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Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 37 records · Page 2Linked to original sources

Antiprothrombin autoantibodies in severe preeclampsia and abortion.

PURPOSE: We examined the levels of autoantibodies against prethrombin-1 and fragment-1 in pregnant women to determine the type of autoantibodies that were associated with severe preeclampsia or spontaneous abortion. SUBJECTS AND METHODS: We measured autoantibodies bound to prothrombin, prethrombin-1, and fragment-1 by using an enzyme-linked immunosorbent assay (ELISA) in 12 healthy nonpregnant women, 36 women with normal pregnancies, 28 pregnant women with severe preeclampsia, and 19 pregnant women who subsequently had spontaneous abortion. RESULTS: Plasma samples in 10 (36%) of the 28 women with severe preeclampsia and 11 (58%) of the 19 women with spontaneous abortion were positive for antiprothrombin antibodies as compared with 3 (9%) of the 36 women with normal pregancies. All 11 of the positive samples from women who had spontaneous abortions were positive for antiprethrombin-1 antibody, but only 1 was positive for antifragment-1 antibody. The mean (+/- SD) titer of antiprethrombin-1 antibodies in patients with spontaneous abortion (36 +/- 9 U) was higher than that in women with normal pregnancies (10 +/- 4 U; P < 0.01). Antiprethrombin-1 antibody was detected in only 2 women with severe preeclampsia, whereas all 10 women with antiprethrombin antibodies were positive for antifragment-1 antibody. The antifragment-1 antibody titer in patients with severe preeclampsia (49 +/- 15 U) was higher than in women with normal pregnancies (13 +/- 6 U, P < 0.01). CONCLUSIONS: There is a strong and specific association between various types of antiprothrombin antibodies with severe preeclampsia and spontaneous abortion.

Abortion, Spontaneous↗

HNS-32, a novel azulene-1-carboxamidine derivative, inhibits nifedipine-sensitive and -insensitive contraction of the isolated rabbit aorta.

The vasorelaxant profile of a novel azulene-1-carboxamidine derivative, HNS-32 [N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethyl-azulene-1-carboxamidine, CAS 186086-10-2], was investigated in the isolated rabbit aorta precontracted with high KCl, noradrenaline (NA) or phorbol 12, 13-dibutyrate (PDBu) and compared with those of nifedipine and nitroglycerin. In preparations without endothelium, HNS-32 elicited concentration-dependent, full inhibition of contractions elicited by high KCI (80 mM), NA (3x10(-6) M) or PDBu (10(-6) M). In contrast, nifedipine inhibited only the contraction elicited by membrane depolarization with high KCl. Nitroglycerin also attenuated high-KCl-, NA- and PDBu-elicited contractions effectively, although full suppression was obtained only for NA-elicited contraction. Whilst the relaxant effect of HNS-32 was not affected by the presence of endothelium, the relaxant response to acetylcholine was endothelium dependent. Addition of excess Ca2+ restored both the HNS-32-reduced tension in muscle precontracted with high KCI and the nifedipine-mediated tension decrease. Relaxation elicited by HNS-32 was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2'-furyl)adenine (SQ 22,536, 10(-4) M), the soluble guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10(-5) M) or a cocktail of K+ channel blockers (glybenclamide 10(-6) M, tetraethylammonium 2x10(-3) M, apamin 10(-7) M, 4-aminopyridine 10(-4) M and Ba2+ 10(-5) M). These findings indicate that HNS-32 inhibits both L-type Ca2+ channel-dependent and -independent vascular contraction. Blockade of Ca2+ entry through L-type Ca2+ channels may be involved in the inhibitory effect of HNS-32 on the contraction due to membrane depolarization with high KCl. On the other hand, HNS-32 seems to inhibit Ca2+ channel-independent contraction via mechanism(s) other than elevation of cyclic nucleotides (cAMP and cGMP) and opening of K+ channels.

Animals↗

Connatal tuberculosis in an extremely low birth weight infant: case report and management of exposure to tuberculosis in a neonatal intensive care unit.

UNLABELLED: A case of connatal tuberculosis in an extremely low birth weight infant is reported. The patient was a female with a birth weight of 973 g born in the 27th week of pregnancy. She developed respiratory distress and signs of infection immediately after birth, which did not respond to mechanical ventilation, antibiotics, and corticosteroid therapy. Connatal tuberculosis was confirmed at 48 days of age by isolation of Mycobacterium tuberculosis from the infant's tracheal aspirate and the mother's menstrual discharge. The infant died of respiratory failure at 90 days of age. Mantoux tuberculin skin tests (TST) were performed on 99 infants, 144 medical staff members, and two family members. TST conversion occurred in three medical staff members, and preventive therapy with isoniazid was initiated. Eight exposed infants had normal chest X-rays and negative gastric aspirates for acid-fast bacilli and all received preventive isoniazid therapy. No case of tuberculosis developed during the 2-year follow-up period. CONCLUSION: Connatal tuberculosis should be considered in neonatal respiratory infection resistant to antibiotics. Prevention of transmission of tuberculosis on the neonatal intensive care unit by chemoprophylaxis is important.

Antitubercular Agents↗

Role of the epithelium in opposing H(2)O(2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole.

1. The role played by the epithelium in H(2)O(2)-induced modulation of the mechanical responses induced by acetylcholine (ACh) in rabbit intrapulmonary bronchioles was investigated in epithelium-intact and -denuded strips. 2. When ACh (3 microM) was applied intermittently, H(2)O(2) (30 microM) enhanced the ACh-induced contractions in epithelium-intact strips. In contrast, in epithelium-denuded strips H(2)O(2) (30 microM) inhibited such contractions. At higher concentrations, H(2)O(2) concentration-dependently attenuated the ACh-induced contractions in both epithelium-intact and -denuded strips, its action being more potent in the latter strips than in the former. 3. Diclofenac (a cyclo-oxygenase inhibitor; 3 microM) reduced the H(2)O(2)-induced enhancement of ACh-contractions in epithelium-intact strips but had no effect on the H(2)O(2)-induced inhibition in epithelium-denuded strips. N(G)-nitro-L-arginine did not alter the effect of H(2)O(2) on ACh-induced contractions in epithelium-intact strips. 4. Catalase (500 u ml(-1)) completely blocked both H(2)O(2)-induced effects on ACh-contractions (enhancement and inhibition). Neither superoxide dismutase (200 u ml(-1)) nor deferoxamine (0.5 mM) had any effect on H(2)O(2)-induced inhibition in epithelium-denuded strips. 5. Aminotriazole (an inhibitor of catalase; 50 mM) significantly potentiated the H(2)O(2)-induced inhibition of ACh-contractions in epithelium-intact strips but not in epithelium-denuded strips. 6. The density ratio for catalase (epithelium-intact over -denuded strips) analysed by Western blot was about 2.1, suggesting that epithelium contains more catalase than smooth muscle. 7. It is concluded that in rabbit intrapulmonary bronchioles, H(2)O(2) has dual actions on ACh-contractions. It is suggested that the epithelium may act as a powerful biochemical barrier via both the action of catalase (scavenging H(2)O(2)) and the release of bronchoconstrictor prostaglandins, thus attenuating the H(2)O(2)-induced modulation of ACh-contractions.

Acetylcholine↗

Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.

Alkaline Phosphatase↗

The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women.

OBJECTIVE: Our purpose was to clarify the influence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on plasma homocysteine (Hcy) concentrations during early pregnancy. METHODS: Between 1996 and 1998, Hcy concentration and MTHFR gene polymorphism were studied in 840 pregnant women between 6 to 12 weeks' gestation. Hcy concentration was measured by amino acid autoanalyzer (DLC-300, Nihon Denshi), and MTHFR genotypes were determined by the PCR/RFLP methods. Pregnancy outcomes were compared in association with Hcy concentration and MTHFR genotypes. RESULTS: A total of 816 of the 840 women were enrolled into the study because MTHFR genotypes were not available in 24 women. Genotypes of C677T in the MTHFR gene were CC: CT: TT (%) = 280 (34.3): 400 (49.0): 136 (16.7). Plasma Hcy concentration was significantly (p < 0.0001) higher in women with TT genotype than other genotypes [CC: CT: TT = 5.67 (2.8-10.6): 5.80 (2.5-20.1): 6.91 (3.5-20.9) nmol/ml, median (range)]. Women with hyperhomocysteinemia had severe preeclampsia (2 of 35 vs 5 of 714, p < 0.01) and stillbirth (2 of 35 vs 10 of 714, p < 0.05) more frequently than normohomocysteinemia. CONCLUSIONS: Plasma Hcy concentration during early pregnancy was higher in women with homozygote for the T677 allele in the MTHFR gene than other genotypes.

Adult↗

[Identification of Vibrio vulnificus from patients with otitis media and septicemia by PCR method].

Sucrose-negative colonies were isolated on TCBS agar plate from otorrhea specimens from otitis media patient in the Adult Diseases Examination Center, Hirosaki Medical Association. The isolate was identified as Vibrio vulnificus by nested PCR method which amplify V. vulnificus-specific sequences directed against 23S rRNA genes. The PCR method was applied to identify 6 strains originally isolated from septicemia patients in Kurashiki Central Hospital and formerly identified as V. vulnificus by phenotypic characteristics. When examined by the API20E system, the above PCR confirmed-V. vulnificus isolates were correctly identified as V. vulnificus with % ID 99.8, though this gave 3 different profiles. Cytotoxin-hemolysin gene was detected in otorrhea strain as well as septicemia strains by PCR method. The above results suggest that PCR method targeted cytotoxin-hemolysin gene is suitable for rapid and accurate identification of the isolate, because the result is obtained in less than 4 h. To our knowledge this is the first report on the V. vulnificus infection in Aomori Prefecture and the isolation from otorrhea.

Bacteremia↗

Helicobacter pylori infection and coronary heart disease in Japanese patients.

Although several independent studies have claimed a link between Helicobacter pylori infection and coronary heart disease (CHD), this association has not been established conclusively. The aim was to determine whether an association between H. pylori infection and CHD can be demonstrated in Japanese patients. Three-hundred and four patients who underwent consecutive coronary arteriography were investigated. Ninety-four patients had single-vessel coronary stenosis and 112 had multi-vessel stenosis. The remaining 98 patients had no significant stenosis in any coronary arteries. H. pylori infection was diagnosed serologically and the association between infection and CHD was estimated by the odds ratio. The serum pepsinogen (PG) I-II ratio was used to estimate the degree of gastric atrophy. Seropositivity for H. pylori was significantly higher in the patients with CHD (67%) than in the controls (50%; p = 0.006). The odds ratio for CHD after having H. pylori infection was estimated as 1.35 (95% confidence interval 1.03-1.78; p = 0.028), after adjustment for the common risk factors of CHD in a logistic regression analysis. The association between CHD and H. pylori infection was more significant among patients without any history of diabetes or smoking. The PG I-II ratio in H. pylori-positive patients was significantly higher in the multi-vessel group (3.46) than in the control or single-vessel group (2.86, p = 0.030; 2.78, p = 0.008; respectively). H. pylori infection was shown to be an independent risk factor for CHD in Japanese patients, especially among those who did not have a history of diabetes or smoking. These data imply that the association between H. pylori infection and CHD is clinically relevant.

Adult↗

Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase.

Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.

Animals↗

Characteristics of an ammonia-oxidizing bacterium with a plasmid isolated from alkaline soils and its phylogenetic relationship.

An ammonia-oxidizing bacterium, strain TCH716, was isolated from alkaline soil at Harbin city, China. The cells of strain TCH716 are lobate (0.8-1.5 x 1.0-2.0 microm), gram-negative, obligately aerobic, and nonmotile. Colonies (1-2 mm in diameter) on gellan gum plate culture are reddish, circular, and smooth. The G + C content of DNA is 54.78 mol%. Its percentage of 16S rRNA gene sequence similarity (%) to Nitrosolobus multiformis ATCC 25196T (type strain) is 98.56%. This bacterium has an optimal growth temperature and pH at 30 degrees C and 8.0-8.5, respectively. The concentration of ammonium sulfate in the HEPES medium for optimum growth of this bacterium is 38 mM. Strain TCH716 was found to have a plasmid (approximately 6.5 kbp) that possessed a plasmid-linked gene for sulfonamide resistance. Phosphoglycerate kinase, RubisCO and PEPC were found to possess high specific activities compared to the activities of these enzymes in strain ATCC 25978T. In identification of strain TCH716, both morphological characteristics (compartmentalized cells) and the phylogenetic relationship based on 16S rRNA gene sequence are important. Based on results obtained, strain TCH716 belongs to the genus Nitrosolobus, and designated as Nitrosolobus sp. TCH716.

Journal Article↗

A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis.

Two types of human breast epithelial cells (HBEC) have been characterized. In contrast to Type II HBEC, which express basal epithelial cell phenotypes, Type I HBEC are deficient in gap junctional intercellular communication and are capable of anchorage-independent growth and of expressing luminal epithelial cell markers, estrogen receptors, and stem cell characteristics (i.e. the ability to differentiate into other cell types and to form budding/ductal organoids on Matrigel). A comparative study of these two types of cells has revealed a high susceptibility of Type I HBEC to immortalization by SV40 large T antigen, although both types of cells are equally capable of acquiring an extended life span (bypassing senescence) after transfection with SV40. The immortalization was accompanied by elevation of a low level of telomerase activity in the parental cells after mid-passage ( approximately 60 cumulative population doubling levels). Thus HBEC do have a low level of telomerase activity, and Type I HBEC with stem cell characteristics are more susceptible to telomerase activation and immortalization, a mechanism which might qualify them as target cells for breast carcinogenesis. The immortalized Type I HBEC can be converted to highly tumorigenic cells by further treatment with X rays (2 Gy x 2) and transfection with a mutated ERBB2 (also known as NEU) oncogene, resulting in the expression of p185(ERBB2) which is tyrosine phosphorylated.

Animals↗

[A case of Marie-Bamberger syndrome caused by growth hormone-producing lung cancer: problems associated with peri- and postoperative management of patients with growth hormone-producing tumors from the standpoint of the "second attack" theory].

Marie-Bamberger syndrome is identical to pulmonary hypertrophic osteoarthropathy, and the causative factors have not been thoroughly clarified yet. Therefore, further studies of each case would seem to be useful to shed some light on the pathogenesis. We reported a 48-year-old man with primary lung cancer associated with clubbing of the fingers and hypertrophic osteoarthropathy. Chest CT portrayed a 10 x 6.5-cm bulky mass with central necrosis in the left upper lobe. The serum level of growth hormone (GH) showed about a twenty-fold increase over the normal upper limit. With the emergence of SIRS (Systemic Inflammatory Response Syndrome), the patient's general condition took a downhill course. We considered this state to be an oncological emergency and performed a semi-urgent operation. Immunohistochemical evaluation revealed a poorly differentiated adenocarcinoma with GH production. After treatment, the serum level of GH normalized and the clubbing and the periosteal changes of the bones resolved, which suggests that GH plays an etiologic role in Marie-Bamberger syndrome. Recent studies have indicated that GH has immunostimulatory effects. From the standpoint of the "second attack" theory, surgical stress seems to act on the immune system already activated by GH (so called "priming") in the form of a second attack, and trigger an excessive inflammatory response leading to postoperative organ injury in patients who suffer from GH-producing tumors. Thus, we should recognize this immanent risk and perform peri- and postoperative management for patients with GH-producing tumors.

Adenocarcinoma↗

[A case report of hemiparesis due to compression of the medulla oblongata by an elongated vertebral artery].

The authors report a case of a 53-year-old woman who developed symptoms and signs of compression of the left medulla oblongata by the elongated and curved left vertebral artery with normal diameter. Twelve days before admission to the hospital, the patient suddenly noticed severe occipital-nuchal headache and nausea with vomiting, while she was unloading a burden. Neurological examination revealed left facial hyperalgesia, right hemihypesthesia and mild right hemiparesis. Hoarseness was observed, but the movement of the uvula and tongue was normal. Hypertension was noticed (180/100). Cerebral and vertebral angiography revealed no aneurysm, but demonstrated an elongated and curved V4 portion of the left vertebral artery with normal diameter. Coronal plain of T2 weighted image of MRI and CT scan with metrizamide administered into the CSF, clearly demonstrated an elongated and curved left vertebral artery compressing the ventro-lateral portion of the left medulla oblongata, neurovascular decompression of the V4 from the medulla oblongata was performed. Through the operating microscope, it was observed that the elongated and curved V4 portion of the left vertebral artery with normal configuration was compressing the left medulla oblongata ventro-laterally, making a compression notch at the outlets of the cranial nerves IX and X. Transposition of the V4 portion was impossible. Some pieces of Taflon felt, thick enough to prevent the pulsatile movement of the V4 from compressing the medulla oblongata, were inserted between the V4 and the medulla oblongata. Two months after the operation, the patient's right hemiparesis and sensory disturbances were gradually improving and her blood pressure had become normal. The authors emphasize that, among patients with symptoms and signs of compression of the medulla oblongata, there is at least one patient for whom neurovascular decompression was an effective treatment.

Female↗

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

Anti-Bacterial Agents↗

[Significance of nucleic acid extraction for the performance of COBAS AMPLICOR Mycobacterium-PCR assay].

On an AMPLICOR-PCR assay for the diagnosis of mycobacterial infections, it has been found that approximately 10% of the routinely performed assays appear as indefinable cases with internal control (IC)-negative, which is caused by contaminant PCR-inhibitory substances in the extracted nucleic sample. To decrease the number of indefinable cases, we studied the IC performance of four nucleic acid extraction methods in one manual method(A) and three commercial kits(B, C and D). Thirty samples from 10 kinds of specimens without mycobacterial infections were subjected to the four nucleic extraction methods and the nucleic extracts were compared on PCR-inhibitory. The frequency of IC-negative samples was different among the four methods and the rates were 33.3%(n = 10) in A, 30.0%(n = 9) in B, 16.7%(n = 5) in C and 6.7%(n = 2) in D. In the PCR-inhibitory experiments using serially diluted IC-negative samples, the recovery of IC positivity was also different according to the method used. Although the IC-negative nucleic samples by D method easily became IC-positive at the 1/5 range of dilution, some of the IC-negative nucleic samples by A, B or C method were still IC-negative in the 1/10 range. These results indicate that the occurrence rate of indefinable cases with IC-negative is markedly different in the nucleic extraction method, suggesting that utilizing a suitable nucleic acid extraction method is important when using the diagnostic AMPLICOR-PCR assay.

DNA, Bacterial↗

[An unconscious patients with ascending aortic aneurysm accompanied by aortic regurgitation successfully treated by emergency operation after cardiopulmonary resuscitation].

A-37-year-old woman in shock condition was transferred to our hospital after cardiopulmonary resuscitation for ventricular fibrillation. She was unconscious and suspected of suffering ischemic brain damage, with pathologic reflexes and weak brain stem reflexes. Brain CT scan showed cerebral edema without hemorrhage or infarction and an electroencephalograph revealed slow alpha-theta waves. Chest CT scan and echocardiogram showed ascending aortic aneurysm with sever aortic regurgitation. An emergent operation was performed for progression of heart failure. There were no distortion or dilatation of the sinus of Valsalva and annuloaortic ectasia and aortic valve leaflets were almost normal. We considered that the aortic valve dysfunction was cause by dilatation of the sinotubular junction. Ascending aortic and aortic valve replacement were carried out to shorten cardiopulmonary bypass time and to prevent the progression of brain damage. Mild hypothermia was employed as a neuroprotective procedure for three days after surgery. The patient's neurological symptoms, which were right hemiparesis, facial apraxia and motor aphasia, improved and she was discharged from the hospital on foot without any neurological complications on the 47th postoperative day and returned to work after two months.

Adult↗

ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction.

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the MAPKKK family in the JNK and p38 mitogen-activated protein kinase cascades and critically involved in stress- and cytokine-induced apoptosis. The transcription factor nuclear factor-kappaB (NF-kappaB) is a pivotal regulator of immune and inflammatory responses and exerts anti-apoptotic roles in various cells. Here we show that ASK1 directly interacts with transforming growth factor-beta-activated kinase 1 (TAK1), another MAPKKK that has been identified as a signaling intermediate in the interleukin 1 (IL-1)-induced NF-kappaB pathway as well as the transforming growth factor-beta superfamily-induced JNK/p38 pathway. Overexpression of ASK1 inhibits IL-1-, TRAF6-, or TAK1-induced, but not NF-kappaB-inducing kinase-induced, NF-kappaB activation. ASK1 dissociates TAK1 but not NF-kappaB-inducing kinase from TRAF6. Moreover, IL-1-induced complex formation of endogenous TAK1 and TRAF6 was blocked by ASK1 overexpression. It thus appears that the inhibition of NF-kappaB by ASK1 may result at least in part from the disruption of the TRAF6.TAK1 complex formation in the IL-1 signaling pathway. These results provide a new insight in the mode of action of MAPKKK family members; two distinct MAPKKKs in the same MAP kinase cascades directly interact and exert opposite effects in another signaling pathway, NF-kappaB.

Cell Line↗