Methylguanine methyltransferase from Thermococcus kodakaraensis KOD1.
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Amino Acid Sequence↗
Biomedical subjects
Y Kai
Publications and source records attributed to Y Kai.
Digital syringomatous carcinoma mimicking basal cell carcinoma.
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Aged↗
Evidence of a role for CD200 in regulation of immune rejection of leukaemic tumour cells in C57BL/6 mice.
Increased expression of the molecule CD200 in mice receiving renal allografts is associated with immunosuppression leading to increased graft survival, and altered cytokine production in lymphocytes harvested from the transplanted animals. Preferential production of IL-4, IL-10 and TGFbeta occurs on donor-specific restimulation in vitro, with decreased production of IL-2, IFNgamma and TNFalpha. These effects are enhanced by simultaneous infusion of CD200 immunoadhesin (CD200Fc) and donor CD200 receptor (CD200r) bearing macrophages to transplanted mice. C57BL/6 mice do not normally resist growth of EL4 or C1498 leukaemia tumour cells. Following transplantation of cyclophosphamide-treated C57BL/6 with T-depleted C3H bone marrow cells, or for the EL4 tumour, immunization of C57BL/6 mice with tumour cells transfected with a vector encoding the co-stimulatory molecule CD80 (EL4-CD80), mice resist growth of tumour challenge. Immunization of C57BL/6 mice with EL4 cells overexpressing CD86 (EL4-CD86) is ineffective. Protection from tumour growth in either model is suppressed by infusion of CD200Fc, an effect enhanced by co-infusion of CD200r+ macrophages. CD200Fc acts on both CD4+ and CD8+ cells to produce this suppression. These data are consistent with the hypothesis that immunosuppression following CD200-CD200r interaction can regulate a functionally important tumour growth inhibition response in mice.
Animals↗
Comparative analyses of the conformational stability of a hyperthermophilic protein and its mesophilic counterpart.
Comparison of the conformational stability of an O(6)-methylguanine-DNA methyltransferase (MGMT) from the hyperthermophilic archaeon Thermococcus kodakaraensis strain KOD1 (Tk-MGMT), and its mesophilic counterpart C-terminal Ada protein from Escherichia coli (Ec-AdaC) was performed in order to obtain information about the relationship between thermal stability and other factors, such as thermodynamic parameters, thermodynamic stability and other unfolding conditions. Tk-MGMT unfolded at Tm = 98.6 degrees C, which was 54.8 degrees C higher than the unfolding temperature of Ec-AdaC. The maximum free energy (DeltaG(max)) of the proteins were different; the value of Tk-MGMT (42.9 kJ.mol-1 at 29.5 degrees C) was 2.6 times higher than that of Ec-AdaC (16.6 kJ.mol-1 at 7.4 degrees C). The high conformational stability of Tk-MGMT was attributed to a 1.6-fold higher enthalpy value than that of Ec-AdaC. In addition, the DeltaG(max) temperature of Tk-MGMT was considerably higher (by 22.1 degrees C). The apparent heat capacity of denaturation (DeltaC(p)) of Tk-MGMT was 0.7-fold lower than that of Ec-AdaC. These three synergistic effects, increasing DeltaGmax, shifted DeltaG vs. temperature curve, and low DeltaC(p), give Tk-MGMT its thermal stability. Unfolding profiles of the two proteins, tested with four alcohols and three denaturants, showed that Tk-MGMT possessed higher stability than Ec-AdaC in all conditions studied. These results indicate that the high stability of Tk-MGMT gives resistance to chemical unfolding, in addition to thermal unfolding.
Bacterial Proteins↗
Neurogenic thoracic outlet syndrome in whiplash injury.
A prospective study of 110 patients was carried out to determine the pathogenic significance of trauma to the upper body in the development of neural compressive irritation at the thoracic outlet. Twenty-nine patients were reviewed as cervical strain injuries (N group), 25 patients as probable neurogenic thoracic outlet syndrome (NTOS) (PT group), 39 patients as definite NTOS (T group), and 17 patients as NTOS associated with cervical disc disease (CD-T group). The time lapse between accident and diagnosis and the duration of treatment were significantly longer in T patients or CD-T patients than those in the N group. Radiography of NTOS patients also showed a higher percentage of cervical spine-length/height ratio. Traumatic NTOS would suggest two types related to direct damage of scalene muscles that included some physical aspects of cervical disc disease. Pathogenesis provided a key to the resolution of more complex posttraumatic problems of whiplash injury.
Adolescent↗
Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus.
Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.
Androstadienes↗
Relationship between insulin resistance, sex hormones and sex hormone-binding globulin in the serum lipid and lipoprotein profiles of Japanese postmenopausal women.
The purpose of the present study was to investigate the relationship between insulin resistance, sex hormones and sex hormone-binding globulin (SHBG) in regard to the serum lipid and lipoprotein profiles of 82 Japanese postmenopausal women. A multiple regression analysis for lipids, lipoproteins, and apoproteins as dependent variables was performed. All regression models included the following variables as potential independent variables; BMI, percentage of body fat, waist-hip ratio, free testosterone (Free T) and SHBG. In addition, model A included insulin resistance evaluated by HOMA-R and model B included fasting insulin (FIRI). In model A, both Free T and HOMA-R were independent predictors of total-C (TC)/high-density lipoprotein-C (HDL-C) and low-density lipoprotein-C (LDL-C)/HDL-C. The BMI was independently associated with HDL-C. The Free T was a single independent predictor of TC and LDL-C. Both BMI and HOMA-R were independent predictors of triglyceride (TG). In addition, SHBG was also independently associated with apoprotein B (Apo B) and Apo B/Apo AI. In model B, FIRI was an independent predictor of lipid metabolism with similar results to those observed in model A. These results suggest that the lipid characteristics in postmenopausal women might be associated with insulin resistance and/or hyperinsulinemia, and relative hyperandrogenicity which thus induces an increase in the amount of Free T and a decrease in the SHBG within physiological ranges.
Adult↗
[Endovascular treatment for facial arteriovenous malformations using new particles: report of two cases].
Facial arteriovenous malformations (FAVM) are difficult to treat because of their highly vascular networks. Intravascular treatment using liquid material to occlude the FAVM occasionally results in skin necrosis after embolization. The use of particulate materials to obliterate the nidus often fails to obtain a permanent cure due to arterial recanalization. We report two patients with FAVM who were successfully treated with endovascular embolization using a new type of particulate material. One patient was treated with embolization only, the other was treated with embolization followed by surgical resection. Both patients showed clinical and angiographic improvement. Intravascular treatment using particles with a smooth surface and optimal size is safe and effective in the treatment of patients with FAVM.
Adolescent↗
[Successful treatment with bypass and interventional surgery for a ruptured pseudo carotid artery aneurysm after transsphenoidal surgery: a case report].
We report case of a patient who suffered a pseudo internal carotid artery (IC) aneurysm following transsphenoidal surgery. He was successfully treated with bypass surgery and IC occlusion involving the pseudoaneurysm using Guglielmi detachable coils (GDCs). This 50-year-old man with recurrent FSH-releasing pituitary adenoma suffered profuse arterial bleeding during transsphenoidal surgery. The hemorrhage was managed, using oxidized cellulose with bio-bond. His postoperative course was uneventful, but, he developed massive epistaxis 20 days after surgery. Cerebral angiograms showed a pseudoaneurysm arising from the C4 portion of the left IC. He could not tolerate the balloon occlusion test. Using GDCs, we immediately performed left IC occlusion involving the pseudoaneurysm followed by bypass surgery between the left EC and the left middle cerebral artery. Postoperative angiograms showed that the pseudoaneurysm was completely occluded and the bypass was fully patent. When massive arterial bleeding is encountered during transsphenoidal surgery, the patient should be carefully monitored to detect early the development of a pseudoaneurysm. When such an aneurysm is found or has ruptured, interventional surgery has proved effective in the management of this complication.
Adenoma↗
[Treatment of spontaneous carotid-cavernous fistula by the transvenous approach via the facial and angular route].
We report a case of a patient with a spontaneous carotid-cavernous sinus fistula (CCF) who was successfully treated by the facial vein approach. This 66-year-old female had a 3-month history of right chemosis and exophthalmos. Angiograms showed a spontaneous right CCF with primary drainage via the superior ophthalmic vein. As both inferior petrosal sinuses were hypoplastic, the transvenous approach could not be used to gain access to the right cavernous sinus. With effort, we were able to traverse the sharp angle at the corner of the angular vein and the superior ophthalmic vein with a microcatheter. Thereafter, it was easily navigated into the right cavernous sinus. Successful placement of Guglielmi detachable coils resulted in complete closure of the fistula. When it is difficult to gain access to the cavernous sinus via the inferior petrosal sinus, the facial vein approach is a useful alternative.
Aged↗
Alteration of V beta usage and cytokine production of CD4+ TCR beta beta homodimer T cells by elimination of Bacteroides vulgatus prevents colitis in TCR alpha-chain-deficient mice.
A major pathogenic factor for the development of inflammatory bowel disease (IBD) is the breakdown of the intestinal homeostasis between the host immune system and the luminal microenvironment. To assess the potential influence of luminal Ags on the development of IBD, we fed TCR alpha(-/-) mice an elemental diet (ED). ED-fed TCR alpha(-/-) mice showed no pathologic features of IBD, and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4(+), TCR betabeta homodimer T cells (betabeta T cells) were developed in the colonic mucosa of ED-fed mice; however, Th2-type cytokine productions were lower than those seen in diseased regular diet (RD)-fed mice. The higher cytokine production in diseased RD-fed mice could be attributed to the high incidence of Bacteroides vulgatus (recovered in 80% of these mice), which can induce Th2-type responses of colonic CD4(+), betabeta T cells. In contrast, ED-fed TCR alpha(-/-) mice exhibited a diversification of Vbeta usage of betabetaT cell populations from the dominant Vbeta8 one associated with B. vulgatus in cecal flora to Vbeta6, Vbeta11, and Vbeta14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4(+), betabeta T cell-induced colitis. These findings suggest that the ED-induced alteration of intestinal microenvironments such as the enteric flora prevented the development of IBD in TCR alpha(-/-) mice via the immunologic quiescence of CD4(+), betabeta T cells.
Administration, Rectal↗
Expression of neuron specific phosphatase, striatal enriched phosphatase (STEP) in reactive astrocytes after transient forebrain ischemia.
We studied the distribution and change of striatal enriched phosphatase (STEP) in the gerbil hippocampus after transient forebrain ischemia. STEP was expressed in the perikarya and in neuronal processes; it was not detected in non-neuronal cells of control animals. After 5-min forebrain ischemia, STEP immunoreactivity (STEP-IR) was preserved for 2 days; it disappeared 4 and more days after ischemia with completion of delayed neuronal death (DND) in the CA1 subfield. Furthermore, only in the CA1 after ischemia, STEP was expressed in reactive astrocytes for 4 to 28 days, showing different patterns of glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. After non-or less-than lethal ischemia, STEP expression in reactive astrocytes corresponded with the degree of neuronal degeneration. Immunoblot analysis of the CA1 subfield revealed the expression of three isoforms, STEP45, -56 and -61; their expression patterns changed with time after ischemia. These data suggest that neuronal STEP is preserved until cell degeneration after ischemia and that STEP is expressed in reactive astrocytes only after lethal ischemia, with different expression patterns for its isoforms. Of STEP45, -56 and -61, STEP61 was the most strongly expressed in the reactive astrocytes; both STEP45 and -61 were expressed in neurons and the expression of STEP56 was weak. STEP may play an important role not only in neurons but also in reactive astrocytes after ischemia, depending on neuronal degeneration.
Animals↗
Evidence for persistent expression of OX2 as a necessary component of prolonged renal allograft survival following portal vein immunization.
Following portal vein (pv) pretransplant immunization of C3H mice, there is an early (within 2 days) increase in expression of the molecule OX2 seen on host dendritic cells (DC), along with increased survival of C57BL/6 renal allografts transplanted within 24 h of pv immunization. In addition, there is a marked polarization in cytokine production from lymphocytes harvested from the transplanted animals, with preferential production of IL-4, IL-10, and TGFbeta on donor-specific restimulation in vitro, and decreased production of IL-2, IFN-gamma, and TNFalpha compared with non-pv-immunized control transplanted mice. Both the increased renal allograft survival and the altered cytokine production are abolished by infusion of anti-mouse OX2 monoclonal antibody (3B6), even when antibody infusion is begun as late as 10 days following transplantation. Quantitative PCR analysis independently shows that OX2 expression is increased in the spleen and liver of transplanted mice as late as 21 days following pv immunization. In vitro studies with an OX2:Fc immunoadhesion had suggested that immunosuppression induced by this soluble form of the OX2 molecule was dependent primarily upon an early (OX2-dependent) signal. This discrepancy between in vivo and in vitro data possibly reflects a role for OX2 in the in vivo recruitment of other (immunregulatory) cells. Consistent with this hypothesis, regardless of the time (posttransplantation) of in vivo infusion of anti-OX2 antibody, within 2 days we observed a decline in the functional activity of a previously characterized immunoregulatory gammadeltaTCR(+) cell population, which can be monitored by its ability to regulate cytokine production in vitro.
Animals↗
Correlation between magnetic resonance images and draining patterns in dural arteriovenous fistulas with leptomeningeal venous drainage.
OBJECTIVE: To compare abnormal intensity areas on intracranial magnetic resonance images (MRI) and the pattern of venous drainage in dural arteriovenous fistulas (DAVFs) with retrograde venous drainage. METHODS: Thirteen patients with retrograde venous drainage of DAVFs were divided into two groups based on the venous drainage pattern determined by detailed angiographic and MRI study. In group 1 there was an accessory route draining into another sinus besides the main draining sinus. In group 2 no such accessory route was present. RESULTS: In group 1 patients (n = 8), MRI detected no unusual intensity areas; 5 patients in this group had episodes of bleeding. Angiographically, in this group retrograde venous drainage tended to occur via multiple varices. On the other hand, none of the 5 group 2 patients experienced a bleeding episode. Angiographically, there was a low incidence of varices. On T2-weighted images, these patients had a hyperintensity area. Following treatment, these areas of abnormality disappeared on T2-weighted MRI. CONCLUSION: Among 13 patients with DAVFs which drained retrogradely, those with a variceal accessory route (Group 1, n = 8) had a higher incidence of haemorrhage. In patients without such an accessory route (Group 2, n = 5) abnormal signal intensity on MRI was indicative of venous congestion. Continuous-mode angiography and MRI study were useful in the precise identification of DAVFs with a venous drainage route.
Aged↗
Structure of the zinc-binding site in the crystal structure of a zinc endoprotease from Streptomyces caespitosus at 1 A resolution.
A zinc endoprotease produced by Streptomyces caespitosus (ScNP) contains a H83E84TGH87VLG90LPD93-Met103 sequence. Except for D93, this amino acid sequence is the same as a characteristic consensus HEXXHXXGXXH-M motif found in one class of zinc endoprotease called 'metzincins'. We analyzed the structural and functional role of the consensus sequence located around a catalytically essential zinc ion based on the crystal structure of ScNP. The structure was determined at the highest level on resolution (1 A resolution) and accuracy among crystal structures of zinc endoproteases ever determined. The zinc ion of ScNP is tetrahedrally coordinated by three amino acid side-chains (H83, H87 and D93) and a water molecule. The distances between the zinc ion and the coordinating atoms are 2.01, 2.01 and 1.95 A for H83N epsilon, H87N epsilon and D93O delta, respectively. These distances agree very well with those normally found in crystal structures of zinc-containing small molecules in the Cambridge Structural Database. On the other hand, the distance between the zinc ion and the coordinating water molecule (1.93 A) is slightly shorter than the typical value (2.01 A) found in the database. In addition, E84O epsilon makes a short hydrogen bond to this water molecule with the distance of 2.54 A. Two hydrogen bonds (H83N delta-L102O, H87N delta-L91O) and van der Waals interactions between the side-chain of M103 and the two imidazole rings of H83 and H87 are also observed. These interactions are probably important for the imidazole rings to construct the tetrahedral coordination arrangement toward the zinc ion.
Amino Acid Motifs↗
Prognostic significance of tumor grade for renal cell carcinoma.
BACKGROUND: The natural history and prognosis of renal cell carcinoma cannot be predicted. Based on the Japanese classification system, the value of nuclear grade were assessed as a possible prognostic factor for renal cell carcinomas. METHODS: In this retrospective study of 116 patients with renal cell carcinoma, radical nephrectomy was performed. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using Cox's proportional hazard model. RESULTS: Distribution by stage and grade in the population of renal cell carcinomas was as follows: pT1 in 13 cases (11.3%), pT2 in 65 cases (56.5%), pT3 in 36 cases (31.3%) and pT4 in one case (0.9%) and grade 1, 28 (24.1%), grade 2, 69 (59.5%) and grade 3, 16 (13.8%). Three cases could not be determined because of pre-operative embolization of the renal cell carcinomas. Nuclear grade was correlated with stage (P=0.0002), the presence of perirenal fat involvement (P=0.003) and metastases (P=0.007). A significant difference in survival was found between grades 1 and 3 (P=0.0001) and grades 2 and 3 (P=0.0001), respectively. Survival was significantly correlated with sex (P=0.0125), tumor size (P=0.0001), the presence of lymph node metastasis (P=0.0001), renal vein involvement (P=0.0001), perirenal fat involvement (P=0.002) or distant metastasis (P=0.0001). The multivariate analysis showed that the occurrence of tumor grade (P=0.0006) or distant metastasis were independent prognostic values. CONCLUSION: The observations lead us to conclude that the nuclear grade according to the Japanese classification system appears to be of reliable prognostic value for renal cell carcinomas.
Adult↗
Structure and photodimerizations of 1-alkylthymines in single crystals.
1-Alkylthymine gave four kinds of crystals depending on the solvents used. Photodimerizations of 1-alkylthymine in single crystals were found to depend on the crystal structure. In inactive crystals, the terminal methyl group of alkyl chains approached to the double bond of thymine, and inhibited rotation of thymine bases during photodimerization.
Alkylation↗
The role of structural intersubunit microheterogeneity in the regulation of the activity in hysteresis of ribulose 1, 5-bisphosphate carboxylase/oxygenase.
Many enzymes are composed of subunits with the identical primary structure. It has been believed that the protein structure of these subunits is the same. Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) comprises eight large subunits with the identical amino acid sequence and eight small subunits. Rotation of the side chains of the lysine residues, Lys-21 and Lys-305, in each of the eight large subunits in spinach RuBisCO in two ways produces microheterogeneity among the subunits. These structures are stabilized through hydrogen bonds by water molecules incorporated into the large subunits. This may cause different effects upon catalysis and a hysteretic, time-dependent decrease in activity in spinach RuBisCO. Changing the amino acid residues corresponding to Lys-21 and Lys-305 in non-hysteretic Chromatium vinosum RuBisCO to lysine induces hysteresis and increases the catalytic activity from 8.8 to 15.8 per site per second. This rate is approximately five times higher than that of the higher-plant enzyme.
Catalysis↗