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ABSTRACT: Pyrrole-imidazole (PI) polyamides are a novel group of gene-silencing compounds, which bind to a minor groove of double stranded (ds)DNA in a sequence-specific manner. To explore the RNA binding properties of PI polyamides targeting rat transforming growth factor-β1 (TGF-β1 Polyamide) and influenza A virus (PA polyamide), we designed dsRNAs with an identical sequence to the target DNA and analyzed RNA binding properties of the polyamide. Biacore assay showed fast binding of TGF-β1 Polyamide to the dsRNA, whereas mismatch polyamide did not bind to the dsRNA. KD value was 6.7 x 10(-7) of the target dsRNA. These results indicate that PI polyamide could bind to RNA with a 2 log lower binding affinity than its DNA-binding affinity. We designed a PI polyamide targeting the panhandle stem region of influenza A virus. KD value of the PI polyamide to dsRNA targeting influenza A virus was 4.6 x 10(-7). Gel-shift assay showed that TGF-β1 and PA Polyamides bound to the appropriate dsDNA, whereas these PI polyamides did not show obvious gel-shift with the appropriate dsRNA. Structural modeling suggests that PI polyamide binds to the appropriate B-form dsDNA in the minor groove, whereas it does not fit in the minor groove to dsRNA. Thus PI polyamides have a lower binding affinity with target dsRNA than they do with dsDNA. The distinct binding properties of PI polyamides to dsRNA and dsDNA may be associated with differences of secondary structure and chemical binding properties between target RNA and DNA.
Biological & Pharmaceutical Bulletin 04/2013; · 1.66 Impact Factor
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ABSTRACT: Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Microcrystal-line deposition most often consists of calcium pyrophosphate dehydrate crystals and/or hydroxyapatite crystals.
This report describes the case of an 89-year-old woman who presented with sudden onset, high fever, severe occipital headache, and neck stiffness. A laboratory examination revealed a markedly elevated white blood cell count (11,100/µl) and C-reactive protein level (23.8 mg/dl). These clinical findings suggested severe infection such as meningitis with sepsis. However, the results of blood culture, serum endotoxin, and procalcitonin were all negative, and cerebrospinal fluid studies revealed only a slight abnormality. The patient was first diagnosed with meningitis and treated with antiviral and antibiotic agents as well as non-steroidal anti-inflammatory drugs, but they only had limited effects. A cervical plain computed tomography (CT) scan and its three-dimensional (3D) reconstruction detected a remarkable crown-like calcification surrounding the odontoid process. On the basis of the CT findings, the patient was diagnosed as a severe case of CDS and was immediately treated with corticosteroids. The patient's condition drastically improved within a week after one course of corticosteroid therapy.
Some atypical symptoms of CDS are misleading and may be misdiagnosed as meningitis, as happened in our case. A CT scan, especially a 3D-CT scan, is necessary and useful for a definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for fever, headache, and cervical pain of unknown origin.
Case Reports in Neurology 01/2013; 5(1):40-6.
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ABSTRACT: Thalamic lesions give rise to a variety of clinical syndromes such as pure sensory stroke, ataxic hemiparesis, and rarely involuntary movements including chorea. Generally and classically, lacunar infarction in the subthalamic nucleus has been regarded as the lesion mainly responsible for hemi-chorea and hemi-ballismus, on the basis of previous anatomical studies.
This report describes the case of an 81-year-old man who developed sudden-onset pure hemi-chorea in the right limbs resulting from an acute phase of left thalamic lacunar infarction detected on a diffusion-weighted image (DWI) in an MRI study. The patient had no other neurological symptoms such as ataxic hemiparesis and sensory disturbance. A single-photon emission computed tomography (SPECT) study using the (99m)Tc-ECD Patlak plot method demonstrated significant perfusional asymmetry between the right and left thalami (p = 0.0035), consistent with the left thalamic lesion on DWI.
It is speculated that this perfusional asymmetry, in particular the hypoperfusion in the left thalamus, detected by SPECT might play the most important role in the contralateral pure hemi-chorea as a rare neurological manifestation in this case.
Case Reports in Neurology 09/2012; 4(3):194-201.
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ABSTRACT: Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional "gold standard" based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional "gold standard", the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented.
Tuberculosis research and treatment. 01/2012; 2012:831292.
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The Journal of Antibiotics 07/2009; 62(6):345. · 1.65 Impact Factor
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Teruyuki Takahashi,
Yukihiro Asami,
Eiko Kitamura,
Tsukasa Suzuki,
Xiaofei Wang,
Jun Igarashi,
Aiko Morohashi,
Yui Shinojima,
Hisao Kanou,
Kosuke Saito, [......],
Kazumichi Kuroda,
Takayoshi Watanabe,
Satoshi Kumamoto,
Takahiko Aoyama,
Yoshiaki Matsumoto,
Toshikazu Bando,
Hiroshi Sugiyama,
Chikako Yoshida-Noro,
Noboru Fukuda,
Nariyuki Hayashi
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ABSTRACT: Pyrrole-imidazole polyamide (PIP) is a nuclease-resistant novel compound that inhibits gene expression through binding to the minor groove of DNA. Human aurora kinase-A (AURKA) and -B (AURKB) are important regulators in mitosis during the cell cycle. In this study, two specific PIPs (PIP-A and PIP-B) targeting AURKA and AURKB promoter regions were designed and synthesized, and their biological effects were investigated by several in vitro assays. PIP-A and PIP-B significantly inhibited the promoter activities, mRNA expression, and protein levels of AURKA and AURKB, respectively, in a concentration-dependent manner. Moreover, 1:1 combination treatment with both PIPs demonstrated prominent antiproliferative synergy (CI value [ED(50)] = 0.256) to HeLa cells as a result of inducing apoptosis-mediated severe catastrophe of cell-cycle progression. The novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents for AURKA and AURKB.
Chemistry & Biology 09/2008; 15(8):829-41. · 5.83 Impact Factor
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Teruyuki Takahashi,
Masato Tamura,
Yukihiro Asami,
Eiko Kitamura,
Kosuke Saito,
Tsukasa Suzuki,
Sachiko Nonaka Takahashi,
Koichi Matsumoto,
Shigemasa Sawada,
Eise Yokoyama,
Toshiaki Takasu
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ABSTRACT: Previously, we designed an internally controlled quantitative nested real-time (QNRT) PCR assay for Mycobacterium tuberculosis DNA in order to rapidly diagnose tuberculous meningitis. This technique combined the high sensitivity of nested PCR with the accurate quantification of real-time PCR. In this study, we attempted to improve the original QNRT-PCR assay and newly developed the wide-range QNRT-PCR (WR-QNRT-PCR) assay, which is more accurate and has a wider detection range. For use as an internal-control "calibrator" to measure the copy number of M. tuberculosis DNA, an original new-mutation plasmid (NM-plasmid) was developed. It had artificial random nucleotides in five regions annealing specific primers and probes. The NM-plasmid demonstrated statistically uniform amplifications (F = 1.086, P = 0.774) against a range (1 to 10(5)) of copy numbers of mimic M. tuberculosis DNA and was regarded as appropriate for use as a new internal control in the WR-QNRT-PSR assay. In addition, by the optimization of assay conditions in WR-QNRT-PCR, two-step amplification of target DNA was completely consistent with the standard curve of this assay. Due to the development of the NM-plasmid as the new internal control, significantly improved quantitative accuracy and a wider detection range were realized with the WR-QNRT-PCR assay. In the next study, we will try to use this novel assay method with actual clinical samples and examine its clinical usefulness.
Journal of clinical microbiology 06/2008; 46(5):1708-15. · 4.16 Impact Factor
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Teruyuki Takahashi,
Masato Tamura,
Yukihiro Asami,
Eiko Kitamura,
Kosuke Saito,
Tsukasa Suzuki,
Sachiko Nonaka Takahashi,
Koichi Matsumoto,
Shigemasa Sawada,
Eise Yokoyama,
Toshiaki Takasu
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ABSTRACT: Although the "gold standard" for diagnosis of tuberculous meningitis (TBM) is bacterial isolation of Mycobacterium tuberculosis, there are still several complex issues. Recently, we developed an internally controlled novel wide-range quantitative nested real-time PCR (WR-QNRT-PCR) assay for M. tuberculosis DNA in order to rapidly diagnose TBM. For use as an internal control calibrator to measure the copy number of M. tuberculosis DNA, an original new-mutation plasmid (NM-plasmid) was developed. Due to the development of the NM-plasmid, the WR-QNRT-PCR assay demonstrated statistically significant accuracy over a wide detection range (1 to 10(5) copies). In clinical applications, the WR-QNRT-PCR assay revealed sufficiently high sensitivity (95.8%) and specificity (100%) for 24 clinically suspected TBM patients. In conditional logistic regression analysis, a copy number of M. tuberculosis DNA (per 1 ml of cerebrospinal fluid) of >8,000 was an independent risk factor for poor prognosis for TBM (i.e., death) (odds ratio, 16.142; 95% confidence interval, 1.191 to 218.79; P value, 0.0365). In addition, the copy numbers demonstrated by analysis of variance statistically significant alterations (P < 0.01) during the clinical treatment course for 10 suspected TBM patients. In simple regression analysis, the significant correlation (R(2) = 0.597; P < 0.0001) was demonstrated between copy number and clinical stage of TBM. We consider the WR-QNRT-PCR assay to be a useful and advanced assay technique for assessing the clinical treatment course of TBM.
Journal of clinical microbiology 05/2008; 46(5):1698-707. · 4.16 Impact Factor
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ABSTRACT: As aromatase-deficient mice, which are deficient in estrogens, reportedly have reduced blood pressure, the aromatase gene (CYP19A1) is thought to be a susceptibility gene for essential hypertension (EH). The aim of the present study was to investigate the relationship between CYP19A1 and EH by examining single nucleotide polymorphisms (SNPs).
Five SNPs in the human CYP19A1 gene (rs1870049, rs936306, rs700518, rs10046 and rs4646) were selected, and an association study was performed in 218 Japanese EH patients and 225 age-matched normotensive (NT) individuals.
There were significant differences between these groups in the distribution of genotypes rs700518 and rs10046 in male subjects, and genotypes rs700518, rs10046 and rs4646 in female subjects. On multiple logistic regression analysis, a significant association between rs700518 (p=0.023) and rs10046 (p=0.036) in male subjects and rs700518 in female subjects (p=0.018) was noted. Interestingly, the risk genotypes of rs700518 and rs10046 showed a sex-dependent inverse relationship. Both SBP and DBP levels were higher in total (cases and controls) male subjects with the G/G genotype with rs700518 or the T/T genotype with rs10046 than in male subjects without the G/G genotype or T/T genotype. SBP levels were lower in female subjects with the G/G genotype with rs700518 than in female subjects without G/G. The A-T haplotype constructed with rs1870049 and rs10046 was a susceptibility marker for EH.
We confirmed that rs700518 and rs10046, as well as a haplotype constructed with rs1870049 and rs10046, in the human CYP19A1 gene can be used as genetic markers for gender-specific EH.
International journal of medical sciences 02/2008; 5(1):29-35. · 2.24 Impact Factor
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Yukie Yoshikawa,
Tomohiro Nakayama,
Kosuke Saito,
Peng Hui,
Akihiko Morita,
Naoyuki Sato, Teruyuki Takahashi,
Masaaki Tamura,
Ichiro Sato,
Noriko Aoi,
Nobutaka Doba,
Shigeaki Hinohara,
Masayoshi Soma,
Ron Usami
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ABSTRACT: Uroguanylin (gene name: guanylate cyclase activator 2B, GUCA2B) is a peptide regulator of intestinal salt and water transport. It has been reported that the uroguanylin knockout mouse exhibits elevated blood pressure. Therefore, the GUCA2B gene is thought to be a susceptibility gene for essential hypertension (EH). Despite extensive studies, however, the relationship between the GUCA2B gene and EH has not yet been defined. The aim of this study was to assess the association between the human GUCA2B gene and EH. Using four single nucleotide polymorphisms (SNPs), we conducted a genetic association study in 281 EH patients and 279 age-matched normotensive (NT1) individuals. To derive more reliable data, we performed a duplicate case-control study in which we recruited another normotensive group (NT2). There was no significant difference in the overall distribution of alleles for any of the SNPs between the EH and NT1 groups, or between the EH and NT2 groups. Therefore, these four SNPs cannot be the genetic markers for EH. The occurrences of the C-A haplotype (rs883062-rs1047047) and the C-A-G haplotype (rs883062-rs1047047-rs2297566) were significantly higher in the EH group than in the NT1 group (p<0.0001) or the NT2 group (p<0.0001). These results suggest that the C-A haplotype and the C-A-G haplotype of the GUCA2B gene are the genetic markers for EH, and that GUCA2B or a neighboring gene might be a susceptibility gene for EH.
Hypertension Research 09/2007; 30(9):789-96. · 2.58 Impact Factor
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Peng Hui,
Tomohiro Nakayama,
Akihiko Morita,
Naoyuki Sato,
Mikano Hishiki,
Kosuke Saito,
Yukie Yoshikawa,
Masaaki Tamura,
Ichiro Sato, Teruyuki Takahashi,
Masayoshi Soma,
Yoichi Izumi,
Yukio Ozawa,
Zuheng Cheng
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ABSTRACT: Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.
Hypertension Research 08/2007; 30(7):585-92. · 2.58 Impact Factor
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ABSTRACT: Although the "gold standard" for diagnosis of tuberculous meningitis (TBM) is bacterial isolation of Mycobacterium tuberculosis (M. Tb), there are still several complex issues. Recently, in the diagnosis of TBM, the detection of M. Tb DNA in cerebrospinal fluid (CSF) samples using PCR has been widely performed as more rapid, sensitive, and specific diagnostic method. Based on Taq Man(R) PCR, the authors developed a novel technique of internally controlled quantitative nested real-time (QNRT) PCR assay that provided a prominent improvement in detection sensitivity and quantification. Total 43 CSF samples from 8 serial patients with suspected TBM were analyzed. The CSF samples were collected before and during standard anti-tuberculosis treatments (ATT). The QNRT-PCR assay revealed positive results for 24 out of 43 serial CSF samples (55.8%) collected during the treatment course of ATT. Moreover, the bacterial cell (BC) numbers of M. Tb analyzed by the QNRT-PCR assay decreased gradually, correlating with the improvements of the patient's clinical conditions. Since the QNRT-PCR assay provides the ability to calculate a numerical value for the initial BC numbers of M. Tb in CSF samples, this method is an extremely useful and advanced technique for use in assessing the clinical course of TBM.
Journal of the Neurological Sciences 05/2007; 255(1-2):69-76. · 2.35 Impact Factor
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ABSTRACT: Ischemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to perform a haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p = 0.003). Diplotype analysis also showed a significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32-97.9, p = 0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene is a genetic marker for IS, and that tPA or a neighboring gene is a susceptibility gene for IS.
Thrombosis and Haemostasis 10/2006; 96(3):331-6. · 5.04 Impact Factor
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ABSTRACT: The risk of cerebral infarction (CI) in an individual is dependent on the interplay between genetic risk factors and environmental influences. Binding of thromboxane A2 (TXA2) to its receptor (TP) modulates thrombosis/hemostasis and plays a significant role in the pathogenesis of CI. The aim of the present study was to investigate the relationship between human TP gene single nucleotide polymorphisms (SNPs) and haplotypes and CI in a Japanese population. A genetic association study was performed in 194 CI patients and 365 non-CI subjects by specifically characterizing 6 SNPs in the human TP gene (rs2271875, rs768963, rs2238634, rs11085026, rs4523 and rs4806942). Analysis demonstrated that there were significant differences in the overall distribution of genotypes and dominant or recessive models of rs2271875 and rs768963 between the CI and the non-CI groups. Multiple logistic regression analysis revealed that the C allele of rs768963 was significantly associated with CI (p = 0.029), even after adjusting for confounding factors (odds ratio: 2.41). Further, the C-T-C haplotype of rs768963-rs2238634-rs4806942 was significantly more frequent in the CI group (23.0%) than in the non-CI group (17.7%). These results suggest that specific SNPs and haplotypes may have utility as genetic markers for the risk of CI and that TP or a neighboring gene is associated with the increased susceptibility to CI.
Hypertension Research 10/2006; 29(9):665-71. · 2.58 Impact Factor
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ABSTRACT: The diagnosis of tuberculous meningitis (TBM) remains a complex issue because the most widely used conventional diagnostic tools, such as culture and PCR assay for cerebrospinal fluid (CSF) samples, are unable to rapidly detect Mycobacterium tuberculosis with sufficient sensitivity in the acute phase of TBM. Based on TaqMan PCR, we designed a novel technique consisting of an internally controlled quantitative nested real-time (QNRT) PCR assay that provided a marked improvement in detection sensitivity and quantification. We applied this novel technique to quantitatively detect M. tuberculosis DNA in CSF samples from patients with suspected TBM. For use as the internal control in the measurement of the M. tuberculosis DNA copy numbers in the QNRT-PCR assay, the original mutation (M) plasmid, which included an artificial random 22-nucleotide sequence within an inserted DNA fragment of the MPB64 gene of M. tuberculosis, was prepared. The QNRT-PCR assay showed high sensitivity and specificity that were approximately equivalent to those of the conventional nested PCR assay. Moreover, the QNRT-PCR assay made it possible to precisely and quantitatively detect the initial copy number of M. tuberculosis DNA in CSF samples. Therefore, compared to the conventional PCR assay, the QNRT-PCR assay can be considered a more useful and advanced technique for the rapid and accurate diagnosis of TBM. To establish the superiority of this novel technique in TBM diagnosis, it will be necessary to accumulate data from a larger number of patients with suspected TBM.
Journal of Clinical Microbiology 04/2006; 44(3):1029-39. · 4.15 Impact Factor
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ABSTRACT: AbstrAct Several previous studies have shown that essential hypertension (EH) is associated with fibrinolysis. Tissue plasminogen activator (t-PA) plays a key role in fibrinolysis. Thus, it is possible that the t-PA gene is a susceptibility gene of EH. However, there have been no reported studies of association between EH and the t-PA gene using single nucleotide polymorphisms (SNPs). The aim of the present haplotype-based case-con-trol study was to investigate whether SNPs in the human t-PA gene are associated with EH. We performed a genetic association study using 3 SNPs (rs7007329, rs8178750, rs4471024). The subjects were 276 EH patients and 283 age-matched normotensive (NT) individuals. There were no significant differences in overall distri-bution of genotypes or alleles between EH patients and NT subjects. Also, there were no significant differ-ences in the haplotype-based case-control study. The present results do not indicate an association between the t-PA gene and EH.
International Journal of Biomedical Science. 01/2006;
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ABSTRACT: A 44 year-old woman was diagnosed as having chronic renal failure due to rapidly progressive glomerulonephritis (RPGN) from one year earlier. She has been managed with steroid therapy and hemodialysis. The patient was admitted to our hospital because of fever and sudden disturbance of consciousness with generalized convulsion on October 30, 2003. She showed mild meningeal irritation. Cerebrospinal fluid (CSF) examination demonstrated a cell count of 60/microl, protein level of 70 mg/dl, glucose level of 52 mg/dl, and chloride (Cl) level of 116 mEq/l. Both the CSF culture for Mycobacterium (M.) tuberculosis and the conventional single polymerase chain reaction (PCR) for M. tuberculosis DNA in CSF were negative results on admission. In contrast, nested PCR of preserved CSF samples obtained at admission demonstrated positive results. We diagnosed her conditions as tuberculous meningitis (TBM) and administered a total of 3 anti-tuberculosis agents over a period of about 2 months. Her clinical condition and CSF examinations improved immediately in response to anti-tuberculosis treatment. Serial CSF cultures for M. tuberculosis and the serial single PCRs for M. tuberculosis DNA in CSF were all negative during the course of anti-tuberculosis treatment. However, serial nested PCR results gradually converted from positive to negative, correlating with the improvement in clinical conditions during the course of anti-tuberculosis treatment. Therefore, nested PCRs were much more useful for the rapid and accurate diagnosis of TBM and for assessment of the clinical course and anti-tuberculosis treatment response of TBM than conventional CSF cultures and single PCRs. To the best of our knowledge, there have been few previous reports of diachronic study in which the serial nested PCR was used to test CSF samples obtained earlier in the clinical course of TBM. In conclusion, our findings suggest that nested PCR for M. tuberculosis DNA in CSF was highly useful not only for rapid and accurate diagnosis of TBM, but also for assessment of the antituberculous treatment response in cases highly suspected of TBM despite negative results on conventional cultures and single PCRs.
Nippon Jinzo Gakkai shi 02/2005; 47(2):113-20.
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ABSTRACT: We report a rare case of acute autonomic, sensory and motor neuropathy (AASMN). The patient, a 26-year-old woman, developed fever and common cold around January 20, 2001 and was admitted because of abdominal pain due to ileus on January 30. After admission, the patient complained of muscle weakness and numbness in the extremities, difficulty in seeing with the right eye, and dysuria. Neurologically, marked orthostatic hypotension, right tonic pupil, distal dominant moderate muscle weakness in extremities, areflexia in both lower limbs, glove and stocking type of paresthesia, and neurogenic atonic bladder were noted. Sensation to pin prick, light touch, temperature, and vibration were markedly impaired in upper limbs and below the level of the 5th thoracic cord. Cerebrospinal fluid examination revealed albumino-cytologic dissociation. Peripheral nerve conduction study revealed lower limb dominant axonal type impairment of sensory conduction and slight impairment of motor conduction velocity. Clinical autonomic testings revealed dysfunction of both sympathetic and parasympathetic systems. As having AASMN, she was given the intravenous high-dose immunoglobulin (IVIg) therapy twice. After IVIg, the sensory and motor symptoms improved remarkably, but pandysautonomia did not. To our knowledge, this is the first report of AASMN treated by IVIg, and the notable clinical feature in this case was the favorable motor and sensory recovery to IVIg, as opposed to poor autonomic outcome.
Rinsho shinkeigaku = Clinical neurology 10/2004; 44(9):643-7.
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ABSTRACT: We report a case of central nervous system (CNS) lupus showing peculiar findings on cranial magnetic resonance imaging (MRI) with remarkable improvement after corticosteriod therapy. The patient was a 28-year-old woman, admitted to our hospital with severe fever, general malaise, and facial edema on June 4, 2001. After admission, she was diagnosed with systemic lupus erythematosus (SLE). On June 6, she showed diplopia at a distance, and on June 10, she suddenly became unconscious and developed general convulsions. Cranial MRI showed asymmetrical, multifocal, high signal intensity lesions on T2-weighted image (T2-WI) and low signal intensity on T1-weighted image (T1-WI). These lesions were primarily present in the subcortical white matter, with some detected in the overlying cerebral cortex. Gadolinium (Gd)-DTPA enhanced T1-WI showed marked leptomeningeal enhancement overlying the lesions on T1-WI and T2-WI. Apparent diffusion coefficient image (ADCI) showed high signal intensity in the surrounding areas of the T1-WI and T2-WI lesions, and low signal intensity in the central areas of the lesions. Diffusion weighted image (DWI) showed high signal intensity in the central areas of the low signal intensity on ADCI. Cerebrospinal fluid (CSF) examination revealed albuminocytologic dissociation (cell counts of 2/microliter and protein level of 108 mg/dl). CSF IgG index was elevated to 1.152 (normal < 0.7) and interleukin-6 (IL-6) activity to 27.2 pg/ml (normal < 4.0). On June 10, Intravenous administration of high-dose methylprednisolone (1,000 mg/day for 3 days) was started to treat CNS lesions of SLE. Her CNS manifestations, CSF findings, and the lesions on the cranial MRI improved remarkably. This is the first case report describing the lesions on both ADCI and DWI in a case of CNS lupus. The findings of ADCI and DWI suggest that the lesions of high signal intensity on ADCI indicate interstitial edema caused by inflammatory microangiopathy, and the lesions of high signal intensity on DWI and low signal intensity on ADCI indicate cytotoxic edema caused by ischemic change resembling microinfarction. We speculate that in addition to usual T1-WI and T2-WI, performing ADCI and DWI is useful for understanding the pathogenesis of CNS lupus lesions, and may play a significant role in the prognosis.
Rinsho shinkeigaku = Clinical neurology 07/2003; 43(7):409-16.
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ABSTRACT: We report a case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome. The patient was a 57-year-old woman, who was admitted to our hospital because of numbness and muscle weakness in the four extremities, difficulty in walking, and foot edema. On admission, her skin was dry and rough, and also showing scattered pigmentation, small hemangiomas, and hypertrichosis in both legs. She had distal dominant muscle weakness, more prominent in her legs, and was not able to walk. Deep tendon reflexes in her four extremities were markedly diminished or absent. She had a glove and stocking type of paresthesia, severe impairment of vibration, and absence of joint position sensation in her four extremities. On laboratory data, serum vascular endothelial growth factor (VEGF) was markedly elevated to 5,184 pg/ml (normal: below 220 pg/ml). Cerebrospinal fluid examination revealed cell counts of 2/microliter and protein level of 114 mg/dl. Abdominal echo showed marked hepatosplenomegaly. On peripheral nerve conduction study, both motor and sensory conduction velocity were undetectable in her legs. We diagnosed her condition as Crow-Fukase syndrome, and started IVIg of polyethyleneglycol-treated gamma-globulin (PEG-glob) at 400 mg/kg/day for 5 consecutive days for polyneuropathy. Since the first IVIg mildly improved muscle weakness, we tried the second IVIg of PEG-glob. However, immediately after the initiation of second IVIg of PEG-glob, she developed hypotention, dyspnea, cold sweating, cyanosis, and became lethargic. We immediately stopped IVIg and started first-aid treatment with epinephrine and corticosteroid for these symptoms. This treatment was successful and the patient fully recovered without any sequelae. Since serum IgE level remained unchanged and lymphocyte stimulation test (LST) was positive against the same rot number of PEG-glob, we diagnosed these symptoms as anaphylactoid shock. Based on the results of LST, we speculated that PEG-glob was the causative agent of anaphylactoid reaction. Anaphylactic or anaphylactoid reaction as adverse effects of IVIg is very rare, and to our knowledge, there are only 4 previous reports of anaphylactic or anaphylactoid reaction caused by IVIg. Therefore, we speculated that the prominent high level of serum VEGF in the present patient might play a significant contributory role in the development of anaphylactoid shock, since the vascular permeability of VEGF is 50,000 times stronger than that of histamine. We consider that it is necessary to carefully monitor IVIg of PEG-glob administration for polyneuropathy in patients with high level of serum VEGF, like Crow-Fukase syndrome.
Rinsho shinkeigaku = Clinical neurology 07/2003; 43(6):350-5.