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Biomedical subjects

Yasuo Ikeda

Publications and source records attributed to Yasuo Ikeda.

At least 55 records · Page 3Linked to original sources
PubMed2006

Unusual hemangioendothelioma of the liver with epithelioid morphology associated with marked eosinophilia: autopsy case.

Vascular neoplasms characterized by epithelioid endothelial cells consist of several different entities from benignity to high-grade malignancy. Because of histological overlap between them, there is substantial difficulty in classifying them correctly. The present patient, a 33-year-old man, presented with hepatomegaly, striking eosinophilia and elevated serum interleukin-5 level. Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver, which is histologically distinct from epithelioid hemangioma, epithelioid hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had vasoformative and partly solid growth with no severe nuclear atypia and very low mitotic activity, and the histological features were similar to those of the entity recognized as hemangioendothelioma of bone. Organs other than the liver, for example the testes and bone, were also involved. This tumor should be considered in the differential diagnosis of severe eosinophilia.

Adult↗
PubMed2006

Current status of hematopoietic cell transplantation for adult patients with hematologic diseases and solid tumors in Japan.

A nationwide survey of hematopoietic cell transplantation (HCT) was started in Japan in 1991, and the analyzed survey data have been presented as the annual report of the Japan Society for Hematopoietic Cell Transplantation. The 10-year overall survival (OS) rates after HCT for each disease are as follows: acute myelogenous leukemia, 44.2%; acute lymphocytic leukemia, 33.7%; adult T-cell leukemia, 24.6%; chronic myelogenous leukemia, 53.3%; myelodysplastic syndrome, 37.3%; non-Hodgkin's lymphoma, 41.5%; Hodgkin's lymphoma, 50.8%; aplastic anemia, 72.5%; breast cancer, 37.1%; germ cell tumor, 52.6%; and ovarian cancer, 44.2%. The 5-year OS rates for multiple myeloma and lung cancer were 40.6% and 23.6%, respectively. Except in cord blood transplantation, engraftment was accomplished in more than 90% of patients. The respective frequencies of acute graft-versus-host disease (GVHD) and chronic GVHD were 41.1% and 34.9% for related bone marrow transplantation (BMT), 66.8% and 34.5% for unrelated BMT, 52.9% and 36.0% for allogeneic peripheral blood stem cell transplantation, and 53.3% and 32.1% for allogeneic cord blood transplantation. OS for each disease was analyzed by patient age, stem cell source, donor type, disease status, and disease type. These data provide objective and valuable information for hematologists as well as for patients who need HCT.

Adolescent↗
PubMed2006

Recurrence of autoimmune disease after autologous peripheral blood stem cell transplantation for multiple myeloma.

There have been a number of reports on the improvement of concomitant autoimmune disease (AID) after autologous hematopoietic stem cell transplantation (SCT) performed for hematologic malignancy. However, in some cases of hematologic malignancy with AID, exacerbation of AID after autologous SCT has been reported. We have treated 27 adults with multiple myeloma with single or tandem autologous SCT. After peripheral blood stem cells were collected and stored without CD34+ cell selection or T-cell depletion, all patients received melphalan (200 mg/m2) as a conditioning regimen. In 2 patients with a history of AID (one with rheumatoid arthritis [RA] and the other with bullous pemphigoid [BP]) and in 1 patient with Sjögren syndrome, AID recurred 7 to 12 months after autologous SCT. The RA and BP were in durable remission before SCT, and no Sjögren syndrome-related disease activity was clinically documented at the time of SCT. No progression of the myeloma was observed when the AIDs recurred. The patients required systemic steroid therapy for their AID, and successful control of the disease was achieved. Our experience suggests that autologous SCT with unmanipulated stem cells for myeloma is unlikely to cure preexisting AID; rather, the AID may worsen. Transplantation physicians should be aware of this possible complication.

Aged↗
PubMed2006

Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "lung injury by bortezomib" joint committee of the Japanese society of hematology and the Japanese society of clinical hematology.

Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies to explore the situation and the details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (P = .033, Fisher exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (P = .024; odds ratio, 0.055) and that a previous SCT might increase the risk (P = .042; odds ratio, 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning this matter is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy.

Adrenal Cortex Hormones↗
PubMed2006

Helicobacter pylori and immune thrombocytopenic purpura: unsolved questions and controversies.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. Recent accumulating evidence indicates that eradication of Helicobacter pylori (H pylori) is effective in increasing platelet count in nearly half of ITP patients infected with this bacterium. The H pylori eradication therapy for adult ITP is becoming very popular in Japan and is now chosen as an initial treatment in H pylori-infected patients. The lack of efficacy of the H pylori eradication regimen in H pylori-negative ITP patients clearly indicates that platelet recovery results from the disappearance of H pylori itself. Despite extensive efforts, clinical features characteristic to H pylori-related ITP and factors predicting the response after the H pylori eradication therapy have not been identified. Great variability in the efficacy of the H pylori eradication therapy in ITP patients exists among countries: a higher response rate has been found in Japan and Italy than in the United States and non-Italian European countries. Some children infected with H pylori show the platelet response after successful eradication of H pylori, but the H pylori eradication therapy is ineffective in patients with secondary ITP. The pathogenesis of ITP associated with H pylori remains obscure; the mechanisms are not simple and may involve multiple steps, including cross-reactivity between H pylori antigen and platelets, and suppression of the reticuloendothelial system. Further studies to evaluate the mechanisms responsible for the platelet response in ITP patients after successful eradication of H pylori may be useful in clarifying the pathogenesis of ITP and developing new therapeutic strategies for ITP.

Anti-Bacterial Agents↗
PubMed2006

Prevention of cytomegalovirus infection by valaciclovir after allogeneic bone marrow transplantation from an unrelated donor.

In this prospective single-center study, we evaluated the efficacy and safety of valaciclovir (VACV) in the prevention of cytomegalovirus (CMV) infection after allogeneic bone marrow transplantation (BMT). The study population consisted of 12 patients who underwent allogeneic BMT from an unrelated donor. Patients received acyclovir (ACV) intravenously until they became able to take VACV orally. VACV was administered at a daily dose of 3000 mg and continued until day 100. CMV infection was monitored by CMV antigenemia assay and real-time polymerase chain reaction analysis of plasma. Thirty-five patients who did not receive any form of CMV chemoprophylaxis served as control subjects. CMV infection was detected in 4 (33.3%) of the 12 patients and in 24 (68.6%) of the 35 control subjects (P < .05). The onset of CMV infection was significantly delayed in the VACV group (median, day 43) compared with the control group (median, day 28.5; P < .01). Gastrointestinal symptoms as an adverse event due to VACV administration were observed in 2 patients. The plasma levels of ACV after VACV administration were measured in 8 patients and were similar to those in the healthy subjects. In conclusion, VACV shows normal absorption, even in the early posttransplantation period, and may prevent or delay CMV infection effectively and safely in allogeneic BMT recipients.

Acyclovir↗
PubMed2006

Induction of apoptosis via the modulation of reactive oxygen species (ROS) production in the treatment of myeloid leukemia.

Recent advances in genetic and molecular biology have provided greater insight into the biology of acute myeloid leukemia (AML). These investigations have shown that AML is a heterogeneous disease of biologically different entities. Current therapeutic approaches to AML are based on chemotherapy, but the side effects of the drugs used and various complications, including infections and bleeding, are sometimes fatal. In addition, responses to therapy and long-term outcome differ depending on the subentity in question. Therefore, it is essential to develop new therapeutic strategies such as biology adapted treatment based on the individual molecular pathogenesis of AML. Natural compounds appear to be safer than the current chemotherapeutic drugs, and we have therefore sought new potential agents among various natural compounds with the ability to induce the apoptosis of myeloid leukemic cells. Recently, we found that a highly toxic reactive oxygen species (ROS) generated via the hydrogen peroxide/myeloperoxidase [H(2)O(2)/MPO/halide] system by natural compounds induces apoptosis in MPO-positive leukemic cells. This result is of great interest in establishing novel therapeutic approaches to AML mediated through ROS-induced apoptosis of leukemic cells.

Antineoplastic Agents↗
PubMed2006

p27KIP1 and GATA-1 are potential downstream molecules in activin A-induced differentiation and apoptosis pathways in CML cells.

p27KIP1 is known as a regulator of cellular differentiation and apoptosis in human cancer cells. We have previously reported that human chronic myeloid leukemia (CML) KU812 and K562 cells show inhibited cellular proliferation in response to treatment with activin A, a member of TGF-beta superfamily. Apoptosis and erythroid differentiation can be induced in KU812 and K562 cells, respectively. We report herein that activin A induced the expression of p27KIP1 in CML cells along with the induction of cellular differentiation and apoptosis. There are putative binding sequences of erythroid-related transcription factor GATA-1 in the promoter region of the human p27KIP1 gene. Expression of GATA-1 protein in activin A-treated KU812 and K562 cells showed dissimilar regulation in these two cell lines. Induction of p27KIP1 was commonly observed, but it did not correspond to the expression levels of GATA-1 in either line of activin A-treated CML cells. In addition, ERK protein was rapidly and transiently activated with activin A in both types of CML cells, suggesting that phosphorylation of ERK is required for activin A signaling in CML cells. These results indicate that both p27KIP1 induction and regulation of GATA-1 play essential roles in activin A-induced erythroid differentiation and apoptosis.

Activins↗
PubMed2006

[Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "Lung Injury by Bortezomib" Joint Committee of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology].

Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies in order to explore the situation and details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (p = 0.033 by Fischer's exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (p = 0.024; odds ratio = 0.055) and that a previous SCT might increase the risk (p = 0.042; odds ratio = 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning these matters is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy. Note that this report has the same contents as the article appeared in the International Journal of Hematology (vol. 84, p406-412, 2006) by permission of both the editorials of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology, and should be considered as the Japanese translation of the article.

Adrenal Cortex Hormones↗
PubMed2005

Fulminant Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder with hemophagocytosis following autologous peripheral blood stem cell transplantation for relapsed angioimmunoblastic T-cell lymphoma.

Post-transplant lymphoproliferative disorder (PTLD) is a complication that can develop after either solid-organ or hematopoietic stem cell transplantation (HSCT). T-cell PTLD is a rare disorder, especially following autologous HSCT. Here we report a case of T-cell PTLD which occurred after autologous peripheral blood stem cell transplantation (PBSCT) for relapsed angioimmunoblastic T-cell lymphoma (AILT). Three months after the transplant, the patient developed fever with elevated plasma Epstein-Barr virus (EBV)-PCR values. The patient subsequently developed pneumonitis, hepatomegaly and marked pancytopenia due to hemophagocytosis. The patient died of multi-organ failure, despite antiviral and steroid pulse therapy. Our post-mortem study confirmed the marked proliferation of EBV-infected T-cells that differed from the original AILT clone and macrophages/histiocytes were observed in the marrow, liver, lymph nodes and lungs. Phagocytosis was most evident in the bone marrow. The patient's AILT remained in complete remission. To the best of our knowledge, this is the first case of fulminant EBV-associated T-cell lymphoproliferative disorder (LPD) following autologous HSCT.

Antigens, CD↗
PubMed2005

1'-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of TRAIL.

A component of a traditional Thai condiment, 1'-acetoxychavicol acetate (ACA), is a natural compound, and it is obtained from rhizomes of the ethno-medicinal plant Languas galanga (Zingiberaceae). Our previous studies showed that ACA dramatically inhibited cellular growth of multiple myeloma cells in vivo and in vitro through the induction of apoptosis in association with the activation of caspase-8, inactivation of NF-kappaB, and down-regulation of anti-apoptotic proteins. Subsequently, we investigated the detailed apoptotic pathway of ACA and further demonstrated that ACA up-regulates the expression of both TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) and TRAIL receptor death receptor 5 (DR5). In addition, TRAIL/R-Fc chimera neutralizes the ACA-induced apoptosis. These results suggest that the death signaling of TRAIL is involved in the ACA-induced apoptosis of myeloma cells, and provide a rationale for the induction of TRAIL/Apo2L by ACA, which could potentially be used as a novel therapeutic agent in patients with multiple myeloma.

Apoptosis↗
PubMed2005

Effects of immunosuppressive agents on magnesium metabolism early after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus, cause hypomagnesemia by suppressing reabsorption of magnesium (Mg) from renal tubules. To assess whether the effect on Mg metabolism after allogeneic hematopoietic stem cell transplantation (HSCT) differs among calcineurin inhibitors, we prospectively evaluated the Mg metabolism in recipients of allogeneic HSCT who received CSA or tacrolimus METHODS: Patients who underwent allogeneic HSCT were enrolled. CSA and tacrolimus were given by continuous infusion starting from day -1. Serum Mg and the total amount of urinary Mg excretion were measured once before starting of CSA or tacrolimus, and once weekly after HSCT for 4 weeks. Mg was supplemented with magnesium l-aspartate by continuous infusion to maintain the serum Mg level >1.4 mEq/L. RESULTS: Thirty-six patients were evaluated (12 in the CSA group, 24 in the tacrolimus group). The serum Mg level began to decrease in both groups at the first week after HSCT, and the mean serum Mg levels were significantly lower in the tacrolimus group than in the CSA group from the first to the third week. The total amount of urinary Mg excretion and Mg supplementation began to increase in both groups at the second week after HSCT, and the amounts in the tacrolimus group were significantly higher than those in the CSA group. CONCLUSIONS: Although both calcineurin inhibitors increased urinary Mg excretion and caused hypomagnesemia shortly after HSCT, the effect was more significant with tacrolimus than with CSA. This observation may explain the higher incidence of renal impairment and encephalopathy in patients receiving tacrolimus.

Adult↗
PubMed2005

Formulation study and drug release mechanism of a new theophylline sustained-release preparation.

Two matrix theophylline tablets with different release mechanisms were compared. Tablet A was a swelling/disintegration-type wax matrix made of hydrophobic wax granules, consisting of stearic acid, hydrogenated oil and glycerol esters of fatty acids, and hydrophilic polymer granules composed primarily of hydroxypropyl methylcellulose (HPMC). We named Tablet A the cluster tablet. Tablet B was a gel matrix made of hydrophobic ethylcellulose granules, consisting of ethylcellulose and hydrogenated oil, and hydrophilic polymer granules consisting of HPMC and hydroxylpropylmethylcellulose acetate succinate (HPMCAS). The formulations were screened in vitro according to their dissolution characteristics. The drug release from each preparation was analyzed using release kinetics theories. In Tablet A, the value of the exponent(n) representing the apparent diffusion mechanism determined from the Korsmeyer-Peppas model equation was about 0.6 and was unlikely to be affected by the rotation speed. In Tablet B, the value of the exponent(n) by the Korsmeyer-Peppas model equation changed with the paddle rotation speed. These results suggested that the drug release mechanism of Tablet B is greatly affected by the extent of physical force in the gastrointestinal tract.

Delayed-Action Preparations↗
PubMed2005

Green tea component, catechin, induces apoptosis of human malignant B cells via production of reactive oxygen species.

PURPOSE: Green tea polyphenol, (-)-epigallocatechin-3-gallate, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of (-)-epigallocatechin-3-gallate as a novel therapeutic agent for the patients with B-cell malignancies including multiple myeloma. EXPERIMENTAL DESIGN: We investigated the effects of (-)-epigallocatechin-3-gallate on the induction of apoptosis in HS-sultan as well as myeloma cells in vitro and further examined the molecular mechanisms of (-)-epigallocatechin-3-gallate-induced apoptosis. RESULTS: (-)-Epigallocatechin-3-gallate rapidly induced apoptotic cell death in various malignant B-cell lines in a dose- and time-dependent manner. (-)-Epigallocatechin-3-gallate-induced apoptosis was in association with the loss of mitochondrial transmembrane potentials (Deltapsim); the release of cytochrome c, Smac/DIABLO, and AIF from mitochondria into the cytosol; and the activation of caspase-3 and caspase-9. Elevation of intracellular reactive oxygen species (ROS) production was also shown during (-)-epigallocatechin-3-gallate-induced apoptosis of HS-sultan and RPMI8226 cells as well as fresh myeloma cells. Antioxidant, catalase, and Mn superoxide dismutase significantly reduced ROS production and (-)-epigallocatechin-3-gallate-induced apoptosis, suggesting that ROS plays a key role in (-)-epigallocatechin-3-gallate-induced apoptosis in B cells. Furthermore, a combination with arsenic trioxide (As2O3) and (-)-epigallocatechin-3-gallate significantly enhanced induction of apoptosis compared with As2O3 alone via decreased intracellular reduced glutathione levels and increased production of ROS. CONCLUSIONS: (-)-Epigallocatechin-3-gallate has potential as a novel therapeutic agent for patients with B-cell malignancies including multiple myeloma via induction of apoptosis mediated by modification of the redox system. In addition, (-)-epigallocatechin-3-gallate enhanced As2O3-induced apoptosis in human multiple myeloma cells.

Apoptosis↗
PubMed2005

Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease.

Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.

Adult↗
PubMed2005

1'-acetoxychavicol acetate is a novel nuclear factor kappaB inhibitor with significant activity against multiple myeloma in vitro and in vivo.

1'-Acetoxychavicol acetate (ACA) is a component of a traditional Asian condiment obtained from the rhizomes of the commonly used ethno-medicinal plant Languas galanga. Here, we show for the first time that ACA dramatically inhibits the cellular growth of human myeloma cells via the inhibition of nuclear factor kappaB (NF-kappaB) activity. In myeloma cells, cultivation with ACA induced G0-G1 phase cell cycle arrest, followed by apoptosis. Treatment with ACA induced caspase 3, 9, and 8 activities, suggesting that ACA-induced apoptosis in myeloma cells mediates both mitochondrial- and Fas-dependent pathways. Furthermore, we showed that ACA significantly inhibits the serine phosphorylation and degradation of IkappaBalpha. ACA rapidly decreased the nuclear expression of NF-kappaB, but increased the accumulation of cytosol NF-kappaB in RPMI8226 cells, indicating that ACA inhibits the translocation of NF-kappaB from the cytosol to the nucleus. To evaluate the effects of ACA in vivo, RPMI8226-transplanted NOD/SCID mice were treated with ACA. Tumor weight significantly decreased in the ACA-treated mice compared with the control mice. In conclusion, ACA has an inhibitory effect on NF-kappaB, and induces the apoptosis of myeloma cells in vitro and in vivo. ACA, therefore, provides a new biologically based therapy for the treatment of multiple myeloma patients as a novel NF-kappaB inhibitor.

Adult↗
PubMed2005

Membrane-proximal {alpha}/{beta} stalk interactions differentially regulate integrin activation.

The affinity of integrin-ligand interaction is regulated extracellularly by divalent cations and intracellularly by inside-out signaling. We report here that the extracellular, membrane-proximal alpha/beta stalk interactions not only regulate cation-induced integrin activation but also play critical roles in propagating inside-out signaling. Two closely related integrins, alphaIIbbeta3 and alphaVbeta3, share high structural homology and bind to similar ligands in an RGD-dependent manner. Despite these structural and functional similarities, they exhibit distinct responses to Mn(2+). Although alphaVbeta3 showed robust ligand binding in the presence of Mn(2+), alphaIIbbeta3 showed a limited increase but failed to achieve full activation. Swapping alpha stalk regions between alphaIIb and alphaV revealed that the alpha stalk, but not the ligand-binding head region, was responsible for the difference. A series of alphaIIb/alphaV domain-swapping chimeras were constructed to identify the responsible domain. Surprisingly, the minimum component required to render alphaIIbbeta3 susceptible to Mn(2+) activation was the alphaV calf-2 domain, which does not contain any divalent cation-binding sites. The calf-2 domain makes interface with beta epidermal growth factor 4 and beta tail domain in three-dimensional structure. The effect of calf-2 domain swapping was partially reproduced by mutating the specific amino acid residues in the calf-2/epidermal growth factor 4-beta tail domain interface. When this interface was constrained by an artificially introduced disulfide bridge, the Mn(2+)-induced alphaVbeta3-fibrinogen interaction was significantly impaired. Notably, a similar disulfide bridge completely abrogated fibrinogen binding to alphaIIbbeta3 when alphaIIbbeta3 was activated by cytoplasmic tail truncation to mimic inside-out signaling. Thus, disruption/formation of the membrane-proximal alpha/beta stalk interface may act as an on/off switch that triggers integrin-mediated bidirectional signaling.

Animals↗