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Biomedical subjects

K Imoto

Publications and source records attributed to K Imoto.

At least 91 records · Page 5Linked to original sources
PubMed1996

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella.

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.

Antibodies, Viral↗
PubMed1996

[Surgical treatment for active infective endocarditis : septic embolization and mycotic aneurysms].

From 1978 through 1995, surgical treatment for active infective endocarditis (native valve) was performed in 17 patients. The indication for operation at the active phase was progressive heart failure in 5 (A-group) and uncontrolled infection in 12 (B-group). Operative findings showed vegetations in all cases, perforations of the valve in 6, rupture of tendon in 2, and annular abscesses in 2. One patient in B-group died 14 days after the operation with postoperative mediastinitis and sepsis. There was no perioperative complications in A-group. In B-group before operations 8 patients (66.7%) has an embolic event before operations. The anatomic sites of embolization were the central nervous system (3 patients), viscera (2 patient) and peripheral arteries (3 patients). And after operation there were 2 mycotic aneurysms of the hepatic artery and the popliteal artery, and 1 pyogenic spondylitis. We conclude that the risk of embolization is high in patients undergoing surgery at active phase of infective endocarditis because of uncontrolled infection ; thus, such patients should be carefully monitored for emboli and mycotic aneurysms.

Adult↗
PubMed1996

[Evaluation of sensitivity and specificity of confirmatory assays for lupus anticoagulant (LA) detection].

To evaluate the sensitivity and specificity of confirmatory assays for LA detection, we performed the platelet neutralization procedure (PNP), diluted Russell's viper venom time (dRVVT) confirmatory assay (the ratio of LA-screen and LA-confirm:S/C), and specific hexagonal phase neutralization test (StaLA) on, plasma samples 43 LA-positive in either the ratio of dilute APTT and APTT(dAPTT/APTT) or dRVVT(LA-screen). The sensitivity and the specificity were evaluated by 4 different analyses based on, 1) maximal plasma dilution, 2) correlation between the screening assays and these confirmatory assays, 3) ratio of LA-positive in the confirmatory assays, and 4) receiver operation characteristic (ROC) method. All 4 analyses showed that sensitivity was in the order of PNP > S/C > Staclot-LA. However, the order of the specificity evaluated by the ROC method was Staclot-LA > S/C > PNP. The APTT-based confirmatory assay, PNP can detect LA of the plasma samples that were all positive in the dAPTT/APTT ratio, while the LA-positive plasma samples in dRVVT-confirm were all positive in the dRVVT-screen assay. Our findings suggest that confirmatory assays should be based on the method giving an abnormal screening assay. Accordingly, we recommend the following combinations of screening and confirmatory assays in terms of specificity; 1) dAPTT/APTT ratio and Staclot-LA as the APTT-based assay, and 2) LA-screen and LA-confirm as the dRVVT-based assay.

Blood Coagulation Tests↗
PubMed1996

Lack of voltage-operated calcium channel in rat glioma C6 cells.

We examined whether rat glioma C6 cells have voltage-operated Ca2+ channel (VOC) or not. The addition of high K+ did not affect the cytoplasmic Ca2+ concentration ([Ca2+]i). In addition, BAY K 8644, a VOC against, did not increase [Ca2+]i even in the presence of high K+. Bombesin (BBS), an inositol trisphosphate-generating drug, and thapsigargin (TG), a microsomal Ca(2+)-ATPase inhibitor, increased [Ca2+]i, after which it decreased to a sustained, and still higher than original level. The addition of verapamil, diltiazem and nimodipine did not affect an increase in [Ca2+]i induced by BBS and TG. The addition of SK&F 96365, a receptor-operated Ca2+ channel (ROC) blocker, reduced the sustained increase in [Ca2+]i induced by BBS and TG. The present results suggest that VOC does not exist in rat glioma C6 cells and this cell line is a good model for investigating signal transduction via ROC as glial cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Growth regulation of endothelial cells by tissue fragments: analysis on mechanism of rapid endothelialization of tissue-seeded vascular prosthesis in a three-dimensional culture system.

Rapid endothelialization of the inner surface was reported in an autologous tissue-seeded vascular prosthesis. We applied a three-dimensional in vitro culture system to elucidate the precise mechanism of rapid endothelial coverage of a tissue-seeded vascular prosthesis. Human venous, omental, adipose and striated muscle tissue fragments were harvested from surgical specimens. They were embedded in collagen gel, and 2.0 x 10(5) bovine aortic endothelial cells (BAECs) were seeded on the gel. The number of BAECs was counted on Days 2 and 7. Growth rate of BAECs was facilitated on the collagen gel with omental and striated muscle tissue fragments (p < 0.05). Factor VIII-negative spindle cells migrated around tissue fragments, especially around the omental and striated muscle tissue fragments. Rapid endothelialization of a tissue-seeded vascular prosthesis may result from facilitation of EC proliferation by viable tissue fragments and migrated cells. These results confirm tissue fragments regulate EC growth, and are useful as bioengineering tools.

Animals↗
PubMed1995

[Correlation between pulmonary vascular changes and hemodynamic parameters during exercise before and after mitral valve surgery].

Sixteen cases with mitral valvular disease were studied with regard to the correlation between pathological changes in the pulmonary vasculature and pulmonary hemodynamics during exercise before and after surgery. In muscular pulmonary arteries obtained by open lung biopsy, medial wall thickness (MWT) was 13.8 +/- 3.2% and intimal thickness (IT) was 37.3 +/- 13.5%. MWT was correlated with IT (r = 0.60, p < 0.05). Wall thickness in pulmonary veins was 8.21 +/- 1.8%. Preoperative mean pulmonary arterial pressure (MPAP) during exercise was 45.9 +/- 9.4 mmHg, and decreased significantly to 38.1 +/- 11.3 mmHg postoperatively. However, in 4 patients, MPAP during exercise increased after surgery. Pulmonary vascular resistance (PVR) during exercise was unchanged before and after surgery (2.74 +/- 1.90 U.M2-->2.69 +/- 1.3 U.M2). MWT was significantly correlated with preoperative MPAP at rest only. In patients showing an increase of MPAP during exercise postoperatively, mean MWT was 16.2% and mean IT was 47.4%. In conclusion our data suggest that postoperative pulmonary hemodynamics does not improve in patients whose MWT exceeds 15% and IT exceeds 40% and that irreversibility may be due to pulmonary vascular lesions.

Adult↗
PubMed1994

Involvement of the brain type of ryanodine receptor in T-cell proliferation.

Cloning and sequence analysis of cDNA showed that the brain type of ryanodine receptor (RYR) is expressed in human Jurkat T-lymphocyte cells. Fura-2 measurements revealed that the RYR in T-cells functions as a ryanodine-sensitive, caffeine-insensitive Ca2+ release channel. Furthermore, ryanodine stimulated proliferation and altered the growth pattern of cultured human T-cells when added together with FK506.

Amino Acid Sequence↗
PubMed1994

Proline mutations on the S4 segment of rat brain sodium channel II.

We have studied S4-proline mutants of the rat brain sodium channel II. In mutant A224P one proline was added on the S4 segment of repeat I, and in mutant P1313V a proline was removed from the segment S4 of the repeat II. In both mutants, the activation curve was shifted to more positive potentials, without changing the steepness of the voltage dependence. The time course of inactivation, consisting of two exponential components, was similar in the wild type and in mutant A224P. Differently, the decay of the current in mutant P1313V had only one component, with a time constant similar to that of the fast component of wild type channels. This change in kinetics was accompanied in mutant P1313V by a change in the voltage dependence of the apparent steady-state inactivation. We conclude that the addition or deletion of prolines in segment S4 does not affect significantly the activation of sodium channels, but alters their mode of inactivation.

Animals↗
PubMed1994

Critical roles of the S3 segment and S3-S4 linker of repeat I in activation of L-type calcium channels.

Each of the four repeats (or motifs) of voltage-gated ion channels is thought to contain six transmembrane segments (S1-S6). Mutational analyses indicate that S4 functions as a voltage sensor and that the S5, S6, and S5-S6 linker contribute to formation of the ion pore. However, little information exists regarding the functional role(s) of the amino-terminal portion (S1-S3-S4 linker) of the repeats. Here we report that the amino acid composition of the S3 segment of repeat I and the linker connecting S3 and S4 segments of repeat I is critical for the difference in activation kinetics between cardiac and skeletal muscle L-type calcium channels. Mutant dihydropyridine receptors that have the skeletal muscle dihydropyridine receptor sequence in this region activated relatively slowly with the time constant of current activation (tau act) > 5 ms, whereas mutants that have the cardiac counterpart there activated relatively rapidly with tau act < 5 ms. Comparison of these two mutant groups indicates that a total of 11 conservative and 10 nonconservative amino acid changes from skeletal muscle to cardiac dihydropyridine receptor sequence are sufficient to convert activation from slow to fast. These data demonstrate a functional role for this region of voltage-gated ion channels.

Amino Acid Sequence↗
PubMed1994

Molecular pore structure of voltage-gated sodium and calcium channels.

1. Voltage-gated ion channels have a high homology in their primary structure but yet show quite distinct ion selection properties. Therefore, ion selection was studied in voltage-gated wild-type and mutant sodium (Na RBII) and calcium (Ca BI) channels, which were heterologously expressed in Xenopus oocytes, using two-electrode voltage clamp and patch clamp methods. 2. In order to facilitate the electrophysiological experiments, fast sodium channel inactivation was abolished by introducing the point mutation F1489Q into the linker between the homologous repeats III and IV. 3. The ion pore in rat brain sodium channel II was located by testing single-point mutants for their sensitivity to externally applied tetrodotoxin (TTX), leading to a model in which part of the linker S5-S6 folds into the membrane to form at least part of the ion pore; two amino acids from each domain are thereby of major importance for TTX association and ion permeation, presumably forming two rings of predominantly charged residues in three-dimensional space (outer ring: E387, E945, M1425, D1717; inner ring: D384, E942, K1422, A1714). 4. When the residue F385 in repeat I of Na RBII channel is mutated to a cysteine, the residue being at the homologous position in cardiac sodium channels, the channel lost its high sensitivity for TTX and gained a high sensitivity for external Cd2+ and Zn2+, properties found in cardiac sodium channels. Mutation of the other cysteine in the pore region, C940, had no effect on channel block by TTX or by external divalent cations. 5. The inner ring in sodium channels constitutes a selectivity filter: after mutation of residues K1422 and A1714 into glutamates, the homologous residues in calcium channels, the sodium channels show ion selection properties similar to calcium channels: a) no selectivity among monovalent cations, b) strong block of monovalent current by divalent cations, c) permeation of divalent cations. 6. Reverse mutations in the BI calcium channel, where glutamate residues were mutated into neutral glutamines, showed that also in this channel these amino acids form a selectivity filter. The individual residues interact differently with the permeating ions suggesting an asymmetric spatial arrangement of the four pore-forming regions of the ion channel pore.

Amino Acid Sequence↗
PubMed1994

[Re-coronary artery bypass grafting for anomalous origin of left coronary artery from pulmonary artery (Bland-White-Garland syndrome) after operation in infancy: a case of 18-year follow-up].

Anomalous origin of the left coronary artery from the pulmonary artery is a very rare congenital malformation. Re-coronary artery bypass grafting was performed in a 18-year-old man who had received coronary artery reconstruction with a homologous saphenous vein (from his mother) at 7-months old. After the first operation, clinical course was uneventful, but the patient became symptomatic because of effort angina at age 15. The electrocardiogram showed abnormal ST segments in Lead V2-5 and abnormal T waves in Lead V5-6. Coronary arteriography revealed that saphenous vein graft was occluded. The left internal thoracic artery (LITA) was anastomosed to the left anterior descending artery and a two coronary system was established. Postoperative angiography revealed that LITA was patent, and relief of angina was obtained.

Adolescent↗
PubMed1994

[Delayed sternal closure for life-threatening massive bleeding during re-open heart surgery].

Delayed sternal closure (DSC) was used for 4 patients undergoing various cardiac reoperations to control perioperative hemorrhage. DSC was performed 48-72 hours later. All patients left the hospital alive and in good condition. The only recognized complication was an abscess formation around the bleeding area, which was successfully treated with systemic antibiotics. The remaining 3 patients manifested no infections. In two of these patients, hemodynamic instability was continued because of right ventricular outflow tract obstruction by compression of the packs which were left over the bleeding area. The function of coagulation of the blood was recovered except prothrombin time (PT) at the time of definitive closure of the chest. Recovery of the function of coagulation was useful in deciding the timing of DSC than hemodynamic state.

Aged↗
PubMed1994

[Surgical treatment of active infective endocarditis].

From January, 1978, through December, 1990, surgical treatment for active infective endocarditis was performed in 11 patients. There were 8 men and 3 women who ranged in age from 19 to 54 years with a mean age of 38.8 years. Two patients had ventricular septal defects and 1 patient had rheumatic valve disease. In all patients, the infecting organism was isolated from blood, including streptococcus in 7, staphylococcus in 2, and gram-negative rods in 2. The indication for operation at the active phase was uncontrolled infection in 7 and progressive heart failure in 4. The operation was performed at 7 to 150 days with a mean of 53 days after diagnosis. Operative findings showed vegetations in all cases and perforations of the valve in 6. There were no operative deaths. Perioperative complications developed in 5, whose indication for operation was uncontrolled infection. Complications consisted of 1 prosthetic valve endocarditis, 1 pulmonary suppuration, 1 ruptured mycotic aneurysm of the hepatic artery, 1 ruptured mycotic aneurysm of the popliteal artery, and 1 pyogenic spondylitis. All were successfully treated surgically or with antibiotic therapy. There were no complications in patients whose indication for operation was progressive heart failure. We conclude that the risk of embolism is high in patients undergoing surgery at the active phase of infective endocarditis because of uncontrolled infection; thus, such patients should be carefully monitored for emboli.

Adult↗
PubMed1993

Ion channels: molecular basis of ion selectivity.

Recent mutagenesis studies of the ion channel proteins have allowed us to identify amino acid residues critical in determining ion selectivity. Ion selectivity of a channel can be altered even by single amino acid substitutions. Functional analyses of mutants largely support views in classical biophysics that the pore size and the fixed charges are major determinants of ion selectivity. For full understanding of the molecular mechanism of ion selectivity, elucidation of the tertiary structure of channel proteins remains essential.

Amino Acid Sequence↗
PubMed1993

Requirement of the calcium channel beta subunit for functional conformation.

The cardiac dihydropyridine-sensitive L-type calcium channel was stably expressed in Chinese hamster ovary cells by transfecting the rabbit cardiac calcium channel alpha 1 subunit cDNA with or without coexpression of the beta subunit of skeletal muscle calcium channel. Whereas coexpression of the beta subunit significantly increased DHP binding activity and calcium channel activity, it did not affect the amount of the alpha 1 subunit expressed, as judged by RNA blot hybridization analysis and immunoblotting analysis. The results suggest that association with the beta subunit is necessary for the alpha 1 subunit protein to take a proper conformation suitable for a functional calcium channel.

Animals↗
PubMed1993

Structural determinants of ion selectivity in brain calcium channel.

Glutamic acid residues in the SS2 segment of the internal repeats III and IV of the brain calcium channel BI were subjected to single point mutations. The mutant channels were tested for macroscopic current properties and sensitivities to inorganic blockers. The mutation that replaces glutamic acid 1,469 with glutamine altered ion-selection properties and strongly reduced the sensitivity to Cd2+, whereas the analogous mutation of glutamic acid 1,765 exerted smaller effects on ion-selection properties. Our results indicate that these glutamic acid residues, equivalently positioned in the aligned sequences, play different roles in the selective permeability of the calcium channel.

Amino Acid Sequence↗