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Biomedical subjects

M Oda

Publications and source records attributed to M Oda.

At least 181 records · Page 10Linked to original sources

[The clinico-pathological findings of the patients grouped as respiratory motor paralysis preceded type of ALS].

We reported five autopsied patients grouped as respiratory motor paralysis preceded type of ALS (R-ALS) classified as one clinical type of ALS from the patients living beyond respiratory failure reported in the previous paper, in which ALS the ontogenetically new motor functions in the "first motor system" proposed by Holstege involved first. The neuropathological changes of five patients were not limited in the degeneration of conventional "motor system" such as corticospinal tract and spinal and cranial motoneurons, but extended into the realm of "non-motor system", which could show the anterolateral myelin pallor in spinal cord by myelin staining, and detect the fibrillary gliosis of the anterior commissural area, the spinal grey matter of intemediate zone and anterior horn in all patients, and of medullary reticular formation in three one by Holzer staining. These pathological lesions could be included in the "first motor system". Considered from this study of the clinico-pathological findings of R-ALS based on "a new view of ALS", which respiratory failure in ALS is not terminus in ALS and total course of ALS might be TLS, it might be concluded that the clinico-pathologically involved initial lesions of ALS might be in the "first motor system", and include not only degenerations of "motor system", but also those of "non-motor system", which is the basically pathological lesions in ALS. Furthermore, the hitherto clinico-pathological ALS findings, which respiratory failure in ALS is terminus in ALS, could be included in this group, and showed as a part of ALS discussed from this study. Total clinico-pathological on ALS from the initial ones (R-type) to the advanced ones (TLS) including ALS-dementia should be considered further based on "the second and the third motor systems in addition to the first one".

Adult↗

[Surgical results on N2 lung cancer with special reference to correlation between tumor size and extension of lymph node metastases].

Systematic lymph node dissection was performed for every patients undergoing surgical intervention. Since 1981, there were 218 stage IIIA-N2 patients who underwent resection with two operative mortality. The five-year survival rate of whole cases was 22.6%, and that of 152 completely resected cases was 30.0%. Favorable factors on long-term survival of pN2 patients were cN0, T1-2 N2M0, single mediastinal node involvement, and tumor less than 20 mm or less. The five-year survival rates of stage IIIA-N2 patients with tumor diameter of < or = 20 mm, 21-30 mm, 31-50 mm, and > or = 51 mm were 48.1%, 27.7%, 31.2%, and 16.7%, respectively. When micrometastases to lymph node in the p-stage I patients (diagnosed by H-E staining) were examined by immunohistochemical staining, 36 patients (27%) out of 132 verified micrometastases in the lymph nodes.

Humans↗

[An autopsy case of intracranial T cell type malignant lymphoma with fluctuating neuropsychological symptoms].

A 59-year-old man was admitted to the hospital due to leg edema. He had multiple sclerosis-like episodes of transient diplopia at the age of 36 years and spastic paraplegia at the age of 38. After admission he showed various fluctuating neuropsychological symptoms (disorientation, hallucination, apraxia, aphasia) and cranial nerve palsy. Magnetic resonance imaging revealed abnormal signal intensity in the right thalamus and deep white matter. The patient was diagnosed as having malignant lymphoma and treated with steroid therapy and chemotherapy. Although partial improvement of clinical findings was observed, recurrent cerebral hemorrhage followed. Autopsy findings revealed perivascular infiltration of T cells in the brain, spinal cord and other general organs.

Aphasia↗

[Relation between temporomandibular joint disorder and subjective symptoms of fatigue].

An investigation was performed for the purpose of guaging the relation between temporomandibular joint disorder on the one hand and occupational category and subjective symptoms of fatigue on the other. Subjects were 2,414 workers (1,598 male, 816 female) in small and medium size enterprises at 67 workplaces in Hiroshima Prefecture. A comparison of cases with and without temporomandibular joint disorder showed that there were more complaints of fatigue among those with the disorder. Given these indications that temporomandibular joint disorder was related to occupation, it is possible that temporomandibular joint disease may be a work-related disease.

Adult↗

[A juvenile case of chronic inflammatory demyelinating polyradiculoneuropathy with severe onion bulb-like change mimicking hereditary neuropathy].

A 15-year-old male developed symmetrical weakness of the limb muscles. He had not had any previous developmental disorders except delayed initiation of walking. Flexion contraction of ankle joint and pes cavus deformity were seen. The cerebrospinal fluid protein concentration was elevated. Nerve conduction study showed severe conduction block and temporal dispersion. A sural nerve biopsy revealed remarkable onion bulb-like changes and perivascular infiltration of inflammatory cells. After high-dose corticosteroid treatment, he showed improvement in muscle strength. Although there were no abnormalities of genes related to hereditary neuropathy, the atypical findings of severe demyelinating changes of peripheral nerves mimicked hereditary neuropathy.

Adolescent↗

[Effectiveness of portable toothbrush use on reducing cigarette consumption and improving oral health].

There have been many studies on the influence of smoking on health, and in recent years, there have also been studies examining the relationship between smoking and oral health, concluding that smoking has a considerable detrimental effect on oral health. We introduced in a number of companies the idea of "Non smoking through the use of a portable toothbrush" as a means of giving up smoking while at the same time promoting oral health. The results demonstrated that consumption of cigarettes was reduced in about 50 percent of cases, while some improvement in mouth freshness was seen in about 90 percent. The study also showed that the success rate in reducing cigarette consumption through the use of a portable toothbrush was higher in highly motivated subjects, leading us to conclude that motivation is a major factor in reducing cigarette consumption. The study impressed on us the importance of educating people on the effect of smoking on oral health and the possibility of using a portable toothbrush as a means of reducing smoking.

Adult↗

Genetic alterations in the retinoblastoma protein-related p107 gene in human hematologic malignancies.

Genetic alterations in the p107 gene, a close relative of the retinoblastoma tumor suppressor gene, have never been identified in human malignancies. When we searched for such alterations in human hematologic malignancies by Southern blot analysis, 2 of 21 cell lines and 1 of 88 primary disorders had genomic alterations within the gene. Particularly, an altered p107 gene in a diffuse-large B-cell lymphoma cell line, KAL-1, harbored an intragenic deletion of about 15 kbp leading to the expression of an altered p107 mRNA devoid of 819 nucleotides of the coding sequences, which predicts to encode an approximately 87-kDa protein. This cell line was found to express solely a p107 derivative of 84 kDa by immunoblotting analysis. These results suggest that alterations in the p107 gene are probably related to a limited subset of human hematologic malignancies.

Gene Deletion↗

Analysis of the ternary complex formation of human urokinase with the separated two domains of its receptor.

Human urokinase-type-plasminogen-activator receptor (uPAR) is a glycolipid-anchored membrane glycoprotein comprising three structurally similar domains. We have succeeded in direct observation of the ternary complex formation of single-chain urokinase (scuPA) or its N-terminal fragment (ATF) with the separated domain-1 (N-terminal domain) and domain-(2+3) (internal and C-terminal domain) of human uPAR, by means of gel-filtration HPLC analysis. This complex was found to consist of the three components in an equimolar ratio (thus referred to as the three-part complex). To determine the nature of the interaction between these components, cross-linking experiments involving various kinds of cross-linkers and competitive binding assay on ELISA were performed. These experiments have shown that each uPAR domain can bind directly to scuPA at low affinity, and that both these domains contribute to the high-affinity binding between scuPA and uPAR in a synergistic manner. It can be considered that the synergistic effect of domain-1 and domain-(2+3) on scuPA binding would result from a conformational change, and that this steric event might trigger the signal transduction reported for scuPA/uPAR binding.

Azides↗

Thrombopoietin enhances the production of myeloid cells, but not megakaryocytes, in juvenile chronic myelogenous leukemia.

We previously reported the aberrant growth of granulocyte-macrophage (GM) progenitors induced by a combination of stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in juvenile chronic myelogenous leukemia (JCML). We examined here the effects of thrombopoietin (TPO) on the proliferation and differentiation of hematopoietic progenitors in JCML. In serum-deprived single-cell cultures of normal bone marrow (BM) CD34+CD38high cells, the addition of TPO to the culture containing SCF + GM-CSF resulted in an increase in the number and size of GM colonies. In the JCML cultures, in contrast, the number of SCF + GM-CSF-dependent GM colonies was not increased by the addition of TPO. However, the TPO addition caused an enlargement of GM colonies in cultures from the JCML patients to a significantly greater extent compared with the normal controls. There was no difference in the type of the constituent cells of GM colonies with or without TPO grown by JCML BM cells. A flow cytometric analysis showed that the c-Mpl expression was found on CD13+ myeloid cells generated by CD34+CD38high BM cells from JCML patients, but was at an undetectable level in normal controls. The addition of TPO to the culture containing SCF or SCF + GM-CSF caused a significant increase in the production of GM colony-forming cells by JCML CD34+CD38neg/low population, indicating the stimulatory effects of TPO on JCML primitive hematopoietic progenitors. Normal BM cells yielded a significant number of megakaryocytes as well as myeloid cells in response to a combination of SCF, GM-CSF, and/or TPO. In contrast, megakaryocytic cells were barely produced by the JCML progenitors. Our results may provide a fundamental insight that the administration of TPO enhances the aberrant growth of GM progenitors rather than the recovery of megakaryocytopoiesis.

Cell Differentiation↗

Thermodynamics of specific and non-specific DNA binding by the c-Myb DNA-binding domain.

The thermodynamics of the c-Myb DNA-binding domain (R2R3) interaction with its target DNA have been analyzed using isothermal titration calorimetry and amino acid mutagenesis. The enthalpy of association between the standard R2R3, the Cys130 mutant substituted with Ile, and the cognate DNA is -12.5 (+/- 0.1) kcal mol-1 at pH 7.5 and at 20 degrees C, and this interaction is enthalpically driven throughout the physiological temperature range. In order to understand the DNA recognition mechanism, several pairs of interactions were investigated using single and multiple-base alterations with single and multiple-amino acid substituted mutants. The interactions between the standard R2R3 and many non-cognate DNAs were accompanied by binding enthalpy changes and heat capacity changes, although their affinities were reduced. The roles of the electrostatic interactions in binding to the cognate and the non-cognate DNAs were also analyzed from the dependency of the thermodynamic parameters on the salt concentration. The heat capacity change was found to be significantly dependent upon the salt concentration. Several mutant proteins bound to the multiple-base altered DNA with very small enthalpy changes, although they bound to the cognate and the single-base altered DNAs with detectable enthalpy and heat capacity changes. From the thermodynamic cycles derived from the DNA binding of the amino acid substituted R2R3 to the base substituted DNA duplexes, the individual thermodynamic mechanisms of the specific DNA recognition of R2R3 were dissected. The local folding mechanism was highlighted by the substitution of Pro with either Gly or Ala at the linker between R2 and R3. The characteristic thermodynamic features of specific and non-specific DNA binding are discussed.

Amino Acid Substitution↗

A study of cell death in Werdnig Hoffmann disease brain.

We examined the occurrence of apoptotic cell death in the autopsied brains of four patients with Werdnig Hoffmann disease (WH), using TdT-mediated DIG-dUTP nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related proteins. Three of the four patients, aged over 6 months, exhibited TUNEL-positive cells in the lateral nuclei of the thalamus, and one of the three patients also had TUNEL-positive cells in the cerebral cortex. The labeled nuclei did not show characteristic features such as nuclear fragmentation or apoptotic bodies, and synaptophysin-positive granules were observed around some of the TUNEL-positive cells, although none of the antibodies against glial markers could visualize TUNEL-positive cells. TUNEL-positive cells were not observed in other regions examined, including the spinal cord, medulla and cerebellum or in the brains of three age-matched controls. There were neither immunopositive structures for bcl-2 or p53 nor alteration of in situ expression of bcl-xs/l or bax in any subject, and the TUNEL-positive cells lacked immunopositivity against apoptosis-related proteins. The presence of these TUNEL-positive cells might suggest latent neurodegeneration in the thalamus before central chromatolysis of neurons or neuronal loss appears, although it is not clear whether apoptotic cell death is involved in this degenerative process.

Apoptosis↗

Cerebellar neurodegeneration in human hereditary DNA repair disorders.

Recent findings have focused attention on the role of apoptosis in neurodegenerative diseases, however, the apoptotic process in child-onset brain disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are hereditary disorders characterized by impaired DNA repair and neurodegeneration. We investigated apoptotic cell death in the cerebellum of five cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT-mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in the granule cells of the cerebellar cortex of two patients with XPA and two patients with CS, whereas such cells were not detected in the cerebellar cortex in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression was not altered. Some patients showed nuclear expression of p53 in the granule cells and/or molecular layer, bax-positive glial cells in the cerebellar white matter, and a few Trk B-positive cells in the granular layer. These findings suggest that apoptotic cell death can be involved in the cerebellar degeneration in patients with hereditary defects in DNA repair mechanisms.

Adolescent↗

Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.

We have reported that infusion of recombinant human hepatocyte growth factor (rhHGF) stimulates liver regeneration after hepatectomy in cirrhotic rats and increases the level of serum lipids and secretion of very-low density lipoprotein (VLDL). Studies were now performed to determine whether rhHGF directly influences lipid synthesis and its secretion in cultured rat hepatocytes. Isolated cells were cultured in the presence or absence of rhHGF (20 ng/mL) for 2 days. During the first 12 hours, rhHGF transiently inhibited the release of lipids (triacylglycerol, total cholesterol, and phospholipids), but stimulated their releases with maximal levels achieved at 36 hours. [3H]-glycerol experiment with the transcriptional and translational inhibitors revealed that rhHGF stimulated de novo synthesis of lipids by affecting activities of lipid metabolic gene. [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B by rhHGF. Furthermore, lipid analysis of lipoprotein fractions in the conditioned medium showed that rhHGF enhanced levels of triacylglycerol, total cholesterol, and phospholipids by 50% to 200% in both VLDL and low-density lipoproteins (LDL)/high-density lipoprotein (HDL). Genistein, a tyrosine kinase inhibitor, blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein B stimulated by rhHGF. These results indicate that HGF likely stimulates lipid biosynthesis and lipoprotein secretion in hepatocytes through its tyrosine kinase-associated receptor, c-met, and accelerates the progress of cell maturation in liver regeneration.

Androstadienes↗

Brain tumors in surgical neuropathology of intractable epilepsies, with special reference to cerebral dysplasias.

Surgical specimens from 30 patients (13 males and 17 females) with intractable epilepsy with brain tumors and allied lesions were histopathologically examined: 4 of nonneurogenic origin (1 angiolipoma with cortical dysplasia and 3 cavernous hemangiomas), 2 low-grade fibrillary astrocytomas, 1 pleomorphic xanthoastrocytoma, 3 pilocytic astrocytomas with nuclear polymorphism, 1 oligoastrocytoma, 9 gangliogliomas, 3 gangliogliomatous lesions combined with tuberous sclerosis-like dysplastic changes, and 7 undetermined lesions suspected of being mixed glioma, dysembryoplastic neuroectodermal tumor (DNT), or dysplasia. They were all located supratentorially: in the temporal lobe in 21, frontal lobe in 6, and parietooccipital lobe in 3. The age of onset was under 20 years in most patients. Some kinds of dysplasias, such as focal cortical dysplasia, glioneuronal heterotopia, and clustered neurons in the hippocampus and amygdaloid nucleus, were combined in 11 cases, especially those with age of onset under 10 years. Pilocytic astrocytoma-like features were seen in 5 of the gangliogliomas and 3 of the undetermined lesions, and DNT-like features in 2 of the former and 3 of the latter. Gangliogliomas, pilocytic astrocytomas, mixed gliomas, DNTs, and dysplasias may be closely inter-related in the development of intractable epilepsies of young patients.

Adolescent↗

Hemimegalencephaly: signal changes suggesting abnormal myelination on MRI.

We reviewed the MRI of 17 patients with hemimegalencephaly to investigate abnormal myelination in this condition. On images of seven patients aged 18 months or less, the white matter on the affected side suggested advanced myelination for the age. On T1-weighted images of three patients aged 1 month, the anterior limb of the internal capsule in the affected hemisphere was myelinated, and T1 shortening was not clearly seen in the pre- and postcentral gyri. The cortical grey matter and subcortical white matter was isointense in two patients. Images of two patients aged 4 to 5 months and of five patients aged 8-18 months showed myelination that extended more peripherally in the white matter of the affected hemisphere.

Adolescent↗

Loss of the dentate nucleus neurons is associated with torpedo formation: a morphometric study in progressive supranuclear palsy and dentatorubro-pallidoluysian atrophy.

Cerebellar torpedoes can be induced by direct damage to Purkinje cell axons. This raises the possibility that the loss of dentate nucleus neurons (DNNs) may also cause torpedo formation through synaptic detachment between DNNs and Purkinje cell axon terminals. To investigate this possibility, we conducted a morphometric study with an image analyzer in progressive supranuclear palsy (PSP) and dentatorubro-pallidoluysian atrophy (DRPLA). Using horizontal and sagittal sections of the cerebellar hemispheres containing the greatest proportion of the dentate nucleus, we determined the line densities of torpedoes, Purkinje cells, and DNNs. In PSP and DRPLA, the densities of DNNs were significantly lower, and the densities of torpedoes much greater than in controls, while those of Purkinje cells were normal in both diseases. In addition, the torpedo densities in PSP and DRPLA showed a strong negative correlation with the DNN densities. Thus, this study clearly demonstrated that torpedoes are formed in association with the loss of DNNs, suggesting that they may occur in consequence of synaptic disconnection of Purkinje cells from DNNs.

Adult↗

Blood-nerve barrier in IgM paraproteinemic neuropathy: a clinicopathologic assessment.

We report the pathologic findings in a patient with sensorimotor neuropathy associated with Waldenström's macroglobulinemia, particularly in relation to blood-nerve barrier defects. The monoclonal IgM was of kappa type and possessed anti-HNK-1 activity. A sural nerve biopsy specimen revealed severe loss of myelinated and unmyelinated nerve fibers and gaps between adjacent endothelial cells of small endoneurial vessels. Postmortem findings 3 years later included severe loss of myelinated nerve fibers and diffuse infiltration by lymphoplasmacytic B cells throughout the peripheral nervous system, sparing the central nervous system. Findings in this case suggest an immune attack against endoneurial endothelial cells with permeation of IgM into peripheral nerve tissue.

Aged↗

Decrease of protein kinase C in the spinal motor neurons of amyotrophic lateral sclerosis.

The expression of protein kinase C (PKC), a calcium- and phospholipid-dependent signaling molecule, was studied immunohistochemically in the spinal motor neurons of cases of sporadic amyotrophic lateral sclerosis (SALS). In the normal spinal cord, intense PKC immunoreactivity was found in subsets of large motor neurons. PKC immunoreactivity was markedly decreased in the spinal motor neurons of SALS. The result suggests that down-regulation of PKC is associated with the degeneration of spinal motor neurons in SALS.

Amyotrophic Lateral Sclerosis↗