[Show abstract][Hide abstract] ABSTRACT: PAR-3 is one of the PAR proteins, previously named ASIP, which are indispensable for the establishment of cell polarity in the embryo as well as differentiated epithelial cells. In mammalian epithelial cells, it forms a ternary complex with aPKC and PAR-6, and is localized to the tight junction that has been suggested as being important for creating cell polarity.
To gain insights into the mode of PAR-3 function in mammalian epithelial cells, we examined the effect of PAR-3 over-expression in MDCK cells. Although exogenous PAR-3-expression does not affect the epithelial polarity of confluent cells, it drastically transforms the morphology of cells at low density into a fibroblastic form with developed membrane protrusions. Time-lapse observations have revealed that PAR-3 over-expressing cells show intense motility, even after they have assembled into loose colonies, suggesting that the contact-mediated inhibition of cell migration (CIM) is suppressed. The expressions of E-cadherin and vimentin do not change with PAR-3 over-expression, suggesting that exogenous PAR-3 only disturbs the endogenous equilibrium of cellular states between a fundamental fibroblastic structure and an epithelial one. The co-expression of a dominant negative mutant of Rac1 and the addition of nocodazole strongly antagonize the effect of PAR-3 over-expression, suggesting the involvement of Rac1 activation and microtubule polymerizations.
: The data presented here suggest an intriguing link between the contact-mediated inhibition of cell migration and the regulation of cell polarity. The putative PAR-3 activities demonstrated here may function endogenously in the epithelial cell polarization process by being sequestered from the cytosol to the cell-cell junctional regions with aPKC and PAR-6 upon cell-cell adhesion.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.
No preview · Article · Mar 2002 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: We report a patient with chronic myelogenous leukemia who received a second transplant from a one-locus HLA-mismatched unrelated donor after rejection of an initial bone marrow graft. For the first transplant, HLAs were fully matched, conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A complete chimera was not obtained, and the graft was rejected on day 122. For the second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was occurred at the time of writing. This case suggests that strong immunosuppression may have prevented rejection of the second bone marrow graft.
No preview · Article · Sep 2001 · [Rinshō ketsueki] The Japanese journal of clinical hematology
[Show abstract][Hide abstract] ABSTRACT: We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and that immunological mechanisms may have effected the onset of BOOP after BMT in this case.
Preview · Article · Sep 2001 · Transplant International
[Show abstract][Hide abstract] ABSTRACT: We report on a patient with chronic myelogenous leukemia who developed bronchiolitis obliterans organizing pneumonia (BOOP)
after allogeneic bone marrow transplantation (BMT). A 19-year-old Japanese male complained of dry cough and dyspnea 7 months
after BMT. The chest X-ray and computed tomography revealed patchy infiltrates bilaterally. Lung function test, lung biopsy
and bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient also suffered from suspected graft-versus-host
disease (GVHD) of the liver, after discontinuation of cyclosporine. Furthermore, prednisolone proved effective against the
BOOP and the liver dysfunction. These findings indicate that BOOP is a possible pulmonary manifestation of chronic GVHD, and
that immunological mechanisms may have effected the onset of BOOP after BMT in this case.
No preview · Article · Jul 2001 · Transplant International
[Show abstract][Hide abstract] ABSTRACT: Focal adhesions (FAs) are essential structures for cell adhesion, migration, and morphogenesis. Integrin-linked kinase (ILK), which is capable of interacting with the cytoplasmic domain of β1 integrin, seems to be a key component of FAs, but its exact role in cell–substrate interaction remains to be clarified. Here, we identified a novel ILK-binding protein, affixin, that consists of two tandem calponin homology domains. In CHOcells, affixin and ILK colocalize at FAs and at the tip of the leading edge, whereas in skeletal muscle cells they colocalize at the sarcolemma where cells attach to the basal lamina, showing a striped pattern corresponding to cytoplasmic Z-band striation. When CHO cells are replated on fibronectin, affixin and ILK but not FA kinase and vinculin concentrate at the cell surface in blebs during the early stages of cell spreading, which will grow into membrane ruffles on lamellipodia. Overexpression of the COOH-terminal region of affixin, which is phosphorylated by ILK in vitro, blocks cell spreading at the initial stage, presumably by interfering with the formation of FAs and stress fibers. The coexpression of ILK enhances this effect. These results provide evidence suggesting that affixin is involved in integrin–ILK signaling required for the establishment of cell–substrate adhesion.
Full-text · Article · Jul 2001 · The Journal of Cell Biology
[Show abstract][Hide abstract] ABSTRACT: We describe the case of a 73-year-old woman with secondary myelofibrosis who developed subcutaneous extramedullary hematopoiesis. Although extramedullary hematopoiesis has been generally observed in primary myelofibrosis, in this case it was seen in myelofibrosis secondary to polycythemia vera. Histological examination of the subcutaneous nodule revealed that the lesion included cells from the myeloid and megakaryocytic series. The skin lesion almost disappeared after treatment with hydroxyurea. We report here this rare manifestation in secondary myelofibrosis including a review of literature.
No preview · Article · Feb 2001 · Leukemia and Lymphoma
[Show abstract][Hide abstract] ABSTRACT: Mitogen-activated protein kinase upstream kinase/dual leucine zipper-bearing kinase/leucine-zipper protein kinase (MUK/DLK/ZPK) is a MAPKKK class protein kinase that induces JNK/SAPK activation. We report here a protein named MBIP that binds to MUK/DLK/ZPK. MUK-binding inhibitory protein (MBIP) contains two tandemly orientated leucine-zipper-like motifs with a cluster of basic amino acids located between the two motifs. MBIP interacts with one of the two leucine-zipper-like motifs of MUK/DLK/ZPK and inhibits the activity of MUK/DLK/ZPK to induce JNK/SAPK activation. Notably, no similar effect was observed with another JNK/SAPK-inducing MAPKKK, COT/Tpl-2, showing the specificity of MBIP action. Furthermore, the overexpression of MBIP partially inhibits the activation of JNK by 0.3 m sorbitol in 293T cells. Taken together, these observations indicate that MBIP can function as a regulator of MUK/DLK/ZPK, a finding that may provide a clue to understanding the molecular mechanism of JNK/SAPK activation by hyperosmotic stress.
No preview · Article · Aug 2000 · Journal of Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: The translocation t(1;3)(p36;q21) has been reported previously in patients with the myelodysplastic syndrome and with acute nonlymphocytic leukemia. It has been reported in only 5 cases of chronic myelomonocytic leukemia and t(1;3)(p36;q21). We observed a case of chronic myelomonocytic leukemia with t(1;3)(p36;q21) complicated by a gastric cancer at the time of diagnosis.
No preview · Article · May 2000 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.
No preview · Article · Apr 2000 · American Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: Recently, CD56 (NCAM)-positive lymphomas, such as nasal and nasal-type angiocentric NK/T cell lymphoma, aggressive NK cell leukemia/lymphoma and blastic NK cell lymphoma, were described by several authors as a unique group of lymphoma.
In this study, we intend to clarify the clinicopathological features of cutaneous CD4+ and CD56+ lymphoma.
Four patients with cutaneous CD4+ and CD56+ lymphoma were studied.
Age at the first examination ranged from 71 to 89 years (mean = 81.2 years). One patient was female and 3 were males. The organ mainly involved at presentation was the skin. Lymphadenopathy, splenomegaly, leukemic spread and central nervous system involvement were observed as the disease progressed. The mean survival time was 12.2 months. Epstein-Barr virus was not detected within the tumor cells.
This peculiar lymphoma is different from nasal and nasal-type angiocentric NK/T cell lymphoma and aggressive NK cell leukemia/lymphoma. Similar cases have been reported as blastic NK cell lymphoma/leukemia.
[Show abstract][Hide abstract] ABSTRACT: We describe a 55-year-old Japanese man with acute minimally differentiated myeloid leukemia (M0) with an inversion in the long arm of chromosome 3, i.e., inv(3)(q21q26). Patients with this chromosomal abnormality usually show normal or elevated platelet counts. However, our case had a low platelet count with megakaryocytic dysplasia at diagnosis. Furthermore, the 3q21q26 aberration is generally detected in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome. To the best of our knowledge, it has also been reported in two cases of AML-M0 with 3q21q26 and this is the third case of AML-M0 with 3q21q26. Thus it is suggested that there is some relationship between this type of karyotype abnormality and leukemogenesis and/or thrombopoiesis.
No preview · Article · Nov 1999 · Leukemia and Lymphoma
[Show abstract][Hide abstract] ABSTRACT: A 34-year-old woman of HTLV-I carrier with T-PLL, whose quality of life improved and survival was prolonged after splenectomy, is described. The patient had marked splenomegaly, generalized lymphadenopathy and marked proliferation of abnormal lymphocytes in the peripheral blood with an irregular nucleus, deeply basophilic cytoplasm and a single prominent nucleolus, which were positive for CD2, CD3, CD5, CD7, CD4 and CD8. Although the patient had serum antibody against HTLV-I, HTLV-I proviral DNA integration was not detected. She was diagnosed as an HTLV-I carrier with T-PLL and received combination chemotherapy and 15.1 Gy splenic irradiation. However, the generalized lymphadenopathy and splenomegaly did not improve. The patient underwent splenectomy to palliate abdominal distension and hypersplenism. After the operation, her symptoms improved dramatically and within a week her hemoglobin concentration and platelet count normalized. She was discharged from hospital two weeks after the splenectomy, however 11 months later, she relapsed and despite treatment with chemotherapy and alpha-interferon, she died two months after the second admission. Autopsy findings revealed that PLL cells had invaded the bone marrow, lymph nodes, liver, lungs, kidneys, uterus, ovaries and adrenal glands.
No preview · Article · Nov 1999 · Leukemia and Lymphoma
[Show abstract][Hide abstract] ABSTRACT: To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.
Preview · Article · Sep 1999 · Bone Marrow Transplantation
[Show abstract][Hide abstract] ABSTRACT: A 22-year-old woman was admitted with purpura. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. On the 17th day after treatment with all-trans retinoic acid (ATRA), left subdural hematoma developed. Although coagulation abnormalities were still observed, emergency surgery was performed. Acute epidural hematoma was confirmed by computed tomographic scan after the operation. A second operation for drainage was successful. Post-operative intracranial hematoma may be caused by rapid decompression induced by surgery, but DIC could also be involved. This case underscored the need for careful consideration of the indications for surgical treatment of such DIC patients, with close follow-up monitoring for the postoperative development of neurological symptoms.
No preview · Article · Aug 1999 · [Rinshō ketsueki] The Japanese journal of clinical hematology
[Show abstract][Hide abstract] ABSTRACT: We describe a rare case of de novo acute myelogenous leukemia with trilineage myelodysplasia (AML/TMDS) associated with t(8;21)(q22;q22). The patient was admitted to our hospital with leukocytopenia. AML/TMDS was diagnosed by excess myeloblasts and morphological findings of bone marrow. The karyotype revealed 45, X, -Y, t(8;21)(q22;q22) in 17 of 20 analyzed mitoses, and also AML1/MTG8 transcripts were detected by the reverse transcription polymerase chain reaction (RT-PCR) method. The patient achieved a complete remission with a combination chemotherapy of daunorubicin, cytarabine, and prednisolone. This case suggests that t(8;21)(q22;q22) may participate in the pathogenesis of AML/TMDS, although this type is usually found as one of the chromosomal abnormalities in de novo acute myelogenous leukemia (AML) with maturation.
No preview · Article · Aug 1999 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: We report a 49-year-old female patient with secondary myelodysplastic syndrome who developed liver dysfunction and acute renal failure caused by low-dose cytosine arabinoside (Ara-C) therapy. Treatment of low-dose Ara-C has widely been used for acute myelogeous leukemia and myelodysplastic syndrome, and it is thought to be a low toxicity except for myelosuppression. The patient complained of a transient adverse reaction in the second and third course of therapy. This rare case indicates that careful observation should be carried out during low-dose Ara-C therapy in view of allergic reactions.
No preview · Article · Apr 1999 · Anti-Cancer Drugs