseudoaneurysm-like cavities located at the rupture point. Because these aneurysms have a high risk of repeated rupture during an endovascular procedure, advancing microinstruments to the weaker portion of the aneurysm should be avoided.

Adult↗

Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats.

Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes (CLN) in a number of experimental animals. To investigate the role of CLN in brain tumour immunity, temporal profiles of MHC class II molecule expression and T lymphocyte subsets in brain tumours, CLN and other lymphoid tissues were analysed by immunocytochemistry. A total of 64 Wistar rats weighing 250 g were used. Two weeks after the transplantation of C6 glioma cells (10(6) cells/1 microl) into a rat brain, expression of MHC class II molecules was induced in the brain and all systemic lymphoid tissues examined. However, the subsequent appearance of CD4 or CD8 positive cells was strictly confined to CLN, and coincided with the infiltration of such cells into the brain tumour 2 weeks after transplantation. In the group of animals in which cervical lymphadenectomy was followed by intracerebral transplantation of C6 glioma cells, infiltration of CD4 or CD8 positive cells into the brain tumour was delayed until 3 weeks after the transplantation, and the production of such cells was by the spleen. These results suggest that CLN act as regional lymph nodes in brain tumour immunity.

Animals↗

Isolated histiocytosis X of the pituitary stalk.

A case of histiocytosis X granuloma localized in the pituitary stalk is reported. Coronal and sagittal magnetic resonance imaging views were useful to determine the precise size and location of the mass lesion. The diagnosis was established immunohistochemically and the patient was treated with low-dose irradiation therapy. After irradiation, the patient improved well without endocrine replacement treatment. The pituitary stalk recovered its normal size with no evidence of recurrence on MRI at 7-year follow-up. We emphasize the importance of MRI before initiating therapy to evaluate the pituitary mass lesion and the effectiveness of low-dose irradiation for isolated histiocytosis X.

Adult↗

Middle cerebral artery occlusion in the rat causes a biphasic production of immunoreactive interleukin-1beta in the cerebral cortex.

Interleukin-1beta (IL-1beta) has been implicated in the sequence of events leading to neuronal cell death. We have used an ultrasensitive, highly specific immunometric assay for rat IL-1beta to determine the pattern of protein expression in the rat cerebral cortex following middle cerebral artery occlusion. In the ipsilateral cerebral cortex there was a biphasic pattern of production with a rapid early phase of IL-1beta expression followed by a delayed phase at 4 h which was sustained for up to 72 h. There was a similar but smaller expression of IL-1beta in the contralateral cortex. Sham operated animals showed no IL-1beta expression. These results provide further evidence to show that IL-1beta is expressed in the rat cerebral cortex following cerebral ischaemia.

Animals↗

CREB and memory.

The cAMP responsive element binding protein (CREB) is a nuclear protein that modulates the transcription of genes with cAMP responsive elements in their promoters. Increases in the concentration of either calcium or cAMP can trigger the phosphorylation and activation of CREB. This transcription factor is a component of intracellular signaling events that regulate a wide range of biological functions, from spermatogenesis to circadian rhythms and memory. Here we review the key features of CREB-dependent transcription, as well as the involvement of CREB in memory formation. Evidence from Aplysia, Drosophila, mice, and rats shows that CREB-dependent transcription is required for the cellular events underlying long-term but not short-term memory. While the work in Aplysia and Drosophila only involved CREB function in very simple forms of conditioning, genetic and pharmacological studies in mice and rats demonstrate that CREB is required for a variety of complex forms of memory, including spatial and social learning, thus indicating that CREB may be a universal modulator of processes required for memory formation.

Animals↗

Restricted expression of a member of the transcription elongation factor S-II family in testicular germ cells during and after meiosis.

Whether expression of transcription elongation factors is regulated during development has not been investigated, though genes encoding elongation factor S-II are transcribed in a tissue-specific manner. We investigated the expression profile of tissue-specific S-II during development using an isolated cDNA, termed mouse S-II-T1, whose transcripts are detected almost exclusively in testis. Three experiments were performed with various types of germ and somatic cells in testis to determine in which cells S-II-T1 is expressed. (1) Expression of S-II-T1 is markedly reduced in the testes of adult WBB6F1-W/Wv mutant mice which lack testicular germ cells, indicating its expression is specific to testicular germ cells. (2) The onset of mouse S-II-T1 mRNA appearance in testis is seen about 10-14 days after birth, which is consistent with the start of meiotic events, suggesting that S-II-T1 is not transcribed in premeiotic and early meiotic cells such as spermatogonia, leptotene spermatocytes, or zygotene spermatocytes. (3) Mouse S-II-T1 transcripts accumulate in meiotic pachytene spermatocytes and are detected in postmeiotic haploid cells such as round and elongated spermatids during spermatogenesis, as shown by fractionation of testicular germ cells at four different stages. These results indicate that expression of mouse S-II-T1 is restricted to testicular germ cells during and after meiosis in the course of spermatogenesis. This is the first report that expression of a transcription elongation factor in particular cells is regulated in a stage-specific manner in the course of development.

Amino Acid Sequence↗

Membranous ultrastructure of human arachnoid cells.

The ultrastructure of arachnoid cell membranes was investigated by conventional transmission EM and by freeze-fracture techniques in human arachnoid granulations. Arachnoid cells showed widespread membrane specialization in the granulations including the formation of desmosomes, gap junctions, tight junctions, intermediate junctions, hemidesmosome-like structures, and micropinocytotic vesicles. However, the extent of the specialization varied from portion to portion; this was clearly shown on freeze-fracture replicas. Numerous extracellular cisterns were separated by cytoplasmic bodies or slender processes, joined by these junctional complexes. Uncoated and coated vesicles were abundant along the surface of extracellular cisterns representing the pathway of CSF. Complexes of branching tight junctions were comprised of 1-50 particle strands, which formed elaborate meshworks accompanied by numerous gap junctions and desmosomes. Micropinocytotic vesicles were often concentrated in the arachnoid cell cluster up to 40 per microm2, which is equivalent to the concentration in brain capillary endothelial cells. The results of this study clearly suggest that arachnoid cells in arachnoid granulations are not only tightly adherent to form a firm structure for the passage of CSF, but that the arachnoid cells lining the CSF pathway show intense cell-cell communication and pinocytotic activity. This high transcellular activity probably reflects active transports or secretion of certain molecules by arachnoid cells.

Adolescent↗

[Immunologic significance of lymphatic drainage of the brain].

Despite the evidence for immunological reactions in the human CNS, in viral encephalitis and in multiple sclerosis, connections between the brain and the immune system are poorly understood. In rodents, tracers injected into the interstitial fluid of the brain drain to the cervical lymph nodes by perivascular pathways in the brain and nasal lymphatics. Similar pathways could serve as lymphatics in the human brain. In the present study, we test the hypothesis that lymphatic drainage of the brain and cervical lymph nodes play a key role in T-cell mediated immunity of the brain. Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant into the foot pads. This resulted in paralysis of the hind limbs and infiltration of lymphocytes and microglial activation centred mainly on the spinal cord; little inflammation was seen in the cerebrum. When a brain wound, in the form of cryolesion, was inflicted on one cerebral hemisphere, 8 days after the induction of EAE, there was a 6-fold enhancement of EAE lesions in the brain. This enhancement was reduced by 40% cervical lymphadenectomy at the time of the cryolesion. These results suggest that cervical lymph nodes play a pivotal role in cerebral EAE and may be a major source of brain-directed lymphocytes. If similar mechanisms apply in man, study of cervical lymphocytes and their manipulation could open new therapeutic avenues for the treatment of multiple sclerosis.

Animals↗

Enhancement of eosinophil survival by lipopolysaccharide through releasing granulocyte-macrophage colony stimulating factor from mononuclear cells from patients with bronchial asthma.

BACKGROUND: The mechanism of bronchoobstruction in asthmatics following inhalation of lipopolysaccharide (LPS) is unclear. OBJECTIVE: In this study we have investigated the effects of the LPS on eosinophil survival rate in stimulating peripheral blood mononuclear cells (PBMCs) from patients with asthma. METHODS: PBMC supernatants from 10 asthmatic patients and 4 healthy subjects were compared for eosinophil survival rate using the same purified eosinophils. Two x 10(6) cells/ml of PBMCs were cultured for 24 hours in RPMI 1640 containing 10% fetal bovine serum along with 10 micrograms/ml of LPS. 10(6) cells/ml of eosinophils were incubated for 96 hours in the presence of PBMC-derived culture supernatants at 75% in volume. RESULTS: The viability of eosinophils incubated with PBMC supernatants from asthmatic patients stimulated with LPS was higher, 62.5% +/- 10.6% (mean +/- SD), than that without LPS, 26.9% +/- 10.8%, and also higher than that of PBMCs from healthy subjects with LPS, 40.0% +/- 15.4%. This increasing activity of asthmatic PBMC stimulated with LPS was markedly inhibited from 72.2% +/- 9.7% to 38.5% +/- 6.8% by addition of mouse anti-human GM-CSF antibody to the PBMC supernatant but not mouse anti-human IL-5 antibody. CONCLUSION: These results suggest that LPS enhances eosinophil survival in asthmatics by increasing the production of GM-CSF from PBMCs.

Adult↗

Localization of E-cadherin in peripheral glia after nerve injury and repair.

Peripheral nerve injury results in histological and histochemical changes in neurons and glia. We have recently found that Ca(2+)-dependent cell adhesion molecule E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibers. In the present immunohistochemical and immunoblot analyses, the temporal profile of the subcellular expression of this molecule in spinal nerves was examined after crushing, transecting, or ligaturing the sciatic nerve in mice with special attention paid to E-cadherin expression in glial cells. After axotomy of the sciatic nerve, distal axons of the proximal stump and the fibers of the distal stump degenerated, but E-cadherin was still detectable at the outer mesaxons of the myelinated axons as long as they remained morphologically intact. Subsequently, Schwann cells proliferated and migrated to form Schwann cell columns (Büngner's bands) as initial responses to denervation, and expressed E-cadherin at their site of contact with each other and later with sprouting axons. At the initial stage of myelin formation, slender processes of a single Schwann cell interdigitated with an enveloped axons, and expressed E-cadherin at the contact site elaborated by a single Schwann cell. Immunoblot analysis on day 7 revealed that E-cadherin was detected in both the proximal nerve segments and the regenerative distal segments, but was negative in the degenerative distal segments. On the basis of present data, it is suggested that E-cadherin might be involved in the stabilization of the peripheral glial network which provides the guidance of sprouting axons and myelination.

Animals↗