Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 109 records · Page 6Linked to original sources

PubMed2000

CSF phosphorylated tau protein and mild cognitive impairment: a prospective study.

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.

Aged↗

PubMed2000

Cloning of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from terpenoid antibiotic-producing Streptomyces strains.

We have isolated a mutant lacking 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity from a terpenoid antibiotic (terpentecin) producer, Streptomyces griseolosporeus MF730-N6, which uses both the mevalonate and nonmevalonate pathways for the formation of isopentenyl diphosphate, by screening terpentecin non-producing mutants. Terpentecin is known to be synthesized via the mevalonate pathway. The gene encoding HMG-CoA reductase (hmgg) was cloned and identified by complementation of the mutant, using a self-cloning system developed in this study for strain MF730-N6. The corresponding hmgs gene for HMG-CoA reductase was also cloned from Streptomyces sp. KO-3988, which produces the terpenoid antibiotic furaquinocin. Sequence analysis of hmgg and hmgs showed that both genes encode polypeptides of 353 amino acids which are 84% identical to each other. A search of protein sequence databases revealed that both gene products were also similar to HMG-CoA reductases from a variety of other organisms, including Streptomyces sp. CL190 (hmgg is 89% and hmgs 85% identical to its CL190 homolog), sea urchin (40.3 and 40.5%), German cockroach (37.6 and 38.4%), and Camptotheca acuminata (39.7 and 40.8%).

Amino Acid Sequence↗

PubMed2000

Gene cloning and overproduction of low-specificity D-threonine aldolase from Alcaligenes xylosoxidans and its application for production of a key intermediate for parkinsonism drug.

The dtaAX gene encoding a pyridoxal 5'-phosphate (pyridoxal-P)-dependent low-specificity D-threonine aldolase was cloned from the chromosomal DNA of Alcaligenes xylosoxidans IFO 12669. It contains an open reading frame consisting of 1,134 nucleotides corresponding to 377 amino acid residues. The predicted amino acid sequence displayed 54% identity with that of D-threonine aldolase from gram-positive bacteria Arthrobacter sp. DK-38, but showed no significant similarity with those of other known pyridoxal-P enzymes. This gram-negative bacterial enzyme was highly overproduced in recombinant Escherichia coli cells, and the specific activity of the enzyme in the cell extract was as high as 18 U/mg (purified enzyme 38.6 U/mg), which was 6,000 times higher than that from the wild-type Alcaligenes cell extract. The recombinant enzyme was thus feasibly purified to homogeneity by ammonium sulfate fractionation and DEAE-Toyopearl chromatography steps. The recombinant low-specificity D-threonine aldolase was shown to be an efficient biocatalyst for resolution of L-beta-3,4-methylenedioxyphenylserine, an intermediate for production of a therapeutic drug for Parkinson's disease.

Alcaligenes↗

PubMed2000

Treatment of erectile dysfunction: what should we do next?

Because sildenafil (Viagra) is scheduled to be clinically available in the near future, urologists in Japan must prepare for changes in the treatment of erectile dysfunction. The drug will surely influence our current clinical style of diagnosis and treatment of the dysfunction. We herein discuss this issue, referring to favorable and unfavorable effects that will be brought about by the drug. We also propose several future studies that we should do, including those on testosterone replacement therapy. We present results of our experiment using testosterone replacement therapy in aged rats and speculate about the mechanism by which the hormone replacement works in the sex center of the brain.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2000

Perifoveal microcirculation before and after vitrectomy for diabetic cystoid macular edema.

PURPOSE: To quantify the perifoveal microcirculation in diabetic eyes before and after successful vitreous surgery for cystoid macular edema without posterior vitreous detachment, and to determine whether improvement in perifoveal microcirculation is associated with improvement in postoperative visual acuity. METHODS: In a prospective study, vitreous surgery was performed on 11 eyes of nine consecutive diabetic patients with cystoid macular edema, and their mean perifoveal capillary blood flow velocity was measured by fluorescein angiography with a scanning laser ophthalmoscope. Visual acuity was measured preoperatively and postoperatively, and the results were converted to the logarithm of the minimum angle of resolution (logMAR). The correlation between changes in logMAR visual acuity and capillary blood flow velocity was evaluated. RESULTS: In all nine eyes of seven patients with successful vitreous surgery, the cystoid macular edema resolved within 6 months after surgery, and the mean capillary blood flow velocity was significantly increased compared with that before surgery (2.19 mm per second versus 2.68 mm per second, P =.021); the changes in capillary blood flow velocity were significantly correlated with the changes in the logMAR visual acuity (P =.024). CONCLUSIONS: Vitreous surgery may improve perifoveal microcirculation in the eyes of diabetic patients with cystoid macular edema and resolve the macular edema. Improvement of perifoveal microcirculation may be an important factor affecting visual outcome.

Adult↗

PubMed2000

High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan.

PURPOSE: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.

Adolescent↗

PubMed2000

Subclinical Cushing syndrome due to adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia: changes in plasma cortisol levels during long-term follow-up.

A 63-year-old man with bilateral adrenal tumors was treated for hypertension and diabetes mellitus. Endocrinologic examination during follow-up revealed the production of cortisol to be independent of the regulation of the hypothalamo-pituitary-adrenal axis. Therefore, he was diagnosed as having subclinical Cushing syndrome, and these tumors were removed. Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH) was endocrinologically and histopathologically diagnosed. This is the first report demonstrating that endocrinologic changes of AIMAH can be observed during long-term follow-up.

Adrenal Gland Neoplasms↗

PubMed2000

Risk factors for the development of bladder cancer after upper tract urothelial cancer.

OBJECTIVES: To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. METHODS: This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox's proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. RESULTS: Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer (P = 0.0038) and pathologic stage (P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. CONCLUSIONS: The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.

Adolescent↗

PubMed2000

Cellular zinc status regulates cytomegalovirus major immediate-early promoter.

Diethylenetriaminepenta-acetic acid (DTPA) inhibits human cytomegalovirus (CMV) replication in vitro, although the mechanism has remained unclear. The present study shows that DTPA inhibits CMV major immediate-early (MIE) promoter activity in a luciferase reporter assay, whereas its enhancer-less promoter was not affected. The inhibitory effect of DTPA on CMV MIE promoter activity was abrogated by stoichiometric amounts of cations in the following (decreasing) order, Zn(2+)>Co(2+)>Ni(2+)>Cu(2+)>Fe(3+)>Fe(2+), but not by Mn(2+). These cations bind to DTPA and may limit the zinc-chelating capability. In the absence of DTPA, exogenous zinc activated CMV MIE promoter activity in a dose-dependent manner, but not its enhancer-less promoter. The intracellular metallothionein content of DTPA- and cation-treated cultures was significantly correlated with CMV MIE promoter activity. DTPA may inhibit CMV replication by regulating CMV MIE promoter activity through controlling the availability of cellular zinc. Since the CMV MIE promoter has no consensus sequence for a metal responsive element, a novel mechanism for metal-regulated transcription may be involved in this process.

Antigens, Viral↗

PubMed2000

Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo.

To elucidate roles of fibroblast growth factors (FGF)18 during vertebrate development, we examined expression patterns of Fgf18 in chick embryos and observed effects of FGF18 protein on the Hensen's node, isthmus, and limb buds. Fgf18 is expressed on the right side of the node before the expression of Fgf8 starts. FGF18 protein can induce expression of Fgf8 on the left side of the node, indicating involvement of both FGFs in specification of left-right asymmetry. In the developing brain, Fgf18 is expressed in the isthmus, following the Fgf8 expression. Since Fgf18 is induced ectopically during formation of the second midbrain by FGF8 protein, both FGFs also elaborate midbrain development. In the limb bud, Fgf18 is expressed in the mesenchyme and ectopic application of FGF18 protein inhibits bone growth in the limb. FGF18 is thus likely an endogenous ligand of FGF receptor 3, whose mutation causes bone dysplasia in humans. These results demonstrate that the FGF18-FGF8 signaling is involved in various organizing activities and the signaling hierarchies between FGF18 and FGF8 seem to change during patterning of different structures.

Amino Acid Sequence↗

PubMed2000

Automatic detection of rapid eye movements by discrete wavelet transform.

In order to detect rapid eye movements (REM) automatically, the Discrete Wavelet Transform was applied to each 8-s segment of electrooculogram (EOG) data for 30 min of 8 h of normal sleep. The Haar function was used as an analysing wavelet because this function is similar to the REM waveform. By shifting the phase of the analysing wavelet by pi/4 of the function, 96% of REM could be detected. The artifacts caused by body movements could be detected simultaneously by this method. Computing time required for the detection of REM was only 11 s for 30 min EOG data.

Algorithms↗

PubMed2000

Clinical recurrence of papillary thyroid cancer in the remnant lobe.

OBJECTIVE: To find out which factors predict recurrence of cancer in the remnant after unilateral thyroid lobectomy for patients with papillary cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: One hundred thirty-three patients with a clinically solitary papillary thyroid cancer who had unilateral lobectomy for the primary disease between 1966 and 1990 and were followed up for more than 60 months. Twelve patients had developed recurrences in the remnant gland by the time of the second operation and 121 patients had not as judged by a second operation, an ultrasound examination, or by palpation. RESULT: The primary tumour size in those who developed recurrences was significantly larger than in those who did not (p < 0.0001), and clinical signs of regional lymph node involvement or distant metastases were also significantly more common (p = 0.006). No patient died of their cancer. CONCLUSION: Size of the primary tumour is an important prognostic factor for recurrence of solitary papillary thyroid cancer in the remnant after unilateral lobectomy. Such recurrences are unlikely to be lethal.

Adolescent↗

PubMed2000

[Survey on Toxocara cati in domestic cats].

A total of 542 domestic cats aged from 1 month to 20 years were investigated for Toxocara cati (T. cati) by means of fecal examination. The cats were classified in the groups according to their kept environment (indoor or outdoor) and age (1-6 month, 7 month-1 year, 2-3 year, 4-5 year and over 6 year). The indoor kept cats were major in all ages, and the friendly relationship was suggested between domestic cats and humans. The parasitic rates of T. cati a higher percentage was noted in the groups of indoor kept cats of 1-6 month (27.1%) than that of outdoor kept cats of 1-6 month (17.9%), 7 month-1 year (18.5%) and 4-5 year (14.3%). The high parasitism of T. cati in indoor kept 1-6 month cats, which are may be closely connected to humans, is an important problem from the public health of view, because of the direct source of visceral larva migraine. The parasitism of T. cati in outdoor kept cats is also a serious matter as the origin of environmental contamination. It suggests that a positive sanitary instruction against an owner seems necessary for prevention of visceral larva migraine in humans.

Animals↗

PubMed2000

Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1.

BACKGROUND/AIMS: It is reported by the national surveillance of ocular infectious diseases in Japan that 4.3% of cases of epidemic keratoconjunctivitis (EKC) diagnosed clinically were caused by herpes simplex virus (HSV). Clinical and virological studies of patients with HSV conjunctivitis were carried out. METHODS: The study population consisted of 478 patients with acute follicular conjunctivitis. Virological analysis was carried out for adenovirus (Ad) and HSV by the cell culture method and fluorescein antibody (FA) method. Polymerase chain reaction for Chlamydia trachomatis was also carried out. RESULTS: From 23 patients, HSV type 1 was isolated but Ad or C trachomatis was not isolated. 87% of cases were unilateral. Most cases showed clinical resolution within 9 days. Early corneal lesions and preauricular lymphadenopathy were less frequent in HSV conjunctivitis than in adenoviral conjunctivitis, especially that due to subgenus D. No case showed a positive result for HSV by the FA method using conjunctival swabs; however, the FA test was positive in all strains isolated by cell culture. CONCLUSIONS: These results indicate that it is difficult clinically to differentiate HSV conjunctivitis from adenoviral conjunctivitis in the acute stage, since the clinical features of adenoviral conjunctivitis are similar to those of HSV conjunctivitis. A biological difference may exist between HSV strains causing keratitis and conjunctivitis.

Acute Disease↗

PubMed2000

SM-20220, a potent Na+/H+ exchange inhibitor, improves consciousness recovery and neurological outcome following transient cerebral ischaemia in gerbils.

We studied the cerebroprotective effect of SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulphonate), a newly synthesized Na+/H+ exchanger (NHE) inhibitor, in Mongolian gerbil global ischaemia. Transient cerebral ischaemia was induced by clipping both common carotid arteries for 30 min followed by 24h reperfusion. Intravenous administration of SM-20220 (0.3 or 1.0 mg kg(-1)) immediately after reperfusion significantly shortened the consciousness recovery time (P < 0.01). SM-20220 also improved the neurological outcome (McGraw's scale) after reperfusion. At the dose of 1.0 mg kg(-1), the mortality rate was significantly reduced at 24 h after reperfusion (P < 0.01). This study shows that NHE is involved in the aggravation of cerebral function, represented by consciousness recovery, and neurological outcome following transient forebrain ischaemia, and that its inhibitor may exert protective effects on post-ischaemic brain damage.

Amides↗

PubMed2000

Two metallothioneins in the fresh-water fish, crucian carp (Carassius cuvieri): cDNA cloning and assignment of their expression isoforms.

Two metallothionein cDNAs (MT-A and MT-B) in the fresh-water fish crucian carp (Carassius cuvieri Temminck et Schlegel) were cloned. Sequence analysis of both cDNAs gave the structure of a coding region corresponding to 60 amino acid residues. The homology of their deduced amino acid sequences was completely conserved at the positions of the cysteine residue, but a significant difference existed in the size of their 3'-untranslated regions (130 base pairs for MT-A and 280 base pairs for MT-B). Direct amino acid sequencing of the MT-II isoform purified by HPLC was accomplished for up to 30 residues and its sequence was identical to that deduced from MT-B cDNA. This is the first case in vertebrates that N-terminal methionine in crucian carp MT-II was not blocked. By northern blot analysis, basal and cadmium chloride- or dexamethasone-induced MT-B (MT-II) mRNAs were detected time dependently after treatment. On the other hand, the expression of MT-A mRNA was extremely low. These results indicate that the MT isoform II in crucian carp is coded by the MT-B gene, and that the MT-B-dominant expression of mRNA in crucian carp may be due to the difference in the 3'-untranslated regions of MT mRNAs.

Amino Acid Sequence↗

PubMed2000

Multiple branchial cleft-like cysts in a female patient with Hashimoto's thyroiditis.

We report a case of branchial cleft-like cysts (intrathyroidal lymphoepithelial cysts) associated with Hashimoto's thyroiditis. Palpation did not detect any nodules. Multiple cystic lesions were detected in the lateral side of the thyroid bilateral lobes by imagings of an I-123 scintigram, Tl-201 scintigram, sonography, and computerized tomography. Sonography displayed multiple cysts with strong echogenic spots in the cystic fluid. Repeated fine needle aspiration biopsies of the cysts consistently revealed only normal lymphocytes. Although these lesions could not be given diagnosis, subtotal thyroidectomy leaving the intact isthmus was performed. Microscopic findings revealed multiple branchial cleft-like cysts lined by flattened epithelial cells. Surrounding the epithelial lining were dense lymphoid follicles with large, reactive germinal centers. The remaining thyroid parenchyma showed Hashimoto's thyroiditis. Multiple branchial cleft-like cysts should be considered when sonographic examination reveals multiple cysts in the lateral side of the bilateral lobes, and fine needle aspiration biopsy displays only normal lymphocytes. To our knowledge, this is the first case of branchial cleft-like cysts associated with Hashimoto's thyroiditis reported in Japan.

Adult↗

PubMed2000

Clinical evaluation of a radioimmunoprecipitation assay for IA-2 antibody and comparison of GAD antibody in type 1 diabetes mellitus.

We evaluated a insulinoma-associated protein (IA-2) antibody assay kit using 125I-labelled recombinant IA-2. IA-2 antibodies were present in patients with early-onset type 1 diabetes mellitus (DM) at frequencies of 74%, 67%, 57%, and 50% for respective periods <1 year, 1 < or =years<2, 2< or =years<3, and 3< or =years<4 after onset. IA-2 antibody frequency was low throughout the DM course as compared with glutamic acid decarboxylase (GAD) antibody frequency. No one had IA-2 antibody, but 29% still had positive GAD antibody titers after 11 years. Of the patients with 0<years<7 duration, 42% had IA-2 Ab+/GAD Ab+, 9% IA-2 Ab+/GAD Ab-, and 24% IA-2 Ab-/GAD Ab+. Prevalence of IA-2 and GAD antibody in 1243 patients with type 2 DM were 1.5% and 3.1%, respectively, and 1.1% had both. This new IA-2 antibody kit is easy to use and provides a specific, sensitive method for making routine assays. Furthermore, the combined analysis of GAD antibody provides high detection of type 1 DM.

Adolescent↗