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Biomedical subjects

H Kondo

Publications and source records attributed to H Kondo.

At least 217 records · Page 12Linked to original sources
PubMed1999

Novel related cDNAs (C184L, C184M, and C184S) from developing mouse brain encoding two apparently unrelated proteins.

Three related cDNAs (C184L, C184M, and C184S) were isolated from a developing mouse brain cDNA library. C184S is the 5'-end portion and C184M is the 3'-end portion, respectively, of C184L. C184S and C184M have open reading frames of 199 amino acids (ORF1) and 189 amino acids (ORF2), respectively; C184L has both ORF1 and ORF2 (dicistronic structure), but seems to translate only ORF1. Southern blot analysis suggests that all of the three related mRNAs are transcribed from the same single gene. The intervening region of C184L cDNA between ORF1 and ORF2 contained a promoter sequence for C184M mRNA, which is transcribed from the corresponding genomic sequence. Very recently, a cDNA encoding human homologue of ORF1 (human autoantigen p27) and a cDNA encoding a different mouse isoform of ORF2 (mammary tumor virus receptor) were reported. Our results indicate that the mRNAs encoding these apparently unrelated proteins are transcribed within an adjacent or overlapping area on the genome, suggesting the same origin of the two transcription units.

Aging↗
PubMed1999

Crystal structure of anti-Hen egg white lysozyme antibody (HyHEL-10) Fv-antigen complex. Local structural changes in the protein antigen and water-mediated interactions of Fv-antigen and light chain-heavy chain interfaces.

In order to address the recognition mechanism of the fragments of antibody variable regions, termed Fv, toward their target antigen, an x-ray crystal structure of an anti-hen egg white lysozyme antibody (HyHEL-10) Fv fragment complexed with its cognate antigen, hen egg white lysozyme (HEL), was solved at 2.3 A. The overall structure of the complex is similar to that reported in a previous article dealing with the Fab fragment-HEL complex (PDB ID code,). However, the areas of Fv covered by HEL upon complex formation increased by about 100 A(2) in comparison with the Fab-HEL complex, and two local structural differences were observed in the heavy chain of the variable region (VH). In addition, small but significant local structural changes were observed in the antigen, HEL. The x-ray data permitted the identification of two water molecules between the VH and HEL and six water molecules retained in the interface between the antigen and the light chain complementarity determining regions (CDRs) 2 and 3 (CDR-L2 and CDR-L3). These water molecules bridge the antigen-antibody interface through hydrogen bond formation in the VL-HEL interface. Eleven water molecules were found to complete the imperfect VH-VL interface, suggesting that solvent molecules mediate the stabilization of interaction between variable regions. These results suggest that the unfavorable effect of deletion of constant regions on the antigen-antibody interaction is compensated by an increase in favorable interactions, including structural changes in the antigen-antibody interface and solvent-mediated hydrogen bond formation upon complex formation, which may lead to a minimum decreased affinity of the antibody Fv fragment toward its antigen.

Amino Acid Sequence↗
PubMed1999

Involvement of PITPnm, a mammalian homologue of Drosophila rdgB, in phosphoinositide synthesis on Golgi membranes.

Phosphatidylinositol transfer protein (PITP) is involved in phospholipase C-mediated signaling and membrane trafficking. We previously reported cloning and characterization of a gene encoding for membrane-bound PITP, named PITPnm, that is a mammalian homologue of the Drosophila retinal degeneration B (rdgB) gene (Aikawa, Y., Hara, H., and Watanabe, T. (1997) Biochem. Biophys. Res. Commun. 236, 559-564). Here we report the subcellular localization of PITPnm protein and provide evidence for its involvement in phosphatidylinositol 4-phosphate (PtdIns 4-P) synthesis. PITPnm is an integral membrane protein that largely localized in close association with membranes of Golgi vacuoles and the endoplasmic reticulum (ER). The amino terminus region of PITPnm was exposed to cytoplasmic side. Interaction with various phosphoinositides was observed in the amino terminus region spanning from 196 amino acids to 257 amino acids of PITPnm. At the amino terminus regions of 1-372 amino acids, PITPnm formed a complex with type III PtdIns 4-kinase. The transmembrane and carboxyl-terminal portions (residues 418-1242) functioned to retain the PITPnm in the Golgi vacuole. These results suggest that PITPnm plays a role in phosphoinositide synthesis on the Golgi vacuoles and possibly in the PtdIns signaling pathway in mammalian cells.

1-Phosphatidylinositol 4-Kinase↗
PubMed1999

Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506.

6-N-Amino analogues of NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione] (3b) were synthesized and tested with respect to topoisomerase inhibition, cytotoxicity and anticancer effects. Among them, a 1,3-dihydroxypropane analogue (J-109,404, 5t) showed more than ten times more potent anticancer activity in MKN-45 human stomach cancer cells implanted in mice than NB-506.

Animals↗
PubMed1999

Re-evaluation of sexual dimorphism in human corpus callosum.

To study the sexual dimorphism of human corpus cauosum (CC), we analyzed the midsaggital magnetic resonance imaging (MRI) morphometry in 67 adults aged (mean+/-s.d.) 36.82+/-9.35 years. Four specific angles of the CC were determined. All four angles in 34 females and 33 age-matched males showed a significant difference between females and males. These morphometric findings confirm a gender difference in the orientation of corpus callosum.

Adult↗
PubMed1999

Immunohistochemical localization of amyloid beta-protein with amino-terminal aspartate in the cerebral cortex of patients with Alzheimer's disease.

We investigated immunohistochemically the localization of amyloid beta-protein (Abeta) with amino-terminal aspartate (N1[D]) in brains of patients with Alzheimer's disease, diffuse Lewy body disease and Down's syndrome. A monoclonal antibody, 4G8, which recognizes the middle portion of Abeta, was used as a reference antibody to label the total Abeta deposits. Double staining with anti-Abeta(N1[D]) and 4G8 revealed that Abeta deposits in the subiculum and the neocortical deep layers often lacked N1[D] immunoreactivity, indicating N-terminal truncation of Abeta in these deposits. Abeta deposits in the neocortical superficial layers and the presubicular parvopyramidal layer always contained Abeta with N1[D]. Such regional as well as laminar differences in the distribution of Abeta beginning at N1[D] suggest that some local factors influence N-terminal processing of Abeta deposited in the brain.

Aged↗
PubMed1999

Localization of mRNA for Dri 42, subtype 2b of phosphatidic acid phosphatase, in the rat brain during development.

The expression of a gene termed Dri 42, a differentiation-related gene originally identified from intestine and a gene encoding phosphatidic acid phosphatase 2b isoform, was localized in developing and matured rat brains by in situ hybridization histochemical analysis. The gene expression was dominant in the ventricular germinal zone without significant expression in the intermediate, mantle and marginal zones throughout embryonic brain and spinal cord. The dominant expression in the ventricular germinal zone was maintained at P0 and P7, but it markedly decreased at later postnatal stages, while persistently high expression was detected in Bergmann glial cells of the cerebellar Purkinje cell layer throughout the postnatal development.

Animals↗
PubMed1999

Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer's disease.

Diffuse amyloid beta-protein (Abeta) deposits with numerous glial cells containing C-terminal Abeta fragments occur in the cerebral cortex of patients with Alzheimer's disease. By using a panel of antibodies specific for various epitopes in the Abeta peptide, we have investigated the immunohistochemical nature of the diffuse Abeta deposits. The extracellular material contains Abeta with a C-terminus at residue valine40 (Abeta40) as well as residues alanine42/threonine43 (Abeta42). The N-termini include aspartate1, pyroglutamate3, and pyroglutamate11, with pyroglutamate3 being dominant. Microglia and astrocytes in and around these deposits contain intensely staining granules. Most of these granules are negative for antibodies to the N-terminally located sequences of Abeta. These include 6E10 (Abeta1-17), 6F/3D (Abeta8-17), and the N-terminal antibodies specific to aspartate1, pyroglutamate3, and pyroglutamate11. The C-termini of intraglial Abeta are comparable with those of the extracellular deposits. The microglia and astrocytes have quiescent morphology compared with those associated with senile plaques and other lesions such as ischemia. Complement activation in these deposits is not prominent and often below the sensitivity of immunohistochemical detection. Although factors which may cause this type of deposit remain unclear, lack of strong tissue responses suggests that these deposits are a very early stage of Abeta deposition. They were found only inconsistently and were absent in a number of cases examined in this study. Further analysis of these deposits might provide important clues regarding the accumulation and clearance of Abeta in Alzheimer's disease brain.

Aged↗
PubMed1999

Localization of mRNAs for synaptojanin isoforms in the brain of developing and mature rats.

The localization of mRNAs for synaptojanin 1 and 2, inositol 5-phosphatases, in the brain was examined by in situ hybridization histochemistry. Synaptojanin 1 mRNA was detected in almost all neurons of the central nervous system throughout developing and mature stages, although its splicing variant (synaptojanin 1-p145-I) mRNA was expressed dominantly in forebrain and cerebellar cortex. Synaptojanin 2 mRNA was first detected in neurons of the olfactory bulb, the cerebral cortex, the hippocampus, and the cerebellar cortex on early postnatal days. As the postnatal development proceeded, the expression signal was evident in the white matters, presumptive oligodendrocytes, with the clear expression remaining in neurons of the olfactory tubercle, hippocampal pyramidal cells and cerebellar Purkinje cells.

Animals↗
PubMed1999

Sporadic amyotrophic lateral sclerosis of long duration mimicking spinal progressive muscular atrophy: a clinicopathological study.

We report an autopsy case of amyotrophic lateral sclerosis (ALS) clinically diagnosed as spinal progressive muscular atrophy (SPMA). The patient was a Japanese woman without hereditary burden. She developed muscle weakness of the distal part of the left lower extremity at age 42, followed by muscle weakness and atrophy of the right lower extremity and upper extremities. At age 57, she needed transient ventilatory support. Slight weakness in the facial muscles and fasciculation of the tongue appeared at age 60. At age 61, she died of sudden respiratory arrest. During the clinical course, neurological examination revealed neither Babinski signs nor hyperreflexia. The neuropathological examination revealed not only neuronal loss with gliosis in the facial nucleus, hypoglossal nucleus, and anterior horns of the spinal cord, but also loss of Betz cells and degeneration of the pyramidal tracts. Based on these clinicopathological findings and review of literature, we conclude that sporadic ALS mimicking SPMA is present.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Argyrophilic glial inclusions in the midbrain of patients with Parkinson's disease and diffuse Lewy body disease are immunopositive for NACP/alpha-synuclein.

Argyrophilic glial inclusions occur in the midbrain of patients with Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). These inclusions are immunohistochemically positive for NACP/alpha-synuclein but negative for tau protein. The results of the present study suggest that a primary degenerative process involves NACP/alpha-synuclein in PD and DLBD and that the process takes place not only in neurons but also in glial cells. Argyrophilic cytoplasmic inclusions, both glial and neuronal, in a variety of degenerative diseases may be grouped into two major categories; one related to aggregates of abnormally phosphorylated tau protein and the other to unusual accumulations of NACP/alpha-synuclein.

Aged↗
PubMed1999

No prognostic significance of p53 expression in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: It is generally accepted that the overexpression of p53 protein is associated with poor prognosis in breast, colorectal, and other types of cancer. However, the prognostic significance of p53 aberrations in esophageal squamous cell carcinoma has yet to be determined. We attempted to analyze the relationship between p53 expression and the clinicopathologic features of esophageal squamous cell carcinoma by reviewing the medical records of a large patient population. Our study of esophageal squamous cell carcinoma involves the largest patient population to date. METHODS: p53 expression in formalin-fixed, paraffin-embedded samples of 239 patients with primary esophageal squamous cell carcinoma (TNM stage I:79 cases, stage II: 82 cases, stage III: 78 cases), who underwent esophageal resection without additional treatment, were analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. The relationships between p53 immunoreactivity and prognostic factors were determined by the chi(2) test, and the prognostic impact of p53 protein expression was analyzed by univariate and multivariate survival analyses. RESULTS: In 115 (48.1%) of 239 esophageal tumors, nuclear immunoreactivity for the p53 protein was detected. The expression of the p53 protein did not correlate with sex, age, histological grading, lymph node metastasis, vascular invasion, or TNM stage. Similarly, p53 expression did not correlate with prognosis in univariate and multivariate survival analysis. CONCLUSIONS: The expression of the p53 gene product had no impact on the prognosis of esophageal squamous cell carcinoma.

Adult↗
PubMed1999

Novel synthetic meshwork for glaucoma treatment. I. Design and preliminary in vitro and in vivo evaluation of various expanded poly(tetrafluoroethylene) materials.

A novel drainage implant for glaucoma filtering surgery (MESH) is proposed. After various expanded poly(tetrafluoroethylene) (e-PFTE) materials were evaluated, the feasibility and the short-term safety of the technique were assessed in this first pilot study in the rabbit. The porous structure and the in vitro resistance to aqueous flow of seven different e-PTFE membranes (5-80 microm average pore size) were compared. Eight Dutch pigmented rabbits were implanted with the T-shaped MESH implants made from either 20- or 50-microm average pore size e-PTFE membranes. Clinical examination, intraocular pressure (IOP) measurements, and histology analyses were performed over a period of 3 months. The contralateral nonoperated eyes served as controls. MESH implantation took less than 7 min. No postoperative hypotony, migration, or extrusion of the implant and no intraocular inflammation or infection occurred. A significant IOP reduction in the implanted eyes was obtained past postoperative day 21 with the 20-microm material implant. The drainage efficacy was correlated with the degree of colonization of the porous materials and the inner spacing of the implant as observed by histology. With a filtering patency 3 times longer than conventional trabeculectomy and laser sclerectomy, MESH surgery is a promising technique for glaucoma treatment. Further studies are underway to enhance the device efficacy and understand the mechanism of filtration.

Animals↗