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Biomedical subjects

A Nishino

Publications and source records attributed to A Nishino.

At least 19 recordsLinked to original sources

GABAergic synaptic transmission modulates swimming in the ascidian larva.

To examine the role of the amino acid GABA in the locomotion of basal chordates, we investigated the pharmacology of swimming and the morphology of GABA-immunopositive neurones in tadpole larvae of the ascidians Ciona intestinalis and Ciona savignyi. We verified that electrical recording from the tail reflects alternating muscle activity during swimming by correlating electrical signals with tail beats using high-speed video recording. GABA reversibly reduced swimming periods to single tail twitches, while picrotoxin increased the frequency and duration of electrical activity associated with spontaneous swimming periods. Immunocytochemistry for GABA revealed extensive labelling throughout the larval central nervous system. Two strongly labelled regions on either side of the sensory vesicle were connected by an arc of labelled fibres, from which fibre tracts extended caudally into the visceral ganglion. Fibre tracts extended ventrally from a third, more medial region in the posterior sensory vesicle. Two rows of immunoreactive cell bodies in the visceral ganglion extended neurites into the nerve cord, where varicosities were seen. Thus, presumed GABAergic neurones form a network that could release GABA during swimming that is involved in modulating the time course and frequency of periods of spontaneous swimming. GABAergic and motor neurones in the visceral ganglion could interact at the level of their cell bodies and/or through the presumed GABAergic fibres that enter the nerve cord. The larval swimming network appears to possess some of the properties of spinal networks in vertebrates, while at the same time possibly showing a type of peripheral innervation resembling that in some protostomes.

Animals↗

[Multi-vessel dissection; report of a case].

We report an extremely rare case of multi-vessel dissection including left carotid artery, ascending aorta and thoracoabdominal aorta independently. A 65-year-old man suffered from cerebral infarction due to left carotid artery dissection. Five days later, he complained of severe back pain and was diagnosed as acute DeBakey type IIIb aortic dissection. He had been treated medically. One month later, computed tomography (CT) scan demonstrated DeBakey type II as well as type IIIb aortic dissections. The ascending aorta was replaced on August 8, 2001. Then replacement of the descending thoracic aorta with reconstruction of the eighth and tenth intercostal arteries was performed on September 26, 2001. The left carotid artery dissection has been treated medically.

Aged↗

Clinical manifestations, character of aneurysms, and surgical results for unruptured cerebral aneurysms presenting with ophthalmic symptoms.

OBJECTS: Cases with unruptured cerebral aneurysms presenting with visual symptoms were investigated about their site, size, symptom, operative methods and results. MATERIAL: Between 1984 and 1999, 8 cases were treated in Sendai National Hospital. One man and 7 women, mean age 66.4 years. Ophthalmic symptoms were as follows: diplopia in 6, visual acuity deterioration in 2, impaired visual field in 2 and ptosis in 3. Aneurysm location was IC cavernous in 3, IC ophthalmic in 3, ICPC in 1 and Acom in 1. Aneurysms of more than 25 mm numbered 6 cases. RESULTS: Operative methods and results were as follows: Direct clipping 3 cases, parent artery occlusion + EC/IC bypass 4 cases, Aneurysm trapping + EC/IC bypass 1 case. One patient who underwent direct clipping died following intraoperative complication. Of the remaining 7 cases, visual symptoms were improved in 4, remained unchanged in 2 cases, worsened in 1 case. CONCLUSIONS: These results suggest that in cases with unruptured large or giant aneurysms presenting with ophthalmic symptoms, especially in IC cavernous or IC ophthalmic aneurysms, parent artery occlusion + EC/IC bypass is the safest operative procedure.

Aged↗

The simple tail of chordates: phylogenetic significance of appendicularians.

Appendicularia comprises a group of pelagic tunicates that retain the tail throughout their life without exhibiting the drastic metamorphosis seen in ascidians or doliolids. They are known to possess a simple body architecture that is comparable with that of other chordates. Recent phylogenetic studies suggest that appendicularians represent a sister group of the clade of other tunicates. Very recently, two independent research groups reported molecular-based approaches to the appendicularian development. We review here some general descriptions and results of recent analyses on the anatomy and developmental biology of appendicularians, focusing upon their simple tail architecture. We emphasize future possibilities for a comprehensive understanding of the divergent patterns in lifestyle of tunicates as well as for investigating the phylogenetic novelty and innovation of chordates such as the tail.

Animals↗

Brachyury (T) gene expression and notochord development in Oikopleura longicauda (Appendicularia, Urochordata).

Appendicularia (Larvacea) is a subgroup of Urochordata (Tunicata) comprised of holoplanktonic organisms that retain their tailed architecture throughout their life history, while other tunicates, including ascidians and doliolids, resorb the tail after metamorphosis. In order to investigate the characteristics of the appendicularian unresorbed notochord, we isolated a partial genomic clone and a full-length cDNA sequence homologous to the mouse Brachyury (T) gene from the appendicularian Oikopleura longicauda. Brachyury is known to be predominantly expressed in the notochord cells and plays an important role in their differentiation in other chordates. While phylogenetic analysis robustly supports the orthology of the isolated Brachyury gene, the exon-intron organization found in the genomic clone was distinct from that well-conserved among other T-box genes. In addition to a detailed observation of notochord development in living specimens, whole-mount double in situ hybridization was carried out using a Brachyury probe along with a muscle actin probe. The Brachyury transcripts were found in the notochord of the tailbud embryos and persisted into later stages. The present study highlights characteristics of notochord development in the appendicularian. Furthermore, these results provide basic knowledge for comprehensive understanding of the cellular- and molecular-based mechanisms needed to build the characteristic cytoarchitecture of notochord that varies among tunicate species.

Amino Acid Sequence↗

Gene expression profiles in Ciona intestinalis tailbud embryos.

A set of 3423 expressed sequence tags derived from the Ciona intestinalis tailbud embryos was categorized into 1213 independent clusters. When compared with DNA Data Bank of Japan database, 502 clusters of them showed significant matches to reported proteins with distinct function, whereas 184 lacked sufficient information to be categorized (including reported proteins with undefined function) and 527 had no significant similarities to known proteins. Sequence similarity analyses of the 502 clusters in relation to the biosynthetic function, as well as the structure of the message population at this stage, demonstrated that 390 of them were associated with functions that many kinds of cells use, 85 with cell-cell communication and 27 with transcription factors and other gene regulatory proteins. All of the 1213 clusters were subjected to whole-mount in situ hybridization to analyze the gene expression profiles at this stage. A total of 387 clusters showed expression specific to a certain tissue or organ; 149 showed epidermis-specific expression; 34 were specific to the nervous system; 29 to endoderm; 112 to mesenchyme; 32 to notochord; and 31 to muscle. Many genes were also specifically expressed in multiple tissues. The study also highlighted characteristic gene expression profiles dependent on the tissues. In addition, several genes showed intriguing expression patterns that have not been reported previously; for example, four genes were expressed specifically in the nerve cord cells and one gene was expressed only in the posterior part of muscle cells. This study provides molecular markers for each of the tissues and/or organs that constitutes the Ciona tailbud embryo. The sequence information will also be used for further genome scientific approach to explore molecular mechanisms involved in the formation of one of the most primitive chordate body plans.

Animals↗

[A case of anaplastic astrocytoma arising 8 years after initial treatment by partial resection and irradiation for central neurocytoma].

A 31-year-old female developed the anaplastic astrocytoma in the right basal ganglia and temporal lobe 8 years after partial resection and irradiation of the central neurocytoma. Probably the malignant astrocytoma was an irradiation-induced tumor. Postoperative radiation therapy for the central neurocytoma appears to have a good effect on tumor local control. But it should be carefully decided whether to use radiation therapy for residual tumor because of the risk of delayed complications of irradiation, such as the present case.

Adult↗

Muscle actin genes and muscle cells in the appendicularian, Oikopleura longicauda: phylogenetic relationships among muscle tissues in the urochordates.

Appendicularians (larvaceans) are planktonic tunicates. They possess a tail throughout their life, which marks a distinct difference between appendicularians and the other tunicate groups, including salps, doliolids, pyrosomes, and ascidians. We isolated cDNA clones encoding muscle-type and cytoplasmic-type actin isoforms from the appendicularian, Oikopleura longicauda. The types of the actin isoforms were confirmed by amino acid identities in the diagnostic residues compared to those of the other chordate muscle and cytoplasmic actins. Interestingly the appendicularian muscle actin isoform sequence has an intermediate feature between the ascidian tail (larval) muscle actin isoform and the body-wall (adult) muscle actin isoform. Analysis of a genomic clone from a muscle actin gene revealed that it contains only one intron in the coding region. It is located at a position that does not correspond to those of any introns reported in other deuterostome actin genes. Whole-mount in situ hybridization shows that the muscle actin transcript is detected specifically in the tail muscle cells of late tailbud-stage embryos. A signal is also found transiently in the region where the heart will form. In adults, the gene is expressed in tail muscle cells but not in the heart. Together with results of cytochemical and histochemical studies demonstrating the structure of muscle tissue, the present study highlights characteristics of appendicularian muscle organization, which are compared with those of the larval and adult muscle of ascidians.

Actins↗

Characterization of a hemichordate fork head/HNF-3 gene expression.

Based on anatomical and developmental similarities, hemichordates are thought to be most closely related to chordates. However, so far very few developmental genes have been characterized from hemichordates. To gain molecular insight into the developmental mechanisms involved in the origin and evolution of chordates, we investigated the expression of a fork head/HNF-3 (PfHNF3) gene in the acorn worm embryo. Chordate fork head genes are implicated in the formation of endoderm, notochord and floor plate. We found that a PfHNF3 transcript was first detected at the early blastula stage; the signal of in situ hybridization was found in the vegetal plate cells, invaginating endoderm and then in the archenteron. By the late gastrula and into the early tornaria larva stages, an intense signal remained in the anterior region of the archenteron, while the expression in the other regions of archenteron decreased. The intense signal was retained in the pharynx of the tornaria larva. A comparison of the pattern of PfHNF3 with that of HNF-3 genes of sea urchin, ascidian, amphioxus and vertebrate suggests a possible acquisition of new functions of the gene during deuterostome evolution.

Amino Acid Sequence↗

Mice with markedly reduced PACAP (PAC(1)) receptor expression by targeted deletion of the signal peptide.

In an attempt to study the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 (PAC(1)) receptor (PAC(1)R) function in vivo and to produce a mouse model with altered expression of PAC(1)R, we have used gene targeting in embryonic stem cells to disrupt exon 2 of the PAC(1)R gene, which contains the ATG translation start site and the signal peptide. Un-expectedly, active transcription of PAC(1)R mRNA was detected in the mutant mice; however, exon 1 was spliced to exon 3 (skipping exon 2), and (125)I-PACAP27 binding in brain was greatly reduced. PAC(1)R exon 2(-/-) mice were viable, fertile, and morphologically and histologically indistinguishable from their wild-type counterparts. We next examined the ligand binding and cell surface expression of the mutant receptor lacking the signal peptide in transfected COS-7 cells. (125)I-PACAP27 binding of the mutant receptor was approximately one-tenth of that in the wild-type receptor. Although the wild-type receptor was expressed abundantly in both the plasma membrane and the cytoplasm around the nucleus, the mutant receptor was expressed in the plasma membrane with a markedly reduced level. Digestion of the membranes with endoglycosidase F greatly reduced the size of the wild-type receptor but only slightly reduced that of the mutant receptor. These results demonstrate that the signal peptide is required for efficient cell surface expression and N-linked glycosylation of the PAC(1)R. However, the mutant receptors still functionally coupled to adenylate cyclase in COS-7 cells, suggesting the presence of sufficient spare receptors such that the mutant receptors are capable of activating the second messenger system. We suggest that the mutant mice with markedly reduced PAC(1)R expression can serve as a useful animal model or cell culture system for further studies in PAC(1)R function.

Animals↗

Both cMOAT/MRP2 and another unknown transporter(s) are responsible for the biliary excretion of glucuronide conjugate of the nonpeptide angiotensin II antagonist, telmisaltan.

Canalicular multispecific organic anion transporter (cMOAT/MRP2) is known to play a major role in the transport of anionic xenobiotics including many types of glucuronide and glutathione conjugates across the bile canalicular membrane. In the present study, the biliary excretion of telmisartan (BIBR 277) and its glucuronide was examined in Sprague-Dawley rats (SDRs) and also in mutant strain Eisai-hyperbilirubinemic rats (EHBR), which have a hereditary defect in cMOAT/MRP2. Only a minimal difference was observed in the time profile of the plasma concentration of total radioactivity after administration of an i.v. bolus of BIBR 277. About 45% of the administered dose was excreted into bile up to 240 min in both strains, most of the radioactivity in the bile being BIBR 277 glucuronide. No significant difference was observed in the biliary excretion of BIBR 277 and its glucuronide between SDRs and EHBR although the plasma disappearance of BIBR 277 glucuronide was delayed in EHBR. To explain these data, the extent of glucuronidation of BIBR 277 by liver microsomes was examined in both strains. The V(max) value for the formation of BIBR 277 glucuronide was 2 to 3 times higher in EHBR than in SDRs, whereas both strains had similar K(m) values. After an i.v. bolus administration of BIBR 277 glucuronide, its plasma disappearance was delayed in EHBR, the biliary clearance in EHBR being about half that in SDRs. These results suggest that BIBR 277 glucuronide is transported by both cMOAT/MRP2 and another transporter that is also expressed in EHBR, and that the BIBR 277 glucuronidation is enhanced in EHBR, resulting in comparable excretion of glucuronide in both strains.

Angiotensin-Converting Enzyme Inhibitors↗

[Autopsied case of an extracranial internal carotid artery dissecting aneurysm].

An autopsy case of extracranial internal carotid artery (ICA) dissecting aneurysm due to atherosclerosis was reported. A 74-year-old man was admitted to our hospital with the chief complaints of hoarseness and a pulsatile mass below the left mandibular angle. Neurological examination showed no obvious deficits except left recurrent laryngeal nerve palsy. Angiography revealed narrowing of the original segment of left ICA with dissection and aneurysmal dilation at the level of C3 vertebra. Seven days after admission, the patient had a sudden onset of consciousness disturbance. The second angiography showed no obvious changes compared with the first findings except slight narrowing in the distal portion above the aneurysmal dilation. The possible mechanism was thought to be recanalization following transient occlusion of the left ICA caused by extension of dissection or intracranial embolism due to a thrombus within the aneurysm. He was managed conservatively, but unfortunately he died of pneumonia. Macroscopic autopsy showed that the aneurysm was fusiform. Histologically, it demonstrated dissection of the hematoma between the media and adventitia layer. Hemorrhage in the atheromatous plaque with disruption of the elastic lamina were observed along with severe degenerative changes of the intima, media and, in part, adventitia layer due to atherosclerosis. In addition, a dissecting aneurysm of the right iliac artery and severe arteriosclerosis were observed in the systemic arteries. On the basis of these findings, the dissecting aneurysm presumably developed after disruption of a weak portion of the atherosclerotic wall, where intraplaque hemorrhage occurred earlier. We suggest that atherosclerosis be regarded as one of the pathogenic factors capable of causing dissecting aneurysm of the extracranial ICA in elderly patients.

Aged↗

Genomic organization and chromosomal location of the mouse vasoactive intestinal polypeptide 1 (VPAC1) receptor.

The gene encoding the mouse vasoactive intestinal polypeptide type 1 (VPAC1) receptor was cloned, and its structural organization was determined. The gene (Vipr1) is more than 16 kb in length and is divided into 13 exons. The 5'-flanking region is highly GC-rich and lacks an apparent TATA box, but contains a CCAAT box, three potential Sp1-binding sites, and two potential AP-2-binding sites. Promoter analysis of the 5'-flanking region of Vipr1 using a luciferase gene reporter system revealed that the isolated 5'-flanking region has functional promoter activity. The mouse Vipr1 gene is encoded by a single gene, which was mapped to the distal region of mouse chromosome 9. This region is syntenic with human chromosome 3p, where the human VPAC1 receptor gene has been mapped.

Animals↗

Resumption of work after aneurysmal subarachnoid hemorrhage in middle-aged Japanese patients.

OBJECT: Previous reports on the results of treatment for aneurysmal subarachnoid hemorrhage (SAH) have been based only on activities of daily living after discharge, whereas resumption of work has received insufficient attention. Most Japanese work under a lifetime employment system, and it is best for those who have recovered from SAH to return to work for their previous employer. The present study was conducted to determine the extent to which discharged patients who have suffered an SAH resume their former occupations in Japan, focusing on those between 40 and 49 years of age, who usually have a strong desire to return to work. METHODS: The participants consisted of 193 patients with SAH. Based on the results of telephone interviews or written questionnaires, their work status at 1 year after onset was analyzed. The work resumption rates for patients with Hunt and Kosnik neurological Grades 1 or 2 on admission were higher than for those with Grades 3 or 4 (p = 0.015) and lower for patients with basilar artery aneurysms than for those with aneurysms at other sites (p = 0.028). With regard to premorbid occupation, the work resumption rates were high (80%) for professionals and engineers, many of whom were public servants, or teachers at junior or senior high schools. The resumption rates were also high for primary industry workers (80%), but lowest (20%) for professional drivers (p = 0.04-0.001). The work resumption rate was lower for women than for men (p = 0.01). CONCLUSIONS: These findings indicate that resumption of work is determined not only by medical factors, but also by social factors including gender, type of occupation, employment system, and socioeconomic background.

Activities of Daily Living↗

[Renal cell carcinoma recurrence in the mediastinum lymph node 19 years after nephrectomy: a case report].

A 62-year-old male, who had undergone right nephrectomy to treat renal cancer 19 years earlier, was recently referred to our hospital to receive a detailed examination and treatment of mediastinal lymph node swelling. Biopsy of the swollen lymph nodes allowed a diagnosis of renal cell carcinoma (alveolar type, clear cell subtype, GI) to be made. The pathological features of his tumor were consistent with those of the renal tumor resected 19 years previously. Because there was a high probability of further growth of the swollen mediastinal lymph nodes and consequent high probability of compression of the superior vena cava, we performed mediastinal lymph node excision. Immediately after surgery, prophylactic interferon therapy was started. To date, five cases (including the present case) in which renal tumors recurred more than 15 years after surgical treatment have been reported in Japan.

Carcinoma, Renal Cell↗

[A case of frequent intracerebral hemorrhage from mixed vascular malformation in a child].

We reported a rare case of frequent intracerebral hemorrhage from mixed vascular malformation in an infant. A 1-year and 4-month-old girl was admitted with seizure. She had been diagnosed as having febrile convulsion at the age of 8 months. Computed tomography (CT) indicated a multicystic mass without perifocal edema in the right frontal lobe. The mass was not enhanced by contrast media, but T1-weighted magnetic resonance imaging (MRI) revealed a multicystic mass with mixed signal intensity, while T2-weighted image demonstrated a heterogenous high signal intensity mass with a marginal low intensity rim. These findings suggested a cavernous angioma causing intracerebral hematomas. Because of this, total resection was achieved via a right fronto-temporal craniotomy without neurological deficits. Histologically, numerous dilated venous-type blood vessels interspersed within the normal brain parenchyma were seen. In parts, the vessel walls were abnormally thickened and the lesion coalesced with capillary-like vessels. We diagnosed mixed vascular malformation, mainly composed of venous malformation along with telangiectasia. The number of reports for this so-called mixed vascular malformation have thus been increased. The histopathological criteria for classification of vascular malformation should be reinvestigated carefully.

Cerebral Hemorrhage↗

Cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene.

The gene encoding the mouse precursor of pituitary adenylate cyclase-activating polypeptide (PACAP) has been cloned, and its structural organization was determined. Using the 5'-rapid amplification of cDNA ends (RACE) procedure, three types of transcription initiation produced by alternative exon usage of two untranslated alternative exons (exons 1A and 1B) were defined. The PACAP gene spans 6.6kb of genomic DNA and is composed of six exons including the alternative exons. The signal peptide, PACAP-related peptide and mature 38-amino acid PACAP (PACAP-38) are encoded within exons 2, 4 and 5, respectively. The 5'-flanking region of the PACAP gene contains several sequence motifs homologous to cAMP response element, TPA response element, and growth hormone factor-1 binding site. A dinucleotide repeat sequence is present in an intron. In addition, there are di- and tetranucleotide repeat sequences 2.4kb and 3.2kb upstream to the translation start point, respectively. The overall intron-exon organization and the production of the alternate mRNAs of the PACAP gene are markedly similar to those of the growth hormone-releasing hormone (GHRH), supporting the hypothesis that the two genes encoding GHRH or PACAP were originated from a gene duplication. Promoter analysis of the 5'-flanking region of the PACAP gene using a luciferase gene reporter system revealed that the isolated 5'-flanking region has functional promoter activity and is responsible for inducible expression.

Alternative Splicing↗