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S Homma

Publications and source records attributed to S Homma.

At least 19 recordsLinked to original sources
PubMed2007

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer.

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.

Adolescent↗
PubMed2006

Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines.

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.

Animals↗
PubMed2006

Cancer immunotherapy using dendritic/tumour-fusion vaccine induces elevation of serum anti-nuclear antibody with better clinical responses.

Dendritic cell (DC) vaccines might induce both anti-tumour immunity and autoimmunity. In this report, we demonstrate elevated levels of anti-nuclear antibody (ANA) in the sera of patients with cancer who had received immunotherapy with a dendritic/tumour-fusion vaccine. Twenty-two patients were treated with DC vaccine of fusion cells composed of autologous DCs and tumour cells (DC/tumour-fusion vaccine), which was generated by treating each cell type with polyethylene glycol. Nine of the 22 patients were treated with both the DC/tumour-fusion vaccine and systemic administration of recombinant human interleukin (rhIL)-12. Serum levels of ANA were examined with an enzyme-linked immunosorbent assay kit. One patient with gastric carcinoma (patient 1, DC/tumour-fusion vaccine alone), one patient with breast cancer (patient 2, DC/tumour-fusion vaccine alone) and one patient with ovarian cancer (patient 3, DC/tumour-fusion vaccine + rhIL-12) showed significant elevations of serum ANA levels during treatment. In patient 1 malignant ascitic effusion resolved and serum levels of tumour markers decreased. Patients 2 and 3 remained in good physical condition during treatment for 24 and 9 months, respectively. Immunoblot analysis indicated antibody responses to autologous tumour cells after vaccination in patient 2. None of the treated patients showed clinical symptoms suggesting autoimmune disease. Patients with elevated serum levels of ANA had significantly longer treatment periods than those without it. Elevated serum levels of ANA after DC/tumour-fusion cell vaccine might be associated with anti-tumour immune response induced by the vaccination.

Adult↗
PubMed2005

Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12.

BACKGROUND: Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. MATERIALS AND METHODS: Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated. RESULTS: The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses. CONCLUSIONS: Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.

Cell Fusion↗
PubMed2005

Pulmonary fibrosis in an individual occupationally exposed to inhaled indium-tin oxide.

Despite the increasing industrial use of indium-tin oxide (ITO) to manufacture flat-panel displays, such as liquid-crystal displays or plasma display panels for televisions, little is known about the potential health hazard induced by occupational exposure to indium compounds. The current study describes a case of fibrotic lung disease that developed after a 4-yr exposure to ITO. The pathology of the lung demonstrated pulmonary fibrosis with the presence of cholesterol granulomas. In conclusion, more attention needs to be paid to the possible toxic effects of indium compounds, and maximum healthcare measures should be taken to protect industry workers from these toxicities.

Adult↗
PubMed2004

Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVES: 1) To evaluate the risk of subsequent stroke or death in patients with a cryptogenic stroke and a patent foramen ovale (PFO), atrial septal aneurysm (ASA), or both. 2) To establish the optimal method of stroke prevention in this population of patients. METHODS: MEDLINE, the Cochrane database of systematic reviews, key meeting abstracts from 1997 to 2002, and relevant reference lists were searched to select studies that prospectively collected outcome data in cryptogenic stroke patients with and without interatrial septal abnormalities. Studies were also selected that prospectively compared at least two treatment options. The quality of each study was graded (class I to IV) using a standard classification-of-evidence scheme for each question. Risk analyses were performed and data were pooled when appropriate. RESULTS: The literature search generated 129 articles of which only four fulfilled the inclusion and exclusion criteria. Two studies were graded class I, one study was graded class II, and one study was graded class IV for prognosis. Pooled results of the two class I and one class II studies demonstrated no increased risk of subsequent stroke or death in patients with PFO compared to those without (RR = 0.95, 95% CI 0.62 to 1.44). One class I study found increased risk of recurrent stroke in patients with PFO and ASA (annual rate = 3.8% versus 1.05%, RR = 2.98, 95% CI 1.17 to 7.58) but not increased risk of a composite of stroke and death (annual rate = 3.8% versus 1.8%, RR = 2.10, 95% CI 0.86 to 5.06). Regarding therapy, one study was graded class II, one study class III, and two studies class IV. Among patients with cryptogenic stroke and PFO or ASA, there was no significant difference in stroke or death rate in warfarin-treated patients relative to aspirin-treated patients and the confidence intervals were unable to rule out a benefit of one drug over the other (annual rate = 4.7% versus 8.9%, RR = 0.53, 95% CI 0.18 to 1.58). Minor bleeding rates were higher in the cohort of patients who received warfarin (22.9/100 patient-years versus 8.66/100 patient-years, rate ratio = 2.64, p < 0.001). No studies compared medical therapy with surgical or endovascular closure. CONCLUSION: PFO is not associated with increased risk of subsequent stroke or death among medically treated patients with cryptogenic stroke. However, both PFO and ASA possibly increase the risk of subsequent stroke (but not death) in medically treated patients younger than 55 years. In patients with a cryptogenic stroke and an atrial septal abnormality the evidence is insufficient to determine if warfarin or aspirin is superior in preventing recurrent stroke or death, but minor bleeding is more frequent with warfarin. There is insufficient evidence to evaluate the efficacy of surgical or endovascular closure.

Adult↗
PubMed2004

The herbal medicine Rikkunshi-to stimulates and coordinates the gastric myoelectric activity in post-operative dyspeptic children after gastrointestinal surgery.

Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, has been used for the symptomatic relief of adult patients with dyspepsia. However, its mechanism has yet to be fully elucidated. The aim of this study is to evaluate the effect of TJ-43 on the gastric myoelectric activity in post-operative dyspeptic patients, whose symptoms persisted for over 1 year after gastrointestinal surgery. Electrogastrography (EGG) recordings were performed to calculate the biomechanical parameters on the dominant peak frequency (DPF). Eight pediatric patients with dyspeptic symptoms after gastrointestinal surgery were examined and six age-matched children without any dyspeptic symptoms were used as controls, and they were compared with nine age-matched children without any dyspeptic symptoms after gastrointestinal surgery as subcontrols. All patients exhibited symptomatic relief after the administration of TJ-43, and the mean symptom score decreased significantly after the treatment of TJ-43 over a 1-month period ( P<0.0001). The variability index (VI) and the percentage of normal waves (PNW) were calculated as irregularity parameters of DPF. The power ratio (PR) was calculated as a parameter of the gastric contractile activity. There were no significant differences in the VI and PNW between the controls and patients during the postprandial state after therapy, even though significant differences existed regarding those parameters between the controls and patients before the therapy. There were no significant differences in the DPF, VI, and PNW between the controls and subcontrols. Furthermore, PR exhibited a significant increase after therapy ( P<0.05). However, there was a significant difference in the PR between the controls and subcontrols ( P<0.05). Postprandial dip was observed in all control subjects, eight patients in the subcontrols, and two patients after administration of TJ-43, respectively. An abnormal gastric electrical activity therefore seems to be an important factor in the pathophysiology of post-operative dyspeptic children. The coordinating and stimulating effect of TJ-43 on the gastric myoelectric activity therefore seems to play an important role in the reduction of dyspeptic symptoms.

Adolescent↗
PubMed2004

Production of CA125 by human lung cancer cell lines.

CA125, which until recently was considered an ovary specific tumor marker, is elevated in the serum of patients with many pathological conditions, including lung cancer. In order to investigate the production of CA125 by human lung cancer cell lines, cell culture and immunochemical staining were performed in three cell lines. Our results showed the cell surface expression of CA125 in both adenocarcinoma and large cell carcinoma cell lines and the production of CA125 in culture medium. This is considered as evidence for in vitro production of CA125 by human lung cancer, and suggests that CA125 elevation is not only the result of ovarian cancer but may be due to other pathological conditions, including lung cancer.

Biomarkers, Tumor↗
PubMed2004

Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration.

The primary cardiac response to ischemic insult is cardiomyocyte hypertrophy, which initiates a genetic program culminating in apoptotic myocyte loss, progressive collagen replacement, and heart failure, a process termed cardiac remodeling. Although a few cardiomyocytes at the peri-infarct region can proliferate and regenerate after injury, no approaches are known to effectively induce endogenous cardiomyocytes to enter the cell cycle. We recently isolated, in human adult bone marrow, endothelial progenitor cells, or angioblasts, that migrate to ischemic myocardium, where they induce neovascularization and prevent myocardial remodeling. Here we show that increasing the number of angioblasts trafficking to the infarct zone results in dose-dependent neovascularization with development of progressively larger-sized capillaries. This results in sustained improvement in cardiac function by mechanisms involving protection against apoptosis and, strikingly, induction of proliferation/regeneration of endogenous cardiomyocytes. Our results suggest that agents that increase myocardial homing of bone marrow angioblasts could effectively induce endogenous cardiomyocytes to enter the cell cycle and improve functional cardiac recovery.

Animals↗
PubMed2004

Efficacious pleurodesis with OK-432 and doxorubicin against malignant pleural effusions.

Malignant pleural effusion develops frequently in patients with advanced lung cancer. Chemical pleurodesis is the most effective palliative treatment for these patients. The efficacy of pleurodesis using both OK-432, a preparation of Streptococcus pyogenes, and doxorubicin for 20 patients with cytology-proven malignant pleural effusion associated with lung cancer was evaluated. After complete removal of pleural effusion, OK-432 and 30 mg of doxorubicin were injected via an inserted chest tube. Treatment was terminated when the volume of daily drainage reached <200 mL. If the daily volume remained >200 mL, an additional OK-432 was administered every 3 days. In total, 16 patients (80%) revealed a complete response, two patients (10%) revealed a partial response, and no response was seen in two patients. Eighteen patients with complete or partial responses did not show subsequent reaccumulation of pleural effusion after pleurodesis. The chest tube remained in place for an average of 6.4 days, draining a mean of 2,854 mL. The main side-effects were fever and pain that were easily treated with nonsteroidal anti-inflammatory drugs. Pleurodesis using both OK-432 and doxorubicin showed high efficacy for controlling malignant pleural effusions caused by lung cancer.

Adult↗
PubMed2004

Repeated administration of cytokines improve the ex-vivo generation of human dendritic cells.

The in vitro generation of dendritic cells (DCs) enables us to practice antitumor immune therapy. Peripheral monocytes can differentiate to DCs in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) in vitro. To generate a large number of DCs, we compared the number of DCs generated from leukapheresis products to those from conventional blood samplings in healthy volunteers. The induction rates of the DCs were equal for these two blood samplings, and 10(7) DCs were obtainable from one leukapheresis product. In contrast, the number of DCs varied significantly depending on the individual (30-50% in good responders vs. less than 10% in poor responders). DCs appeared as aggregates of indented cells during culture in good responders, while large cells were floating sparsely in poor responders. Repeated administration of GM-CSF and IL-4 improved the yields of DCs and induced proliferation of autologous lymphocytes in poor responders. As a prototype of cell therapy, the generation of DCs will require a titration of differentiation processes, depending on each individual's responsiveness to cytokines.

Antigens, CD↗
PubMed2003

Non-invasive assessment of cardiac output during exercise in healthy young humans: comparison between Modelflow method and Doppler echocardiography method.

AIMS: The Modelflow method can estimate cardiac output from arterial blood pressure waveforms using a three-element model of aortic input impedance (aortic characteristic impedance, arterial compliance, and systemic vascular resistance). We tested the reliability of a non-invasive cardiac output estimation during submaximal exercise using the Modelflow method from finger arterial pressure waveforms collected by Portapres in healthy young humans. METHODS: The Doppler echocardiography method was used as a reference method. Sixteen healthy young subjects (nine males and seven females) performed a multi-stage cycle ergometer exercise at an intensity corresponding to 70, 90, 110 and 130% of their individual ventilatory threshold for 2 min each. The simultaneous estimation of cardiac output (15 s averaged data) using the Modelflow and Doppler echocardiography methods was performed at rest and during exercise. RESULTS AND CONCLUSION: The Modelflow-estimated cardiac output correlated significantly with the simultaneous estimates by the Doppler method in all subjects (r = 0.87, P < 0.0001) and the SE of estimation was 1.93 L min-1. Correlation coefficients in each subject ranged from 0.91 to 0.98. Although the Modelflow method overestimated cardiac output, the errors between two estimates were not significantly different among the exercise levels. These results suggest that the Modelflow method using Portapres could provide a reliable estimation of the relative change in cardiac output non-invasively and continuously during submaximal exercise in healthy young humans, at least in terms of the relative changes in cardiac output.

Adult↗
PubMed2003

Immature dendritic cell/tumor cell fusions induce potent antitumour immunity.

BACKGROUND: Maturation of dendritic cells (DCs) is important to induce antigen-specific antitumour immunity in cancer immunotherapy with antigen-loaded DCs. However, DCs from tumour-bearing hosts are immature and functionally defective for antigen presentation. We examined whether DCs from tumour-bearing mice could be an effective part of a DC/tumour cell fusion vaccine. MATERIALS AND METHODS: Dendritic cells from healthy (DC-Hs) or MC38 tumour-bearing mice (DC-TBs) were examined for endocytotic capacity of FITC-labelled dextran, antigen-presenting capacity in allogeneic mixed leucocyte reaction (allo-MLR) and expression of I-Ab, CD80, and CD86. Fusion cells (FCs) of DC-Hs or DC-TBs and MC38 cells (FC-Hs or FC-TBs) were generated by treatment with polyethylene glycol (PEG). Mice vaccinated with FC-Hs or FC-TBs were studied for cytolytic activity of splenocytes and suppressive activity against established MC38 pulmonary metastases. RESULTS: Dendritic cell-TBs showed higher endocytotic capacity and lower antigen-presenting capacity than did DC-Hs, results indicating that DC-TBs are more immature and functionally defective for antigen presentation than are DC-Hs. Expression of surface molecules, however, was almost same between DC-Hs and DC-TBs. Splenocytes from mice immunized with FC-Hs or FC-TBs induced the same high cytolytic activity against MC38 cells. Vaccination of mice with FC-Hs or FC-TBs resulted in the same significant suppressive effect against established pulmonary metastases of MC38. CONCLUSION: Dendritic cells from tumour-bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/tumour cell fusion vaccines.

Animals↗
PubMed2003

Coronary flow velocity analysis during short term follow up after coronary reperfusion: use of transthoracic Doppler echocardiography to predict regional wall motion recovery in patients with acute myocardial infarction.

BACKGROUND: A recent study using a Doppler guide wire showed that coronary flow velocity measurements immediately after coronary reperfusion were useful in predicting recovery of regional left ventricular function. The value of coronary flow velocity analyses during follow up after reperfusion has not been established in the clinical setting. OBJECTIVE: To evaluate coronary flow velocity measurements in predicting recovery of regional left ventricular function during short term follow up after acute anterior myocardial infarction, using transthoracic Doppler echocardiography (TTDE). METHODS: 30 consecutive patients with anterior acute myocardial infarction were studied. They all underwent successful coronary angioplasty for lesions in the left anterior descending coronary artery (LAD). Using TTDE, coronary flow velocity in the LAD was recorded on days 1 and 3, and at one and two weeks after reperfusion. Regional wall motion was analysed by the wall motion score index (WMSI), calculated as an average of segmental scores in the LAD territory before reperfusion and one month after the infarction. RESULTS: Deceleration time of diastolic flow velocity (DDT) in patients with viable myocardium (WMSI in LAD territory at one month, < 2.0) was significantly longer after recanalisation than in patients without viable myocardium (WMSI in LAD territory at one month, > 2.0): 657 (226) v 271 (117) ms on day 1, p < 0.001; 732 (219) v 373 (217) ms on day 3, p < 0.01; and 903 (107) v 577 (300) ms at one week, p < 0.01. However, the difference at two weeks (991 (75) v 795 (281) ms) was not significant. For the prediction of viable myocardium, DDT > 600 ms had a sensitivity of 78% and a specificity of 92% on day 1, and a sensitivity of 78% and a specificity of 84% on day 3. At one and two weeks, DDT > 600 ms was sensitive (100% and 100%, respectively) but less specific (46% and 26%, respectively) for predicting viable myocardium. CONCLUSIONS: Non-invasive assessment of coronary flow velocity using TTDE within three days of successful coronary angioplasty in patients with anterior acute myocardial infarction is useful in predicting recovery of regional left ventricular function.

Blood Flow Velocity↗
PubMed2002

Non-invasive automated assessment of the ratio of pulmonary to systemic flow in patients with atrial septal defects by the colour Doppler velocity profile integration method.

BACKGROUND: The recent introduction of the automated cardiac flow measurement (ACM) method, using spatiotemporal integration of the Doppler velocity profile, provides a quick and accurate automated calculation of cardiac output. OBJECTIVE: To evaluate the ACM method against oximetry during cardiac catheterisation for estimating the Qp/Qs (pulmonary to systemic flow) ratio in patients with an atrial septal defect. METHODS: Left and right ventricular stroke volume (LVSV, RVSV) were calculated by ACM in 22 patients with an atrial septal defect who underwent cardiac catheterisation and in 11 patients without heart disease (control group). With ACM, the Qp/Qs ratio was estimated from RVSV divided by LVSV. In the patients with an atrial septal defect, the Qp/Qs ratio was assessed by oximetry at the time of cardiac catheterisation. RESULTS: There was a good correlation between LVSV and RVSV obtained by ACM in the control group (r = 0.98, y = 0.97x + 0.25, SEE = 2.9 ml). The mean difference between LVSV and RVSV by ACM was -1.25 (2.76) ml. The Qp/Qs ratio obtained by ACM in the control group was 0.98 (0.06). The Qp/Qs ratio in patients with an atrial septal defect was significantly higher than in the control group (3.11 (1.20), p < 0.001). ACM determination of the Qp/Qs ratio correlated well with oximetry determination (r = 0.86, y = 0.75x + 0.55, SEE = 0.64). The mean difference between ACM and oximetry for the measurement of the Qp/Qs ratio was -0.28 (0.69). CONCLUSIONS: The newly developed ACM method is clinically useful for non-invasive automated estimations of the Qp/Qs ratio in patients with an atrial septal defect.

Adult↗
PubMed2002

Automated quantification of aortic regurgitant volume and regurgitant fraction using the digital colour Doppler velocity profile integration method in patients with aortic regurgitation.

BACKGROUND: The recently introduced automated cardiac flow measurement (ACM) technique provides a quick and an accurate automated calculation of stroke volume and cardiac output. This is obtained by spatio-temporal integration of digital Doppler velocity profile data. OBJECTIVE: To evaluate the use of the ACM method in the non-invasive assessment of aortic regurgitant volume and per cent regurgitant fraction (%RF) in patients with aortic regurgitation. METHODS: Aortic outflow volume and mitral inflow volume were calculated by the ACM method in 22 patients with isolated aortic regurgitation. Aortic regurgitant volume and %RF were calculated using the following equations: aortic regurgitant volume = [aortic outflow volume] - [mitral inflow volume]; %RF = [aortic regurgitant volume]/[aortic outflow volume] x 100. The results were compared with those obtained using pulsed Doppler cross sectional echocardiography (PD-2D). RESULTS: Aortic regurgitant volumes measured by the ACM method showed a good correlation with the PD-2D measurements (r = 0.95, y = 0.9x + 3.9, SEE = 8.6 ml); the mean (SD) difference between the two methods was -1.5 (8.5) ml. %RF estimated by the ACM method also correlated well with the values obtained by the PD-2D method (r = 0.91, y = 0.9x + 4.9, SEE = 6.0%); the mean difference between the two methods was -1.5 (6.0)%. Total time required for aortic regurgitant volume (for one cardiac cycle) by the ACM method was significantly shorter than by the PD-2D method (130 (16) v 230 (32) s, p < 0.01). CONCLUSIONS: The newly developed the ACM method is quick and accurate in the automated assessment of aortic regurgitant volume and per cent regurgitant fraction in patients with isolated aortic regurgitation.

Adult↗
PubMed2001

The carboxyl-terminal lobe of Hsc70 ATPase domain is sufficient for binding to BAG1.

The molecular co-chaperone BAG1 and other members of the BAG family bind to Hsp70/Hsc70 heat shock proteins through a conserved BAG domain that interacts with the ATPase domain of the chaperone. BAG1 and other accessory proteins stimulate ATP hydrolysis and regulate the ATP-driven activity of the chaperone complexes. Contacts are made through residues in helices alpha2 and alpha3 of the BAG domain and predominantly residues in the C-terminal lobe of the bi-lobed Hsc70 ATPase domain. Within the C-terminal lobe, a subdomain exists that contains all the contacts shown by mutagenesis to be required for BAG1 recognition. In this study, the subdomain, representing Hsc70 residues 229-309, was cloned and expressed as a separately folded unit. The results of in vitro binding assays demonstrate that this subdomain is sufficient for binding to BAG1. Binding analyses with surface plasmon resonance indicated that the subdomain binds to BAG1 with a 10-fold decrease in equilibrium dissociation constant (K(D) = 22 nM) relative to the intact ATPase domain. This result suggests that the stabilizing contacts for docking of BAG1 to Hsc70 are located in the C-terminal lobe of the ATPase domain. These findings provide new insights into the role of co-chaperones as nucleotide exchange factors.

Adenosine Triphosphatases↗