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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 343 records · Page 19Linked to original sources
PubMed2001

No involvement of Erk/MAP kinases in IL-6-induced proliferation of a B cell hybridoma cell line.

Interleukin-6 (IL-6) is a pleiotropic cytokine and acts as a growth factor for murine plasmacytoma and human myeloma. IL-6 activates multiple signal transduction pathways. Among them, signal transducer and activator of transcription3 (STAT3), and the SHP-2-mediated Erk/MAP kinase pathway are important. The roles for the two major pathways in the IL-6-induced growth of B cell hybridoma cells were examined. A mutational analysis of the cytoplasmic domain of exogenously expressed gp130, a signal transducing beta chain of the IL-6 receptor complex, revealed that the proximal 133 amino acid (AA) region of gp130 with the intact Y767 but not Y759 is necessary and sufficient for gp130-signal-induced cell proliferation. Interestingly, no requirement of the Y759-mediated signals, including SHP-2-mediated Erk/MAP kinase pathway, coincided with the failure of SHP-2, Gab1/Gab2, and Erk/MAP kinase activation by IL-6 in MH60 cells. Moreover, we show that another serine/threonine kinase pathway leading to STAT3 Ser727 phosphorylation, which seemed to be derived from the Y767 in the proximal 133 AA residues, is intact in MH60 cells. Since Erk/MAP kinases are known to inhibit the subsequent IL-6-induced STAT3 activation, the impaired activation of Erk/MAP kinases by IL-6 may contribute to the development of B cell neoplasia.

B-Lymphocytes↗
PubMed2001

The roles of the N-terminal portions of various tachykinins in promoting salivation.

OBJECTIVES: In order to determine the active sites for salivation of various tachykinins, the regulatory roles of the N-terminal portion of various newly-synthesized tachykinins were studied after i.p. injection of rats using the submandibular glands as model organs. METHODS: N-shortened oligopeptides from kassinin, eledoisin, neurokinins A (NKA) and NKB were synthesized by the multipin peptide synthesis method. Amino acids were eliminated one by one to form octa- to undeca-peptides adjoining the inactive or less active heptapeptides and various heptapeptides, in which an amino acid in position 8 (Xaa8), numbering as in an undecapeptide, was replaced with Tyr, Phe, Ile or Val. RESULTS: The N-terminal amino acids in positions 1 to 4 could be activators or inhibitors, depending on whether the C-terminal heptapeptide was inactive or less active. The Xaa8 residue, in combination with amino acids in positions 5 and 6, seemed to be very important in determining the sialogogic activity of a heptapeptide. The discrimination between NKA and NKB appeared due to the N-terminal amino acid sequence in positions I to 4 including Phe or Ser in position 6. CONCLUSIONS: It is concluded that the N-terminal amino acids in positions I to 4 serve as either activators or inhibitors depending upon the sialogogic activity of the C-terminal heptapeptide, in which particular amino acids in positions 5, 6 and 8 regulate its activity.

Analysis of Variance↗
PubMed2001

Scanning electron microscopic observation of Merkel cells in the lamprey epidermis.

The Merkel cell in the epidermis has generally been regarded as a mechanoreceptor which detects tissue deformations with its microvilli, and subsequently releases certain transmitters to nerve endings. In order to analyze the mechanism of mechanoreception, the fine structure of lamprey Merkel cells and their relationships with surrounding tissue were examined by scanning electron microscopy (SEM) after exposure of the cells by NaOH maceration, as well as by transmission electron microscopy (TEM) according to a conventional method. By SEM, lamprey Merkel cells revealed small round cell bodies bearing numerous microvilli on the upper and lower poles in accord with previous TEM reports. Combined SEM and TEM observations showed that the Merkel cell bodies were tightly held in corresponding concavities of other epidermal cells, with some desmosomes connecting the cells with each other. On the other hand, microvilli of the Merkel cells extended freely in intercellular spaces bound with complex microplicae of epidermal cells. The regional difference in mechanical anchorage of the Merkel cells probably leads to transient deflection and subsequent recovery of their microvilli during a given mechanical stimulation, suggesting rapidly adapting mechanoreception by the cells.

Animals↗
PubMed2001

[Talks on evaluation of students' writing (discussion)].

We talked about the evaluation of students' writing; this is thought to be difficult for teachers. We have a class "history of medicine" for freshmen in the second semester of the medical course. Students give lecture by themselves on famous historical persons in medicine such as Hippocrates, Vesalius, Pasteur and Sackett, referring to their historical significance in present medicine. As the final work of the subject they write report on "clinical medicine or medical researches 20 years in future and myself". We talked generally about educational evaluation in various aspects, concerning the methods for writing. We discussed mainly on two themes--ability to write and originality in thinking. We give a larger point to the originality, which correlates to ability to write, though we feel difficult in evaluating students' originality only by reading their reports. We also emphasize the importance of active interaction between students and teachers, and to evaluate educational activities of teachers in Japanese universities.

Aptitude↗
PubMed2001

Lateral geniculate nucleus: anatomic and functional identification by use of MR imaging.

BACKGROUND AND PURPOSE: MR imaging has the potential capacity for noninvasively depicting the anatomy and function of thalamic nuclei. The purpose of this study was to identify the lateral geniculate nucleus (LGN), which is the thalamic relay nucleus for vision, with anatomic and functional MR imaging at 1.5 T. METHODS: Three-millimeter-thick axial images were obtained from eight volunteers by using a double-echo turbo spin-echo sequence for proton density- and T2-weighted contrast and a spin-echo 3D gradient-echo sequence for T1-weighted contrast. Each participant underwent a visual activation experiment using gradient-echo echo-planar imaging at the same location as that of the anatomic study. RESULTS: In all cases, the LGN was recognized on proton density-weighted images as a small wedge-shaped area of high signal intensity relative to that of the surrounding white matter tracts. However, it was difficult to identify the LGN on T1- and T2-weighted images because of the smaller contrast-to-noise ratios between the LGN and the adjacent white matter tracts, compared with those of proton density-weighted images (P <.001). Bilateral thalamic activation and activation in the occipital cortex were shown in all participants. Each region of thalamic activation (23 +/- 3 mm2) was localized to the anatomically identified LGN. CONCLUSION: The excellent correspondence between the anatomically and functionally identified LGN confirms that MR imaging is an indispensable method for visualizing functional neuroanatomy in thalamic nuclei.

Adult↗
PubMed2001

Developmental morphology of blood and lymphatic capillary networks in mammalian hearts, with special reference to three-dimensional architecture.

The development of blood and lymphatic capillaries in the cardiac ventricles was studied using the rat and monkey hearts from later gestation to adulthood. For scanning electron microscopy, the tissue was treated with ultrasonication followed by HCl in order to remove epicardial mesothelial cell, subepicardial connective tissue and basement membrane. At the end of fetal life and neonate, the blood capillaries ran in parallel between the bundles consisting of several cardiac myocytes with small size. Endothelial extensions were found frequently. Numerous pericytes with short processes were observed on the capillary wall. Blood capillaries in the pubertal myocardium ran between cardiac myocytes to form a dense network. Processes of pericytes became elongated along the capillaries. In the adult, the capillaries showed occasionally Y-shaped branching and H-shaped anastomoses. The lymphatic capillaries were identified by large, variable sizes and absence of pericytes. In early postnatal rats, they appeared in the subepicardial region. In young and adult animals, the lymphatic capillary networks with relatively dense reticular meshes surrounded the bundles of several myocytes. It was noted that numerous nerve fibers were in close to the lymphatic capillary wall.

Aging↗
PubMed2001

[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction].

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.

Friedreich Ataxia↗
PubMed2001

[Gene therapy and neurotrophic factor treatment for amyotrophic lateral sclerosis].

Although excitotoxic and oxidative stress play important roles in spinal neuron death, the exact mechanisms are not fully understood. We examined cell damage of primary culture of 11-day-old rat spinal cord by addition of glutamate, nitric oxide (NO) or peroxynitrite (PN) with detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL). With addition of glutamate, NOC18 (a slow NO releaser) or PN, TUNEL positive nuclei were found in spinal large motor neurons from 24 h, and the positive cell proportion greatly increased at 48 h in contrast to the vehicle. The present results suggest that both excitotoxic and oxidative stress play important role in the apoptotic pathway in cultured rat spinal neurons. To examine a possible protective effect of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression in transgenic (Tg) mice carrying a Gly 93Ala (G93A) mutant SOD1 gene found in human familial ALS, a replication defective adenoviral vector containing GDNF gene was directly injected unilaterally into leg muscles. There were significantly more large motoneurons in GDNF-treated Tg mice than in untreated and Ad-Laz-treated group. The number of large motoneurons in GDNF-treated side of Tg mice were significantly more than that in untreated side. These observations demonstrate that GDNF gene therapy in a mouse model of FALS promotes the survival of motoneurons, suggesting that a similar approach might delay the progression of neurodegeneration of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Structure/function relationships in OxlT, the oxalate-formate transporter of oxalobacter formigenes. Assignment of transmembrane helix 11 to the translocation pathway.

OxlT, the oxalate:formate antiporter of Oxalobacter formigenes, has a lone charged residue, lysine 355 (Lys-355), at the center of transmembrane helix 11 (TM11). Because Lys-355 is the only charged residue in the hydrophobic sector, we tested the hypothesis that lysine 355 contributes to the binding site for the anionic substrate, oxalate. This idea was supported by mutational analysis, which showed that of five variants studied (Lys-355 --> Cys, Gly, Gln, Arg, or Thr), residual function was found for only the K355R derivative, in which catalytic efficiency had fallen 2,600-fold. Further insight came from a study of TM11 single-cysteine mutants, using the impermeant, thiol-specific reagents, carboxyethyl methanethiosulfonate and ethyltrimethylammonium methanethiosulfonate. Of the five reactive positions identified in TM11, four were at the cytoplasmic or periplasmic ends of TM11 (S344C and A345C, and G366C and A370C, respectively), whereas the fifth was at the center of the helix (S359C). Added study with carboxyethyl methanethiosulfonate and ethylsulfonate methylthiosulfonate showed that the attack on S359C could be blocked by the presence of the substrate, oxalate, and that protection could be predicted quantitatively by a kinetic model in which S359C is accessible only in the unliganded form of OxlT. Parallel study showed that the proteoliposomes used in such work contained OxlT of right side-out and inside-out orientations in about equal amounts. Accordingly, full inhibition of S359C by the impermeable methanethiosulfonate-linked probes must reflect an approach from both the cytosolic and periplasmic surfaces of the protein. This, coupled with the finding of substrate protection, leads us to conclude that S359C lies on the translocation pathway through OxlT. Since position 359 and 355 lie on the same helical face, we suggest that Lys-355 also lies on the translocation pathway, consistent with the idea that the essential nature of Lys-355 reflects its role in binding the anionic substrate, oxalate.

Bacterial Proteins↗
PubMed2000

Three-dimensional solution structure of oryzacystatin-I, a cysteine proteinase inhibitor of the rice, Oryza sativa L. japonica.

The three-dimensional structure of oryzacystatin-I, a cysteine proteinase inhibitor of the rice, Oryza sativa L. japonica, has been determined in solution at pH 6.8 and 25 degrees C by (1)H and (15)N NMR spectroscopy. The main body (Glu13-Asp97) of oryzacystatin-I is well-defined and consists of an alpha-helix and a five-stranded antiparallel beta-sheet, while the N- and C-terminal regions (Ser2-Val12 and Ala98-Ala102) are less defined. The helix-sheet architechture of oryzacystatin-I is stabilized by a hydrophobic cluster formed between the alpha-helix and the beta-sheet and is considerably similar to that of monellin, a sweet-tasting protein from an African berry, as well as those of the animal cystatins studied, e.g., chicken egg white cystatin and human stefins A and B (also referred to as human cystatins A and B). Detailed structural comparison indicates that oryzacystatin-I is more similar to chicken cystatin, which belongs to the type-2 animal cystatins, than to human stefins A and B, which belong to the type-1 animal cystatins, despite different loop length.

Amino Acid Sequence↗
PubMed2000

Full-length nucleotide sequence of a simian TT virus isolate obtained from a chimpanzee: evidence for a new TT virus-like species.

Recently, we identified TT virus (TTV) isolates from nonhuman primates and named them simian TTV (s-TTV). To characterize the genomic structure of these isolates in more detail, the full-length nucleotide sequence of the s-TTV isolate (designated s-TTV CH65-1), recovered from a chimpanzee born in West Africa, was amplified by nested PCR with inverted primers deduced from the untranslated region of s-TTV DNA. CH65-1 was composed of 3899 nucleotides (nt) and had two open reading frames (ORF) spanning 2295 nt (ORF1) and 402 nt (ORF2). The sequence had only 52.3% similarity to the prototype TA278 human isolate. Phylogenetic analysis demonstrated that CH65-1 was distinct from the human TTV isolates. These results suggested that s-TTV may represent a new TTV-like viral species or genus.

Animals↗
PubMed2000

Amyloid beta neurotoxicity not mediated by the mitogen-activated protein kinase cascade in cultured rat hippocampal and cortical neurons.

It has recently been reported that Alzheimer's disease amyloid beta protein (Abeta) activates the mitogen-activated protein kinase (MAPK) cascade in certain types of cells. In the present study, we investigated whether this signal transduction cascade is involved in Abeta neurotoxicity by using cultured rat hippocampal and cortical neurons. Exposure of the cells to Abeta (1-20microM) resulted in a progressive cell death with no change in phosphorylation of p44/42 MAPK (ERK1/2). Furthermore, Abeta-induced neuronal death was not at all affected by U0126 and PD98059, inhibitors of the MAPK-activating enzyme MEK. These results suggest that the MEK/ERK signal transduction cascade is not crucial for Abeta neurotoxicity.

Amyloid beta-Peptides↗
PubMed2000

Fluctuating monoplegia due to venous insufficiency by spinal arachnoiditis ossificans.

This is the first report of a patient with venous insufficiency following compressive arachnoiditis ossificans (AO). Symptoms of fluctuating monoplegia and sensory disturbance appeared monthly, lasting several weeks each time. Spinal magnetic resonance imaging (MRI) showed high T2-weighted signal intensity in the posterior portion of the column from T11 to T12 and an intradural lesion with low T2-weighted signal intensity. Neurological function and MRI improved markedly following an operation on AO. The symptoms seen in the present case were due to posterior venous insufficiency following compressive AO.

Aged↗
PubMed2000

High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan.

Autosomal dominant cerebeller ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders that differ in both the clinical manifestations and modes of inheritance. At present, eight different genes causing ADCAs have been found: spinocerebeller ataxia type 1 (SCA1), SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubropallidoluysian atrophy (DRPLA). The relative prevalence of each mutation varies according to race and native place. We studied 117 unrelated ADCA families that originated from the Tohoku District in the northernmost part of Honshu Island in Japan (mainly Miyagi Prefecture in the central part of Tohoku District). The SCA1 mutation was the most frequent among the known disorders (24.8% of all such families). The relative prevalence of SCA1 in the Tohoku District is very high compared with the values already reported from other regions in the world. Because the population of this area had seldom moved, the alleles with SCA1 mutations (including alleles with an intermediate CAG repeat number) are assumed to have been present in this area for a long time.

Ataxin-1↗
PubMed2000

HTLV-I-associated myelopathy manifested after renal transplantation.

We report a patient with HTLV-I-associated myelopathy (HAM), who developed symptoms of myelopathy 4 years after cadaveric renal transplantation. Since he was seronegative before the transplantation, it is suggested that HTLV-I infection was transmitted via renal graft transplantation. He has been treated with immunosuppressive agents such as cyclosporin A (CsA), mycophenolate mofetil (MMF), and prednisolone (PSL) to prevent graft rejection. This case suggested that these immunosuppressive agents are poorly effective in suppressing either the onset or progression of HAM/TSP.

Humans↗