Biomedical subjects

M Nakao

Publications and source records attributed to M Nakao.

At least 109 records · Page 6Linked to original sources

PubMed2001

Identification of the cis-acting region in the NF2 gene promoter as a potential target for mutation and methylation-dependent silencing in schwannoma.

BACKGROUND: Although mutational inactivation and allelic loss in the NF2 gene appear to be causal events in the majority of vestibular schwannomas, involvement of another potentially important mechanism, transcriptional inactivation, has not been investigated. RESULTS: We cloned and functionally characterized the 5'-flanking region of the human NF2 gene and identified the molecular mechanisms that regulate NF2 expression. Luciferase assay and site-directed mutagenesis demonstrated that a 70-base pair (bp) region (-591 to -522 bp from the translation start site) was essential for the basic expression of the NF2 gene. A gel mobility shift assay indicated recognition by nuclear protein of the unusually long ( approximately 66 bp) sequences in this region. Recognition was inhibited by either mutation of the binding core sequence or by methylation of three CpG sites. Point mutations at these CpG sites significantly decreased promoter activity, suggesting the importance of these sites. In 14 of 23 vestibular schwannomas, these three CpG sites were methylated in a site-specific manner and the methylation status was consistent with the expression of NF2 mRNA. CONCLUSIONS: Suppressed expression by aberrant methylation or mutation of the promoter elements could be an alternative mechanism for inactivation of the NF2 gene.

Animals↗

PubMed2001

Synchronization between hippocampal theta waves and PGO waves during REM sleep.

We investigated the temporal relationship between hippocampal theta waves (referred to as 'theta waves') and ponto-geniculo-occipital (PGO) waves in cats. We measured the time intervals between an occurrence of a PGO wave and the prior and posterior adjacent positive peaks of the theta wave. The unimodal distributions of these intervals suggested a close temporal relationship between PGO and theta waves (i.e. synchronization). In addition, the period of a theta wave during which a PGO wave occurred was not statistically different from that without a PGO wave. This result suggests that the synchronization found here is characterized by phase-locking rather than phase-resetting. Common mechanisms are suggested to underlie the generation of PGO and theta waves.

Animals↗

PubMed2001

Quantitative characteristics of alpha and theta EEG activities during sensory deprivation.

Our previous study showed that theta and alpha electroencephalographic (EEG) activities occurred together during sensory deprivations (SD). The respective activities are expected to manifest different physiological states. In this study, we investigate statistical properties of both types of EEG activities during SD. Wavelet analyses of the original EEG activities during SD and the corresponding surrogation data can distinguish meaningful alpha and theta activities in the original data from accidentally detected ones. As a result, the mean duration of the theta wave is found to be longer than that of the alpha wave. This result could be useful to disclose physiological processes during SD.

Adult↗

PubMed2001

A circadian system model with feedback of cross-correlation between sleep-wake rhythm and oscillator.

Recent findings suggest that social entrainment factors work on an oscillator other than the temperature and melatonin rhythms. This indicates that there is a feedback loop affected on oscillators. In the present study, a circadian system model, including mutually coupled two oscillators and sleep-wake rhythm, is constructed, where cross-correlation between a sleep-wake rhythm and an oscillator is set to modify the coupling from one oscillator to the other. Based on the model simulation, a mechanism underlying delayed sleep phase syndrome is elucidated by the reduction in the cross-correlation resulting from dissociation between the delayed sleep phase and the oscillator.

Body Temperature↗

PubMed2001

Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

AIMS: Reduced coronary flow reserve has been reported in patients with traditional risk factors, in particular hyperlipidaemia, despite angiographically normal coronary arteries. However, it is recognized that traditional risk factors do not explain the presence of coronary atherosclerosis in a large proportion of patients. The aim of this study was to assess whether coronary flow reserve is preserved in the myocardium supplied by normal coronary arteries in patients with one-vessel coronary artery disease without traditional risk factors. METHODS AND RESULTS: Positron emission tomography using [13N]ammonia was performed at baseline and after intravenous dipyridamole administration (0.56 mg x dl(-1)over 4 min) in 30 subjects: six patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis without traditional risk factors (coronary artery disease patients without risk factors, aged 59+/-13), five patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis with multiple risk factors (coronary artery disease patients with risk factors, aged 69+/-7), 11 age-matched controls (aged 58+/-6), and eight healthy young volunteers (aged 34+/-4). Myocardial blood flow calculated in the myocardium supplied by normal coronary arteries in the coronary artery disease patients was compared with those of the two control groups. Coronary flow reserve was defined as the ratio of hyperaemic blood flow after dipyridamole infusion to baseline blood flow. Although coronary flow reserve in the coronary artery disease patients with risk factors was significantly lower than that in the age-matched controls (1.62+/-0.37, 2.58+/-0.71, P=0.0428), coronary flow reserve in the coronary artery disease patients without risk factors was similar to that in the age-matched controls (2.54+/-0.17 vs 2.58+/-0.71, P=ns). CONCLUSION: Coronary flow reserve is preserved in regions supplied by angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

Adult↗

PubMed2001

Fourteen-year experience of acetylcholinesterase staining for rectal mucosal biopsy in neonatal Hirschsprung's disease.

BACKGROUND/PURPOSE: Acetylcholinesterase (AChE) staining of rectal mucosal biopsy specimens is the most important and popular examination for making a definite diagnosis of Hirschsprung's disease. This examination often is performed for patients with constipation in the daily clinic. The results of this examination are reflected immediately in the treatment. However, the authors sometimes encountered difficult cases to diagnose, especially in neonates. Therefore, a retrospective investigation was conducted on the benefits and problems of AChE staining of rectal mucosal biopsy specimens in neonates. METHODS: The authors encountered 459 cases (91 neonates) of suspected Hirschsprung's disease, clinically, from April 1986 to March 2000. Mucosal specimens were taken by punch biopsies. Samples were stained by the modified Karnovsky Roots method using rubeanic acid as an amplifier and immediately examined with a light microscope. These results were collected and assessed mainly on neonatal cases. The authors also analyzed the 104 cases of Hirschsprung's disease diagnosed in patients less than 1 year of age to evaluate the relationship between the grade of proliferation of AChE positive fiber and age. RESULTS: Forty-one neonatal cases of Hirschsprung's disease were diagnosed based on the findings of AChE staining. A definite diagnosis of Hirschsprung's disease was confirmed based on the pathologic findings of operative samples. Forty-eight cases that were diagnosed as normal included 4 cases that turned out to be false-negative (3 Hirschspurung's disease cases and 1 case of an allied disorder of Hirschsprung's disease). There were no major complications in mucosal punch biopsy. In the cases of Hirschsprung's disease diagnosed in a patient less than 1 year of age, the grade of AChE-positive fiber tended to increase with the aging of patients. CONCLUSIONS: The specificity of AChE staining was high (100%), but its sensitivity was slightly low (91%). Careful long-term follow-up is required for any cases diagnosed as normal. Mucosal biopsies should be repeated in cases of persistent clinical symptoms.

Acetylcholinesterase↗

PubMed2001

Nitric oxide participates in cataract development in selenite-treated rats.

PURPOSE: The role of nitric oxide in the development of selenite-induced cataracts in rats was examined using nitric oxide synthase (NOS) inhibitors. METHODS: Subcutaneous injection of sodium selenite was used to induce cataracts in rats, with or without pretreatment with NOS inhibitors. The anterior eye segment analysis system (EAS-1000, Nidek) was used to measure lens opacity. The glutathione content of the lenses was determined by an HPLC method and the Ca2+ content by atomic absorption spectrometry. Nitrite, a stable metabolite of nitric oxide, was determined fluorometrically. NADPH-diaphorase activity staining and Western blot analysis were used to determine NOS levels. RESULTS: Administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited lens opacification in selenite-treated rats. NG-nitro-d-arginine methyl ester, an inactive enantiomer of l-NAME, had no effect. Aminoguanidine, another NOS inhibitor, also inhibited the development of cataracts in a dose-dependent manner. On the other hand, L-arginine, a substrate of NOS, accelerated the development of cataracts. Although the opacification of the lenses was apparent approximately 3 days after selenite injection, the nitrite level was increased within one day. In addition, NOS was induced in the eye within one day of selenite injection. CONCLUSIONS: The present study demonstrated that NOS inhibitors prevented the development of cataracts in selenite-treated rats. The results also suggest that nitric oxide had an important role in the development of selenite-induced cataracts.

Animals↗

PubMed2001

Effects of gender and marital status on somatic symptoms of patients attending a mind/body medicine clinic.

To clarify the mechanisms of gender-related mind/body relationships, the authors analyzed the characteristics of 1,132 outpatients (848 women and 284 men) attending a mind/body medicine clinic. At entry in the program, the patients completed the Medical Symptom Checklist, Symptom Checklist-90 revised (SCL-90R), and Stress Perception Scale. Women reported 9 out of 12 symptoms (fatigue, insomnia, headache, back pain, joint or limb pain, palpitations, constipation, nausea, and dizziness) more frequently than the men did. Being a woman was a predictor of the total number of somatic symptoms endorsed. SCL-90R somatization scores were significantly higher in nonmarried women than in married women. Perceived stress ratings of family and health were higher in women than in men, despite the lower degree of perceived stress concerning work. Women, especially nonmarried women, were more likely to report somatic discomfort. Gender appears to be an important factor in relation to the report of somatic symptoms in stress-related conditions.

Adult↗

PubMed2001

Somatization and symptom reduction through a behavioral medicine intervention in a mind/body medicine clinic.

The authors assessed data from 1,148 outpatients in a 10-week medical symptom reduction program to determine the effectiveness of a behavioral medicine intervention among somatizing patients. The program included instruction in the relaxation response, cognitive restructuring, nutrition, and exercise. Before and after the intervention, the patients were evaluated on the Symptom Checklist-90 Revised (SCL-90R), the Medical Symptom Checklist, and the Stress Perception Scale. They were divided into high- and low-somatizing groups on the basis of the pretreatment SCL-90R somatization scale. At the end of the program, physical and psychological symptoms on the Medical Symptom Checklist and the SCL-90R were significantly reduced in both groups, with the reductions greater in the high-somatizing group. Improvements in stress perception were about the same in both groups, but the absence of an untreated control group precluded estimates of how much the improvements resulted from the behavioral medicine intervention and how much from natural healing over time.

Ambulatory Care Facilities↗

PubMed2001

Depression and education as predicting factors for completion of a behavioral medicine intervention in a mind/body medicine clinic.

The authors compared characteristics of 1,012 outpatients completing a 10-week behavioral medicine intervention with 300 outpatients who dropped out. They administered the Symptom Checklist-90 Revised (SCL-90R) before and after the program. Patients who completed the treatment, compared with dropouts, tended to be more highly educated, married, and gainfully employed. Their pretreatment scores on the SCL-90R were significantly lower than those of the dropouts on somatization, depression, and obsessive-compulsive scales and on the global severity index. Multiple logistic regression analysis indicated that lower depression and higher education marked the group who completed the intervention in contrast to the dropouts. After the intervention, all of the SCL-90R scores were significantly lower among patients who completed the treatment. Pre- to postintervention score changes were not significantly associated with the number of sessions attended. The findings suggest that the intervention had salutary effects in patients with mind/body distress and that its effectiveness was not diminished by a few absences. Depressed or less educated patients might benefit from preparatory interventions or from a modified approach to their treatment.

Adult↗

PubMed2001

Enhanced sensitivity of bladder cancer cells to tumor necrosis factor related apoptosis inducing ligand mediated apoptosis by cisplatin and carboplatin.

PURPOSE: The development and acquisition of multiple drug resistance in cancer cells are a consequence of cancer chemotherapy and remain a major obstacle in treatment. Therefore, there is an obvious need for alternative approaches, such as immunotherapy and gene therapy. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is one of the tumor necrosis factor ligand families and it selectively induces apoptosis against cancer cells. Several cytotoxic anticancer drugs also mediate apoptosis and may share the common intracellular pathways leading to apoptosis. We reasoned that combination treatment of cancer cells with TRAIL and drugs may overcome this resistance. We evaluated whether bladder cancer cells are sensitive to TRAIL mediated cytotoxicity and whether TRAIL may synergize with anticancer agents in cytotoxicity and apoptosis against bladder cancer cells. MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. RESULTS: Human T24 bladder cancer line was relatively resistant to TRAIL and TRAIL was not cytotoxic against normal bladder cells. Treatment of T24 cells with TRAIL in combination with 5-fluorouracil or mitomycin C did not overcome resistance to these agents. However, treatment of T24 cells with a combination of TRAIL and cisplatin resulted in a synergistic cytotoxic effect. Synergy was also achieved in the cisplatin resistant T24 line (T24/CDDP), 2 other bladder cancer lines and 3 freshly derived bladder cancer cells. The combination of TRAIL and carboplatin resulted in a synergistic cytotoxic effect on T24 cells. However, the combination of TRAIL and trans-diamminedichloroplatinum (II) resulted in an antagonistic cytotoxic effect. The synergy achieved in cytotoxicity with TRAIL and cisplatin was also achieved in apoptosis. Treating T24 cells with cisplatin enhanced the expression of bax but not bcl-2. Incubation of T24 cells with TRAIL increased the intracellular accumulation of cisplatin. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with TRAIL and cisplatin overcomes their resistance. The sensitization obtained with established cisplatin resistant and freshly isolated bladder cancer cells required low subtoxic concentrations of cisplatin, supporting the in vivo potential application of a combination of TRAIL and cisplatin for treating TRAIL resistant and cisplatin resistant bladder cancer.

Antineoplastic Agents↗

PubMed2001

[Detection of mupirocin resistant staphylococci from patients treated with mupirocin].

Susceptibility testing of mupirocin (MUP) was performed by an agar dilution method according to the National Committee for Clinical Laboratory Standard (NCCLS) to detect the MUP resistance. A total of 434 isolates of methicillin-resistant staphylococci were examined and all of 205 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from 43 hospitals nationwide in 1993 were sensitive to MUP. However, MUP resistance emerged among 228 isolates [185 isolates (88 cases) of MRSA and 43 isolates (28 cases) of methicillin-resistant coagulase negative staphylococci (MR-CNS)] from nasal swabs of patients with MUP treatment between Sep 1996 and Feb 2000 in the Nagoya University Hospital. The high-level MUP resistance (MIC > or = 512 micrograms/mL) was isolated from two patients, one isolate of MRSA and four of S. hominis, respectively. Low-level MUP resistance (MIC 8-128 micrograms/mL) was isolated from three patients, 11 isolates of MRSA, one of S. chromogenes and five of S. epidermidis, respectively. The mupA which encodes the MUP resistant isoleucyl-tRNA synthetase (IRS) were investigated by PCR in these MUP resistant isolates. The mupA was detected only in high-level MUP resistant S. hominis, but not detected in high-level MUP resistant MRSA and low-level MUP resistant isolates. We also investigated the characteristics of the patients with MUP resistance. All of MUP resistant staphylococci were isolated after initiation of MUP treatment. Four patients with MUP resistant MRSA and low-level MUP resistant MR-CNS had MRSA infectious disease and MUP resistant strains were successfully eradicated with vancomycin treatment in two patients. MUP high-level resistant S. hominis, has emerged after MUP treatment for eradication of MRSA. Clinical guidelines for the prudent use of MUP should be generally adopted with careful monitoring of emergence of MUP resistance.

Adult↗

PubMed2001

In vitro and in vivo antibacterial activities of TAK-083, an agent for treatment of Helicobacter pylori infection.

The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 microg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

Amoxicillin↗

PubMed2001

Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia.

Most patients diagnosed with secondary hemochromatosis have had repeated blood transfusions. Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure. A 23-year-old woman with hemochromatosis had, despite significant left ventricular dysfunction, liver function within the normal range on biochemical evaluation. She was treated for congestive heart failure and given desferoxamine intravenously. She did not have primary hemochromatosis, and had not received multiple blood transfusions or iron supplement. As a child the patient had been diagnosed with congenital non-spherocytic hemolytic anemia not requiring transfusion; thus, this is a unique case of secondary hemochromatosis.

Adult↗

PubMed2001

Isolation of five laccase gene sequences from the white-rot fungus Trametes sanguinea by PCR, and cloning, characterization and expression of the laccase cDNA in yeasts.

To obtain laccase-gene-specific sequences from the white-rot fungus Trametes sanguinea M85-2, a PCR screening method was used. Degenerate primers were designed based on highly conserved copper-binding regions I and IV of known laccases and used to amplify laccase sequences from T. sanguinea M85-2 genomic DNA. A single 1.6-kbp DNA band was amplified and cloned into a vector. Partial sequences of 21 clones were classified into five groups (lcc1-5) and the deduced amino acid sequences were all homologous to known laccase sequences. Based on the partial sequence of lcc1, the 5'-end of its cDNA was obtained by a PCR termed 5' rapid amplification of cDNA ends (5'-RACE), and RT-PCR was then carried out using the 5'-primer and the poly-dT primer to obtain the full-length lcc1 cDNA. The obtained cDNA encoded a protein consisting of 518 amino acid residues and its first 21 amino acid residues were predicted to be the signal peptide for secretion. The conserved characteristic structures of laccase, such as copper-binding ligands, N-glycosylation sites, and cysteine residues for disulfide bridges, were observed. The genomic DNA sequence of the lcc1 gene was also cloned by PCR method and the sequence revealed 10 introns. The lcc1 cDNA was inserted into yeast vectors for heterologous expression by Saccharomyces cerevisiae and Pichia pastoris. Phenol-oxidizing activity was detected from transformants of the yeasts, indicating that the obtained cDNA encodes a laccase. Previously, two laccase isozymes were biochemically characterized and purified from T. sanguinea M85-2. Using the sequential PCR method presented here, we have obtained partial sequences of at least five laccase genes and one cDNA clone encoding a protein with laccase activity but without any enzymatic information, suggesting that expressed enzymes under restricted conditions may not represent all the isozymes in target microorganisms. PCR cloning and heterologous expression of the cloned genes can be an alternative method of screening enzymes if these enzymes have conserved sequences.

Journal Article↗

PubMed2001

Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.

The aim of this study was to evaluate the acute effects of E-3174, a human active metabolite of the AT1 receptor antagonist, losartan, on hemodynamic functions in dogs with severe heart failure (HF). In dogs, insignificant plasma levels of E-3174 are present following administration of losartan, and therefore, the effects of these two drugs can be studied independently in the dog. HF was established by rapid pacing of the right ventricle (250-270 beats/min) for 4 weeks. We examined changes in cardiovascular functions after acute intravenous administration of losartan (1 mg/kg) and E-3174 (0.3 and 1 mg/kg), as well as an ACE inhibitor, enalapril (0.3 and 1 mg/kg), under condition of HF. The HF before treatment was characterized by increases in pre- and after-load of the left ventricle (LV), consequent low cardiac output, and LV dilatation. E-3174 at 0.3 and 1 mg/kg reduced pulmonary artery pressure (-13+/-6% and -22+/-3% from baseline, respectively, p<0.05), pulmonary capillary wedge pressure (-18+/-4% and -36+/-10%, p<0.05) and mean arterial pressure (-24+/-2% and -36+/-7%, p<0.05), increased stroke volume (SV: +12+/-7% p>0.05; +36 +/-19%, p<0.05), and reduced peripheral resistance (-23+/-5% and -41+/-9%, p<0.05), but had no effect on the first derivative of left ventricular pressure (dP/dt/P) or the time constant for relaxation. Effects of losartan at 1 mg/kg were similar to those of 0.3 mg/kg of E-3174. Enalapril at 1 mg/kg caused changes comparable to those seen after E-3174 administration (1 mg/kg), except that the increase in SV (+16+/-8%, p<0.05) with enalapril was not as great as that with E-3174. Both losartan at 1 mg/kg and E-3174 at 0.3 and 1 mg/kg increased fractional shortening to a similar extent (FS: +52+/-12%, +47+/-8% and +56+/-8%), while enalapril at 0.3 and 1 mg/kg had no significant effects on FS. Reflex elevation of plasma renin activity induced by 1 mg/kg of E-3174 was similar to that caused by 1 mg/kg of enalapril, suggesting that the two drugs achieved similar inhibition of the endogenous renin angiotensin system. Our study demonstrated that acute blockade of the AT1 receptor with E-3174 reduced elevated pre- and after-load and consequently increased stroke volume in a canine HF model. With the exception of changes in stroke volume, these effects of E-3174 were comparable to those produced by enalapril, and were 3 times stronger than those by losartan.

Angiotensin Receptor Antagonists↗

PubMed2001

Depressive mood accompanies hypercholesterolemia in young Japanese adults.

Screening of young hypercholesterolemics is important because they are highly susceptible to atherosclerotic diseases. However, in some cases, serum cholesterol level may be elevated temporarily due to stress or other psychological factors. This study examined the effects of mood states on 'persistent' hypercholesterolemia in comparison with 'temporary' hypercholesterolemia among students entering a university. The subjects were 114 untreated first-year students aged 18 to 20 years old. All had been screened positive for hypercholesterolemia (serum total cholesterol > or = 220 mg/dl) upon enrolling in the university. Three months after the screening, they were divided into two groups according to the re-examined serum total cholesterol level; a persistent hypercholesterolemic group (n=41) with >220 mg/dl and a temporary hypercholesterolemic group (n=73) with <220 mg/dl. At that time, they completed the Profile of Mood States (POMS) with tension-anxiety, depression, anger-hostility, vigor, fatigue and confusion scales. The POMS depression scores and the female ratio were higher (both p<0.01) and body mass index was lower (p<0.05) in the persistent hypercholesterolemic subjects than in the temporary hypercholesterolemic subjects; the POMS depression scores were still higher (p<0.05) after controlling for the effects of gender, body mass index, and other POMS scales by multiple logistic regression analysis. Depressive mood appeared to relate to hypercholesterolemia when the university students were screened. Assessment of mood states may be important in screening young hypercholesterolemic patients.

Adolescent↗

PubMed2001

Pyloricidins, novel anti-helicobacterpylori antibiotics produced by Bacillus sp. I. Taxonomy, fermentation and biological activity.

Novel anti-Helicobacter pylori antibiotics, pyloricidins A, A1, A2, B, C and D, were discovered in the culture broth of two bacilli strains. Pyloricidins selectively inhibited the growth of H. pylori. Pyloricidin B was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils and may be promising for cure of H. pylori infection as a single agent.

Amoxicillin↗