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Biomedical subjects

Keiko Tanaka

Publications and source records attributed to Keiko Tanaka.

At least 55 records · Page 3Linked to original sources
PubMed2004

Quantitative evaluation of brainstem involvement in multiple system atrophy by diffusion-weighted MR imaging.

In multiple system atrophy (MSA), symptoms associated with dysfunctions of the brainstem and autonomic nervous system are important prognostic factors. We investigated brainstem involvement in 12 patients with MSA with predominant cerebellar symptoms (MSA-C) (mean age, 56.3 +/- 9.9 years, median disease duration, 3 years), and 11 controls (57.6 +/- 12.0 years) matched for age using diffusion-weighted MR imaging (DWI). We demonstrated that apparent diffusion coefficients (ADCs) in the pons and middle cerebellar peduncle of MSA-C patients are significantly higher than those of normal controls even though the patients are in the early stage of the disease. Furthermore, we demonstrated that increased ADC values correlated well with the disease duration. The current study demonstrated that DWI is a useful noninvasive method for the quantitative evaluation of the brainstem involvement in MSA-C patients.

Aged↗
PubMed2004

Gene polymorphisms of the mu opioid receptor in methamphetamine abusers.

In drug addiction, the opioid system is thought to mediate motivational effects through dopamine-independent mechanisms. We have investigated associations of the mu-opioid receptor gene (OPRM) variations with methamphetamine (MAP) dependence/psychosis. The allelic frequency of A118G (Asn40Asp) in exon 1 of ORPM was 45.3% in our control subjects, but only 7.5-25.8% in the Caucasian or African-American population of previous studies. We have identified several novel polymorphisms in intron 1 and the 5' untranslated region (5'UTR) of OPRM. Polymorphisms in the functionally relevant 5' regulatory region of OPRM were different in our Japanese population from Caucasian or African-American populations. No significant differences between controls and MAP abusers were found in either genotype or allele frequency at any single nucleotide polymorphism (SNP) or (AC)n dinucleotide repeat in intron 1. A subdivision of our MAP group revealed that A118G of OPRM shows a significant association with MAP psychosis having latency less than three years. Further analysis should be capable of identifying associations between the OPRM variations and MAP dependence/psychosis.

Adult↗
PubMed2004

[Detection method of injured Escherichia coli O157 in noodles and vegetables].

An enrichment procedure and a polymerase chain reaction (PCR) method for the detection of injured Escherichia coli O157 in foods were examined. Freeze-injured E. coli O157 inoculated in boiled spaghetti could be detected in 6-h culture within 12 h by the PCR method. Cells injured by heating in boiled spaghetti and cells injured by chlorine treatment in raw lettuce and carrot did not grow sufficiently to be detected in 6-h culture but were detected in 18-h culture using selective agar media. The injured cells could be also detected in 18-h culture within 24 h by the PCR method. Enrichment at 42 degrees C in trypticase soy broth (TSB) was more effective than that at 42 degrees C in modified EC broth with novobiocin. These results indicated that the usage of enrichment in TSB for 18 h at 42 degrees C in combination with the PCR method is suitable for screening for E. coli O157 in boiled or chlorinated foods, even if the O157 cells are injured.

Caseins↗
PubMed2004

[An autopsy case of systemic vasculitis associated with hepatitis C virus-related mixed cryoglobulinemia presenting severe peripheral neuropathy].

A 75-year-old man, previously diagnosed as having chronic hepatitis C virus (HCV) infection, suddenly developed left foot drop, followed by progressive motor weakness and sensory disturbance in all of the extremities. Because of an elevated level of the rheumatoid factor (RF), he had been treated with antirheumatic drugs three years before the onset of his neurological symptoms. Within two months, he became unable to walk any more, and was transferred to our hospital. Neurologic examination showed asymmetrical severe muscular weakness and atrophy of all the limbs, and a sensory deficit under the level of the wrists and knees. Livedo reticularis was also noted in bilateral legs. Nerve conduction study revealed severe sensorimotor axonal neuropathy, and muscle biopsy specimens showed necrotizing vasculitis of small arteries in the perimysium. Serological tests indicated type II cryoglobulinemia (monoclonal IgAkappa + polyclonal IgG). A diagnosis of vasculitic neuropathy associated with HCV-related mixed cryoglobulinemia was made. A high-dose intravenous immunoglobulin therapy (IVIg) and a high-dose steroid therapy were not effective, and he died of alveolar hemorrhage probably due to pulmonary vasculitis. Postmortem pathological examination revealed severe vasculitis, accompanied by fibrinoid degeneration and the infiltration of predominant mononuclear cells into the small and medium-sized vascular walls of multiple organs such as the liver, kidney, pancreas and intestine as well as the peripheral nerves and skeletal muscles. A severe loss of myelinated fibers were also observed in the multiple peripheral nerves examined. We emphasize that patients with HCV infection and mixed cryoglobulinemia may develop severe systemic vasculitis resembling polyarteritis nodosa leading to often life-threatening polyvisceral failure, particularly in patients showing progressive mononeuropathy multiplex.

Aged↗
PubMed2004

[Diagnostic significance of autoantibodies in neurological diseases].

Significance of autoantibodies in neurological diseases is roughly grouped into three, as 1) disease process is thought to be directly caused by the antibodies because the antibody can reproduce the disease process, like anti-acetylcholine receptor antibody in myasthenia gravis, anti-P/Q type voltage-gated calcium channel antibody in Lambert-Eaton myasthenic syndrome, etc., 2) antibodies are thought to be closely related to the disease because plasma exchange ameliorate the disease promptly, however without success of transfer experiments, like Guillain-Barré syndrome/Miller Fisher syndrome and anti-ganglioside antibodies and 3) antibodies are very specific and become the useful markers for the diagnosis, however without direct evidence of disease transfer, like paraneoplastic neurological syndromes and anti-Yo or Hu antibodies. Overall, the roles of antibodies are different between diseases, but the presence of antibodies support the basis of intervening immunotherapy, antibody titers predicted the activity of the diseases, or they are useful markers for exploring underlying cancers in paraneoplastic neurological syndromes.

Autoantibodies↗
PubMed2003

Local calcium signaling in neurons.

Transient rises in the cytoplasmic concentration of calcium ions serve as second messenger signals that control many neuronal functions. Selective triggering of these functions is achieved through spatial localization of calcium signals. Several qualitatively different forms of local calcium signaling can be distinguished by the location of open calcium channels as well as by the distance between these channels and the calcium binding proteins that serve as the molecular targets of calcium action. Local calcium signaling is especially prominent at presynaptic active zones and postsynaptic densities, structures that are distinguished by highly organized macromolecular arrays that yield precise spatial arrangements of calcium signaling proteins. Similar forms of local calcium signaling may be employed throughout the nervous system, though much remains to be learned about the molecular underpinnings of these events.

Animals↗
PubMed2003

Mutational analysis of human papillomavirus type 16 major capsid protein L1: the cysteines affecting the intermolecular bonding and structure of L1-capsids.

Human papillomavirus 16 major capsid protein L1 (composed of 505 amino acids (aa) including 12 cysteines) assembles by itself into virion-like icosahedral particles (L1-capsids), each of which is dissociated into 72 pentameric capsomeres when intermolecular disulfide bonds are disrupted. To identify the cysteines affecting the bonding and the structural integrity of the L1-capsids, we constructed a series of L1 mutants with substitution of serine for cysteine, which were expressed from recombinant baculoviruses in the insect Sf9 cells. From infected cells, the self-assembled L1-capsid fractions were purified by CsCl-equilibrium centrifugation and examined for velocity sedimentation profiles, for the presence of intermolecular bonding by SDS-PAGE with or without a reducing agent, for morphology under an electron microscope, and for susceptibility to trypsin digestion. Mutants C175S (C at aa 175 was replaced with S) and C185S were sedimented in sucrose-density gradients slightly slower than the wild type (WT) capsids, and mutant C428S stayed near the top as WT-capsomeres did. In the nonreducing SDS gel, where WT-capsids were separated into two bands of L1-trimers and L1-dimers, the C175S-trimer band was not detected, the C185S-dimer band was much less dense, and the C428S-trimer and C428S-dimer bands were not detected. Thus, it seems likely that C175, C185, and C428 are involved in L1 trimerization, in L1 dimerization, and in both, respectively. Morphologically, the C175S, C185S, and C428S fractions appeared to consist mostly of heterogeneous rod-shaped tubules, of smaller spherical particles, and of only capsomeres, respectively, whereas C102S, C229S, and C379S resembled WT. The C161S, C175S, C185S, C229S, C379S, and C428S capsids were more sensitive to degradation caused by trypsin than WT. The results indicate that C175, C185, and C428 are required for the normal assembly of L1-capsids through trimerization and dimerization of L1 bound by the intercapsomeric disulfide bonds between cysteines, and that C161, C229, and C379 are necessary for the integrity of L1-capsids probably through intramolecular bonding.

Amino Acid Substitution↗
PubMed2003

Steroid-responsive limbic encephalitis.

A 71-year-old man presented with gradually progressing cognitive decline following acute febrile exanthematous disorder. The MRI showed an abnormality in the bilateral limbic systems. An elevation of cerebrospinal fluid (CSF) protein with lymphocyte pleocytosis was noted. Immunoblot of the CSF revealed the presence of anti-white matter antibodies that mainly recognized astrocytes. Intravenous steroid followed by oral steroid reduced the symptoms to a remarkable degree. The patient has now been successfully sustained with steroid for more than two years. We considered that this case is classified as non-paraneoplastic limbic encephalitis, and acquired autoimmunity played a major role in the pathogenesis of this case.

Aged↗
PubMed2003

Changes in the fatty acid composition and hydroxyproline content in rat lung in relation to collagen synthesis after paraquat administration.

OBJECTIVES: Effect of paraquat on the fatty acid composition (weight percentage) of rat lung was studied with particular reference to the change of hydroxyproline content in the course of paraquat-induced dysfunction and subsequent repair. METHODS: Eight-week-old male Wistar rats were administered paraquat at 20 mg/kg body weight subcutaneously, and the wet weight, hydroxyproline content and fatty acid composition of lungs of each group rats were analyzed at 2, 7, 14 or 28 days after treatment, respectively. RESULTS: The percentage of palmitic acid (C16:0), arachidonic acid (C20:4) and docosahexaenoic acid (C22:6) significantly increased, and the percentage of oleic acid (C18:1) and the ratio of monounsaturated fatty acids/saturated fatty acids (M/S) significantly decreased comparing to control on day 28 after paraquat administration. The time-course of each fatty acid was observed for 28 days after paraquat administration. M/S ratio decreased after paraquat administration up to the 28th day, but the polyunsaturated fatty acids/saturated fatty acids (P/S) ratio decreased during the first 7 days, followed by a increase, and then reached higher level than the 0 day control at the 28th day. Hydroxyproline also increased between the 14th and the 28th days. Eicosapentaenoic acid (C20:5) had once increased during the first 2 days and decreased gradually, while C20:4 maintained high level in this period. C22:6 increased after paraquat administration and maintained high level up to the 28th day. This result indicated that desaturation and elongation in n-3 series fatty acids were accelerated after paraquat treatment, and consequently C20:5 was rapidly converted into C22:6 and decreased. CONCLUSIONS: Paraquat might cause elevation of unsaturated fatty acids, espe- cially C20:4 but not C20:5 by the stimulation of the fatty acid desaturase system, and could consequently stimulate local collagen synthesis by C20:4 metabolites in the healing stage.

Animals↗
PubMed2003

Retrospective study of preventive effect of maize on mortality from Parkinson's disease in Japan.

The findings of a negative association between past maize (Zea mays) production and current Parkinson's disease mortality by each prefecture in Japan tends to support the hypothesis that the nutritional condition that causes niacin deficiency might protect people from Parkinson's disease. Specifically, the negative association between both the area planted for dried corn in 1960, 1970 or 1977 and the area planted for sweet corn in 1960 and age-adjusted death rates for Parkinson's disease is ecological evidence supporting the hypothesis. Extending the analysis to other cultivated crops, even stronger negative associations of age-adjusted death rates for Parkinson's disease and cultivation of rice and soybeans were found, but associations were not significant for a large variety of vegetables. The findings for soybean and rice are attributed to the correspondence (co-linearity) of cultivation of these other two seed-crops with maize. Hence, further testing of the theory of niacin deprivation and prevention of Parkinson's disease finds some circumstantial support in the cultivation patterns of a grain of poor niacin and tryptophan availability.

Crops, Agricultural↗
PubMed2003

[Two cases of generalized tetanus presenting with dysphagia as an initial symptom].

We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.

Aged↗
PubMed2003

[A case of mitochondrial myopathy with external ophthalmoplegia and ataxic neuropathy].

We report a 70-year-old woman with bilateral optic atrophy, external ophthalmoplegia, bilateral blepharoptosis, and sensory ataxic neuropathy. She had a visual disturbance since childhood. She had dysarthria and gait disturbance at 28 years old. She had bilateral blepharoptosis, marked gait disturbance and dysphagia at 50. On neurological examination, external ophthalmoplegia, bilateral blepharoptosis, mild weakness and muscular atrophy of promixal muscles, hyporeflexia, positive Romberg sign, glove and stocking type sensory disturbance including hypesthesia, hypalgesia, and bathyhypesthesia were found. She did not show pigmented retinopathy, cognitive dysfunctions, hearing loss, cerebellar ataxia, Hoffman reflex nor Babinski sign. She did not show increased lactic acid nor pyruvic acid in the cerebrospinal fluid but mild increase of pyruvic acid (1.0 mg/dl) in her serum. The conduction velocity and amplitude of CMAP of tibial nerve was 37.4 m/sec and 2.9 mV, respectively. The SNAP of ulner and sural nerve were not evoked. Brain MRI showed no pathological findings. Muscle biopsy from the biceps muscle showed many ragged-red fibers (5.3%) and some fibers with decreased or absent COX activity. Sural nerve biopsy showed a marked loss of large myelinated fibers with thin myelinated fibers, and onion-bulb formation. The clinical findings of our patient is similar to that of SANDO (the triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis), however, large mtDNA deletion reported by Fadic in patients with SANDO was not found in our patient. It might be possible that her mtDNA deletion is small or point mutation is existed.

Aged↗
PubMed2002

Effects of FK506 (tacrolimus hydrate) on chronic oxazolone-induced dermatitis in rats.

Chronic allergic contact dermatitis was induced in rat ear by repeated application of oxazolone. This dermatitis was accompanied by sustained ear swelling and marked epidermal hyperplasia. In the induced ear, there was marked inflammatory cell infiltration into the dermis site and the interferon-gamma amount increased in both protein and mRNA, while the interleukin-4 amount changed minimally. Topical administration of FK506 (tacrolimus hydrate) dramatically suppressed ear swelling and epidermal hyperplasia as well as the increase in interferon-gamma expression. Betamethasone valerate also showed suppressive effects, but 1,25-dihydroxyvitamin D(3) (calcitriol) had no effect. These results suggest that interferon-gamma plays an important role in dermatitis and this model could be a useful pharmacological model for chronic dermatitis featuring epidermal hyperplasia in which interferon-gamma plays a crucial role, such as psoriasis. FK506 demonstrating suppressive effects as potent as those of betamethasone valerate shows potential as a topically usable drug for such skin disorders.

Animals↗
PubMed2002

Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells.

Abnormal protein accumulation and cell death with cytoplasmic vacuoles are hallmarks of several neurodegenerative disorders. We previously identified p97/valosin-containing protein (VCP), an AAA ATPase with two conserved ATPase domains (D1 and D2), as an interacting partner of the Machado-Joseph disease (MJD) protein with expanded polyglutamines that causes Machado-Joseph disease. To reveal its pathophysiological roles in neuronal cells, we focused on its ATPase activity. We constructed and characterized PC12 cells expressing wild-type p97/VCP and p97(K524A), a D2 domain mutant. The expression level, localization, and complex formation of both proteins were indistinguishable, but the ATPase activity of p97(K524A) was much lower than that of the wild type. p97(K524A) induced cytoplasmic vacuoles that stained with an endoplasmic reticulum (ER) marker, and accumulation of polyubiquitinated proteins in the nuclear and membrane but not cytoplasmic fractions was observed, together with the elevation of ER stress markers. These results show that p97/VCP is essential for degrading membrane-associated ubiquitinated proteins and that profound deficits in its ATPase activity severely affect ER quality control, leading to abnormal ER expansion and cell death. Excessive accumulation of misfolded proteins may inactivate p97/VCP in several neurodegenerative disorders, eventually leading to the neurodegenerations.

Adenosine Triphosphatases↗
PubMed2002

Cytotoxic T cell activity against peptides of Hu protein in anti-Hu syndrome.

Half of all patients with limbic encephalitis and small cell lung carcinoma (SCLC) have anti-Hu antibodies that react with all of central and peripheral nervous system neuronal nuclei in immunohistochemical studies and 35- to 40-kDa reactive bands on western blots of extracts from isolated central nervous system neurons. The roles of anti-Hu antibodies in neuronal damage, however, have yet to be shown. Evidence of infiltration of CD8-positive T cells to tumors and affected nervous tissues and limited use of the T cell receptor repertoire in the central nervous system suggests that CD8-positive cytotoxic T cells (CTL) cause neuronal loss. We found the HLA B7 supertype in all of seven Japanese patients with anti-Hu syndrome. We identified HLA class I-restricted, CD 8-positive cytotoxic T cell activity in peripheral blood from three patients with anti-Hu syndrome for five peptides with binding motifs for the HLA B7 supertype in the amino acid sequence of the Hu protein. This study support the involvement of CD8-positive cytotoxic T cells in the development of paraneoplastic neurological syndrome with anti-Hu antibodies.

CD8-Positive T-Lymphocytes↗
PubMed2002

Genetic variants of the receptors for thromboxane A2 and IL-4 in atopic dermatitis.

Thromboxane A2 (TXA2) is an arachidonate metabolite which is considered to relate to chronic inflammation in atopic diseases characterized by elevated immunoglobulin E productivity. The elevation of immunoglobulin E levels involves many molecules including interleukin-4 (IL-4) and interleukin-4 receptor alpha chain (IL-4R alpha). To assess whether genetic variants of TXA2 receptor, IL-4 and IL-4R alpha genes relate to the elevation of serum immunoglobulin E levels in patients with atopic dermatitis (AD), we conducted an association study of genetic polymorphisms of TXA2 receptor (795C/T), IL-4 (-589C/T), and IL-4R alpha (Ile50Val) in a Japanese population (n = 789). The TXA2 receptor 795TT genotype strongly related to AD with high serum immunoglobulin E concentrations. AD patients with both TXA2 receptor 795TT genotype and the IL-4R alpha Ile50/Ile50 genotype showed the greatest immunoglobulin E concentrations. These results suggest TXA2 receptor polymorphism strongly interacts with IL-4R alpha polymorphism as a major determinant of high serum immunoglobulin E levels in AD.

Adolescent↗