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Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 145 records · Page 8Linked to original sources

Inhibitory effect of 1alpha-hydroxyvitamin D3 on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastrointestinal carcinogenesis in Wistar rats.

The effect of 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on gastrointestinal carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in male Wistar rats. After oral treatment with 0.01% MNNG for 24 weeks, rats were given 0.04 microg of 1alpha(OH)D3 or its vehicle by gastric intubation three times a week for 24 weeks. The incidence of gastrointestinal tumors was 16/30 (53%) in rats treated with MNNG alone, 16/30 (53%) in those treated with MNNG plus vehicle and 8/30 (27%, P < 0.05) in those treated with MNNG plus 1alpha(OH)D3. The number of tumors per rat in the group treated with MNNG plus 1alpha(OH)D3 was half those in the control groups (P < 0.05). Results indicated that a non-hypercalcemic dose of 1alpha(OH)D3 had an inhibitory effect on MNNG-induced duodeno-intestinal carcinogenesis.

Animals↗

Cutting-out of the lag screw after internal fixation with the Asiatic gamma nail.

Sixty consecutive intertrochanteric femoral fractures were treated with the Asiatic gamma nail followed by early postoperative weight bearing. Cutting-out of the lag screw from the femoral head occurred in six fractures and were analysed radiographically with regard to fracture type (Evans' classification), osteoporosis (Singh grade), accuracy of post-operative reduction (neck-shaft angle and diastasis of the fracture), and location of the lag screw in the femoral head (depth, height, and antero-postero-posterior radiograph and large antero-posterior deviation of the lag screw were significantly related to the increased incidence of the screw cutting-out. This suggests that deep insertion of the lag screw on the antero-posterior view with central placement on the lateral view is an optimal location in the femoral head. The ¿cut-out index' (the multiplication value of the depth and the anteroposterior deviation of the lag screw in the femoral head) is an excellent measure of the risk of the lag screw cutting-out.

Aged↗

Recurrent dorsal angulation of the distal radius fracture during dynamic external fixation.

Thirty-three fractures of the distal radius treated with a dynamic external fixator (that allowed for wrist motion between 2 to 4 weeks after surgery) were analyzed, focusing on loss of fracture reduction during external fixation. Fractures with preoperative dorsal angulation greater than 20 degrees and those involving the distal radioulnar joint had a significantly larger loss of reduction of dorsal angulation (8.9 degrees and 6.9 degrees, respectively) than fractures with less severe preoperative dorsal angulation or those with an intact distal radioulnar joint (3.0 degrees and 2.6 degrees, respectively). In contrast, preoperative radial shortening (>2 mm) and involvement of the radiocarpal joint did not significantly increase the loss of dorsal angulation. Neither of the 2 dynamic external fixation systems studied consistently stabilized Colles' fractures with preoperative dorsal angulation of greater than 20 degrees or involvement of the distal radioulnar joint.

Adult↗

Recurrence with histological transformation 40 days after autologous peripheral blood stem cell transplantation (APBSCT) for cutaneous CD30-negative large T cell lymphoma.

Localized cutaneous nontender nodules appeared on the back of a 52-year-old Japanese woman. Skin biopsy revealed atypical large T-lymphocytes infiltrating the dermis. CD30 staining was negative in tumor cells. The diagnosis was CD30-negative cutaneous large T cell lymphoma. There was no evidence of peripheral lymphadenopathy or bone marrow involvement. Six cycles of induction chemotherapy were administered and a complete clinical remission (CCR) was attained. Local irradiation was not given. As the clinical course of CD30-negative cutaneous large T cell lymphoma is recurrent and often incurable with conventional chemoradiotherapy, she received high-dose chemotherapy without total body irradiation (TBI) followed by unpurged autologous peripheral blood stem cell transplantation (APBSCT). A relapse in the skin followed 40 days after APBSCT, but tumor cells transformed into a CD30-positive anaplastic large cell lymphoma (ALCL). We question the need for TBI in conditioning and for purged stem cells for APBSCT in patients with high risk cutaneous lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

Characterization and expression of a stage specific antigen by monoclonal antibody TRA 54 in testicular germ cells.

To study the mechanism of spermatogenesis, we have isolated many monoclonal antibodies (mAb) which recognize specific steps of mouse germ cell differentiation and then have evaluated the specific expression and characterization of antigenic molecules using immunohistochemistry and Western blotting. Monoclonal antibody TRA 54 recognized specific organelles in germ cell cytoplasm from spermatocytes to spermatids; that is, a large granule was stained in mid-late pachytene, diplotene and secondary spermatocytes and in round spermatids at stage I while the acrosome of spermatids at steps 2-3 to step 12 were also positive. Thereafter, the antigens disappeared from spermatids at more advanced stages of differentiation. Western blots using TRA 54 revealed broad bands with approximate molecular weights of >200, 190 and 85 kDa in the testis. The expression of these antigens during testicular germ cell development should be of interest in relation to the biogenesis of organelles such as the chromatoid body and acrosome and will be a useful stage-specific molecular marker for the study of spermatogenesis.

Animals↗

Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia.

Fetal anemia causes hydrops fetalis and fetal ascites/hydrothorax, and in severe cases the prognosis is poor. Little other than alloimmunity and viral infections are known as mechanisms causing fetal anemia. The aim of this study was to elucidate any pathogenesis in fetal anemia due to otherwise idiopathic etiology. The levels of three hematopoietic cytokines, IL-3, erythropoietin (EPO), and granulocyte colony-stimulating factor (G-CSF) were measured in blood samples obtained by cordocentesis from six fetuses with anemia (Hb <10.0 g/dl) and 34 fetuses without anemia. Cordocentesis was performed prior to the onset of labor or uterine contractions in all pregnant women. The concentration of IL-3 in fetuses with anemia [M+/-(SD), 8.3 (10.1) pg/ml] was significantly lower than that in fetuses without anemia [59.9 (71.0) pg/ml]. EPO and G-CSF levels were not different between the two groups. In addition, through in vitro colony formation assay, using blood stem cells from two fetuses with severe anemia and three fetuses without anemia, it was found that colony forming unit-erythroid, burst forming unit-erythroid and granulocyte macrophage-colony forming unit were significantly suppressed in blood stem cells from the two fetuses with severe anemia. Thus, the malfunction of differentiation and proliferation of blood stem cells and the decrease of hematopoietic cytokine levels in the fetal circulation may be responsible for the occurrence of fetal anemia.

Colony-Forming Units Assay↗

Therapeutic cytapheresis for inflammatory bowel disease.

Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.

Humans↗

Complications of leukocytapheresis.

Recently leukocytapheresis (LCAP) has attracted attention as a new therapy for ulcerative colitis. We reviewed the complications associated with LCAP carried out in our department during the period from December 1992 to September 1997. There were side effects during 195 (9.9%) of the 1,978 sessions performed, involving 47 (51.1%) of the 92 patients treated. Moderate reactions, which caused considerable discomfort to the patients and required the transient interruption of the administration or some medical treatment depending on the state, occurred during 31 (1.6%) of all therapy sessions, involving 15 (16%) patients. All patients recovered soon and never fell into a life-threateningly severe state. They also did not have any symptoms afterwards. The common side effects were nausea, vomiting, fever, chills, and nasal obstruction. Reactions such as palpitations, respiratory distress, or chest oppressions were common, especially when heparin sodium (HS) was used as the anticoagulant. The type and frequency of side effects depended somewhat on the length of the therapy series or the duration of one session. Other complications such as clotting in the leukocyte removal filter and/or blood line during administration were encountered frequently. These latter problems occurred during 46% of all sessions, but most of them had little significance. Sessions in which HS was used as the anticoagulant showed more severe clotting than those in which nafamostat mesilate (NM) was used. In our series, we experienced a relatively low rate of serious complications. We require, of course, careful observation during and after each session.

Adult↗

Three-dimensional ultrasonographic visualization of multiple pregnancy.

Our purpose was to describe interrelationships and contacts between twins in utero by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Thirteen twin pregnancies (3 monochorionic and 10 dichorionic pairs) and one triplet pregnancy (trichorionic triplet) from 9 to 36 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. Interrelationships and contacts between twins or triplets are described. Various types of contacts (head/body/arm/leg) and interrelationships were clearly visualized. Crowding of in utero twin fetuses increased with advancing gestation. Sometimes two placentas and dividing membrane were beautifully depicted. In one triplet pregnancy, the interrelationships among 3 fetuses and dividing membranes were easily recognized. Three-dimensional ultrasonography provides a novel means of visualizing multiple pregnancies in utero. These results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and would be useful in evaluating the interhuman contacts and crowdings of twin and triplet fetuses in utero.

Female↗

(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I).

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.

5-alpha Reductase Inhibitors↗

Growth characteristics of myelodysplastic CD34+ cells.

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders of hematopoiesis entailing hyperproliferative and ineffective hematopoiesis associated with morphologic evidence of marrow cell dysplasia resulting in refractory cytopenia(s), and an increased risk of transformation into acute myeloblastic leukemia (AML). The administration of colony-stimulating factor(s) (CSFs) to patients with MDS increased blood neutrophil concentrations, in most patients, and it was anticipated to be of benefit to prevent infections. The progression to AML while being treated with CSFs has come under close scrutiny. In vitro studies are expected to produce more pertinent criteria for selection of patients who are likely to benefit, as well as the overall benefits of various therapies. For this purpose, in vitro colony assays are an excellent approach for investigation of the biologic characteristics of MDS progenitor cells. The stem cell phenotype CD34 is the one of the best markers of progenitor cells, and can be used for the purification of these cells to unify levels of maturation; a direct comparison of proliferative and differentiative capacity of MDS progenitor cells with normal CD34+ cells can thus be made. The properties of MDS CD34+ cells are described here in association with proliferation and differentiation, with special emphasis on the role of stem cell factor (a ligand for c-kit) in leukemic type growth of MDS CD34+ cells.

Antigens, CD34↗

Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologous peripheral blood stem cell transplantation.

We monitored 30 laboratory hemostatic parameters in an attempt to better comprehend alterations in coagulation and fibrinolysis in 10 patients with hematological malignancies subjected to autologous peripheral blood stem cell transplantation (APBSCT). These parameters were assessed before and just after high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical manifestations associated with fibrino-coagulation disorders never occurred, including veno-occlusive disease, a statistically significant increase was seen in 7 of 30 parameters, compared to values seen before conditioning chemotherapy. These were subdivided into early and late phase parameters. The early phase parameters, which increased during the first day after the conditioning chemotherapy was given, then returned to baseline values, included protein C, plasma tissue factor and tissue-plasminogen activator. The late phase parameters, which increased over baseline values during days 7 to 28, included free-protein S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble-thrombomodulin. The increase of early phase parameters, as produced by the liver and by endothelial cells, may reflect tissue damage by conditioning chemotherapy. Late phase parameters increased in parallel with C-reactive protein, which suggests a correlation with the degree of inflammation, such as the presence of infective disease during neutropenia. These subclinical alterations in coagulation and fibrinolysis which take on a biphasic pattern during the course of APBSCT should be kept in mind by the attending physicians during therapy.

Adolescent↗

[Pilot study of relapsed osteosarcoma and brain tumor with ifosfamide, carboplatin and etoposide (ICE therapy)].

Ifosfamide, Carboplatin and Etoposide (ICE) therapy was used to treat 4 patients, 2 with refractory osteosarcoma, and one each with relapsed brain tumor and newly diagnosed brain tumor. ICE therapy was administered in doses of Ifosfamide 1,800 mg/m2 x 5, Carboplatin 400 mg/m2 x 2 and Etoposide 100 mg/m2 x 5. A total of 30 courses were administered. Two cases of osteosarcoma had a stable disease (range, 3-9 months) and 2 cases of brain tumor had a complete response by magnetic resonance imaging. Moderate or severe toxicity evaluated on a per course basis included: neutropenia 83%, thrombocytopenia 93%, fever 30%, hepatotoxicity 3%, and hemorrhagic cystitis 3%. The median time to hematologic recovery was 20 days. ICE therapy is highly effective for the treatment of refractory or recurrent solid tumors with acceptable toxicity.

Adolescent↗

Role of glutamate receptors and voltage-dependent calcium and sodium channels in the extracellular glutamate/aspartate accumulation and subsequent neuronal injury induced by oxygen/glucose deprivation in cultured hippocampal neurons.

Ischemia is believed to induce neuronal damage by causing a sustained increase in the level of extracellular excitatory amino acids. In our study, we have examined the relationship between oxygen/glucose deprivation-induced changes in extracellular glutamate/aspartate level and subsequent neuronal injury by pharmacological manipulation of glutamate receptors and calcium and sodium channels. Cultured hippocampal neurons were exposed to combined deprivation of oxygen/glucose for 40 to 50 min. These cultures developed acute neuronal swelling and widespread neuronal degeneration over the next 20 hr. The extracellular levels of glutamate and aspartate at the end of the oxygen/glucose deprivation period were measured by high-performance liquid chromatography, and neuronal injury was assessed by lactate dehydrogenase efflux assay after subsequent aerobic incubation of the cells in normal medium for 20 hr. Both N-methyl-D-aspartate and non- N-methyl-D-aspartate receptor antagonists attenuated the extracellular level of glutamate/aspartate and the neuronal injury. L-type, N-type and P-type calcium channel blockers each significantly attenuated the neuronal injury, although the increase in the extracellular glutamate/aspartate was not significantly inhibited by any subtype-specific calcium channel blocker alone. A combination of calcium channel blockers of the three subtypes showed the most prominent neuroprotective effect and inhibited glutamate release. The sodium channel blocker tetrodotoxin also attenuated both glutamate efflux and neuronal injury. These observations suggest that the overactivation of glutamate receptors, calcium channels and sodium channels leads to excitotoxic neuronal injury through enhancing glutamate efflux into the extracellular space under the condition of oxygen/glucose deprivation.

Animals↗

[A study of Article 32 of the Mental Health Act analysis of those who made applications under Article 32].

Article 32 of the Mental Health Act was enacted in 1965 and entitles psychiatric outpatients to financial aid towards payment of psychiatric care costs. Psychiatric outpatients can make applications under Article 32 voluntarily at local public health centers. These centers are operated by the prefectural governments. Therefore, records of the applications are kept by the local public health centers. In order to study the effects of Article 32 on psychiatric care, we analyzed the records of those who applied for such benefits in I. County of Shiga Prefecture, at the K. local Public Health Center, and performed a comparative analysis of applicants vs. non-applicants. We also tried to find out which psychiatric illnesses were more significantly represented among those who applied than among those who did not. Our study showed that about 43.5 percent of all psychiatric outpatients in I. County had made applications for Article 32 benefits. This was significantly higher than any former percentages that had been anticipated. We also discovered that a significantly higher number of people with schizophrenia, atypical psychosis and epilepsy could be identified among those who had applied for benefits than those who had not applied. On the other hand, the number of people with neurosis and emotional disorders seemed higher among those who did not apply for the benefits. In addition, the study indicated that a large proportion of those who applied belonged to the 40 s and 50 s age group and to the group with chronic psychiatric problems. All of the above make it clear that Article 32 has been effective in making psychiatric care accessible to those people who suffer from chronic mental diseases over quite a long period time.

Adult↗

[Gamma-heavy chain disease associated with MALT lymphoma of the duodenum].

We report a case of a 63-year-old woman with gamma heavy chain disease (HCD) associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum. She was suffering from drug-resistant tonsillitis with high fever. Examination on admission showed leukocytopenia and thrombocytopenia. Bone marrow aspirate revealed granulocytosis and a hypocellular marrow with no increase in plasma cells or atypical lymphocytes. Serum electrophoresis disclosed, in addition to hypogamma-globulinemia, an abnormal band due to the presence of gamma HCD protein. This abnormal protein was a molecular weight of approximately 40 kd as determined by Western blots technique, and belonged to the IgG1 subclass as determined by ELISA with monoclonal antibodies against IgG. An endoscopic examination of the patient's duodenum found a small tumorous lesion, which was confirmed pathologically to be MALT lymphoma. HCD is known to be associated with lymphoproliferative diseases. In this case, gamma HCD had developed as a secondary complication of MALT lymphoma. gamma HCD associated with MALT lymphoma of the duodenum is rare in the literature.

Biomarkers↗

[Autoimmune thrombocytopenia following syngeneic peripheral blood stem cell transplantation].

A 35-year-old man with non-Hodgkin's lymphoma (NHL) (follicular small cleaved, B cell, stage IVB) received double myeloablative chemotherapy with syngeneic peripheral blood stem cell transplantation (PBSCT). Although platelet recovery was delayed until day 29 after the second transplantation, thereafter trilineage hematopoietic reconstitution was achieved. The evaluation after PBSCT did not detect any residual tumor. The patient was in good health until day 138, when his platelet count suddenly began falling; on day 150, it had fallen to 1.5 x 10(4)/microliter, and the patient was re-admitted for treatment. The bone marrow was normocellular with a normal count and megakaryocyte structure. Other examinations, including serological tests and computed tomography of the neck, chest, abdomen, and retroperitoneum, did not indicate a recurrence of NHL or reveal the cause of thrombocytopenia. The patient's platelet-associated IgG (PAIgG) level was at 70.9 ng/10(7) platelets (normal range: 9-25 ng/10(7) platelets); a diagnosis of thrombocytopenia due to an autoimmune mechanism such as idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone therapy increased the platelet count and reduced the PAIgG level. Thrombocytopenia with an ITP-like mechanism rarely occurs more than 100 days after autologous or syngeneic stem cell transplantation, and should be taken into consideration as a late complication of PBSCT.

Adult↗

[Myelodysplastic syndrome (RAEB in T) developed in a renal allograft recipient].

A 46-year-old man who had been treated with azathioprine (150 mg/day) and prednisolone (7.5-10 mg/day) for 16 years after allogeneic renal transplantation was admitted to our hospital in July 1996 for evaluation of pancytopenia. Three years earlier he had been given a diagnosis of renal pelvic and ureteral cancer, and underwent left nephrectomy with total uretectomy. His bone marrow was normocellular with excess of blasts (27.6%), and displayed trilineage myelodysplasia. A chromosomal analysis of the bone marrow revealed 43-45, XY with del (1) (p13), -5, del (7) (q22), -17, -18, and -19. The patient was given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T), and treated with idarubicin and cytosine arabinoside. Two months later, overt acute leukemia developed and reinduction chemotherpay was started, but the patient died of cerebral hemorrhage in October. This case suggests that immunosuppressive agents such as azathioprine might play an important role in the pathogenesis of MDS (RAEB in T) and renal pelvic and ureteral cancer after renal transplantation.

Anemia, Refractory, with Excess of Blasts↗