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Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 19 recordsLinked to original sources

Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells.

We recently identified a differentiation inhibitory factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product. nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes, although their mechanisms of action are still unknown. Although all nm23 proteins contain nucleoside diphosphate (NDP) kinase activity, it has not been established that the enzyme activity mediated the various functions of nm23 proteins. In the present experiment, we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60, U937, HEL/S, KU812F, K562, and HEL cells. Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL, KU812 and K562 cells, but not the induction of monocytic or granulocytic differentiation of HL-60, U937 and HEL/S cells. The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1, -H2, mouse nm23-M1, and -M2 proteins. Moreover, both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal (1-60) peptide, which do not have NDP kinase activity, also inhibited erythroid differentiation of HEL cells. These results suggest that (1) the differentiation inhibitory activity of I-factor/nm23 protein is not restricted to monocytic differentiation of M1 cells, (2) the inhibitory activity is exhibited without species specificity, and (3) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides.

Base Sequence

A new function of Nm23/NDP kinase as a differentiation inhibitory factor, which does not require it's kinase activity.

We recently identified a differentiation inhibiting factor (I-factor) in mouse myeloid leukemia M1 cells as a murine homolog of nm23-H2/nucleoside diphosphate kinase (NDPK)-B gene product. We examined the I-factor activities of several authentic nm23/NDPK proteins, i.e. recombinant rat NDPK alpha and beta, recombinant mouse nm23-M1 and -M2, and recombinant human nm23-H1 and -H2 containing a mutant nm23-H2His protein lacing NDPK activity. Almost all these nm23/NDPK proteins showed I-factor activity. Moreover, to understand the active domain exhibiting I-factor activity of nm23-H2 protein lacking NDPK activity, we have investigated the I-factor activities of some truncated nm23-H2 proteins. The truncated nm23-H2 protein containing N-terminal peptide 1-60 retained the I-factor activity. These results provide the first evidence for a function of nm23/NDPK as a differentiation inhibiting factor in leukemic cells, that is independent of its NDPK activity and dependent on the presence of N-terminal peptide.

Animals

Treatment of Philadelphia-chromosome-positive human leukemia in SCID mouse model with herbimycin A, bcr-abl tyrosine kinase activity inhibitor.

The molecular basis of the Philadelphia chromosome (Ph1) is a structurally altered c-abl (bcr-abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin a, which effectively reduced intracellular phosphorylation by bcr-abl tyrosine kinase, preferentially inhibited the growth of Ph1-positive leukemia cell lines. Injection of Ph1-positive and -negative leukemia cell lines into mice with severe combined immunodeficiency (SCID) resulted in the death of all mice due to leukemia, although the severity of illness varied according to the cell lines used. Administration of herbimycin A significantly enhanced the survival of mice inoculated with the Ph1-positive leukemia cell lines tested but barely affected the survival of mice inoculated with the Ph1-negative leukemia cell lines tested. These results suggest that herbimycin A and related compounds may be useful for the treatment of Ph1-positive leukemia. The disease that developed using the Ph1-positive leukemia cell line NALM-20 resembled human Ph1-positive acute lymphoid leukemia. There was an inverse relationship between the survival time of mice and the number of cells inoculated. The SCID mouse-NALM-20 human leukemia chimera would be a good experimental model for screening tyrosine kinase inhibitors as therapeutic agents against Ph1-positive leukemia.

Animals

Macrophage-lymphocyte cell clusters in the hypothalamic ventricle of some elasmobranch fish: ultrastructural analysis and possible functional significance.

BACKGROUND: Previous studies have demonstrated the existence of lympho-haemopoietic tissue in the meninges and choroid plexuses of various primitive vertebrates, including the stingray Dasyatis akajei and in early human embryos. In the present study, we extend these results analyzing macrophage-lymphocyte cell clusters found in the floor of the hypothalamic ventricle of several specimens of elasmobranchs. METHODS: After aseptical isolation of the brain from several specimens of smooth dogfish Triakis scyllia, cloudy dogfish Scyliorhinus torazame, gummy shark Mustelus manazo, and stingray Dasyatis akajei their hypothalamic regions were processed routinely by light, scanning, and transmission electron microscopy. RESULTS: The study of serial histological sections demonstrated that the macrophage-lymphocyte cell clusters proceeded from the meningeal lymphohaemopoietic tissue, reaching the ventricular lumen along large blood vessels. In this tissue, macrophages, different sized lymphocytes, lymphoblasts, granulocytes, monocytes, and developing and mature plasma cells were closely packed among a meshwork of fibroblastic reticular cell processes. It never invaded the brain parenchyma. A cell layer of glial elements and a continuous basement membrane interposed between the lymphoid tissue and the neural elements although some macrophages had migrated across the ependymal cell layer. In the ventricular lumen very irregular macrophages with long cell processes and containing abundant engulfed material of unknown origin formed big cell clusters with neighboring lymphocytes, lymphoblasts, and plasma cells, similar to those described during the immune response. Moreover, electron lucent cells which resembled the antigen-presenting cells of higher vertebrates established intimate surface cell contacts with the surrounding lymphocytes. In the third ventricle of several specimens of gummy shark, Mustelus manazo, morphologically similar cell clusters appeared but these were not connected to the meningeal lympho-haemopoietic tissue. No intraventricular cell aggregates were found in the stingray brain. CONCLUSIONS: Although we cannot rule out that these macrophage-lymphocyte cell clusters represent a permanent structure in the elasmobranch brain they rather seem to be only established after specific stimulation for preventing the entrance of noxious, foreign materials into the elasmobranch brain parenchyma.

Animals

Intraoperative radiotherapy for gliomas.

Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas. Twenty or 25 Gy of irradiation was delivered in a single fraction intraoperatively, followed by external beam irradiation. The electron beam energy was selected so that the 80% isodose line fell at 2 or 3 cm below the residual tumor surface. Median survival time of IORT group was 14 months and that of the control group was 10 months. Difference of survival curve was significant. There were 6 incidences of complication caused by IORT; 1 radionecrosis, 1 convulsion, 1 abscess, and 3 severe brain edemas. IORT is suited for the treatment of malignant gliomas.

Adult

A comparison of intraarterial carboplatin and ACNU for the treatment of gliomas.

BACKGROUND: Intraarterial chemotherapy with carboplatin for malignant gliomas has been tried recently, but its therapeutic efficacy and toxicity have not yet been elucidated. METHODS: We treated patients with malignant glioma by intraarterial chemotherapy using carboplatin, and compared the efficacy as well as the side effects with intraarterial ACNU. RESULTS: Twenty patients were treated with carboplatin (300 mg/m2) and 22 patients were treated with ACNU (80-200 mg/m2). Response (complete remission+partial response) rate for carboplatin was 12.5% compared to 45% for ACNU. Despite higher response rate for ACNU, the difference in the survival curves of the two groups was not significant. Three patients who were treated with high dose (150-200 mg/m2) of ACNU developed hemiparesis and aphasia. Seven patients treated with carboplatin developed 10 incidences of neurotoxicities; two hemiparesis, one aphasia, one blindness, one visual field disturbance, three convulsions, and two developed incidences of disturbances of consciousness. CONCLUSIONS: Intraarterial carboplatin was not superior to intraarterial ACNU in achieving remissions, and showed much greater tendency to produce neurotoxicities.

Adolescent

Expression of Ah receptor (TCDD receptor) during human monocytic differentiation.

We have previously found a high expression of human Ah receptor (TCDD receptor) mRNA in peripheral blood cells of individuals. In this paper, the expression of this gene in blood cells was first investigated in fractions of nucleated cells, revealing predominant expression of the Ah receptor gene in the monocyte fraction. Then the expression levels of AhR mRNA in various hematopoietic cell lines were examined together with those of Arnt and P450IA1. AhR was expressed at high levels in monocytoid U937, THP1, and HEL/S cells, and at moderate levels in promyelocytic HL60 cells and erythroblastic HEL cells. However, it was not detected in lymphoid cells MOLT4 (T cell) and BALL1 (B cell), nor in K562 erythroblasts. Furthermore, a specific induction of AhR during monocytic differentiation was investigated in HL60 and HEL cells. HL60 cells were induced to differentiate toward monocytes-macrophages by incubation with phorbol ester, showing a 5- to 2-fold increase of AhR mRNA. The incubation with transforming growth factor beta 1 and 1 alpha,25-dihydroxyvitamin D3 resulted in a 5- to 7-fold increase of AhR mRNA. The HEL cells also exhibited a similar elevation of AhR mRNA level, when they had differentiated toward monocyte-macrophage cells by these combined inducers, but little change in the mRNA level was observed when the cells were induced to differentiate into other cell types. Treatment of the differentiated HL60 cells with 3-methylcholanthrene, a ligand of AhR, induced the expression of the P450IA1 gene. These results indicated that expression of AhR mRNA was significantly induced during monocytic differentiation and that the differentiated cells were responsive to xenobiotics. Our results suggest that AhR may play an important role in the function of monocytes and also in the eventual activation of environmental carcinogens.

Aryl Hydrocarbon Receptor Nuclear Translocator

Comparison of a reversed passive latex agglutination and a polymerase chain reaction for identification of cholera toxin producing Vibrio cholerae O1.

Production of cholera toxin (CT) in AKI medium and conservation of CT gene (ctx) of 49 strains of Vibrio cholerae O1 were compared by reversed passive latex agglutination (RPLA) and polymerase chain reaction (PCR). The production of CT agreed with conservation of the ctx in 48 out of the 49 strains. Ten strains were positive, and 38 strains were negative by both methods. Only one strain was negative in RPLA and positive in PCR. This suggested that the combination of AKI-SW and RPLA is comparable to PCR to identify CT-producing V. cholerae O1.

Agglutination Tests

Morphological changes in human cerebral arteries after percutaneous transluminal angioplasty for vasospasm caused by subarachnoid hemorrhage.

Light and electron microscopy were used to study morphological changes in cerebral arteries after percutaneous transluminal angioplasty (PTA) for vasospasm in two patients with aneurysmal subarachnoid hemorrhage. One patient died of gastric bleeding 5 days after PTA. Postmortem examination of the inflated middle cerebral arteries revealed heterogeneously extended walls and dilated lumina. Throughout the vessel walls, the extracellular matrix, which was composed of nonmuscle components such as increased collagen, was stretched in conjunction with the medial muscle component. Also, torn and thinned areas of the wall and intramural hemorrhages were caused by overinflation. The second patient died of massive cerebral infarction caused by diffuse vasospasm 5 days after PTA. Prominent stretching of the walls at the atheromatous plaque margin in the dilated vessel was found in addition to the morphological changes observed in the first patient. These observations suggest that characteristic pathological alterations might be present in the vessel wall at the site of angioplasty. The major mechanism of the long-lasting effects of PTA seems to be the stretching and disruption of both the degenerative muscle and the proliferative nonmuscle components, mainly in the media of the vasospastic vessels.

Adult

Growth, hemorrhage, and regression of multiple intracerebral vasoformative tumors: report of an unusual case.

A rare case of multiple hemorrhagic vascular tumors of the cerebrum and cerebellum is reported. Computed tomographic scans in a 16-year-old girl revealed multifocal brain lesions with "jewel ring"-like areas of contrast enhancement. An old hematoma cavity was found inside the surgical specimen. Histologically, it was a vascular tumor composed of anastomosing vascular channels with proliferating endothelial cells and hemorrhages at different stages. Upon further histopathological study, this lesion could not be classified as any known vascular tumor entity, although it resembled some vascular tumors, such as cavernous hemangioma and hemangioendothelioma. The patient received steroid and alpha interferon treatment. The lesions initially increased in number once, then resolved 10 months after onset. The neuroradiological and histopathological features in the present case were characteristic, and the clinical course was unusual.

Adolescent

[Evaluation of advanced bladder tumor].

Ninety-two cases of advanced bladder tumor treated at the University of Tokyo and branch hospital from January 1977 to December 1992 were analyzed. The advanced bladder tumor was defined as that of higher than pT2 (according to the General Rule for Clinical and Pathological Studies on Bladder Cancer) or that with distant metastases. The following variants were evaluated, the therapeutic methods, the histological type, grade, stage, type of infiltration. The evidence of lymphatic infiltration, vessel infiltration, and lymph node metastases were also reviewed. The survival rate was calculated using Kaplan-Meier's method. In the cases with lymph node metastases, the survival rate was significantly lower than in the cases without metastases (p < 0.01), while no other factors affected the survival rate.

Combined Modality Therapy

[A Japanese family with congenital abnormal plasminogen].

A Japanese family with congenital abnormal plasminogen is reported. The patient was a 44-year-old male with no past history of thrombosis. Since only the plasminogen (PLG) activity was reduced on laboratory tests before surgery for lumbar disc herniation, coagulation and fibrinolysis studies were performed in the patient and his family. The patient underwent resection of the nucleus pulposus and posteriorlateral fixation of the lumbar spine. The PLG activity was 8% in the patient and his sister, 55% in his father, and 53% and 48% in his nephew brothers. The PLG antigen level was normal in all members of his family examined. IEF of PLG antigen showed abnormal patterns in which all bands were shifted slightly to the cathode side in the patient and his sister, but his father and nephew brothers exhibited duplicated bands showing combinations of normal and abnormal patterns. From these results, the proband and his sister were considered to be homozygotes, and his father and nephew brothers to be heterozygotes for congenital abnormal plasminogen. Acute reactant substances (fibrinogen, CRP, CPK, C1IN, alpha 1AT, etc.) and PIC (plasmin, alpha 2-plasmin inhibitor complex) increased after the operation due to the surgical insult, but the surgery did not trigger thrombosis. This patient is considered not to have developed thrombosis although he was a homozygote for congenital abnormal plasminogen, because the anticoagulation process until thrombogenesis was normal.

Adult

Characterization of YM022: its CCKB/gastrin receptor binding profile and antagonism to CCK-8-induced Ca2+ mobilization.

We investigated the antagonistic activity of (R)-1-[2,3-dihydro-1-(2'- methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]-3- (3-methylphenyl) urea (YM022), a benzodiazepine derivative, at CCKB/gastrin receptors. This compound potently inhibited [125I]CCK-8 binding to rat brain CCKB/gastrin receptors with a Ki value of 0.26 nM, but it showed weak affinity for rat pancreas CCKA receptors (Ki = 270 nM). Selectivity for CCKB/gastrin receptors was 1000-fold greater than that for CCKA receptors. Changes in intracellular free Ca2+ concentration ([Ca2+]i) in response to CCK-8 were measured in a rat anterior pituitary cell line GH3 by fura-2 fluorometry. CCK-8 (1-100 nM) dose-dependently increased [Ca2+]i in these cells, whereas YM022 had no effect on baseline [Ca2+]i even at the highest concentration of 100 nM. YM022 inhibited the mobilization of [Ca2+]i elicited by 10 nM CCK-8 in a concentration-dependent manner with an IC50 value of 4 nM. In conclusion, YM022 is an extremely potent and highly selective antagonist of CCKB/gastrin receptors. This compound is therefore useful for studying the physiological and pharmacological roles of CCKB/gastrin receptors.

Animals

Ontogenetic development of gonadotropin-releasing hormone-like immunoreactive neurons in the brain of the chum salmon, Oncorhynchus keta.

In the chum salmon, gonadotropin-releasing hormone-immunoreactive (GnRH-ir) cells were first detected in the olfactory placode of embryos at 16 days after fertilization, and then appeared sequentially in the olfactory nerve and the distal part of the forebrain by hatching. Four months after hatching, the terminal nerve was differentiated along the olfactory nerve, and GnRH-ir fibers extended to the hypothalamus and hypophysis. GnRH-ir cells occurred later in the preoptic area in about 1-year-old juveniles. These data suggest that GnRH neurons originate in the olfactory placode and then migrate into the brain along the olfactory nerve.

Aging

Purification and characterization of vibrio cholerae O139 fimbriae.

A Vibrio cholerae O139 (strain Al-1841) isolated from a patient with a cholera-like disease in Bangladesh predominantly produced new curved, wavy fimbriae (Al-1841 fimbriae) and small numbers of previously reported V. cholerae non-O1 S7-like pili. The former was purified and characterized. The molecular mass of the Al-1841 fimbrial subunit was less than 2.5 kDa, and it was immunologically different from that of V. cholerae non-O1 S7 pili. This novel fimbrial antigen was detected in all 182 Gram-negative strains from five genera tested but was absent from the Gram-positive bacteria tested. The purified Al-1841 fimbriae did not agglutinate human or rabbit erythrocytes.

Antibodies, Bacterial

Treatment of vasogenic brain edema with arginine vasopressin receptor antagonist--an experimental study.

We determined the effect of a centrally administered V1 receptor antagonist of arginine vasopressin on the brain water content in an animal model of vasogenic brain edema. Using adult rats, a cold injury was induced in the left hemisphere of the brain by applying a frozen copper rod. 50 ng of V1 receptor antagonist was administered into the left lateral ventricle 10 minutes prior to and/or 1 hour after injury. Twenty four hours after the cold injury, the brain water and sodium contents and plasma osmolality were measured. The V1 receptor antagonist significantly suppressed the increase of the brain water and sodium contents in the cortical structure adjacent to the lesion without any changes in plasma osmolality. Our results demonstrate the effectiveness of a V1 receptor antagonist of vasopressin on vasogenic brain edema.

Animals

Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene.

Several missense mutations within exons 1, 2, 4 and 5 of the gene for Cu/Zn-binding superoxide dismutase (SOD1) have been discovered to be involved in the development of chromosome 21q-linked familial amyotrophic lateral sclerosis (FALS). We describe here an autopsied patient with FALS, in whom we have recently identified a novel missense mutation in exon 1 of the SOD1 gene. The neuropathological findings were compatible with those described previously in patients with FALS with posterior column involvement. This suggests that mutations of the SOD1 gene may be responsible for this form of FALS.

Adult