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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 865 records · Page 48Linked to original sources

[A preliminary analysis of unrelated marrow transplantations facilitated by the Japan Marrow Donor Program (JMDP)].

Between January 1993 and June 1994, the JMDP facilitated marrow donations from unrelated donors for 171 patients with malignant and non-malignant disorders. The median age of the patients was 21 years. All patients received marrow from phenotypically HLA -A, -B, -DR identical donors. About half of the patients wrer treated with total body irradiation (TBI)-containing regimens and about 80% of the patients received short-courses methotrexate and cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Eight out of 171 patients, (4.7%) had graft failure and 63 out of 144 patients (44%), who survived for more than 30 days posttransplant, developed grade II to IV acute GVHD. The incidence of chronic GVHD was 47% (extensive form; 27%); most of them were progressive/quiscent type. The incidence of moderate to severe acute GVHD was higher than that observed in sibling transplants. On the other hand, the incidence of chronic GVHD was similar to that observed in sibling transplants. Overall survival at 1.5 years posttransplant was about 50% with no significant differences between diseases. The age correlated significantly with the survival in standard risk leukemia but not in high-risk leukemia. Despite the risk of graft failure and acute GVHD, this preliminary analysis demonstrates that transplantation of marrow from unrelated donors can be an effective treatment for certain hematologic disorders.

Acute Disease↗

[Recent progress in treatment and prophylaxis of graft-versus-host disease].

Graft-versus-host disease (GVHD) is one of major causes of mortality in allogeneic bone marrow transplantation (BMT). GVHD prophylaxis for HLA matched sibling BMT is widely done by methotrexate and/or cyclosporine. More intensive modalities are necessary for HLA mismatched related or HLA matched unrelated BMT; T cell depletion, ALG/ATG in preconditioning or following BMT and FK-506 with short term methotrexate are currently used with certain success. Moderate to severe GVHD may develop despite of these preventions, and standard to high dose of steroid with or without ALG/ATG is currently used as the first line therapy. GVHD, however, is an important component to cure malignant diseases through its anti-tumor effect called graft-versus-leukemia (GVL) effect. Several attempts have been made to induce mild to moderate GVHD both in allogeneic and in autologous BMT; low dose of cyclosporine, IL-2, ubenimex and donor buffy coat or peripheral lymphocyte transfusion are shown to be effective with some limitation.

Bone Marrow Transplantation↗

[Determination of source position for four radiography systems with orthogonal projections in brachytherapy].

Four configurations of two X-ray tube positions are available for determining the position of a point using two orthogonal films. For each configuration, there are many formulas for calculating the coordinate of a point: the least squares methods with and without physical meaning, such as six sets of geometrical solutions, an approximation method with constant magnifications and so on. It is troublesome for a person in charge of treatment planning to directly derive a formula or select an appropriate formula from numerous ones for the four configurations. Thus, a method to easily apply the published formula for a configuration to the other three configurations is described in simulations and a clinical case using rotation matrixes of the right-handed coordinate system. Each diagonal element of the rotation matrixes is 1 or -1, and the other elements are 0.

Brachytherapy↗

[Two-color flow cytometry analysis of lymphocyte subsets in patients with acute myocardial infarction and post-myocardial infarction syndrome].

Serial changes in lymphocyte subsets were analyzed in 37 patients with acute myocardial infarction (AMI), in 2 patients with postmyocardial infarction syndrome (PMIS), and in healthy subjects (control group) using two-color flow cytometry to investigate cellular immunity after AMI and PMIS. Peripheral blood lymphocyte subsets were measured on admission and at weeks 2, 4, 8, and 16 after the onset of AMI. The white blood cell count was significantly higher on admission and at week 2 in the AMI group compared with the control group. The percentage of CD4-positive helper T cells was significantly higher on admission and at weeks 2 and 4 in the AMI group compared with the control group, and the percentage of CD8-positive suppressor T cells was significantly lower in the AMI group at week 2 than in the control group. The ratio of helper-to-suppressor T cells peaked 2 weeks after the AMI and then decreased gradually. There were no significant changes in the CD4/CD8 ratio, the percentage of cytotoxic T cells, or the percentage of inducer T cells, throughout the observation period. There were no significant differences in the percentage of T cells, B cells, CD4-positive T cells, CD8-positive T cells, and natural killer cells between AMI patients and control subjects. The percentage of activated CD4- and CD8-positive cells was higher in the AMI group at weeks 4 and 8 than in the control group. There was no significant correlation between changes in lymphocyte subsets and infarct size. The percentage of activated CD8-positive cells was consistently higher in the PMIS group compared with the control and AMI groups. The percentage of cytotoxic T cells in one of the PMIS patients was significantly higher than in the AMI group. There were no significant differences in the proportions of other subsets between PMIS and AMI patients. The changes in lymphocyte subsets observed in patients with AMI suggested that immunological competence was enhanced in these patients. Abnormalities in humoral immunity, such as the appearance of anticardiac antibody, have been observed in patients with PMIS. Our results suggest that PMIS is also associated with changes in cellular immunity.

Adult↗

Essential hypertension and neurovascular compression at the ventrolateral medulla oblongata: MR evaluation.

PURPOSE: To investigate, using MR imaging, neurovascular compression at the ventrolateral medulla oblongata in patients with essential hypertension. METHODS: Thirty-two patients with essential hypertension (57.6 +/- 7 years of age), 6 patients with secondary hypertension (56.7 +/- 10.3 years of age), and 18 control subjects (50.5 +/- 11 years of age) were evaluated. Transaxial three-dimensional fast low angle shot images were obtained (38/6/1 [repetition time/echo time/excitations]). The center of a 40-mm-thick slab (16 partitions) was placed at the pontomedullary junction. We evaluated the relationships between the upper ventrolateral medulla and the vertebral arteries and branches identified by their flow-related hyperintensities in each group. RESULTS: In the essential hypertension group, 29 (90.6%) of 32 cases showed neurovascular compression. Of those, 22 demonstrated neurovascular compression on the left side, 3 on both sides, and 4 on the right side. In the control group, 4 cases of 18 showed neurovascular compression. In the secondary hypertension group, 1 of 6 cases showed neurovascular compression. The rates of observed neurovascular compression between controls and essential hypertension group were statistically significant. CONCLUSION: We found a close correlation between essential hypertension and neurovascular compression at the ventrolateral medulla oblongata on the left side. MR with a 3-D fast low-angle shot sequence has acceptable spatial resolution and depicts blood vessels simultaneously by flow-related phenomena.

Adult↗

Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts.

Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.

Acetaldehyde↗

Bispecific antibody-mediated cytotoxicity by CD4+ and CD8(+)-activated T cells generated from leukemia patients after allogeneic bone marrow transplantation.

The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti-CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.

Antibodies, Monoclonal↗

[Clinical statistics at the urological clinic of Sanjukai Hospital--statistics on new outpatients during the last five years].

We report the clinical statistics of new outpatients for five years since 1989 at our hospital. The average total number of new outpatients in a year was 8309.8 (8122-8691) and new outpatients tended to show little change. The male to female ratio was 1.57:1, and 24.3% of the outpatients were referred to us by others sources. The representative operations on outpatients were circumcision, vasectomy, resection of condyloma and resection of caruncle. A statistical study was made on new outpatients according to the international classification of disease. There were 140.6 (1.97%) malignant urogenital tumors per year. Sexually transmitted diseases showed a tendency to increase for the last five years. In males the major disease was upper urinary tract stone (21-24%), prostatistis (21-24%) and benign prostatic hypertrophy (17-20%) and in females they were cystitis (58-61%), upper urinary tract stone (15-17%) and pyelonephritis (3-4%). We conclude that our hospital plays a major role as a private urological hospital.

Female↗

Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following Fanconi anemia.

We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB) which developed following Fanconi anemia. The patient received BMT from an HLA-identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment was successful. The patient has maintained normal trilineage hematopoiesis with > 90% Karnofsky score for 30 months with disappearance of a clonal chromosomal abnormality (47,XY, +i(lq)) which was detected before BMT.

Adolescent↗

[Li-Fraumeni syndrome].

The Li-Fraumeni syndrome was initially recognized through clinical observations at the bed side, which was followed by epidemiological studies. Children suffering from rhabdomyosarcoma were shown to have two or more of six forms of cancer in their parents, grandparents and other relatives, indicating cancer family syndrome. This syndrome has been shown to involve tumor suppressor gene p53 mutations in the germ-line. The patients in the family most often have a proband with soft tissue sarcoma or osteosarcoma, and relatives with breast cancer, brain tumor, leukemia and adrenocortical cancer. Members of the family also appear to be at risk for developing second independent malignancies during their life span. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals have been made by the subcommittees, which were sponsored by National Cancer Institute and the National Center for Human Genome Research.

Animals↗

[Techniques for determining position from more than two radiographs intersecting at arbitrary angles in brachytherapy].

The least squares method and geometrical solution for calculating position were used in the two-projection method. Five coordinate systems were defined as a normal system, image system on film intersecting the beam central axes at an arbitrary angle and the projection, virtual coordinate and virtual image coordinate systems with beam central axis as one of the three coordinate axes to determine the geometrical relationship between a point and image on the film. Normal coordinates of the point were calculated by six geometrical solution sets and two forms of the least squares method using the rotation matrixes of the coordinate systems. One least squares method solves simultaneous nonlinear equations, and the other derives a strict solution from simultaneous linear equations. The latter least squares method has little physical meaning and is not as useful as the former. Although the former has physical meaning, the iterative approximation method should be used to determine position since a strict solution cannot be obtained directly. By these least squares methods, position is determined with less error using the projections at more than two focal spots.

Brachytherapy↗

Effect of NG-nitro-L-arginine methyl ester, the nitric oxide synthase inhibitor, on duodenal alkaline secretion and mepirizole-induced duodenal lesions in rats.

We investigated the HCO3- stimulatory mechanism of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the anesthetized rat duodenum and examined whether L-NAME protects against mepirizole-induced duodenal damage. The proximal duodenal loop was perfused with saline and HCO3- secretion was measured at pH 7.0 using a pH-stat with added HCl (10 mM). L-NAME (1-5 mg/kg, i.v.) increased HCO3- secretion in a dose-dependent manner, with concomitant elevation in arterial blood pressure and an apparent decrease in heart rate. These changes were mimicked by another NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 50 mg/kg, i.v.) but not by NG-nitro-D-arginine methyl ester (D-NAME), and were all antagonized by co-administration of L-arginine but not by D-arginine (200 mg/kg, i.v.). The HCO3- stimulatory effect of L-NAME was also inhibited by vagotomy and pretreatment with atropine (1 mg/kg, s.c.) or indomethacin (5 mg/kg, s.c.). Vagotomy and atropine did not affect blood pressure response, but both inhibited the decrease of heart rate caused by L-NAME, whereas indomethacin did not affect either of these changes. In addition, L-NAME increased HCO3- secretion in the presence of mepirizole (200 mg/kg, s.c.) and prevented duodenal lesions caused by this agent. These results suggest that L-NAME stimulates duodenal HCO3- secretion in association with the inhibition of endogenous NO production, mediated by neural reflex through vagal efferent nerves, resulting from the pressor response to this agent, and may protect the duodenal mucosa against acid-related damage.

Animals↗

Tissue IgA antibody against Helicobacter pylori in patients with gastroduodenal diseases: comparison with bacterial culture, serum IgG antibody, and [13C]Urea breath test.

Helicobacter pylori infection is often associated with gastrointestinal diseases, such as chronic gastritis, peptic ulcer, and gastric cancer. After total gastrectomy, positive to negative seroconversion of the H. pylori IgG antibody assayed by enzyme-linked immunosorbent assay (ELISA) was found in 10/15 patients (67%) an average of 8.5 months after surgery. Therefore, the IgG antibody persists for a long time after total removal of the stomach in about 30% of patients. Immunoglobulin A (IgA) is a major component of the local immunity of the stomach mucosa and has a short half-life. Therefore, tissue H. pylori IgA antibodies in biopsy specimens from patients with various gastric diseases were assayed by ELISA and compared with the bacterial culture, serum IgG antibody (ELISA), and [13C]urea breath test results from 144, 170, and 123 endoscopic examinations, respectively. Positivity and negativity of tissue H. pylori IgA coincided with the culture results in 67% of the examinations, and positive IgA antibody but negative culture results were found in 23%. The coincidence of tissue IgA and serum IgG antibodies against H. pylori was 64% and that of negative tissue IgA but positive serum IgG antibody results was 36%. Positivity and negativity of tissue H. pylori IgA antibody coincided with the [13C]urea breath test results in 72%. One month after completion of treatment of peptic ulcer patients for H. pylori infection with lansoprazole and benexate HCl betadex plus amoxicillin, 6/9 (67%) patients showed positive to negative conversion of the tissue IgA antibody, in contrast to no IgG antibody seroconversion. In conclusion, the tissue H. pylori IgA antibody assay is useful for detection of local immunity against H. pylori in the stomach and during follow-up after treatment.

Adult↗

I-cell disease: report of an autopsy case.

The history and findings at autopsy of a 9-year-old female with I-cell disease are reported. She manifested gargoyle face, progressive psychomotor retardation, and increased serum levels of lysosomal enzymes with decreased activities in peripheral blood lymphocytes. She received a bone marrow transplantation from her HLA-mismatched father when she was 8 years old. Rejection followed, and 9 months later, she died of cardiac failure secondary to aortic regurgitation. The characteristic inclusion bodies, ultrastructurally corresponding to double-membranous lamellar vacuoles and empty single membrane-bound vacuoles, were identified in dermal fibro blasts, macrophages, glomerular epithelial cells, cardiomyocytes and smooth muscle cells. Pale bodies, faintly eosinophilic cytoplasmic globular inclusions immunoreactive for plasma proteins, were observed in hepatocytes and renal collecting tubular epithelial cells. Enzyme histochemical analyses were performed for N-acetyl-beta-glucosaminidase, beta-glucuronidase, nonspecific esterase and acid phosphatase. Decreased activities of the acid hydrolases and their diffusion in the cytoplasm were seen in Kupffer's cells. Ultrastructural localization of acid phosphatase activity suggested the labilization of the lysosomal membrane. The abnormality in the intracellular transport of the acid hydrolases into the lysosomes in I-cell disease is briefly reviewed and discussed.

Acid Phosphatase↗

Brain tumor: immunohistochemical studies on the stress-response proteins, p53 protein and proliferating cell nuclear antigen.

This retrospective immunohistochemical study compares the expression of five stress-response (heat-shock) proteins (srp's) [srp 90, srp 72, srp 27, alpha B-crystallin and ubiquitin], p53 protein and proliferating cell nuclear antigen (PCNA) in 118 primary brain tumors and 21 carcinoma metastases to the central nervous system. Serial sections of formalin-fixed, paraffin-embedded tissues were used. Most astrocytomas (9/13), ependymomas (5/5), glioblastoma multiforme (GBM) (11/12), schwannomas (19/21), meningiomas (22/23) and breast carcinoma metastases (Br-Mt) (9/10), and some medulloblastomas (5/15), primitive neuroectodermal tumors (PNETs) (5/11), pituitary adenomas (4/7) and lung carcinoma metastases (6/11), but none of 10 oligodendrogliomas had tumor cells that expressed one or more (up to five) srp's. The percentage of tumors with p53-positive cells was variable; the proportion was highest among srp-expressing GBMs (mean: 16.1%) and Br-Mts (mean: 15.3%). The mean PCNA-labeling index (LI) also varied, ranging from 1.2% in the group of pituitary adenomas to 24.5% in Br-Mts, with GBMs (20.4%) and medulloblastomas (18.4%) approaching the latter value. PCNA-LI was higher in the astrocytomas, GBMs, medulloblastomas and PNETs that expressed srp's than in those did not. A high proportion of p53-positive cells (31.3 to 59.0%) and the highest PCNA-LIs (41.0 to 49.0%) were seen in two GBMs and one Br-Mt that expressed all five srp's. We conclude that primary and metastatic tumors of the brain produce one or more stress-related proteins, and that a variable proportion of the tumor cells have immunohistochemically-detectable p53, the expression of which may depend, at least in part, on the growth potential of a given tumor.

Brain Neoplasms↗