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Biomedical subjects

T Soma

Publications and source records attributed to T Soma.

At least 37 records · Page 2Linked to original sources

[A case of aseptic osteomyelitis with heel ulcer improved by steroid application].

A 43-year-old male patient was admitted to our hospital because of left heel pain and fever. He had had swelling of the left ankle joint and pain 4 years prior to this, and 4 years later, he was admitted to another hospital when left heel ulcer and fever developed. The ulcer was diagnosed and treated as a diabetic ulcer because of hyperglycemia. In spite of good control of blood sugar, the ulcer became enlarged and the pain deteriorated, so he was transferred to orthopedics. Antibiotics produced no response, and culture from a specimen of the ulcer was negative. However, severe inflammatory response was seen in blood examination. MRI and scintigram of his left foot showed disseminated low intensity areas and accumulation in the tarsal bone area, so osteomyelitis was suspected. A biopsy of the ulcer showed infiltration of inflammatory cells into the dermis. We considered amputation of the left lower leg at first. However the biopsy result suggested an autoimmune mechanism, so prednisolone was administered. As a result, the ulcer and pain both diminished. This case was similar to pyoderma gangenosum, however this diagnosis cannot explain osteomyelitis or all its symptoms. We expect that there must be other case report with the same symptoms.

Adult↗

[A case of primary macroglobulinemia with acute pulmonary edema].

A 54-year-old man with acute respiratory failure underwent emergency admission to our hospital. Acute pulmonary edema combined with severe pneumonia was strongly suspected, and treatment with diuretics, antibiotics, and corticosteroids was effective. The diagnosis, primary macroglobulinemia, was made from the following findings: a high level of the lgM 1 type monoclonal protein, and an elevated serum viscosity with characteristic "linked sausage effects" seen in the retinal veins. Lymphoplasmacytoid cells, plasma cells, and small lymphocytes were seen in the bone marrow and lymphoplasmacytoid cells were also seen in the smear of the patient's peripheral blood. The types of malignant cells found in his bone marrow were also seen in both infiltrative lesions in the lung parenchyma and the pleural effusion. We concluded that this was a case of primary macroglobulinemia with acute pulmonary edema, which was caused partly by the hyperviscosity syndrome. The antitumor effect of the corticosteroid might have some effect on the recovery from acute respiratory failure and primary macroglobulinemia. He was transferred to the Department of Hematology to receive suitable chemotherapy.

Acute Disease↗

[Diagnostic efficacy of 18F-fluorodeoxy glucose-positron emission tomography in multiple solitary pulmonary nodules].

A 73-year-old man was admitted to our hospital for evaluation of abnormal lung shadows in the left lung. Chest computed tomography revealed a cavitary lesion with irregular edges in the right S10 and a nodular lesion with well-defined margins in the left S6. Histological examination of a specimen obtained by transbronchial lung biopsy revealed squamous cell carcinoma in the right S10 but no significant findings in the left S6. Thirdly, 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) demonstrated that the nodular shadow in the left S6 was a low-uptake structure and that the cavitary lesion in the right S10 was a high-uptake lesion. We therefore considered that the nodular shadow in the left S6 was not one of neoplastic disease. Partial lung resection of the left S6 was carried out by videoassisted thoracoscopic surgery. The pathological diagnosis of the left S6 was epithelial granuloma with caseation. A culture of the same resected specimen was positive for Mycobacterium avium. The eventual clinical staging for the squamous cell carcinoma in the right S10 was cT2N0M0 (IB). Radical surgical treatment and right lower lobectomy were performed for the S10 lesion. We considered that 18F-FDG-PET was an effective noninvasive procedure for diagnosis of solitary or multiple solitary nodular shadows in the lung.

Aged↗

Quasiperiodic patterns generated by mixing lattices derived from a dodecahedral star and an icosahedral star.

A 3D quasiperiodic pattern by projection from an nD lattice can be defined by an orthonormal n x n lattice matrix which produces basis vectors in pattern space with a prescribed arrangement and basis vectors in perpendicular or test space satisfying the quasicrystallographic condition. A 16 x 16 lattice matrix is derived which produces basis vectors in pattern space as a combination or mixing of dually positioned dodecahedral star and icosahedral star. It is shown that the mixed star constitutes a eutactic star. Since the module generated by the mixed eutactic star is totally irrational, patterns generated by projection using the lattice matrix are quasicrystallographic and the equilateral pattern is generated for 1:1 mixing.

Journal Article↗

Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF).

Bone marrow (BM) cells that were concentrated for hematopoietic progenitor cells by in vivo treatment with 5-FU were infected with a recombinant retrovirus containing a human full-sized, non-spliced type WT1 (Wilms' tumor gene 1) cDNA and then colony-assayed in the presence of granulocyte-colony stimulating factor (G-CSF). Significantly more colony-forming units granulocyte-monocyte (CFU-GM), colony-forming units granulocyte (CFU-G), and colony-forming units monocyte (CFU-M) colonies were formed in response to G-CSF from the BM cells infected with the WT1-containing retrovirus than from the control BM cells infected with an empty vector. Furthermore, FACS analysis of cell surface differentiation markers showed the inhibition of differentiation by constitutive WT1 expression resulting from the infection with the WT1-containing retrovirus. These results thus showed that the constitutive WT1 expression promoted the proliferation of myeloid progenitor cells but inhibited their differentiation in response to G-CSF, suggesting the alteration of G-CSF signaling pathway. The results also supported our hypothesis that the WT1 gene performs an oncogenic rather than a tumor suppressor gene function in hematopoietic progenitor cells, although the WT1 gene potentially performs both functions. This finding implies an important role of the WT1 gene in leukemogenesis.

Animals↗

The relationship between modified pulse wave transit time and cardiovascular changes in isoflurane anesthetized dogs.

OBJECTIVE: To clarify the relationship between blood pressure and pulse wave transit time at the peripheral artery from the R wave of the electrocardiogram (m-PWTT), the effects of cardiovascular interventions on this relationship was evaluated. METHODS: Ten mongrel dogs were anesthetized by isoflurane inhalation, and catheter tip pressure transducers were inserted into the ascending aorta and at the bifurcation of abdominal aorta to measure central and peripheral pulse wave arrival. Pulse wave arrival at the ascending aorta from the R wave represents pre-ejection period (PEP) and pulse wave arrival between the ascending aorta and bifurcation of aorta represents pulse wave transit time (PWTT), thus m-PWTT = PEP + PWTT. Hypertension was induced by the continuous infusion of dobutamine and phenylephrine, and hypotension was induced by deepening isoflurane anesthesia, acute blood loss and nitroglycerine infusion. The relationship between timing components (PWTT, PEP, and m-PWTT) and blood pressure was recorded and analyzed by using the least squares method. RESULTS: The relationship between timing components (PWTT, PEP and, m-PWTT) and blood pressure was significant and highly correlated. When the change in blood pressure was due to the myocardial contractility, such as after dobutamine infusion, the relationship between all timing components and blood pressure was consistent and negative. However, when the change in blood pressure was due to the vasoactive agents, such as phenylephrine, the relationship between timing components and blood pressure was dependent on the reflex change in PEP. CONCLUSIONS: Change in m-PWTT is a good parameter to predict blood pressure changes, although the absolute blood pressure value cannot be obtained.

Anesthetics, Inhalation↗

The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes.

The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.

Adult↗

Leiomyosarcoma of the spermatic cord.

BACKGROUND: A rare case of leiomyosarcoma from the spermatic cord is described. A 72-year-old man complained of a hard, golf-ball sized mass in the right inguinal canal. METHODS: Transinguinal radical orchiectomy was performed and histologic examination revealed leiomyosarcoma originating from the spermatic cord. Distant metastases were not observed by further examinations. Radiation as adjuvant therapy was carried out in order to prevent the local recurrence. RESULTS/DISCUSSION: The patient has been alive for 16 months with no evidence of disease. In leiomyosarcoma of the spermatic cord, locoregional recurrence is common. In addition to transinguinal radical orchiectomy, local radiation therapy should be carried out as an adjuvant.

Aged↗

Granulocyte apheresis as a possible new approach in cancer therapy: A pilot study involving two cases.

Patients with advanced cancer often develop immunodeficiency which may be associated with granulocytosis. The granulocytes have the potential to deplete cytotoxic T cells, resulting in accelerated tumor growth and metastasis. To study the elimination of excess granulocytes using granulocyte apheresis in patients with elevated granulocyte to lymphocyte ratios, 2 patients with recurrent metastatic tumors, were selected. Granulocyte apheresis was performed by extracorporeal vein-to-vein circulation with the G-1 granulocyte and monocyte/macrophage apheresis column filled with cellulose acetate beads, each 2 mm in diameter to adsorb granulocytes and monocytes/macrophages. The patients received 1 or 2 apheresis of 30 to 50 min duration per week, at a flow rate of 30-50 ml/min, with 15 sessions constituting one therapeutic course. Apheresis markedly reduced tumor size and prolonged patient survival time without causing any serious adverse events. The results of the present study suggest that granulocyte and monocyte/macrophage apheresis may be beneficial in patients with metastasizing tumors.

Biomarkers, Tumor↗

Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth.

To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines (four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer cell lines, four breast cancer cell lines, one germ cell tumor cell line, two ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell line, and one hepatocellular carcinoma cell line) by means of quantitative reverse transcriptase-polymerase chain reaction. WT1 gene expression was detected in three of the four gastric cancer cell lines, all of the five colon cancer cell lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28 (82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ-521, lung cancer cell line OS3, and ovarian cancer cell line TYK-nu) were further analyzed for mutations and/or deletions in the WT1 gene by means of single-strand conformation polymorphism analysis. However, no mutations or deletions were detected in the region of the WT1 gene ranging from the 3' end of exon 1 to exon 10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore, when AZ-521, OS3, and TYK-nu cells were treated with WT1 antisense oligomers, the growth of these cells was significantly inhibited in association with a reduction in WT1 protein levels. Furthermore, constitute expression of the transfected WT1 gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on cell growth. These results indicated that the WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor-suppressor gene function.

DNA-Binding Proteins↗

Successful treatment of relapsed T-cell non-Hodgkin's lymphoma with allogeneic peripheral blood stem cell transplantation with double conditioning.

We report a patient with T-cell non-Hodgkin's lymphoma (NHL) who relapsed after treatment with relatively intensive third-generation chemotherapy, VACOP-B, and who was safely and effectively treated with allogeneic peripheral blood stem cell transplantation (allo PBSCT) with double conditioning. The first conditioning consisted of carboplatin and etoposide. Twenty-one days later, the second conditioning was performed with cytosine arabinoside, cyclophosphamide, and total body irradiation (AraC/Cy/TBI). Between the periods of the first and second conditioning, autologous (auto) PBSCT (4.4 x 10(5) colony-forming units granulocyte/macrophage (CFU-GM)/kg, 3.8 x 10(6) CD34+ cells/kg) was performed to rescue marrow aplasia after the first conditioning. After the second conditioning, allo PBSCT (2.1 x 10(5) CFU-GM/kg, 8.2 x 10(6) CD34+ cells/kg) was performed from a human leukocyte antigen-identical sibling. Marrow reconstitution after allo PBSCT was rapid. Grade I acute graft-vs.-host disease (GVHD) involving skin and chronic GVHD on the eye was observed. No severe transplantation-related complications occurred. With a follow-up of 22 months after allogeneic PBSCT, the patient is alive without evidence of the disease. This case shows that allo PBSCT with intensive double conditioning may become a new treatment strategy to achieve long-term disease-free survival for young NHL patients of resistant relapse with a great deal of tumor burden and invasion of lymphoma cells in bone marrow.

Adult↗

[Body surface ultrasonography-guided bronchofiberscopy].

Transbronchial lung biopsies and cytologic studies under ultrasonographic guidance from the body surface were conducted in 39 patients whose lesions were adjacent to the thoracic wall. In 26 patients, biopsy, curettage, or brushing forceps were visualized in the mass or infiltrative lesion by thoracic echogram. Positive findings were obtained in 23 patients, for a conclusive diagnostic rate of 88.5%. Of the 13 patients in whom forceps could not be visualized by echogram, 10 had positive findings, for a diagnostic rate of 76.9%. For visualization by thoracic echogram, abnormal lung lesions must be in direct contact with the thoracic wall. Occasionally, diagnostic procedures may be impeded by anatomical structures such as shoulder joints or scapula. Despite these disadvantages, the ultrasonography-guided bronchofiberscope is quite useful because it facilitates real-time confirmation of the positioning of the forceps relative to the lesions. It is also useful in cases when the peripheral lesions are too small or vague to be demonstrated by fluoroscopy alone, because the echo probe can be the target of the forceps instead of the missing shadows. The diagnostic rate should be higher when the forceps are visualized in the lesions ultrasonographically.

Adult↗

Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells.

The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that the WT1 gene is strongly expressed in leukemia cells with an increase in its expression levels at relapse and an inverse correlation between its expression levels and prognosis, thus making it a novel tumor marker for leukemic blast cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth of leukemic cells. These results strongly suggested the involvement of the WT1 gene in human leukemogenesis. The present study was performed to prove our hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells, rather than a tumor-suppressor gene function. 32D cl3, an interleukin-3-dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to granulocyte colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene was constitutively expressed in 32D cl3, the cells stopped differentiating and continued to proliferate in response to G-CSF. As for signal transduction mediated by G-CSF receptor (G-CSFR), Stat3alpha was constitutively activated in wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected 32D cl3, activation of Stat3alpha was only transient. However, most interesting was the fact that G-CSF stimulation resulted in constitutive activation of Stat3beta only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D cl3. Thus, WT1 expression constitutively activated both Stat3alpha and Stat3beta. A transient activation of Stat1 was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation was found. No activation of MAP kinase was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation. These results demonstrated that WT1 expression competed with the differentiation-inducing signal mediated by G-CSFR and constitutively activated Stat3, resulting in the blocking of differentiation and subsequent proliferation. Therefore, the data presented here support our hypothesis that the WT1 gene plays an essential role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells and represent the first demonstration of an important role of the WT1 gene in signal transduction in hematopoietic progenitor cells.

Animals↗

Desmoplastic response in biopsy specimens of early colorectal carcinoma is predictive of deep submucosal invasion.

PURPOSE: The aim of this study was to evaluate the role of histopathology of biopsy specimens in predicting depth of infiltration in early colorectal carcinomas before treatment. METHODS: Early colorectal carcinomas that had been resected surgically or endoscopically between 1984 and 1995 were analyzed. Histopathologic findings, including differentiation of adenocarcinoma and a desmoplastic response were investigated. RESULTS: One hundred nine early colorectal carcinomas consisted of 73 lesions of carcinoma in situ, 13 submucosal carcinomas with minimum invasion, 8 lesions with moderate invasion, and 15 lesions with deep invasion. Of 73 carcinoma in situ lesions, 72 (approximately 99 percent) showed well-differentiated adenocarcinomas and no desmoplastic response. Twelve (92 percent) of 13 submucosal carcinomas with minimum invasion also revealed well-differentiated adenocarcinoma without a desmoplastic response. Sixty-three percent (5/8) of lesions with moderate invasion revealed well-differentiated adenocarcinoma. None of the lesions had a desmoplastic response. Among lesions with deep invasion, 73 percent (11/15) demonstrated moderately differentiated adenocarcinoma, and 11 lesions had a prominent desmoplastic response (73 percent; P < 0.01). CONCLUSIONS: These results suggest that if histopathologic findings of biopsy specimens taken from them before treatment demonstrated adenocarcinoma associated with a desmoplastic response, the lesions had at least deep invasion carcinomas. These lesions should be resected surgically. Submucosal carcinomas with minimum invasion, which have no desmoplastic response, could be treated endoscopically.

Adenocarcinoma↗

Successful donor leukocyte transfusion at molecular relapse for a patient with acute myeloid leukemia who was treated with allogenic bone marrow transplantation: importance of the monitoring of minimal residual disease by WT1 assay.

We report here that a patient with relapsed AML after allogeneic bone marrow transplantation achieved and maintained complete remission (CR) after effective donor leukocyte transfusion (DLT), without the occurrence of GVHD and marrow aplasia, for more than 21 months. This continuous CR maintenance is mainly due to the application of DLT at molecular relapse that was diagnosed by monitoring minimal residual disease (MRD) by the quantitation of WT1 (Wilms tumor gene) expression levels (WT1 assay). The present case demonstrates that early application of DLT at molecular relapse is essential for the improvement of the efficacy of DLT for relapsed AML after BMT.

Acute Disease↗

Abrogation of TGF-beta activity during retroviral transduction improves murine hematopoietic progenitor and repopulating cell gene transfer efficiency.

Transforming growth factor-beta has complex activities on hematopoietic cells. We have previously shown that murine long-term repopulating activity is compromised by ex vivo culture in TGF-beta 1 and conversely is increased by abrogating endogenous TGF-beta activity with a neutralizing antibody. In the current study, we investigated the effect of abrogation of autocrine or paracrine TGF-beta present during retroviral transduction on gene transfer efficiency to primitive hematopoietic cells. Murine marrow cells were cultured and retrovirally transduced for 4 days in the presence of interleukin-3, interleukin-6 and stem cell factor, and either a neutralizing anti-TGF-beta antibody or an isotype control. Committed progenitor cells were analyzed for gene transfer efficiency, and cells were also injected into W/Wv recipient mice for analysis of transduction of long-term repopulating cells. The progenitor (CFU-C) transduction efficiency in the presence of anti-TGF-beta was significantly greater. Semiquantitative PCR analysis and Southern blot analysis for the retroviral marker gene in the blood and bone marrow of recipient mice revealed a significant increase in the transduction efficiency of long-term repopulating cells after culture and transduction in the presence of the anti-TGF-beta. Thus neutralization of TGF-beta activity during retroviral transduction allows more efficient gene transfer into primitive murine hematopoietic cells and may prove beneficial in future clinical gene transfer or therapy trials.

Animals↗