Biomedical subjects
Publications and source records attributed to Y Ohta.
In the course of our screening for microbial compounds which possessed inhibitory activities against biosynthesis of cholesterol from mevalonate, we isolated four new compounds from the cultural broth of Streptomyces sp. A7361. They are structurally related to, but distinct from chlorothricin.
We developed an enzyme-linked immunosorbent assay (ELISA) system for antibodies to the hepatitis C virus (HCV), using two new recombinant antigens (c11 and c7) derived from the HCV genome. The performance of this ELISA system (Imucheck HCV Ab) was examined. The CV values for both intra-assay precision and reproducibility of identifying HCV antibody in the panel sera ranged from 3.5% to 6.4%. The blood elements in serum and anticoagulants did not interfere in this ELISA system. The specificity of Imucheck HCV Ab to samples from patients with non-A, non-B (NANB)-type chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma was 93.7%, 93.5%, and 81.4%, respectively. These results are more sensitive than those obtained by the first-generation anti-HCV ELISA system. In the samples from patients with NANB-type acute hepatitis, Imucheck HCV Ab enabled detection of HCV antibodies at an early stage. This system increased the sensitivity for blood donor screening and for monitoring patients with acute hepatitis.
Psychotic side effects of steroids have been observed at relatively high frequency if mild cases, such as euphoria, are included, while it has been said that incidences differ among kinds of steroids. We reported a case developing severe schizophrenia-like symptoms following the treatment with betamethasone although this drug is believed to be rarely involved in steroid-induced psychosis, and its psychotic side effects have been rarely reported. When betamethasone was administered for progressive peripheral facial paralysis at a mean daily dose of 7mg, psychotic symptoms appeared from the 15th treatment day. Psychosis began with interrupted appearance of excitation, autism, and misanthropia. Although the steroid was gradually decreased in dose because of abatement of facial paralysis, not only psychotic symptoms were aggravated, but also appeared hallucination. Thus the steroid was withdrawn before the scheduled date while its dose was gradually decreased, and haloperidol was administered. Psychotic symptoms were gradually eliminated and completely disappeared about 40 days after onset.
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We performed a clinical evaluation of repeated arterial infusion chemotherapy using an implantable drug delivery system for 41 patients with inoperable hepatocellular carcinoma (HCC). About half of our patients could not undergo transcatheter arterial embolization (TAE) because of extreme tumor extension and/or accompanying advanced cirrhosis. In most patients we implanted a 5 Fr. catheter non-surgically and connected it to an implanted injection port through a subcutaneous tunnel. The treatment schedule was weekly or biweekly intrahepatic one-shot administration of mitomycin C, adriamycin, 5-fluorouracil and epirubicin. The response rate (CR + PR) was 24.4%. The median survival period was 401.1 days. The 6 month, 1-year and 2-year survival rates were 73%, 48% and 24%, respectively. There were no severe side effects nor complications. The implantable drug delivery system will contribute not only to improved therapeutic efficacy for inoperable HCC but also improve the quality of life for patients.
Anti-hepatitis C virus immunoglobulin M antibody titers were measured by enzyme-linked immunosorbent assay in 28 patients with chronic hepatitis C. Nine patients were treated with alpha-interferon at a dosage of 3 MIU/day for 4 weeks. Anti-HCV IgM was positive in 12 of the 28 patients, and these 12 patients also had significantly higher anti-HCV antibody titers than those patients who were negative for anti-HCV IgM. Among the 9 patients treated with alpha-interferon, anti-HCV IgM positivity was significantly lower in 4 good responders than in 2 non-responders and 3 transient responders at 12 months after the completion of treatment (p < 0.01). These results suggest that anti-HCV IgM titers might be useful for monitoring the antiviral effect of interferon treatment in CH C.
A 38-year-old man was admitted with persistent productive cough and right anterior chest pain. Chest X-ray showed two large masses connected with each other, one in the right lung field and the other in the anterior mediastinum. A tentative diagnosis of either lung abscess or bronchogenic carcinoma was initially made, because of elevated serum tumor markers (SLX and SCC) and persisting refractory inflammatory sings. However, open chest drainage revealed a few fine hairs and atheromatous materials within the masses, and the diagnosis of teratoma was made. We removed these masses, and investigated the reason for the elevation of tumor markers. Staining with SLX monoclonal antibody demonstrated that the pancreatic tissue in the masses contained SLX. Although this is the first reported case of teratoma producing tumor marker (SLX), it is highly possible that tumor markers may be elevated in the majority of patients with teratoma because of the genesis of this tumor.
The effects of psychotropic drugs and local anaesthetics on the fluidity of Escherichia coli cell membranes were examined. Chlorpromazine was shown to increase 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, indicating that it decreased the membrane fluidity. This increase was significant at a temperature of more than 24 degrees C. Dibucaine, lignocaine, imipramine, tetracaine and procaine also increased the fluorescence anisotropy.
Epidural spinal cord stimulation was carried out in 4 patients with denervation caused by spinal cord lesion, and we reviewed previously reported cases. Initial result showed at 1 week in 100% of our cases, but about 1/3 of the cases, even those with the same denervation caused by spinal cord lesion, had no pain relief at this stage in previously reported cases. In our cases, excellent pain relief was gained temporarily, even though the painful area and the spinal cord lesion were separated somatotopically in 2 cases (case 3, 4). Temporary success bore no relationship to quality and duration of pain. In all cases except case 1, a rapidly decreasing effectiveness was noted, and finally no pain relief was gained at all after 4, 3 and 5 months, respectively. In case 1 there was persistent pain relief estimated at 70-80% after 19 months, only when the spinal cord was stimulated. Epidural stimulation also produced sensations in the painful area. Spinal cord stimulation would suppress at least the dorsal horn neurons which were destroyed by various kinds of diseases. A decline in effectiveness with time would occur due to essential causes of the deafferentation pain, such as anatomical and regeneration factors.
The lymphocyte subpopulations in the peripheral blood and liver were studied in 17 patients with chronic active hepatitis type C (CAH C) by immunoenzymatic and immunofluorescence techniques, using mono-specific T cell antibodies and other reagents. The peripheral blood subsets showed no significant differences between the patients with CAH C and normal controls. In the liver, CD8-positive cells were predominant over CD4- and Leu 7-positive cells. Leu 7-, CD4-, and CD11-positive lymphocytes were all few in number. HLA class I antigen was expressed diffusely on the cell surfaces of the hepatocytes. Serum levels of soluble interleukin 2 receptor (sIL2R) in the CAH C patients were significantly higher than in normal controls (p less than 0.01). In CAH C, sIL2R levels were higher during exacerbations than during remissions (p less than 0.01). These results suggest that cytotoxic T cells (CD8- positive, CD4-negative, and CD11-negative) may play an important role in the pathogenesis of hepatocyte injury in patients with CAH C.
There have been no successful cases reported of organ transplantation in application of neonatal immunological tolerance. Isolated myocardial cells from Lewis (LEW/Crj) rat hearts were inoculated into the thymus of incompatible King (WKAH/Hkm) rats. Ten weeks later the heart from LEW donor was transplanted heterotopically to the WKAH rat that had inoculated intrathymic myocardial cells without immunosuppression (n = 4, Group 1). Group 2 was made up of 4 isografts of heart transplantation (nontreated isograft). Group 3 was made up 4 allografts of heart transplantation (nontreated allograft). The animals were killed 7 days after transplantation, and early rejection was evaluated by accumulation of iodine-125 (125I)-labeled antimyosin antibody (AMA) uptake and confirmed by histological examination. In Group 1 & 2, the value of I-125 AMA uptake ratio was small (Group 1; RV: 1.28 +/- 0.28, IVS: 1.29 +/- 0.28, LV: 1.43 +/- 0.25, Group 2: RV: 1.14 +/- 0.07, IVS: 0.95 +/- 0.06, LV: 1.16 +/- 0.21). This level of the value indicates that the rejection does not occur. On the other hand, in Group 3, the value was high (RV: 4.63 +/- 1.92, IVS: 4.42 +/- 1.75, LV: 4.45 +/- 1.73) compared with Group 1 & 2. This level indicate that the rejection is severe. In the histological studies, Group 3 showed necrosis of myocardial cells, while Group 1 with neonatal immunological tolerance showed only very mild lymphocytic infiltration. The histology of thymic tissue in Group 1, the LEW myocardial cells are surviving in the WKAH rat thymus.
Activity of the respiratory muscles during natural defecation was studied in two anesthetized and two decerebrate dogs. In anesthetized dogs, excitation of the abdominal muscles and an increase in gastric pressure were observed during defecation. However, pleural pressure was little influenced by such increase in abdominal pressure, maintaining the same rhythmic changes as observed during spontaneous respiration. The rhythmic changes in pleural pressure were associated with rhythmic activity of the diaphragm. When gastric pressure increased during defecation, the diaphragmatic activity also increased during both the inspiratory and expiratory phases. In a decerebrate dog, airflow and airway pressure changed similarly to during defecation. The diaphragm was continuously active, with superimposed rhythmic augmentation. In a paralyzed and artificially ventilated dog with open-chest, the phrenic nerve similarly developed discharges. We conclude that the non-respiratory activity and rhythmic augmentation of phrenic nerve discharge during defecation is pre-programmed in the command for defecation. The activity of phrenic motoneurons may be further modulated by changes in thoracic and abdominal pressure. These mechanisms may act together to coordinate respiration and defecation.
The present paper deals with the microvascular architecture of the palatine mucosa in primates, carnivorae, and rodentia utilizing microvascular corrosion castings and epithelium-separated specimens. The submucous vascular network is under-developed since the hard palatine mucosa was designated the mucoperiosteum, except some areas. The palatine venous plexus appears to show regional differences with animal species differences. The well-developed plexus is observed to be two-layered and may contribute to the process of regurgitation of rough food and assist in mastication with the palatine plicae. Formation and patterns of the arterial network in the lamina propria are in a close relation with connective tissue elements. The subepithelial capillary network constitutes an advanced base for the ascending crus of the capillary loop and its pattern is affected by the properties of the connective tissue papillae and the diverging fashion of the capillary loops. Capillary loops of the transverse palatine plica are arranged parallel to the sagittal axis and at right angles to the top line of each plica. Features of the capillary loops are characteristics in the top, the anterior and posterior slopes of the plica, respectively. High connective tissue papillae in both the anterior slope and plical top may be of a resistant form for mollifying exhaustion, affected by the periodicity and mastication function. Although it is difficult to elucidate the lamination of the palatine mucosa in histological slides, it was resolved by examination on its vascular architectures.
A 63-year-old male had squamous cell carcinoma in the left upper lobe. CT scan suggested the invasion of the tumor into the vertebral body and the descending aorta. Left pneumonectomy and combined aortic resection under the temporary bypass using Anthron tube was performed. The bypass using Anthron tube provides us no systemic heparinization and the procedure is easy. So the danger of massive bleeding during and after the operation can be decreased and the operative time can also be shortened. This procedure may be a great help for carrying out the operation with combined aortic resection more safely and speedily.
The present experiment was designed to locate spinal neurons which are activated by afferent fibers in the ventral roots, and once found, to study their receptive field and rostral projection. After dorsal roots L1 approximately S4 on the left side were cut under a binocular microscope, stimulus was applied to ventral roots and extracellular responses were recorded using a glass microelectrode filled with fast green FCF. Sixty-four neurons were activated by stimulating ventral roots at 1.2-27.8 x T of the lowest threshold fibers of the ventral root. Six neurons were classified as wide dynamic neurons and 29 as high threshold neurons according to their response patterns to the periphery. Twelve neurons out of 29 were unresponsive to cutaneous stimulation, and located lamina V, suggesting that they innervate visceral organs. Thirty-five neurons (54.6%) were nociceptive nerons, most of which were located in laminae V and VI. In 6 neurons out of 35 nociceptive neurons (17.1%), rostral projection was confirmed by the collision block method and the ability to respond to high frequency stimuli with constant latency. Our results suggest that some spinal neurons activated primary affernt fibers in ventral roots stimulation are nociceptive and some of them are rostral projecting neurons which are antidromically activated ventral quadrants of the spinal cord.
Correlation between the callus formation and its microvascular regeneration during the fracture healing process in the rat femur was examined under SEM and TEM utilizing the plastic injection method. Stabilization of bony fragments was provided by a miniature external fixator. Normal periosteal microvasculature consisted of 2 layers. In the outer layer, arterioles and venules formed the course network. In the inner layer, capillaries were situated in contact with the compact bone, forming polygonal meshes. In the medulla, the central longitudinal artery gave rise to numerous arterioles, which communicated with sinusoidal capillaries. The proliferation of the internal layer of the periosteal capillary network was observed in the periosteal callus. It is revealed that the trabecular structure of the periosteal and medullary calluses depended on their microvascular architecture. The anastomoses of newly-formed capillaries at the fracture site started first from the outer layer of the periosteum extended to the medulla then finally to the inner layer of the periosteum.
Soluble interleukin 2 receptor (sIL2R) level in the serum of 10 patients with drug-induced allergic hepatitis (DIAH) were quantified with a solid-phase enzyme immunoassay using two monoclonal antibodies against the receptor. The sIL2R levels in patients with DIAH were significantly higher than in 15 normal subjects (p less than 0.01). The high sIL2R levels observed during the florid stage of DIAH returned to normal during convalescence (p less than 0.05). SIL2R from the serum of DIAH patients was found to bind to a recombinant IL2 affinity column. It seems likely that sIL2R inhibits the hyper-immune reaction that occurs in drug allergies due to bind IL2. But, we have no data that sIL2R inhibits actually the biological activity of IL2.
Natural suppressor (NS) activity has been identified in several sites of active hematopoiesis. In this study we characterized NS activity in murine bone marrow (BM) using monoclonal antibodies (mAbs) to interleukin 3 (IL-3) receptor-associated antigen (IL-3RAA) and various cytokines that exert a strong influence on hematopoiesis or lymphocyte interaction. NS activity of BM cells of relatively low density was enhanced by IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). When the BM cells were separated into IL-3RAA+ cells and IL-3RAA- cells, the IL-3RAA+ cells demonstrated potent NS activity, whereas IL-3RAA- cells had either no or weak NS activity. The IL-3RAA+ cells showed non-T- and non-B-cell phenotype and had high affinity to wheat germ agglutinin (WGA), a marker for hematopoietic progenitors. In assays for hematopoietic activity, it appeared that the early differentiating progenitors (day 8 spleen colony-forming units [CFU-S], granulocyte-macrophage colony-forming units [CFU-GM]) were enriched in the IL-3RAA+ cell population, whereas more immature multipotent progenitors (day 12 CFU-S, granulocyte erythrocyte macrophage megakaryocyte colony-forming units [CFU-GEMM]) were contained in the IL-3RAA- cell population. Both suppressor cells and IL-3RAA+ cells spontaneously developed from the IL-3RAA- cell population. These findings suggest that NS cells in murine BM are early hematopoietic progenitors and are probably committed to the myeloid lineage. Hybridoma cells established between the IL-3RAA+ cells and BW5147 cells produced suppressor factor(s). This finding suggests that the NS cells produce soluble mediator(s) that may be responsible for their suppressive action.