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Biomedical subjects

A Nakamura

Publications and source records attributed to A Nakamura.

At least 325 records · Page 18Linked to original sources

Graft damage after a single lung transplantation for pulmonary hypertension in a rat model.

The hemodynamic effect and degree of damage in grafts of single lung transplants for pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred male Lewis rats (weight 200-230 g) were divided into two groups. Group 1 (control group, n = 16) underwent isogenic left lung transplantation, while group 2 (n = 15) received an intravenous administration of monocrotaline (80 mg/kg i.v.) and underwent isogenic left single lung transplantation 3 week later. Hemodynamic evaluations were performed prior to transplantation, at 1 h postoperatively, and on days 3 and 7 after transplantation. Mean pulmonary arterial pressure (mPAP) rapidly declined after transplantation in group 2, from 39.3 +/- 8.7 mmHg to 18.5 +/- 3.0 mmHg 1 h after transplantation, and remained stable on day 7 after transplantation. No significant difference in the mPAP between the two groups was observed after transplantation. The extravascular lung water volume (ELWV: dry/wet ratio) in the right lung of group 2 significantly increased on day 3 (0.86 +/- 0.02) (P < 0.01), and subsequently decreased to control levels on day 7 (0.83 +/- 0.02). There was no significant difference in the ELWV in the grafted lungs between the two groups (0.84 +/- 0.03 vs 0.86 +/- 0.04), but there was tendency toward an increase in ELWV in group 2 on days 3 and 7. These data thus demonstrated that a hemodynamic improvement was obtained by single lung transplantation; however the degree of graft damage was remarkable in the pulmonary hypertension group.

Animals↗

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Adult↗

Upper gastrointestinal bleeding arising from metastatic testicular tumor.

We report a young man with a testicular tumor in whom the first symptom was upper gastrointestinal bleeding. This was caused by invasion of the duodenum by a metastatic lesion in a retroperitoneal lymph node. Metastatic testicular tumor is a rare cause of upper gastrointestinal bleeding. Diagnosis was difficult because the primary lesion could not be found initially. In young men with upper gastrointestinal bleeding, the possibility of metastatic testicular tumor should be investigated.

Adult↗

Identification of motor and sensory brain activities during unilateral finger movement: spatiotemporal source analysis of movement-associated magnetic fields.

We investigated the movement-related cortical fields (MRCFs) recorded by magnetoencephalography (MEG) to identify the motor and sensory brain activities at the instant of the unilateral finger movement using six normal subjects. We focused our investigation on the source analysis of the events tightly linked to movement onset, and we used brain electric source analysis (BESA) to model the sources generating MRCFs during the interval from 200 ms before to 150 ms after the movement onset. Four sources provided satisfactory solutions for MRCF activities in this interval. Sources 1 and 2, which were located in the pre-central regions in the hemisphere contralateral and ipsilateral to the moved finger, respectively, generated the readiness fields (RF), but source 1 was predominant just before movement onset. The motor field (MF), the peak of which was just after movement onset, was mainly generated by source 1. Sources 3 and 4 were located in the post-central regions in the hemisphere contralateral and ipsilateral to the moved finger, respectively. The first motor evoked field (MEF-I), the peak of which was about 80 ms after the movement, was mainly generated by source 3, but with the participation of sources 1, 2 and 4. The results indicated that the activities of both pre -and post-central regions in bilateral hemispheres were related to voluntary movements, although the predominant areas varied over time. This is the first noninvasive study to clarify the complex spatiotemporal activities relating movements in humans using a multi-channel MEG system.

Adult↗

Quantitative assays for hepatitis C virus in serum as predictors of the long-term response to interferon.

BACKGROUND/AIMS: Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy. METHODS: HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype. RESULTS: From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicor-monitor and CRT-PCR, in contrast to 60% (187/312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r = 0.680 to 0.731). Serum HCV RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with < 1 x 10(4) copies/ml of HCV RNA by Amplicor-monitor assay, < 2 x 10(5) copies/ml by CRT-PCR, < 0.5 Meq/ml by bDNA assay, and < 20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (< 11%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype. CONCLUSIONS: Quantitation of HCV core protein and HCV RNA in useful for prediction of the interferon response.

Adolescent↗

High altitude training increases reactive carbonyl derivatives but not lipid peroxidation in skeletal muscle of rats.

The oxidative stress related consequences of physical training at high altitude are not known. The hypothesis was tested that physical training and exposure to high altitude have adverse effects on free radical generation and activities of antioxidant enzymes. The present results showed that 4 weeks of exercise at an altitude of 4000 m increased the activity of Mn-SOD in both white and red types of skeletal muscle. The activities of Cu,Zn-SOD, catalase, and glutathione peroxidase, as well as the level of lipid peroxidation measured by TBARS and lipid hydroperoxides, did not change significantly. In contrast, the level of reactive carbonyl derivatives measured by anti-2,4-dinitrophenylhydrazone antibodies and spectrophotometry showed an increase in both types of muscle of altitude trained rats compared with sea level trained and control groups. It was suggested that the oxidative modification of certain amino acids is due to the increasing gap between activity of SOD and peroxide scavenging enzymes, which results in increases in the number of hydrogen peroxide molecules. Thus, since the mechanism of generation and/or the mode of action of radicals resulting in lipid peroxidation and protein oxidation appears to be different in vivo, both processes should be studied during oxidative stress.

Altitude↗

Bony foramina facilitate magnetic stimulation: an experimental cat sciatic nerve model.

We have established an experimental bony foramen model in vivo using a cat sciatic nerve, a section of skull bone and a column made from methylmethacrylate. In each model, a foramen-like slit or fissure was created. Motor responses of the cat right gastrocnemius were elicited with a figure-of-8-shaped magnetic coil. Very high intensities of magnetic stimulation were necessary to evoke motor responses with the coil placed on the thigh. However, when the bone section or methylmethacrylate column was placed under the thigh muscle layer with the sciatic nerve fitted into the foramen-like slit or fissure, motor responses could be elicited with a smaller intensity of magnetic stimulation. Despite changes in stimulation intensity or shifts in the magnetic coil, the latency of the motor responses remained constant. By comparing the latency with the electrical recording, the site of excitation was predicted to be at the exit of the foramen. Our studies have confirmed that bony structures, especially bony foramina, facilitate excitation of the nerve by magnetic stimulation and that the exit of the foramen could be the preferential site for magnetic stimulation.

Animals↗

Effects of movement and movement imagery on somatosensory evoked magnetic fields following posterior tibial nerve stimulation.

We examined the "gating" effects caused by active and passive movements of toes and by "movement imagery" (mental moving of the toe without actual movements) on somatosensory evoked magnetic fields (SEFs) following stimulation of the posterior tibial nerve in normal subjects. Active and passive movements significantly attenuated the short- and middle-latency cortical components (P < 0.001) with no latency change, and the effects of the active movements were larger than those of the passive movements. In contrast, the subsequent long-latency component with a latency of about 100 ms was enhanced only by the active movements. Therefore, both centrifugal and centripetal mechanisms should be considered. The gating effects by movements on all components may occur in the primary sensory cortex (SI) in the hemisphere contralateral to the stimulated nerve, because all of the equivalent current dipoles (ECDs) of the components in the "control" and each "interference" waveform were located there. Active movements of the toes contralateral to the stimulated nerve caused no significant gating effect. The short-latency components were not consistently changed by "movement imagery", but the middle- and long-latency components were enhanced. Their ECDs were located in the SI contralateral to the stimulated nerve and in the SII in bilateral hemispheres. Therefore, we speculated that brain responses to somatosensory stimulation, particularly components generated in SII, were affected by volitional changes.

Adult↗

Visual evoked cortical magnetic fields to pattern reversal stimulation.

We studied visual evoked magnetic fields to pattern reversal stimulation in six healthy subjects. Similar to the N75-P100-N145 components in visual evoked potentials, triphasic deflections, N75m-P100m-N145m, were clearly observed around the midoccipital position. A very small component, P50m, was occasionally observed preceding the N75m. Equivalent current dipoles (ECDs) of the main deflection, P100m, to quadrant-field stimulation were estimated near or around the calcarine fissure contralateral to the stimulation. The vertical ECD location of the P100m to the upper quadrant-field stimulation was estimated significantly lower (0.81 +/- 0.45 cm) than those to lower stimulation. These results were compatible with the retinotopic organization of the visual cortex (cruciform model) and suggested that the P100m originated in the striate cortex. The small P50m, although only a small number of ECDs could be estimated reliably, was located in the contralateral visual cortex. ECDs of the N75m were estimated mainly near or around the contralateral calcarine fissure. ECDs of the N145m were estimated also retinotopically, but with a greater vertical distance (2.90 +/- 1.09 cm) between upper and lower quadrant-field stimulation. MR-overlaid ECDs of the N145m suggested that these originated in the extrastriate cortex. No ECD was estimated when a probe was placed at the midfrontal position.

Adult↗

Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries.

1. This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120-200 microns in diameter, incubated with a selective agonist and the novel 'antisense' peptide to part of the human endothelinA receptor. 2. Groups of vessels (n = 6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC50 of 8.16 +/- 0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum). 3. Preincubation of six vessels with the antisense peptide ETR p1/f1 at 1 microM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 microM ETR p1/f1, there was a significant shift of the concentration-response curve and a lower pEC50 at 7.78 +/- 0.09 M (P < 0.05). At the highest concentrations of ETR p1/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 microM, only reached some 10% of the maximal achievable contraction. 4. Increasing ET-1 concentrations up to 2 microM in vessels incubated with 40 microM ETR-p1/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P < 0.001) by approximately one log unit with a pEC50 of 7.13 +/- 0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors. 5. At the highest concentrations tested, 40 microM, ETR-p1/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions. 6. Together, these data suggest that at the rat renal arcuate artery the endothelinA receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel type of 'antisense' peptide in blocking receptor activation.

Amino Acid Sequence↗

Bh (black at hatch) gene appears to be expressed in melanocytes of feather germs in the Japanese quail (Coturnix coturnix japonica).

The Bh (black at hatch) gene was examined to determine whether it is expressed in plumage melanocytes by analyzing pigmentation patterns of Bh melanocytes placed in the micro-environment of the feather germs of quail embryos with pink eyes. These host quails genetically lack a large part of plumage melanin. The Bh locus in these almost white quails is wild-type. When Bh neural crest cells were transplanted orthotopically into the host embryos, wild-type and Bh/+ melanocytes, which differentiated from the transplanted neural crest cells, formed plumage pigmentation patterns characteristic of each genotype in the micro-environment of the host feather germs. Brown plumage pigmentation, which was very similar to that of 10-day Bh/Bh embryos, was also observed in the feather germs of host embryos that received Bh neural crest cells, although the genotype of the donors could not be determined. These donors died before pigmentation of their feather germs occurred. The results demonstrate that pigmentation patterns of Bh melanocytes are not altered in the micro-environment of the host germs, suggesting that the Bh gene is autonomous in Bh melanocytes and is expressed in melanocytes of both Bh and the host feather germs, and that it causes the normal pigmentation pattern to be altered.

Animals↗

Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo-Chiba Hepatitis Research Group.

BACKGROUND & AIMS: The relative role of virus load and hepatitis C virus (HCV) subtype as predictor of the efficacy of interferon (IFN) therapy is still in dispute. To resolve this issue, a multicenter, randomized, prospective study of 272 patients with chronic hepatitis C but without cirrhosis was conducted. METHODS: The patients were randomly assigned to two different dose groups: 6 million units (MU) or 9 MU IFN three times a week for 6 months. Serum HCV RNA levels and HCV subtypes were determined. RESULTS: HCV RNA negativity rate at the completion of treatment with 9 MU IFN was higher than that with 6 MU (75% vs. 44%; P < 0.05). Virus eradication at 12 months after completion of treatment was higher in the 9 MU group than in the 6 MU group (36% vs. 25%; P < 0.05), especially in patients who had an intermediate virus load (10(4)-10(5) copies/mL by Amplicor monitor assay) (52% vs. 19%; P = 0.029). Virus eradication rate in patients with serotype 2 was higher than in those with serotype 1 for both regimens (6 MU, 53% vs. 15%; 9 MU, 76% vs. 29%; each P < 0.05). CONCLUSIONS: This prospective study showed that virus load, HCV serotype, and IFN dose are important predictors of the virological response to IFN therapy but virus load is the most important factor influencing the efficacy of IFN.

Adult↗

N-oxidation of irsogladine by the CYP2C subfamily in the rat, dog, monkey and man.

1. The metabolism of irsogladine (ISG) was studied in hepatic microsomes from the rat, dog, monkey and man, and marked species differences were observed in N-oxidation of ISG. The rank order of the activity of the N-oxidation was shown to be man < monkey < dog < rat. 2. Anti-NADPH-P450 reductase antibody inhibited the formation of the N-oxidized metabolite of ISG (ISG-N-oxide) in hepatic microsomes from rats by 74%. Anti-CYP2C11 antibody also inhibited the formation of ISG-N-oxide in hepatic microsomes from rat by 73%, whereas anti-CYP2E1, 3A2 and 4A1 antibody did not inhibit N-oxidation. Thus, CYP2C11 in the rat is at least partially responsible for the N-oxidation of ISG in the rat. 3. Anti-CYP2C11 antibody also inhibited the formation of ISG-N-oxide in hepatic microsomes from the dog and monkey by 61 and 46% respectively. Therefore, a isoform(s) similar to CYP2C11 partially contributed to the N-oxidation of ISG in the dog and monkey. In contrast, human CYP2C9, a member of the human CYP2C subfamily, did not catalyse the N-oxidation of ISG. 4. These findings show that the marked species difference in the N-oxidation of ISG is caused by the difference in the catalytic properties of CYP2C among the species examined.

Animals↗

Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen breakage syndrome at chromosome 8q21-24.

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by microcephaly, short stature, immunodeficiency, and a high incidence of cancer. Cultured cells from NBS show chromosome instability, an increased sensitivity to radiation-induced cell killing, and an abnormal cell-cycle regulation after irradiation. Hitherto, patients with NBS have been divided into the two complementation groups V1 and V2, on the basis of restoration of radioresistant DNA synthesis, suggesting that each group arises from a different gene. However, the presence of genetic heterogeneity in NBS has been considered to be controversial. To localize the NBS gene, we have performed functional complementation assays using somatic cell fusion between NBS-V1 and NBS-V2 cells, on the basis of hyper-radiosensitivity, and then have performed a genomewide search for the NBS locus, using microcell-mediated chromosome transfer followed by complementation assays based on radiosensitivity. We found that radiation resistance was not restored in the fused NBS-V1 and NBS-V2 cells and that only human chromosome 8 complements the sensitivity to ionizing radiation, in NBS cell lines. In complementation assays performed after the transfer of a reduced chromosome, merely the long arm of chromosome 8 was sufficient for restoring the defect. Our results strongly suggest that NBS is a homogeneous disorder and that the gene for NBS is located at 8q21-24.

Abnormalities, Multiple↗

Isolation of a novel human gene from the Down syndrome critical region of chromosome 21q22.2.

Down syndrome is the most common birth defect, and is caused by trisomy 21. We identified a novel gene in the so-called Down syndrome critical region by means of computer-aided exon prediction and subsequent cDNA cloning. The gene, designated as DCRA (Down syndrome Critical Region gene A), consists of eight exons of 3,252 bp in total and encodes a large open reading frame of 297 amino acid residues. The open reading frame shows significant homology to Hbeta58, a mouse gene essential for embryogenesis, PEP8, a yeast homologue of Hbeta58, and an expressed sequence tag of Arabidopsis thariana, suggesting that DCRA has some important function that has been conserved during the course of evolution. DCRA is expressed in most tissues examined, including fetal and adult brain, heart, lung, liver, and kidney. The cDNA of the DCRA mouse homologue, Dcra, was also cloned. It is 2,157 bp long and has an open reading frame of 297 amino acid residues, which shows 92% identity to human DCRA. Dcra is expressed in all the embryo and adult tissues examined.

Adult↗

[Trend of bacterial meningitis in children over a 14 year period (1981 through 1994) in Japan--an analysis based on studies in 27 institutions].

We observed 266 children with purulent meningitis in 27 institutions in Japan during the 14 years from 1981 on dividing these years into 3 periods, 1981-1985, 1986-1990 and 1991-1994, and studied the trend of causative organisms identified in 254 among the 266 patients. Their ages were less than 3 months after birth in 50 children and 3 months or older in 216: there were 141 boys and 125 girls. The causative organisms were H. influenzae in 134 patients and S. pneumoniae in 50, most of them being aged 3 months or older. Next to the above bacteria ranked S. agalactiae in 29 and E. coli in 12, many of the patients were aged less than 3 months. Staphylococcus spp. was found in 7 patients and about 70% of them were aged 3 months or older. L. monocytogenes was found in 4 patients and N. meningitidis in 3 and they were aged 3 months or older in both patient groups. S. pyogenes, Enterococcus spp., Peptostreptococcus spp., P. Mirabilis and Enterobacter spp. were detected each in 1 patient. The causative organism was unknown in 21 patients and there was no double infection. H. influenzae were detected in 18 patients in 1981-1985 period (36.7%), in 56 in 1986-1990 (54.9%) and in 60 in 1991-1994 (63.8%) showing an increasing tendency, but S. pneumoniae exhibited neither an increasing nor decreasing tendency. There was a decreasing tendency with S. agalactiae and E. coli, but the details were not clear because there were few patients aged less than 3 months. Although the period of coexistence of 4 main bacterial species was not made clear in this study. Listeria is considered to develop mainly in the early childhood, and we believe that the conventional way of using a cephem preparation and ampicillin combined for patients under 6 years need not be altered. However, panipenem (phonetic) is likely to be effective for insensible S. pneumoniae for the time being.

Escherichia coli↗

[Prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in a children's hospital].

Eleven hundreds and seventy-six strains of Streptococcus pneumoniae were isolated from pediatric clinics of Chiba Children's Hospital during 1990 through 1995. Annual penicillin-resistant rates of these strains were as follows; 24.0% (1990), 29.0% (1991), 36.2% (1992), 55.8% (1993), 58.6% (1994), and 59.3% (1995). Overall penicillin-resistance during these 6 years was 45.8%. Nine out of 11 cases of systemic pneumococcal infections were due to penicillin-resistant S. pneumoniae (PRSP) during the same period. Of PRSP strains, their PCG-MIC levels had become higher and their spectra of resistance had expanded not only to beta-lactam but also to non-beta-lactam antimicrobials. Although panipenem was the most efficacious antibiotics in this study and was recommended currently to use in the case of pneumococcal meningitis, it should be noted that a strain with high-level MIC (2 micrograms/ml) had emerged in 1995. Close surveillance of pneumococcal antimicrobial susceptibility including panipenem is necessary.

Anti-Bacterial Agents↗

[Biochemical and molecular characterization of Salmonella serovar enteritidis phage type 4 isolated from food poisoning outbreaks in Tokyo].

Since 1989, outbreaks of Salmonella ser. Enteritidis (S. Enteritidis) food poisoning have dramatically increased in Tokyo, and a total of 31 outbreaks has been reported in 1989. Twenty-one of these 31 outbreaks were caused by S. Enteritidis PT34, but 8 outbreaks were caused by S. Enteritidis PT4. After 1990 instead of SE PT34, food poisoning due to PT4, which was a very common phage type in the UK, has increased in Tokyo. Between 1989 and 1995, there were 144 food poisoning outbreaks caused by S. Enteritidis, and 64 of these outbreaks were by due to S. Enteritidis PT4, which was one of the main phage types in Tokyo. To characterize these strains of phage type (PT) 4,293 isolates from patients, and vehicle foods, eggs and environment in Tokyo were examined for plasmid DNA profiles, acid productivity from glycols (propylene and ethylene) and antimicrobial resistance patterns. Plasmid DNA was extracted by Kado's method, and analyzed by agarose gel electrophoresis. The acid productivity from propylene glycol or ethylene glycol were tested using Barsicow medium with 1% propylene glycol or ethylene glycol. Antimicrobial susceptibility to AM, CP, TC, SM, KM, NA, ST, FOM and NFLX was tested by the K-B disc method. The strains of PT4 were further subdivided into 9 types by those epidemiologic marker analysis. The prevalent pattern of PT4 strains was type A plasmid profile carrying only one plasmid (60 kb) and there were 2 kinds of antibiograms. One was SM resistant, while the other was susceptible. A total of 56 (87.5%) of 64 outbreaks was found to have been caused by these types of S. Enteritidis. Several kinds of egg-related foods were suspected as the vehicles of transmission among 24 outbreaks. Especially, in 5 outbreaks, S. Enteritidis strains were isolated both from patients and suspected food which were cooked with egg. This strongly suggests that these foods may be the potential source of infection in S. Enteritidis PT4 outbreaks.

Anti-Bacterial Agents↗