Biomedical subjects
Publications and source records attributed to H Murakami.
We report a very rare case of primary Hodgkin's disease of the bone in a 56-year-old male. It presented with sudden onset of paraparesis which suggested an extradural tumor. Early appropriate therapy for similar patients with Hodgkin's disease can improve their prognosis.
The fruits of Prunus mume Sieb. et Zacc. (Japanese name, ume) have been used as a traditional drug and health food. In order to study the active components of P. mume, the polysaccharide fractions were extracted with cold water, hot water and aqueous sodium hydroxide from the kernels of P. mume. We found that some of the polysaccharide fractions exhibited various types of biological activities such as mitogenesis, activation of the alternative pathway of complement and activation of clot formation in human plasma. A polysaccharide, P-1, obtained from the cold 0.5 M NaOH extract was purified by ion-exchange chromatography and gel-filtration, P-1 contained 62.0% neutral sugar as glucose and 38.4% uronic acid (as galacturonic acid), and was free from protein. The neutral sugars of P-1 were arabinose, xylose, rhamnose and galactose in a molar ratio of 9.4:3.4:1.1:1.0, following analysis by gas-liquid chromatography. In addition, galacturonic acid was identified by thin-layer chromatography. The molecular weight of P-1 was found to be more than 2,000,000 by gel-filtration on Toyopearl HW 65F. P-1 showed mitogenic activity towards spleen cells of both C3H/HeN and C3H/HeJ, suggesting that it was free from bacterial endotoxic lipopolysaccharides.
Immunoglobulin M productivity of a human-human hybridoma line, HB4C5, was enhanced by the addition of histones H1, H2A, and H2B in serum-free medium, which are lysine-rich histones. On the contrary arginine-rich histones, histone H3 and H4, did not stimulate immunoglobulin production at all. Another arginine-rich protein, protamine also did not significantly stimulate immunoglobulin production. These results suggested that there is a correlation between amino acid residues of basic proteins and stimulation of immunoglobulin production. In this connection, immunoglobulin production stimulating activities of poly-lysine and poly-arginine were investigated. Both poly-L-lysine and poly-D-lysine stimulated IgM productivity of the human-human hybridomas. These results show that the enhancing effect of lysine residues was derived from its physiochemical features. On the other hand, poly-L-arginine did not enhance the productivity.
Although endothelins were originally discovered as peptides with vasoconstrictor activity, recent studies have indicated a number of endothelin (ET)-induced hormonal functions in various tissues. We have studied the interaction of endothelins with porcine thyroid cells in culture. Specific binding of 125I-labelled ET-1 was demonstrated in porcine thyroid cells. The binding was displaced equally by unlabelled ET-1 and ET-2, but receptor affinity for ET-3 was lower than that for ET-1 and -2. Scatchard analysis of the data revealed a single class of high-affinity ET-1 receptors with a Kd of 0.45 nmol/l and a binding capacity of 2100 sites/cell. SDS-PAGE and autoradiography of 125I-labelled ET-1 cross-linked with thyroid cell membranes demonstrated ET-1 binding sites with an apparent molecular weight of 50 kDa. These results indicated that ET-1 receptors in thyroid cells are type A ET receptors. In association with the presence of ET-1 receptors, porcine thyroid cells responded to ET-1 and ET-2 with an increase in c-fos mRNA expression. Although ET-1 did not affect DNA synthesis stimulated by either EGF or IGF-I, it dose-dependently inhibited TSH-induced iodide uptake and also inhibited iodide uptake stimulated by forskolin and 8-bromo-cAMP. ET-1 had no effect on TSH-stimulated cAMP production. Thus, ET-1 inhibited TSH-induced iodine metabolism by acting at the steps distal to cAMP production. In agreement with a recent report, immunoreactive ET-1 was detected in medium conditioned by porcine thyroid cells. Antibody to ET-1 was found to increase TSH-induced iodide uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
We investigated the hematological and clinical status of 145 patients with de novo myelodysplastic syndrome (MDS), 14 of whom (10%) had eosinophilia in the bone marrow (MDS-Eo). Most of these 14 patients had severe anemia. Their bone marrow cells exhibited trilineage dysplasia and some morphological abnormalities in the eosinophils, including disproportion of eosinophilic granules, basophilic granules, a ring-shaped nucleus, and vacuolation in the cytoplasm. However, these abnormalities were less prominent than those of acute myelomonocytic leukemia with eosinophilia (FAB: M4Eo). Three of the 14 MDS-Eo patients had refractory anemia (RA), seven had RA with excess of blasts (RAEB), and four had RAEB in transformation. Cytogenetic analysis revealed chromosomal abnormalities in 12 of 13 MDS-Eo patients (92%), in particular, there were major karyotypic abnormalities (MAKA) in eight patients (62%). Cytotoxic agents were not effective in the treatment of four patients after leukemic transformation occurred. These four patients died of the leukemic transformation while seven died of bone marrow failure. The other three MDS-Eo patients are still alive; two of them have already transformed to a leukemic phase. The duration of survival of these patients was significantly shorter than that of the other MDS patients. These findings suggest that bone marrow eosinophilia in MDS may be a poor prognostic factor that is strongly related to the existence of MAKA.
Three experiments were conducted with view of a more suitable bioassay system for determination of energy utilization in newly hatched chick based on the TME assay system. The optimum duration for feed deprivation prior to tube feeding was determined with chicks aged 0, 2, 6, and 13 d old. In order to determine an appropriate duration for excreta collection after feeding, chicks deprived of feed for 24 h were force-fed and energy excretion was monitored every 12 h for the next 72 h. Irrespective of the age, energy excretion decreased to a low level at 24 h after feeding and then reached a constant rate: the endogenous energy excretion. In 0- and 2-d-old chicks, N excretion tended to increase from 12 h after commencement of feed withdrawal. On the other hand, energy excretion in the chicks force-fed paste or pellet of basal diet attained constant rates beyond 24 h after force-feeding at all ages, and the rates of excretion were almost comparable to the endogenous energy excretion for the corresponding age. In the chicks force-fed a high-fat diet, however, 36 h was required for the excreted energy to attain a constant rate. The increase in N excretion was also observed following 24 h after feeding in 1- and 3-d-old chicks. Deutectomy at 1 d posthatch modified the patterns of energy and N excretion after the commencement of feed withdrawal but not TME and TMEn values of diets. A modified bioassay system for the determination of energy utilization in newly hatched chicks based on TME assay system is proposed.
The effects of passive (no pump) and active (using centrifugal pump) shunting on hemodynamics and metabolisms during cross-clamping of the descending thoracic aorta were compared in mongrel dogs. In Group I (control), the aorta was cross-clamped for 2 hours without shunting; in Group II (passive), a temporary shunt was placed between the left common carotid and left femoral arteries during cross-clamping; and in Group III (active), left heart by-pass, matching flow to that in group II, was performed. Hemodynamic and metabolic parameters were recorded prior to cross-clamping and following every 30 min for 4 hours. All animals in Group I suffered from hemodynamic instability, metabolic abnormal and neurologic injury and died within 12 hours. Hemodynamic changes were unstable in Group III than II, and three dogs in Group III, but none in Group II, suffered from neurologic injury. Metabolic changes between Group II and III were not significant. We conclude that passive shunting is superior to active shunting for aortic by-pass.
We describe a 31-year-old patient with ulcerative colitis who was successfully treated with prednisolone (PSL). Immunologic analyses were performed during the treatment course. Suppressed natural killer (NK) cell activity and increased levels of the CD4/CD8 ratio were observed on admission. Transient restoration of NK cell activity was obtained by PSL treatment. However, it returned to the initial low level in spite of the improvement of clinical symptoms. Possible mechanisms are discussed for involvement of the immune system in the pathogenesis of ulcerative colitis (UC).
We describe here a patient with chronic hepatitis C and liver hemosiderosis whose serum ferritin level was notably reduced by long-term interferon-alpha (IFN alpha) therapy. The decrease of the elevated serum ferritin level was considered to have been mostly obtained by the improvement of liver dysfunction. However, at the beginning of the therapy, in spite of alanine aminotransferase (ALT) improvement, his serum ferritin level increased transiently, and after cessation of IFN alpha therapy, the serum ALT increased again, but the serum ferritin had not increased. This indicates that IFN alpha has an effect on the iron-related measurement, partly due to improvement of hepatic status.
We have conducted four prospective multicenter studies for acute promyelocytic leukemia (APL) using oral 45 mg/m2 all-trans retinoic acid (ATRA) daily. The first three studies were for relapsed/refractory APL, and the fourth study for newly diagnosed APL. In the first study with ATRA alone, 18 (82%) of 22 evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study, if initial leukemia cell counts were more than 200/microliters, chemotherapy with daunorubicin and behenoyl cytarabine was first given, and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. In the third study, if initial leukemia cell counts were more than 200/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 46 evaluable patients, 36 (78%) achieved CR. Patients achieving CR received standard consolidation and maintenance chemotherapy, and the 29-month predicted disease-free survival (DFS) rate is 72% for 41 cases achieving their first CR with ATRA, and 20% for 49 cases achieving their second CR with ATRA. In the fourth study for newly diagnosed APL, if leukocyte counts were more than 3000/microliters, chemotherapy was concomitantly given with ATRA, and if during the ATRA therapy leukemia cell counts became more than 1000/microliters, chemotherapy was added. Of 109 evaluable patients, 97 (89%) achieved CR, and the 19-month predicted event-free survival rate for all patients is 78%, and the DFS rate is 88% for 97 cases achieving CR. ATRA produces a high CR rate in both relapsed/refractory and newly diagnosed APL, and should be incorporated in the first-line therapy of this disease.
We report a rare case of occipital lobe epilepsy following cerebral infarction in bilateral occipital lobes. The patient is a seventeen-year-old female, who had cerebral infarction in bilateral occipital regions a few days after an open-heart surgery at 15 years of age. Thereafter she sometimes complained of visual field defects and ictal amaurosis. Seventeen months later, she developed a tonic seizure with ictal amaurosis, visual field defects and head deviation. On admission, results of the neurological examinations were all normal with the exception of peripheral visual field defects. Scalp electroencephalographic (EEG) findings showed paroxysmal discharges that were more prominent in the frontal to parietal leads than in the occipital leads. Sometimes the laterality of paroxysmal discharges changed. Her visual defects were diagnosed as psychogenic activity by the ophthalmological visual fields test. Simultaneous recordings of pattern reversal visual evoked potential (VEP) and electroretinograms (ERG) showed normal in 15 minute checks, but prolongation of bilateral P100 latency in 30 minute checks. These findings suggested that peripheral visual fields were disturbed. In this case, EEG findings and the initial symptoms of amaurosis and visual fields defect suggested occipital epilepsy following cerebral infarction in bilateral occipital lobes. We wish to emphasize that simultaneous VEP and ERG recording is a useful diagnostic tool for estimating visual functions.
The aim of this study was to assess the effectiveness of pregraft immunomodulatory artificial blood exchange (IABX) in a guinea pig-to-rat xeno discordant heart transplantation, using an artificial blood (FC43 emulsion: The Green Cross, Japan) in exchange for a large volume of whole blood to remove humoral immune factors en bloc from the recipient rat. In the rats treated with IABX, rhythmic beating of the grafted heart was maintained for 2 hr, whereas the untreated heart beat lasted for only 15.2 +/- 5.2 min (n = 6). In the graft hearts treated with IABX, no pathologic changes such as multiple coronary thromboses due to hyperacute rejection (HAR) were observed. Humoral immune factors (natural-IgM titer, ACH50 and CH50 complement activities, platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen serum concentration), which are thought to contribute to HAR, decreased significantly following the IABX treatment. We conclude that IABX is an efficient method for prolonging the survival time of guinea pig heart xenografts by inhibiting thrombus formation in the xeno-graft heart. It was confirmed that IABX could remove recipient humoral immune factors en bloc.
Characterization of the receptors mediating contractions to endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin S6c (STXc), or IRL 1620 in isolated epithelium-denuded hilar bronchus of guinea pig using as antagonists BQ-123 (ETA receptor-selective) and Ro 46-2005 (ETA/B nonselective) was investigated. ET-1, ET-3, STXc, and IRL 1620 produced only contraction, and their concentration-response curves were obtained at the same concentration range (10(-10)-10(-7) M). The potency order was the following: STXc = ET-3 = ET-1 > IRL 1620. BQ-123 (10(-5)M) had no marked effect on the contraction induced by ET-3 or STXc, whereas it attenuated the response induced by high concentration of ET-1 (3 x 10(-8)-10(-7)M). The contraction induced by IRL 1620 was antagonized by BQ-123 (3 x 10(-6)-10(-5)M). Ro 46-2005 (10(-5)M) failed to inhibit the responses to ET-1 and ET-3. Ro 46-2005 (10(-5)M) slightly, but significantly, shifted the concentration-response curve for STXc to the right (pKB = 4.94 +/- 0.10, n = 7), and the maximum response was potentiated to about 127%. The curve for IRL 1620 was shifted in parallel by Ro 46-2005 (3 x 10(-6)-10(-5)M) to the right (mean pKB = 6.35 +/- 0.09, n = 8). These results suggest that ETB receptors primarily mediate contraction to ET-1, ET-3, STXc, and IRL 1620, and the relative inhibitory activities of ET antagonists vary with the agonist used. However, ET-1 and ET-3 might also activate non-ETB receptor or unknown mechanisms.
The patient was a 2-year-old who was admitted with the diagnosis of liver tumor. The diagnosis at admission was stage III A hepatoblastoma complicated with tumor thrombosis of portal vein. Soon after the admission, the patient's general condition became deteriorated with increased ascites and severer jaundice. As the patient was considered to be in oncogenic emergency, chemotherapy with systemic administration of ADR and CDDP was started. Despite decreases in tumor marker and tumor shrinkage on imaging examinations, tachycardia and arrythmia occurred from the end of the second course of chemotherapy, suggesting ADR-induced cardiomyopathy, when the systemic administration of ADR was switched to less cardiotoxic hepatic arterial infusion of THP-ADR. Following 13 courses of intra-arterial infusion with the total dose of THP-ADR of 200 mg/m2, the tumor was found to have reduced markably in size and thus surgical resection of the tumor was performed. Our experience of this case indicates that, considering the pharmacokinetics and side effects, THP-ADR should be a very effective anti-tumor agent for intra-arterial hepatic infusion. The patient died 10 months after surgery because of multiple metastases into the brain and lungs.
A case of 58-year-old man with a left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis was reported. Surgical treatment was performed following intensive chemotherapy. The communication was found in the center of a vegetation on the septal leaflet. Closure of the communication and replacement of the tricuspid valve were done successfully. His postoperative course was uneventful.
Free radicals have just begun to be studied in medical science. There are various opinions regarding the initiator of lipid peroxidation, and there will be many new discoveries in basic medicine in the future. In cardiovascular surgery, the mechanisms of producing free radicals have gradually become clarified for ischemic-reperfusion injury of the heart or cardiopulmonary bypass, and effects of antioxidants or inhibitors are expected. As to the value of plasma lipid peroxide used ordinarily, the absolute value, the cause of lipid peroxidation and the value corrected influence of environmental factors, and the effect of lipid peroxidation should be used properly to explain the lipid peroxidation. In cardiovascular surgery the discoveries in basic medicine should be put to use. Discoveries which contribute to the advancement of free radical study may be expected, elucidation of the mechanism of lipid peroxidation should be determined, and a method for dealing with it should be established.
UNLABELLED: The fractional uptake of intact monoclonal antibodies by tumors is relatively low. Various methods to alter the molecular structure have been used to augment tumor uptake. These chemical manipulations, however, may alter the specificity of antibody binding. METHODS: Comparative studies of biodistribution, radioimmunoimaging and macroautoradiography in LC-6 xenografted mice were conducted with the 125I-labeled intact and N-terminal deglycosylated monoclonal antibodies to evaluate the effect on deglycosylation on antibody binding. RESULTS: The removal of N-glycosyl residues from this monoclonal antibody significantly enhanced specific localization of the radioactivity to the tumor, especially to its necrotic fraction. Nonspecific accumulation of radioactivity to the necrotic fraction of the tumor was excluded by biodistribution studies demonstrating selective accumulation of 125I-labeled monoclonal antibody after coadministration of 125I-monoclonal antibody (intact or N-deglycosylated) with 131I-labeled control IgM. CONCLUSION: The lung cancer-associated human monoclonal antibody HB4C5, which recognizes histone H2B as the antigen, accumulates specifically to the necrotic fraction of tumor. The uptake is enhanced by removal of N-terminal glycosyl residues from the antigen-binding site of the light chain.