[Throat discomfort developing immediately after left ventriculography].
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Cineangiography↗
Biomedical subjects
S Ikeda
Publications and source records attributed to S Ikeda.
[A family of SCA1 with pigmentary macular dystrophy].
Pigmentary macular dystrophy (PMD) was detected in a 57-year-old Japanese man with SCA1, five years after the onset of ataxia. Family history revealed 7 other ataxic members in three generations. Among them, only his younger brother, who had already died, had developed central scotoma with normal peripheral fields, 15 years after the ataxia had appeared. None of the other family members, with or without ataxia, had visual disturbances. The numbers of CAG repeats in the patient's SCA1 gene were 27 and 47, the latter of which was within pathological range and belonged to mild to moderate CAG expansion in previously reported cases. The PMD seen in our patient could be one of the clinical features associated with SCA1, since patients with SCA1 often show various ocular changes. Although genetic analysis ruled out SCA7 in this patient, the phenotypic resemblance of this patient to SCA7 may reflect the necessity in the future, for genetic differentiation between SCA1 and SCA7 in patients with autosomal dominant cerebellar ataxia and PMD.
Adult↗
Cell-specific expression of tubby gene family members (tub, Tulp1,2, and 3) in the retina.
PURPOSE: The family of tubby-like proteins (TULPs), consisting of four family members, are all expressed in-the retina at varying levels. Mutations within two members, tub and TULP1, are known to lead to retinal degeneration in mouse and humans, respectively, suggesting the functional importance of this family of proteins in the retina. Despite a high degree of conservation in the carboxy-terminal region (e.g., putative functional domain of the genes) among family members, they are unable to compensate for one another. The purpose of this study was to provide a rationale for this lack of compensation by investigating the spatial distribution of tubby gene family members in the retina and to investigate the mechanism of photoreceptor cell death in tubby mice. METHODS: In situ hybridization using riboprobes specific for each tubby gene family member and immunohistochemistry for TUB and TULP1 were performed to determine their expression patterns in the retina of tubby and wild-type control mice. The terminal dUTP nick-end labeling (TUNEL) assay was performed to detect apoptotic cells in the retina of tubby and wild-type control mice. RESULTS: tub mRNA was found to be expressed throughout the retina, with highest expression in the ganglion cell layer (GCL) and photoreceptor cells. In contrast, Tulp1 expression was observed only in photoreceptor cells and Tulp3 mRNA was expressed at a moderate level only in the inner nuclear layer (INL) and GCL. The results of the immunohistochemical analysis paralleled those observed in the in situ studies. TUB immunoreactivity was most highly concentrated in the GCL, in the inner and outermost regions of the INL, in the outer plexiform layer (OPL), and in the inner segments of photoreceptor cells. Similarly, TULP1 immunoreactivity was observed in the OPL and inner segments of the photoreceptor cells. No differences in expression at the mRNA or protein level were observed for any of the molecules tested in tubby or wild-type mice. TUNEL-positive cells were detected in the ONL of tubby mice, whereas very few were seen in the same layer of age-matched control mice. CONCLUSIONS: Although all tubby gene family members are expressed in the retina, they each have different cell-specific expression patterns, which may account in part for their inability to compensate for the loss of one family member. The photoreceptor cell death in tubby mice occurs through an apoptotic mechanism, which is known to be the common final outcome of other forms of retinal degeneration.
Adaptor Proteins, Signal Transducing↗
[Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage].
From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.
Carcinoma, Non-Small-Cell Lung↗
Structure-activity relationship of hydroxamate-based inhibitors on membrane-bound Fas ligand and TNF-alpha processing.
Both Fas ligand (FasL) and tumor necrosis factor-alpha (TNF-alpha) are type II integral membrane proteins. Recently, we have reported that FasL is processed to a soluble form by an unknown metalloproteinase at the cell surface and some hydroxamate matrix metalloproteinase (MMP) inhibitors inhibit the processing similar to the case observed with TNF-1alpha. We studied the inhibitory effects of various hydroxamate MMP inhibitors on FasL and TNF-alpha processing in order to characterize the processing enzymes using human FasL cDNA transfectants and LPS-stimulated THP-1 cells. It turned out that (1) the P1' group of hydroxamates was very important for the selective inhibitory activity toward TNF-alpha and FasL processing, (2) P1' 3-phenylpropyl group was favorable for the inhibition of FasL processing, and (3) P1' isobutyl and isopropyl groups were favorable for that of TNF-alpha processing. These differences in sensitivity to inhibitors imply that (1) membrane-bound FasL and TNF-alpha might be processed by distinct metalloproteinases, (2) the S1' site of FasL processing enzyme differs from that of MMP-1 and MMP-9, but appears to be similar to that of MMP-3, and (3) the S1' site of TNF-alpha processing enzyme is smaller than that of FasL processing enzyme. These results would be helpful in designing a more selective inhibitor.
Humans↗
[A case of neurofibromatosis with intrathoracic meningocele presenting respiratory failure caused by pleural effusion].
We reported a 58-year-old man with neurofibromatosis and an intrathoracic meningocele. He was admitted to our hospital because of left-sided chest pain and dyspnea on exertion. He presented with severe kyphoscoliosis and showed a round, well circumscribed mass lesion in the paravertebral region of the left upper lung on a chest roentgenogram. Just before admission, pleural effusion accumulated in the left thoracic cavity, which had caused the respiratory symptoms. The mass was diagnosed as an intrathoracic meningocele by MRI and iotrolan CT myelography. The pleural effusion was transudate fluid and no leakage from the meningocele to pleural cavity was demonstrated. Posterolateral extradural approach with laminectomy was done and dural plasty to close the connection between the meningocele and the subarachnoidal space was carried out. After the operation, both the intrathoracic meningocele and the pleural effusion disappeared with remarkable improvement in the respiratory function. Intrathoracic meningocele is known to be seen in association with neurofibromatosis and scoliosis, but it is very rare to see an intrathoracic meningocele which causes respiratory failure due to massive pleural effusion like this report.
Humans↗
Ratio of bacteria to polymorphonuclear neutrophils (PMNs) determines PMN fate.
This study was designed to investigate how live Escherichia coli influence the fate of polymorphonuclear neutrophils (PMNs) in vitro. PMNs from 10 healthy volunteers were cocultured with or without live E. coli at different ratios. Heat-killed E. coli (Hk) were also added to PMNs at a ratio of 1:10. The PMNs were then analyzed by flow cytometry for cell death, reactive oxygen intermediates (ROI) production, and CD16 expression. Morphologic features were also assessed. PMN apoptosis was confirmed by DNA gel electrophoresis. Low doses of E. coli (PMN:E. coli ratios of 1:0.01 and 1:0.1) inhibited PMN apoptosis. In contrast, a high dose of E. coli (PMN:E. coli ratio of 1:10) increased PMN necrosis. ROI production was significantly greater at PMN:E. coli ratios of 1:10 and 1:10 (Hk) than at ratios of 1:0.01 and 1:0.1, or in PMNs cultured alone after a 15 or 30 minute coculture. CD16 expressions were significantly lower in PMNs cocultured with E. coli than in those cultured alone after a 4 or 12-h coculture. Tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 levels in cell-free supernatants were also measured. The mean percentages of apoptosis at PMN:E. coli ratios of 1:0.01 and 1:10 (Hk), and in PMNs cultured alone after a 12-h coculture showed significant inverse correlations with these cytokine levels in cell-free supernatants at 12 h. Our results demonstrate that low doses of live E. coli inhibits predominantly PMN apoptosis, whereas a high dose of E. coli increases necrosis. Augmented PMN bactericidal function, via inhibition of PMN cell death, may be beneficial for host defense against bacterial infection and/or sepsis.
Apoptosis↗
[Extra-intestinal complications of ulcerative colitis: arteriovenous thrombosis/embolism].
Thromboembolic episode is a well known extraintestinal complications of ulcerative colitis, but it is a rare complication in clinically. In the literature there are some interesting observations concerning the factors, may play a major role both in the pathogenesis and in the hypercoagulability in ulcerative colitis. However the exact mechanism of hypercoagulability in patients with ulcerative colitis is still unknown. We reviewed the incidence, the activity and severity of the basic disease, the pathogenesis, the treatment, the prognosis of thromboembolic phenomena in patients with ulcerative colitis.
Anticoagulants↗
Hypertrophic cardiomyopathy with mid-ventricular obstruction and splenic infarction associated with paroxysmal atrial fibrillation: a case report.
A 54-year-old woman had been treated for hypertrophic cardiomyopathy and paroxysmal atrial fibrillation since 1992. She was admitted with paroxysmal atrial fibrillation which was resolved by medical treatment. However, on the next day, left lateral chest pain appeared. Computed tomography disclosed a low density area in the spleen. She received anticoagulant therapy under a diagnosis of splenic infarction, and the pain disappeared. Echocardiography showed hypertrophic cardiomyopathy with mid-ventricular obstruction. She was treated with cibenzoline to prevent paroxysmal atrial fibrillation attack and attenuate the hemodynamic load. After treatment, the pressure gradient decreased from 41 to 7 mmHg. This patient with hypertrophic cardiomyopathy suffered a rare isolated splenic infarction associated with paroxysmal atrial fibrillation.
Anti-Arrhythmia Agents↗
[Ultrasonogram of carotid artery in endoarterectomy patients].
Ultrasonograms of the carotid artery were compared with the intraoperative finding of atheroma plaque in terms of stenosis, fragility, ulceration and calcification. Soft type, intermediate type and these mixed type plaques were fragile plaques in almost all cases. All hard type plaques were tough plaques. The detection of stenosis and calcification was satisfactory, however that of ulceration was not sufficient. The stenotic lesions frequently existed in bilateral carotid arteries and the intima was easy to become thick even after the endoarterectomy. The ultrasonogram was thought to be the essential study for the carotid artery lesions.
Aged↗
[A peculiar MRI findings in a case with slowly progressive cerebral ischemia caused by internal carotid artery stenosis possibly due to fibromuscular dysplasia].
A 47-year-old man developed progressive muscular weakness in the left arm. MR images revealed low intensity signal lesions with ring enhancement by Gd-DTPA in right fronto-parietal lobes. At that time cerebral angiography was not performed because he refused. A tuberculin skin test showed strongly positive reaction and then administration of anti-tuberculous drugs was started. His symptom had remained stable for one year, but left facial palsy and dysarthria added about two years later. MR images revealed expansion of the lesions in right parietal lobe, adding cortical high intensity signal lesions with Gd-DTPA enhancement on T1-weighted images. Angiography disclosed tubular stenosis of right internal carotid artery at the portion of cervical to petrous segment and the local stenosis at right renal artery. These lesions were considered to be caused by fibromuscular dysplasia, but not atherosclerosis, because we could not find any atherosclerotic lesions in other arteries including right carotid bifurcation. His manifesting symptoms were ascribed to slowly progressive cerebral ischemia. And peculiar MRI findings in his early stage resembled those of inflammatory granulomatous diseases.
Arterial Occlusive Diseases↗
Biologically selective potassium channel openers having 1,1-diethylpropyl group.
To find out selective potassium channel openers (PCOs), we synthesized several 3,5-disubstituted phenylcyanoguanidine derivatives and investigated their structure-activity relationships (SAR). As a result, we discovered selective PCOs having 1,1-diethylpropyl group toward antihypertensive activity.
Animals↗
Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes.
Genomic cloning and sequencing of a human homologue (the gene name, endonuclease III-like 1; gene symbol, NTHL1 or NTH1) for Escherichia coli endonuclease III, that is involved in pyrimidine base excision repair, were performed. The sequence covered the entire NTHL1 gene consisting of six exons and five introns spanning 8kb with 5' flanking (8kb) and 3' flanking (3.8kb) regions. Southern blot analysis suggested that the NTHL1 gene exists as a single copy in a haploid genome. The sequenced 5' flanking region lacks typical TATA and CAAT boxes, but contains a CpG island having putative binding sites for several transcription factors such as Ets1 and Sp1. The NTHL1 gene lies immediately adjacent to the tuberous sclerosis 2 (TSC2) gene on chromosome 16p13.3 in a 5'-to-5' orientation. Transcription initiation sites of both NTHL1 and TSC2 genes were suggested to be multiple by 5' RACE experiments. The northern hybridization experiment suggested that both genes are expressed in all tissues, but at different levels. Downstream of the NTHL1 gene, the gene for the regulatory factor 2 (SLC9A3R2/E3KARP; also called OCTS2, TKA-1 and SIP-1) of the solute carrier family 9 (sodium/hydrogen exchanger), isoform A3, lies in a 3'-to-3' orientation. This paper demonstrates for the first time the spatial relationship of these three genes (TSC2, NTHL1 and SLC9A3R2) at the nucleotide level, and the presence of multiple transcription initiation sites of the NTHL1 and TSC2 genes.
Base Sequence↗
Selective suppression of stress-activated protein kinase pathway by protein phosphatase 2C in mammalian cells.
Protein phosphatase 2Calpha (PP2Calpha) or PP2Cbeta-1 expressed in COS7 cells suppressed anisomycin- and NaCl-enhanced phosphorylations of p38 co-expressed in the cells. PP2Calpha or PP2Cbeta-1 expression also suppressed both basal and stress-enhanced phosphorylations of MKK3b and MKK6b, which are upstream protein kinases of p38, and of MKK4, which is one of the major upstream protein kinases of JNK. Basal activity of MKK7, another upstream protein kinase of JNK, was also suppressed by PP2Calpha or PP2Cbeta-1 expression. However, basal as well as serum-activated phosphorylation of MKK1alpha, an upstream protein kinase of ERKs, was not affected by PP2Cbeta or PP2Cbeta-1. A catalytically inactive mutant of PP2Cbeta-1 further enhanced the NaCl-stimulated phosphorylations of MMK3b, MKK4 and MKK6b, suggesting that this mutant PP2Cbeta-1 works as a dominant negative form. These results suggest that PP2C selectively inhibits the SAPK pathways through suppression of MKK3b, MKK4, MKK6b and MKK7 activities in mammalian cells.
Animals↗
Isoform-specific phosphorylation of fission yeast type 2C protein phosphatase.
Protein phosphatase 2C (PP2C) is one of the four major protein serine/threonine phosphatases of eukaryotes and is implicated in the regulation of various cellular functions. With the goal of elucidating the mechanism responsible for regulating PP2C functions, we investigated the significance of phosphorylation of fission yeast Ptc1, Ptc2, and Ptc3, the yeast orthologs of mammalian PP2C. Both Ptc2 and Ptc3 but not Ptc1 were phosphorylated stoichiometrically by casein kinase II on serine residues at their carboxy-terminal regions. Mutational analysis of Ptc2 and Ptc3 revealed that serine residues of the conserved sequence (Ser-X-Ser-X-X-Glu/Asp) of these proteins were the phosphorylation sites. Interestingly, the activities of Ptc2 and Ptc3 were decreased 25 +/- 7.5% and increased 55 +/- 3.7%, respectively, by phosphorylation. In addition, the same site(s) of Ptc2 was phosphorylated when the protein was expressed in fission yeast cells. These results suggest that phosphorylation of PP2C plays important physiological roles in fission yeast cells.
Amino Acid Sequence↗
Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III.
Endonuclease III (endoIII; nth gene product) of Escherichia coli is known to be a DNA repair enzyme having a relatively broad specificity for damaged pyrimidine bases of DNA. Here, we describe the cloning and characterization of the cDNA and the gene for a mouse homologue (mNthl1/mNth1) of endoIII. The cDNA was cloned from a mouse T-cell cDNA library with a probe prepared by PCR using the library and specific PCR primers synthesized based on the reported information of partial amino acid sequences of bovine NTHL1/NTH1 and of EST Data Bases. The cDNA is 1025 nucleotides long and encodes a protein consisting of 300 amino acids with a predicted molecular mass of 33.6 kDa. The amino acid sequence exhibits significant homologies to those of endoIII and its prokaryotic and eukaryotic homologues. The recombinant mNthl1 with a hexahistidine tag was overexpressed in a nth::cmr nei::Kmr double mutant of E. coli, and purified to apparent homogeneity. The enzyme showed thymine glycol DNA glycosylase, urea DNA glycosylase and AP lyase activities. Northern blot analysis indicated that mNthl1 mRNA is about 1 kb and is expressed ubiquitously. A 15 kb DNA fragment containing the mNthl1 gene was cloned from a mouse genomic library and sequenced. The gene consists of six exons and five introns spanning 6.09 kb. The sequenced 5' flanking region lacks a typical TATA box, but contains a CAAT box and putative binding sites for several transcription factors such as Ets, Sp1, AP-1 and AP-2. The mNthl1 gene was shown to lie immediately adjacent to the tuberous sclerosis 2 (Tsc2) gene in a 5'-to-5' orientation by sequence analysis and was assigned to chromosome 17A3 by in situ hybridization.
Amino Acid Sequence↗
Effects of troglitazone and pioglitazone on the action potentials and membrane currents of rabbit ventricular myocytes.
The effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on action potentials and membrane currents were studied in rabbit ventricular myocytes. Troglitazone (10 microM) reversibly reduced excitability of the myocytes and modified their action potential configuration. It significantly increased the stimulation threshold required to elicit action potentials and decreased action potential amplitude and the maximum upstroke velocity of the action potentials. The Inhibition of the maximum upstroke velocity by troglitazone was also significant at 1 microM. Voltage-clamp experiments revealed that troglitazone (10 microM) reversibly inhibited both the slow inward Ca2+ current and the steady-state K+ current. In contrast to troglitazone, pioglitazone (1-10 microM) had no significant effect on the excitability, action potential configuration, or membrane currents of myocytes. These results suggest that troglitazone, but not pioglitazone, modulates Na+, Ca2+ and K+ currents, leading to the changes in excitability and action potential configuration of ventricular myocytes.
Action Potentials↗
A monoclonal antibody that recognizes a common carbohydrate epitope shared by various glycoproteins in human secretions.
A monoclonal antibody (mAb; a mouse IgM referred to as 1CF11) recognizing various human glycoproteins was obtained. While the immunoreaction of glycoproteins from human secretions including milk, saliva, and bronchus was demonstrated as a typical dose-responded S-shaped reaction curve on ELISA, no reaction was detected with milks and sera of animal origin as well as human serum. In the constituting polypeptides of the human milk secretory IgA molecule, only the secretory component was recognized by this mAb. Among various chemical treatments of the purified human milk lactoferrin (Lf), only either periodate or mild alkaline treatment abolished the immunoreactivity of the glycoprotein. A recombinant human Lf was not immunoreactive. Finally, the immunoreactive fragments were isolated from human milk Lf, which remained reactive with PAS reagent while lacking the previously reported N-glycans. These results strongly suggest that the mAb 1CF11 recognizes a new glycan O-glycosidically linked to glycoproteins in human secretions.
Animals↗