Search PubMed⌕ Search

Biomedical subjects

Y Itoh

Publications and source records attributed to Y Itoh.

At least 199 records · Page 11Linked to original sources
PubMed1999

Five different genes, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region of mouse chromosome 11.

We characterized a region of the mouse genome disrupted by integration of a gene trap (GT) vector in ES cells. On 5' rapid amplification of cDNA ends analysis of the fusion transcripts containing the GT vector, we identified the eukaryotic protein synthesis initiation factor 4A1 gene (Eif4a1) as a promoter-trapped gene. Plasmid rescue was used to show that the other end of the integrated vector disrupted the murine homolog of the human fragile X mental retardation syndrome-related protein 2 gene (Fxr2h). Structural analysis of P1 clones, isolated from the wild-type mouse genome by PCR with Eif4a1-specific primers, indicated that the integration of the GT vector was accompanied by the deletion of about 35 kb of genomic DNA and that the disrupted region also included three genes, Cd68, Supl15h and Sox15, the latter two of which are transcribed in opposite directions with overlapping 3' ends. These five different genes at least, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region. The chromosomal location of this region was mapped by means of interspecific backcross panel DNAs to the central part of mouse chromosome 11, exhibiting a known region of synteny with human chromosome 17.

Animals↗
PubMed1999

Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family.

Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavage within the interglobular domain. Two major sites of cleavage have been identified in this region at Asn(341)-Phe(342) and Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a pivotal role in cartilage damage. We have identified and cloned a novel disintegrin metalloproteinase with thrombospondin motifs that possesses aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11 possesses a number of conserved domains that have been shown to play a role in integrin binding, cell-cell interactions, and extracellular matrix binding. We have expressed recombinant human ADAMTS11 in insect cells and shown that it cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and inhibitor profile being indistinguishable from that observed with native aggrecanase. A comparison of the structure and expression patterns of ADAMTS11, ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of the mechanisms of cartilage degradation and provide targets to search for effective inhibitors of cartilage depletion in arthritic disease.

ADAM Proteins↗
PubMed1999

An inherited prion disease with a PrP P105L mutation: clinicopathologic and PrP heterogeneity.

OBJECTIVE: To clarify a clinical and neuropathologic phenotype of an inherited prion disease associated with a missense mutation at codon 105 in the prion protein (PrP) gene that was originally described as a variant of Gerstmann-Sträussler-Scheinker disease demonstrating spastic paraparesis. METHODS: Two siblings from a Japanese family are described. PrP gene analyses, neuropathologic studies with immunohistochemistry, and Western blot analysis of the PrP were performed. RESULTS: Both patients showed a missense (proline-->leucine) mutation at codon 105 and a methionine/valine polymorphism at codon 129 of the PrP gene. Clinically, Patient 1 presented with progressive spastic paraparesis, ataxia, and dementia. Patient 2, the sister of Patient 1, showed prominent action myoclonus and dementia. Neuropathologically, multiple PrP-positive amyloid plaques and diffuse PrP deposition in the deep cortical layers were found in the cerebral cortex with primarily frontal dominant atrophy in both patients. Tau-positive pathologic structures including neurofibrillary tangles, neuropil threads, and dystrophic neurites around the plaques were abundant in the brain of Patient 2. In contrast, the tau pathology was scarce in Patient 1. Western blot analysis of the brain showed different patterns of detergent-insoluble PrP fragments between the patients. CONCLUSIONS: Despite the identical codon 105 mutation and codon 129 polymorphism of the PrP gene, remarkable clinical and neuropathologic differences, and PrP heterogeneity were present between the affected siblings. The phenotypic variability might be related to PrP heterogeneity.

Amino Acid Substitution↗
PubMed1999

Structure analysis of a class II transposon encoding the mercury resistance of the Gram-positive Bacterium bacillus megaterium MB1, a strain isolated from minamata bay, Japan.

A unique transposon was found in the chromosome of Bacillus megaterium MB1, a Gram-positive bacterium isolated from mercury-polluted sediments of Minamata Bay, Japan. The transposon region of a 14.5kb DNA fragment was amplified by PCR using a single PCR primer designed from the nucleotide sequence of an inverted repeat of class II transposons. The molecular analysis revealed that the PCR-amplified DNA fragment encodes a transposition module similar to that of Tn21. The transposon also encodes a broad-spectrum mercury resistance region having a restriction endonuclease map identical to that of Bacillus cereus RC607, a strain isolated from Boston Harbor, USA. The result of a phylogenetic analysis of the amino acid sequence of putative resolvase of the transposon showed that the transposon is phylogenetically closer to the transposons of Gram-positive bacteria than those of Gram-negative bacteria. Besides the transposition module and mer operon, the transposon encodes a mobile genetic element of bacterial group II introns between the resolvase gene and mer operon. The intron, however, does not intervene in any exon gene. The discovery of this newly found combination of the complex mobile elements may offer a clue to understanding the horizontal dissemination of broad-spectrum mercury resistance among microbes.

Bacillus megaterium↗
PubMed1999

Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.

We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.

ADAM Proteins↗
PubMed1999

Effects of an interleukin-1beta analogue [Lys-D-Pro-Thr], on incomplete cerebral ischemia-induced inhibition of long-term potentiation in rat hippocampal neurons in vivo.

Although interleukin-1beta (IL-1beta) has recently been implicated in neuronal cell death in vitro and in vivo after global forebrain ischemia, the role of IL-1beta in the functional injuries, i.e. impairment of synaptic transmission, after cerebral ischemia that does not cause neuronal death in the nervous system remains unknown. To address this question, we investigated the effect of short-term incomplete ischemia without apparent neural death on hippocampal long-term potentiation (LTP) in anesthetized rats, and examined the possible role of IL-1beta as an intermediary in this effect. Short-term incomplete cerebral ischemia (10 min) was induced in halothane-anesthetized rats by bilaterally clamping the common carotid arteries. Four days after ischemia, functional injuries in neuronal transmission in the hippocampal formation were observed without significant changes in pathological studies such as neuronal cell death. The LTP elicited in both Shaffer-CA1 synapses and perforant path-dentate gyrus synapses was significantly inhibited by the short-term incomplete ischemia. This inhibition of LTP was blocked by IL-1beta tripeptide antagonist (Lys-D-Pro-Thr), suggesting that the inhibitory effect of mild ischemia on synaptic potentials and LTP may be mediated by the generation of IL-1beta. These findings have important implications for the role of IL-1beta in not only neuronal cell death but also functional injuries without cell loss, perhaps elicited by transient cerebral ischemia.

Anesthesia↗
PubMed1999

Serial TCR engagement and down-modulation by peptide:MHC molecule ligands: relationship to the quality of individual TCR signaling events.

In the present study, we examined the relationships among quantitative aspects of TCR engagement as measured by receptor down-modulation, functional responses, and biochemical signaling events using both mouse and human T cell clones. For T cells from both species, ligands that are more potent in inducing functional responses promote TCR down-modulation more efficiently than weaker ligands. At low ligand density, the number of down-modulated TCR exceeds the number of available ligands by as much as 80-100:1 in the optimal human case, confirming the previous description of serial ligand engagement of TCR (Valitutti, et al. 1995. Nature 375:148-151). A previously unappreciated relationship involving TCR down-modulation, the pattern of proximal TCR signaling, and the extent of serial engagement was revealed by analyzing different ligands for the same TCR. Functionally, more potent ligands induce a higher proportion of fully tyrosine phosphorylated zeta-chains and a greater amount of phosphorylated ZAP-70 than less potent ligands, and the number of TCR down-modulated per available ligand is higher with ligands showing this full agonist-like pattern. The large number of receptors showing partial zeta phosphorylation following exposure to weak ligands indicates that the true extent of TCR engagement and signaling, and thus the amount of sequential engagement, is underestimated by measurement of TCR down-modulation alone, which depends on full receptor activation. These data provide new insight into T cell activation by revealing a clear relationship among intrinsic ligand quality, signal amplification by serial engagement, functional T cell responses, and observable TCR clearance from the cell surface.

Amino Acid Sequence↗
PubMed1999

Effects of experimental hypercapnia on hippocampal long-term potentiation in anesthetized rats.

The effects of hypercapnia, which has been reported to impair consciousness, on the long-term potentiation of the population spike in the CA1 pyramidal cell of the hippocampus in anesthetized rats were studied. Experimental hypercapnemia was induced by inspired 13% CO2 with 21% O2. Arterial blood gas analysis after 80 min inspired 13% CO2 showed pH 7.08+/-0.05, PCO2 = 104.09+/-12.86 mmHg, PO2 = 90.71+/-18.89 mmHg, BE -4.64+/-2.97 (mean +/- SD, n = 18). Inspired 13% CO2 reduced the amplitude of the population spike to 50% of the baseline. After delivery of tetanic stimulation (400 Hz, five bursts of eight pulses, inter-burst interval 1 s) population spike height was enhanced to pre-tetanic levels. Withdrawal of inspired CO2 unmasked an increase in population spike amplitude. These findings suggest that acute retention of carbon dioxide, which is designated as pure hypercapnemia without hypoxemia, may suppress hippocampal synaptic transmission but not its plasticity.

Anesthesia↗
PubMed1999

Involvement of the spinal posterior horn in Gerstmann-Sträussler-Scheinker disease (PrP P102L).

OBJECTIVE: The authors studied the pathomechanisms of the characteristics associated with Gerstmann-Sträussler-Scheinker disease (GSS). BACKGROUND: GSS, associated with a missense mutation at codon 102 of the prion protein (PrP) gene (GSS102), is a hereditary disorder that presents with progressive ataxia and dementia, and is characterized by the loss of deep tendon reflexes and painful dysesthesias of the legs in its early stage. METHODS: The authors conducted immunohistochemical studies of the spinal cord and peripheral nervous system in one of two patients from a Japanese family with GSS102 in comparison with patients with GSS105. RESULTS: The authors found intense PrP immunoreactivities mainly in the posterior horn of the spinal cord, but not in the dorsal root ganglia or peripheral nerves. In addition to PrP amyloid plaques, synaptic-type, fine granular PrP deposits were distributed in the spinal posterior horns. In contrast to the GSS102 patient, the spinal cords of the GSS105 patients showed no granular PrP deposits. CONCLUSIONS: The PrP abnormalities in synaptic structures of the spinal posterior horn may cause synaptic dysfunction that leads to loss of deep tendon reflexes and painful dysesthesias in patients with GSS102.

Adult↗
PubMed1999

Serum levels of Clara cell 10-kDa protein are decreased in patients with asthma.

Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (>/=10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.

Asthma↗
PubMed1999

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Vaginal nylon sling: loop length and surgical outcomes in those with urethral hypermobility and intrinsic sphincter deficiency.

Fifty-four women with stress incontinence underwent a vaginal nylon sling procedure. Of these, 15 were diagnosed as having type I, 27 as type II, and 12 as type III genuine stress incontinence. Follow-up averaged 25 months (range 6-42). The total suture length prior to ligation, which supports the bladder neck with no tension, varied from 200 to 313 mm and demonstrated weak correlation with body mass index (R2 = 0.076, P = 0.043) and body weight (R2 = 0.082, P = 0.036). The objective success rate was 89% (48 of 54 patients) 25 months later; the subjective rate was 93% (50 of 54 patients). Kaplan-Meier analysis demonstrated that the cumulative continence rate was 85.6% at 42 months for those with type I, 88.4% at 42 months for those with type II, and 91.7% at 40 months for those with type III incontinence (P>0.05). The main postoperative complication was retention or difficulty in urination. It was concluded that the total suture length cannot be determined in relation to patient's physical parameters, but rather on surgical experience, and that this operation is recommended to those with not only intrinsic sphincter deficiency but also with urethral hypermobility, provided surgery is executed with safe precautions.

Adult↗
PubMed1999

Phosphatidylcholine-specific phospholipase C, but not phospholipase D, is involved in pemphigus IgG-induced signal transduction.

The precise mechanism of the acantholysis after pemphigus IgGs bind to desmoglein (Dsg) 3 and/or Dsg 1 on the cell surface is as yet unknown. We have previously reported that pemphigus IgG (P-IgG) causes a transient increase in intracellular calcium and inositol 1,4,5-trisphosphate concentration, and subsequent activation of protein kinase C (PKC) in DJM-1 cells, a squamous cell carcinoma line. In order to see whether phosphatidylcholine (PC)-specific phospholipase C (PLC) or phospholipase D (PLD) is involved in the P-IgG-induced signaling process, the production of 1,2-diacylglycerol (DAG) and phosphatidylbutanol (PBut), a potential marker for the determination of PLD activity in the presence of butanol, was determined in DJM-1 cells. A biphasic accumulation of DAG, which consisted of a first transient phase and a second sustained phase, was observed. The second phase of DAG accumulation was profoundly inhibited by pretreatment with D609, a selective inhibitor of PC-PLC, but not by propranolol, an inhibitor of phosphatidate phosphohydrolase. Pemphigus serum after preadsortion of antibodies to Dsg 3 and Dsg 1 with recombinant Dsg 3 and Dsg 1 did not show formation of DAG. PBut was not generated following the addition of P-IgG. In addition, the levels of [3H]phosphocholine, a direct metabolite of PC-PLC, were elevated after the addition of P-IgG. These results suggest that the PC-PLC pathway plays a major role in P-IgG-induced transmembrane signaling by causing prolonged generation of DAG, which may lead to long-term activation of PKC.

Bridged-Ring Compounds↗
PubMed1999

Distribution of adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide, and AM mRNA in the rat gastric mucosa by immunocytochemistry and in situ hybridization.

Adrenomedullin (AM) is a novel vasorelaxant peptide isolated from pheochromocytoma. Proadrenomedullin N-terminal 20 peptide (PAMP) is a hypotensive peptide generated by posttranslational enzymatic processing of a 185-amino acid pro-AM molecule, the same precursor as AM. In this study, we investigated localizations of these peptides by immunocytochemistry and AM mRNA by non-radioisotopic in situ hybridization followed by the streptavidin and biotin complex (ABC) method and catalyzed signal amplification (CSA) in the rat adrenal medulla and gastric mucosa. In the gastric mucosa, both AM- and PAMP-like immunoreactivities were found in the neuroendocrine cells, but PAMP-positive cells were more abundant than AM-positive ones. By immunoelectron microscopy, AM and PAMP were localized exclusively in the secretory granules. The distribution pattern of AM mRNA-positive cells, only a limited portion of which had AM and/or PAMP, was also similar to that of the two peptides. But AM mRNA was detected also in a few epithelial cells as well as neuroendocrine cells. The two peptides might play an important role in the control of local circulation in the rat stomach.

Adrenomedullin↗
PubMed1999

Relationship between mechanomyogram and force during voluntary contractions reinvestigated using spectral decomposition.

A mechanomyogram (MMG) is considered to represent the pressure waves resulting from the lateral expansion of contracting muscle fibers. However, the actual MMG recording appears not only to reflect lateral changes of active fibers, but also to include the effect of their longitudinal shortening, because the fiber orientation, particularly in pennate muscles, is not parallel with the MMG transducer attached at the skin surface. In the present investigation, a spectral decomposition method was developed to eliminate the interference due to fiber longitudinal movement from the MMG recording. The MMG was recorded over the belly of the rectus femoris muscle, which is a pennate muscle. Vibration over the tibial tuberosity (VTT) was used as a measure of the integrated longitudinal movement of the muscle fibers. The lateral and longitudinal components included in the MMG were separated by a spectral decomposition method that is based on the coherence function of the MMG and VTT. The MMG/force relationship was compared between the original and decomposed MMG. One-third of the 12 subjects demonstrated a curvilinear relationship between the original MMG and force throughout the range of force. In the other two-thirds, the MMG saturated or reduced beyond 70% of the maximum voluntary contraction (MVC). After decomposition, the MMG increased progressively with force up to 70% MVC, beyond which it decreased in all subjects. The spectral decomposition method described here is considered to be a useful tool with which to examine in more detail the MMG/force relationship of different pennate muscles.

Adult↗
PubMed1999

Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis with alcoholic liver cirrhosis.

Budd-Chiari syndrome is a rare disease, but there are many known causes. Recent studies showed that it can be an acquired lesion resulting from thrombosis in some elderly patients. We report a 74-year-old man with Budd-Chiari syndrome attributed to chronic deep venous thrombosis and alcoholic liver cirrhosis. When he was aged 45 years, stasis ulcers of the lower extremities appeared. Cerebral infarction and left hemiparesis occurred at age 71. Ultrasonography, venacavography, and three-dimensional-magnetic resonance imaging on admission demonstrated total obstruction of the inferior vena cava with several massive thrombi and developed collateral vessels. Although the etiology of the thrombosis remained obscure, we made some speculative assumptions that chronic disseminated intravascular coagulation (which is frequently observed in cirrhosis) or hereditary coagulopathy could be involved, from his familial history of thrombotic phenomena and a severe deficiency of clotting inhibitors. Despite the high mortality of untreated Budd-Chiari syndrome reported in previous studies, this patient had been alive for about 30 years from the suspected onset.

Adult↗
PubMed1999

Preheparin serum lipoprotein lipase mass level: the effects of age, gender, and types of hyperlipidemias.

To clarify the factors regulating preheparin serum lipoprotein lipase mass (preheparin LPL mass), the correlations between preheparin LPL mass and age, gender and types of hyperlipidemias were investigated in 377 persons who underwent annual health examinations. Preheparin LPL mass level did not significantly differ in individuals from 19 to 70 years old, for both men and women. Preheparin LPL mass level correlated negatively with triglyceride (TG), positively with high density lipoprotein-cholesterol (HDL-C), and not at all with total cholesterol (TC) or low density lipoprotein-cholesterol (LDL-C). Preheparin LPL mass levels were apparently higher in women than in men, but when serum lipid levels were adjusted, preheparin LPL mass levels were identical. In type IV and IIb hyperlipidemia, preheparin LPL mass levels were lower than in type IIa patients and in normals. Remnant positive individuals had lower levels of preheparin LPL mass than the negative individuals. In conclusion, preheparin LPL mass levels were not affected by aging and gender, but were lower in the conditions in which TG catabolism was disturbed, indicating that preheparin LPL mass might reflect somewhat the amount of LPL working in the body.

Adult↗