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Biomedical subjects

M Morimatsu

Publications and source records attributed to M Morimatsu.

At least 55 records · Page 3Linked to original sources

The evaluation of the potential of botulinum C3 enzyme as an exogenous differentiation inducing factor to neurons.

Botulinum C3 enzyme produced by Clostridium botulinum type C and D strains modifies Rho proteins. In a previous study, we observed that the LDH isozyme pattern of neurons treated with C3 enzyme was different from that induced with endogenous growth factor of neurons such as NGF [21]. This type of change is considered to have an advantage in the medical use of C3 enzyme for neural disorder. To determine the functional similarity of C3-treated neurons to control and NGF-treated neurons, we examined the responses of C3-treated neurons to various drugs, including some neurotransmitters, by measuring the rise of intracellular Ca ions into the neurons. The time course of the rise of intracellular Ca ions induced by high concentration of potassium in the C3-treated neurons was similar to that in the NGF-treated neurons. The C3-treated neurons responded to glutamic acid, aspartic acid, kainic acid, gamma-aminobutylic acid, muscarine and ACh with similar time courses and magnitudes as the control neurons. These results suggest that the C3 enzyme induces the functional differentiation of neurons, and that C3 enzyme has the potential for the medical use as an exogenous differentiation-inducing factor of neurons.

ADP Ribose Transferases↗

Coordinate regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human vascular smooth muscle cells.

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77+/-2.4-95+/-0.5%, and that of TIMP-1 by 34+/-0.5-59+/-1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78+/-2.9-85+/-1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.

Adult↗

[Comparison of complications in elderly and non-elderly patients with neurological diseases during admission to a rehabilitation hospital].

Medical complications seen in admitted patients in a one-year period in a rehabilitation hospital were evaluated, and patients with neurological diseases were subdivided with age in order to determine trends of complications with occurred in the aged patients. Ninety-five of 117 patients (81.2%) suffered from complications, the most common were respiratory diseases, genitourinary diseases and psychoneurological diseases and events. Infectious diseases were very common throughout all ages. Significantly more cases and occasions of complications occurred in the aged patients (ages 65 or more, n = 59) than in the younger patients (aged under 65, n = 58), which suggests that complications tended to recur in the same patient in the aged group. Genitourinary diseases, especially urinary tract infection, was far more common in the aged group, predominating in women. Recurrences of stroke or poststroke epilepsy were more frequently seen in patients aged under 65. Traumas and fractures related to falls occurred more commonly in the aged group. Elderly patients were more susceptible to complications not directly related to the illness for which they were admitted. Complications occur quite commonly in aged patients admitted to our rehabilitation hospital, and careful attention should be paid to conditions unrelated to the illness causing admission, such as infectious diseases, especially for aged patients.

Aged↗

A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment.

A 68-year-old male was admitted for interstitial pneumonia associated with scleroderma. High-dose methylprednisolone was administered for treatment of the pneumonitis. Two weeks later, anemia, thrombocytopenia and progressive increase in BUN, creatinine and LDH were observed. Although the blood pressure remained normotensive, renal biopsy showed thrombosis of the polar arterioles and glomerular capillaries. The affected interlobular artery included concentric intimal thickening and thrombosis in the lumen. Our findings suggested that the antecedent use of high-dose corticosteroids is involved in precipitating normotensive renal crisis. Corticosteroids should be used in low doses and with great caution in scleroderma patients.

Aged↗

A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.

Many clinical and pathological discussions have been focused on the difficulty of differential diagnosis between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) in recent years. This study was conducted to evaluate the usefulness of tau proteins in cerebrospinal fluid (CSF) for the differentiation of these two diseases. Subjects consisted of 10 patients with CBD (four males and six females with a mean age of 67.9+/-5.8 years), 12 patients with PSP (eight males and four females with a mean age of 62.6+/-5.8 years) and 36 control subjects (CTL) (16 males and 20 females with a mean age of 65.8+/-9.9 years). The CBD group included patients with probable CBD, while all the patients in the PSP group satisfied the diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP). CSF tau proteins were measured with the sandwich ELISA method (Innogenetics, Belgium). The CSF tau protein level was 320.1+/-86.5 pg/ml in the CBD group, 151.5+/-52.7 pg/ml in the PSP group and 128.7+/-91.7 pg/ml in the CTL group. Significant differences were noted in tau protein levels between the CBD group and both the PSP group (P<0.001) and the CTL group (P<0.005). We suggested that the measurement of CSF tau proteins may be useful for the differentiation between CBD and PSP.

Aged↗

Primary amebic meningoencephalitis due to Naegleria fowleri: an autopsy case in Japan.

Free-living amebas represented by Naegleria fowleri, Acanthamoeba and Balamutia have been known to cause fatal meningoencephalitis since Fowler and Carter (1965) reported the first four human cases. An autopsy case of a 25-year-old female with primary amebic meningoencephalitis (PAM) due to Naegleria fowleri is described. Headache, lethargy and coma developed in this patient, and her condition progressed to death 8 days after the onset of clinical symptoms. Cerebral spinal fluid examination confirmed clusters of amebas, which were grown in culture and identified as Naegleria fowleri. At autopsy, lesions were seen in the central nervous system (CNS) and the ethmoid sinus. The CNS had severe, suppurative meningoencephalitis with amebic trophozoites mingled with macrophages. This case is the first report of PAM due to Naegleria fowleri in Japan.

Adult↗

Pineal malignant rhabdoid tumor with chondroid formation in an adult.

A pineal tumour in a 27-year-old male is presented with the characteristic histological features of a pineal malignant rhabdoid tumor (MRT) with chondroid formation. Occasionally, tumor cells contained a single well-demarcated hyaline globular inclusion within the cytoplasm adjacent to the nucleus. The stroma of these tumors tends to be densely hyalinized and become chondroid. Immunohistochemical staining was positive for vimentin, epithelial membrane antigen, chromogranin A, synaptophysin, neuron-specific enolase, S-100 protein, and muscle actin. Despite surgery and radiochemotherapy, the tumor recurred in the pineal region and metastasized to the lower lobe of right lung. The patient died 2 years after the initial diagnosis. This is the second published case of central nervous system-MRT appearing in an adult. The clinical and pathological features of pineal MRT in this patient are presented.

Adult↗

Movement velocity dependent muscle strength in Parkinson's disease.

We measured isokinetic muscle strength of knee extension and flexion in 18 patients with Parkinson's disease who showed marked laterality in symptom severity and compared strength between the sides in the same patient. In all patient groups, the maximum peak torque of the more affected side was significantly less than for the less affected side at 15 revolutions per minute (r.p.m.) and 30 r.p.m. with the difference between the sides being larger at 30 r.p.m. than at 15 r.p.m., while at 5 r.p.m. there were no significant differences between sides. In the Yahr stage I group, the maximum peak torque in both extension and flexion at each velocity showed no significant difference between the sides. In contrast, in the stage II and III groups the maximum peak torque at 5 r.p.m. showed no significant difference between the sides, while at 15 r.p.m. and 30 r.p.m. these values showed a tendency and a significant difference between the sides, respectively, with the more affected side being weaker. These results suggest that muscle weakness in patients with Parkinson's disease increases with performance velocity, especially as the disease progresses.

Acceleration↗

Adenovirus-mediated over-expression of p21Waf-1 differentially affects the proliferation, telomerase activity, and expression of glial fibrillary acidic protein in human glioma cells.

Over-expression of p21Waf-1 was performed in 5 human glioma cell lines (U251MG, U87MG, T98G, NMC-G1, and KALS-1). p53 gene status was examined by PCR-SSCP and direct sequence method. The endogenous p21Waf-1 expression was evaluated by RT-PCR. Adenovirus-mediated over-expression of p21Waf-1 inhibited the proliferation of human glioma cells expressing wild-type p53 (U87MG, NMC-G1, KALS-1) irrespective of endogenous p21Waf-1 expression. Telomerase activity was also reduced in these cells. In U87MG, GFAP expression was stimulated by the transfection with p21Waf-1, but was reduced in NMC-G1. Over-expression of p21Waf-1 thus affects the cellular behavior of human glioma cells in a cell-type specific manner.

Adenoviridae↗

Modulation of fas-mediated apoptosis in osteosarcoma cell lines.

Fas/APO-1 (or CD95) is a 45-kDa cell surface glycoprotein that transduces cellular death signals for apoptosis upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. We examined the Fas expression at the protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, in 14 osteosarcoma cell lines. Ten of 14 ostesarcoma cell lines constitutively expressed detectable levels of Fas on the cell surface with positive cell rates ranging from 10.2 to 72.4%. Four other cell lines expressed Fas almost exclusively in the cytoplasm. An antibody against Fas was able to induce Fas-mediated cell death only in two cell lines with high levels of surface Fas. In the presence of the protein synthesis inhibitor cyclohexamide, antibody to Fas led to an induction of apoptosis in ten of the osteosarcoma cell lines antibody-concentration dependently. These data suggest that Fas is a potential protein related to apoptosis in osteosarcomas when the sensitizing activity of cyclohexamide on anti-Fas-mediated cytotoxicity was exerted.

Antibodies, Monoclonal↗

Cells deleted for Brca2 COOH terminus exhibit hypersensitivity to gamma-radiation and premature senescence.

The putative Brca2-MmRad51 interaction is analyzed in mouse cells deleted for the COOH terminus of Brca2 (amino acids 3140-3328), which contains a region that associates with MmRad51 by yeast two-hybrid. These cells are hypersensitive to gamma-radiation (suggesting defective recombinational repair) but not UV light (suggesting intact nucleotide excision repair) and maintain the G1-S and G2-M checkpoints after exposure to gamma-irradiation. Cells deleted for the COOH terminus of Brca2 progress through the cell cycle at a similar rate as wild-type cells but undergo senescence more rapidly. These data support the hypothesis that deletion of Brca2 stimulates cancer by defective MmRad51-mediated DNA repair and not by defective cell cycle regulation.

Animals↗

Is IgG anti-GT1a antibody associated with pharyngeal-cervical-brachial weakness or oropharyngeal palsy in Guillain-Barré syndrome?

The pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) has clinical features similar to those of botulism and diphtheria. Mizoguchi et al. (1994) [Mizoguchi, K., Hase, A., Obi, T., Matsuoka, H., Takatsu, M., Nishimura, Y., Irie, F., Seyama, Y., Hirabayashi, Y., 1994. Two species of antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. J. Neurol. Neurosurg. Psychiatry 57, 1121-1123] reported a patient with PCB-like symptoms who had serum IgG anti-GT1a antibodies which did not cross-react with GQ1b. We assumed that PCB is associated with anti-GT1a antibodies that do not have reactivity to GQ1b and made a serological study of a PCB patient. We searched for PCB patients prospectively and found one with PCB. This patient had IgG anti-GT1a antibodies which were not absorbed with GQ1b in an absorption study, whereas IgG anti-GT1a antibodies from Fisher's syndrome patients were. The frequency of positive IgG anti-GT1a antibody did not differ in patients with and without bulbar palsy. Our findings indicate that IgG anti-GT1a antibodies which do not cross-react with GQ1b are specifically detectable in PCB and can be used as a diagnostic marker of PCB.

Adult↗

Expression of the cyclin-dependent kinase inhibitor, p21Waf-1/Cip-1/Sdi-1, in human vascular smooth muscle cells in the proliferating state.

Excess proliferation of vascular smooth muscle cells (SMC) is an important aspect of atherogenesis. Cell-cycle regulatory proteins such as cyclin and cyclin-dependent kinases are vital for cell-cycle progression. To understand the role of the cyclin-dependent kinase inhibitor, p21Waf-1/Cip-1/Sdi-1 (p21Waf-1), on human atherogenesis, we tested p21Waf-1 expression in human atherosclerotic lesions and cultured SMC. Immunohistochemical staining revealed that SMC in neointimal lesions expressed p21Waf-1. No evidence of the p53 protein could be detected. By Western blotting, cultured SMC obtained from a neonate revealed that a higher level of p21Waf-1 expression correlated with a higher expression of proliferating cell nuclear antigen and a lower expression of the contractile protein than that observed in cells obtained from aged donors. When the phenotypes of SMC were changed by modification of serum concentration and cell densities, p21Waf- expression was maximal in serum-stimulated SMC at low cell densities despite the low expression of p53. Furthermore, serum stimulation transiently increased the p21Waf-1 expression of quiescent SMC, which was synchronized with the transition from the G0/G1 to the S phase as well as with cyclin D1 expression. These results may suggest that the negative regulator of cell-cycle progression also plays a role in regulating the appropriate cell-cycle progression in SMC. Growth stimuli may induce both growth-promoting and growth-inhibitory factors in SMC. The balance between these two opposing factors may play an important role in the determination of cell-cycle progression.

Arteriosclerosis↗