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Biomedical subjects

A Nakamura

Publications and source records attributed to A Nakamura.

At least 181 records · Page 10Linked to original sources
PubMed2000

[Concurrent chemoradiotherapy for T4 and/or M1 LYM squamous cell carcinoma of the esophagus].

A phase II study was conducted to investigate the efficacy and feasibility of chemoradiotherapy for locally advanced carcinoma of the esophagus. Fifty-four patients with clinical T4 and/or M1 LYM squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusions of fluorouracil 400 mg/m2/24 hours on days 1 to 5 and 8 to 12, 2-hour infusions of cisplatin 40 mg/m2 on days 1 and 8, and concurrent radiotherapy at a dose of 30 Gy in 15 fractions over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy followed by two courses of fluorouracil (800 mg/m2/24 hours for 5 days) and cisplatin (80 mg/m2 on day 1). There were 36 patients with T4 disease and 33 with M1 LYM. Forty-nine patients (91%) completed the chemoradiotherapy segment. The 18 patients (33%) who achieved a complete response included nine (25%) of the 36 with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities were leukopenia and esophagitis; there were four (7%) treatment-related deaths. Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia without improving dose-intensity or response. With a median follow-up duration of 43 months, median survival time was 9 months. The 3-year survival rate was 23%. Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.

Adult↗
PubMed2000

Human visual motion areas determined individually by magnetoencephalography and 3D magnetic resonance imaging.

We used magnetoencephalography to study inter-individual locational difference in the extrastriate region which responds to visual motion. Magnetic responses to visual motion onset from the right temporo-occipital area were recorded from 12 subjects. All the subjects had clear responses to apparent or random dot coherent motion. The origins of these responses was investigated by use of the single equivalent current dipole model. The nearest scalp to the origin also was identified for each subject, which may be useful in transcranial stimulation studies. Although the magnetic responses of all the subjects should have the same functional properties; be related to neural activities synchronized exclusively to the onset of motion, the estimated origins varied greatly among the subjects. The location of origin could be classified as one of three types: temporo-occipital, occipital, or parietal, according to the sulcal anatomy investigated in the individual's three-dimensional magnetic resonance image. Temporo-occipital types were found for seven subjects, and anatomically the regions were around human MT/V5. Two subjects had the occipital type, with regions posterior to the anatomical MT/V5 and corresponding to V3A anatomically. The other three subjects had origins classified as the parietal type dorso-rostral to the anatomical MT/V5, with regions around the posterior end of the superior temporal sulcus. Although all these cortical regions appear to be related to the neural process of visual motion, whether they correspond functionally to the same names or migrated MT/V5 must now be determined.

Adult↗
PubMed2000

[Pattern visual evoked potentials visual acuity--the evaluation of visual acuity of less than 0.1].

PURPOSE: We previously developed a new method for estimating objective visual acuity by means of pattern visual evoked potentials (PVEP). In this study, this method was applied to the evaluation of visual acuity of 0.05 and 0.01. METHODS: Ten subjects with visual acuity of 0.05 and ten normal subjects with visual acuity of 0.01 were examined. The visual acuity of the subjects was decreased step by step by means of plus spherical lenses of increasing power. In the PVEP study, the stimulus consisted of black and white checkerboards with a visual angle of 8 degrees (central stimulus) and a global field with a 5 degrees central circular scotoma (peripheral stimulus), contrast level of 15%, and a frequency of 0.7 Hz. One hundred PVEP responses were averaged per session. We reported that there was a linear relation between log subjective visual acuity of 0.1-1.0 and log check size of the patterns with PVEP. In reference to that, the check sizes of the patterns were estimated at 66' with visual acuity of 0.05, and 107' with visual acuity of 0.01. Each visual acuity was then used with other check sizes of three patterns. RESULTS: With central stimulus the P100 components of O1, O2, and Oz were recorded with 66' and 82' patterns at visual acuity of 0.05(central stimulus). The P100 components of O1, O2, and Oz were 107', 137' and 161' at visual acuity of 0.01(central stimulus). There was no P100 component at visual acuity of 0.05 and 0.01(peripheral stimulus). CONCLUSION: This method of PVEP is a useful tool as an objective estimation of visual acuity less than 0.1 and is presumed to stimulate preferentially the X retinal ganglion cell to parvocellular pathway.

Adult↗
PubMed1999

Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients.

Cells from Nijmegen breakage syndrome (NBS) display multiple phenotypes, such as chromosomal instability, hypersensitivity to cell killing from ionizing radiation, and possibly abnormal cell cycle checkpoints. NBS1, a gene mutated in NBS patients, appears to encode a possible repair protein, which could form the foci of a sensor-like molecular complex capable of detecting DNA double strand breaks, however, it has no kinase domain for signaling DNA damage. Here, we report that the stable expression of NBS1 cDNA in NBS cells after transfection results in the complete restoration of foci formation in the nucleus, and in normal cell survival after irradiation. The prolonged G2 block observed after irradiation was also abolished by expression of NBS1, providing additional confirmation that the G2 checkpoint is abrogated in NBS cells. These results suggest that a defective NBS1 protein could be the sole cause of the NBS phenotype, and that NBS1 likely interacts with another protein(s) to produce the entire range of NBS phenotypic expression.

Base Sequence↗
PubMed1999

Different time course between scene processing and face processing: a MEG study.

Using magnetoencephalography (MEG), the neural response to scenes was recorded and compared with that to faces. The prominent MEG signals in response to scenes appeared 200-300 ms after the stimulus presentation while those in response to faces appeared between 150 and 200 ms. Source locations of the signals were estimated in the right parahippocampal and parieto-occipital regions with a latency of 300 ms for the scene response, whereas those were estimated in the lingual or fusiform gyri bilaterally with a latency of 160 ms for the face response. These data suggest that both the temporal and parietal regions process scenes, while the occipito-temporal regions process faces, and that scene processing takes a longer time than face processing.

Adult↗
PubMed1999

Chimeric nature of pinopsin between rod and cone visual pigments.

Chicken pineal pinopsin is the first example of extra-retinal opsins, but little is known about its molecular properties as compared with retinal rod and cone opsins. For characterization of extra-retinal photon signaling, we have developed an overexpression system providing a sufficient amount of purified pinopsin. The recombinant pinopsin, together with similarly prepared chicken rhodopsin and green-sensitive cone pigment, was subjected to photochemical and biochemical analyses by using low-temperature spectroscopy and the transducin activation assay. At liquid nitrogen temperature (-196 degrees C), we detected two kinds of photoproducts, bathopinopsin and isopinopsin, having their absorption maxima (lambda(max)) at 527 and approximately 440 nm, respectively, and we observed complete photoreversibility among pinopsin, bathopinopsin, and isopinopsin. A close parallel of the photoreversibility to the rhodopsin system strongly suggests that light absorbed by pinopsin triggers the initial event of cis-trans isomerization of the 11-cis-retinylidene chromophore. Upon warming, bathopinopsin decayed through a series of photobleaching intermediates: lumipinopsin (lambda(max) 461 nm), metapinopsin I (460 nm), metapinopsin II (385 nm), and metapinopsin III (460 nm). Biochemical and kinetic analyses showed that metapinopsin II is a physiologically important photoproduct activating transducin. Detailed kinetic analyses revealed that the formation of metapinopsin II is as fast as that of a chicken cone pigment, green, but that the decay process of metapinopsin II is as slow as that of the rod pigment, rhodopsin. These results indicate that pinopsin is a new type of pigment with a chimeric nature between rod and cone visual pigments in terms of the thermal behaviors of the meta II intermediate. Such a long-lived active state of pinopsin may play a role in the pineal-specific phototransduction process.

Amino Acid Sequence↗
PubMed1999

Vitellogenin-6 is a major carbonylated protein in aged nematode, Caenorhabditis elegans.

Recently we found that protein carbonyl content increases with age in wild-type as well as long- and short-lived Caenorhabditis elegans nematodes in inverse correlation with life span (Adachi et al., J. Gerontol. 53A, B240-B244, 1998; Yasuda et al., J. Gerontol. 54A, B47-B51, 1999). In the present study, we investigated carbonyl modification of individual proteins in young and old wild-type nematodes by two-dimensional immunoblot using antibodies against 2, 4-dinitrophenylhydrazones. A protein with apparent molecular weight of 110 kDa was found to be a major carbonylated protein in aged animals. Amino acid sequence of peptide fragments of the protein was identical to that of vitellogenin-6, a yolk protein synthesized in and secreted from the intestine during egg-laying stage. Although the function(s) of the protein in aged nematodes is unclear, we suggest that the protein may have a role to protect other cellular components from oxidation because of its metal binding capacity.

Age Factors↗
PubMed1999

Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study.

Spinocerebellar ataxia type 2 (SCA2) is associated with an expansion of CAG/polyglutamine-repeat of a gene of unknown function. We performed an immunohistochemical study to identify the immunolocalization of the disease protein ataxin-2 in normal and SCA2 patients. Although normal and expanded ataxin-2 were ubiquitously localized to the cytoplasm of neurons, ubiquitinated intranuclear inclusions were observed selectively in 1-2% of neurons of affected brain regions except the cerebellum. Triple-labeling immunofluorescence revealed that ataxin-2, expanded polyglutamine and ubiquitin were colocalized to these neuronal intranuclear inclusions (NIs), indicating that SCA2 shares morphological characteristics common to other neurological disorders associated with an expansion of CAG/polyglutamine-repeat. Lack of NIs in the cerebellar lesion, however, suggests the discrepancy between formation of NIs and neuronal degeneration in SCA2.

Ataxins↗
PubMed1999

Molecular cloning and expression of the Na+/H+ exchanger gene in Oryza sativa.

Na+/H+ exchanger catalyzes the countertransport of Na+ and H+ across membranes. We isolated a rice cDNA clone the deduced amino acid sequence of which had homology with a putative Na+/H+ exchanger in Saccharomyces cerevisiae, NHX1. The sequence contains 2330 bp with an open reading frame of 1608 bp. The deduced amino acid sequence is similar to that of NHX1 and NHE isoforms in mammals, and shares high similarity with the sequences within predicted transmembrane segments and an amiloride-binding domain. The expression of the gene was increased by salt stress. These results suggest that the product of the novel gene, OsNHX1, functions as a Na+/H+ exchanger, and plays important roles in salt tolerance of rice.

Amino Acid Sequence↗
PubMed1999

Myosin light-chain kinase of smooth muscle stimulates myosin ATPase activity without phosphorylating myosin light chain.

Myosin light-chain kinase (MLCK) of smooth muscle is multifunctional, being composed of N-terminal actin-binding domain, central kinase domain, and C-terminal myosin-binding domain. The kinase domain is the best characterized; this domain activates the interaction of smooth-muscle myosin with actin by phosphorylating the myosin light chain. We have recently shown that the Met-1-Pro-41 sequence of MLCK binds to actin to inhibit this interaction. However, it is not known whether the myosin-binding domain modifies the actin-myosin interaction. We designed MLCK.cDNA to overexpress the Asp-777-Glu-972 sequence in Escherichia coli. The purified Asp-777-Glu-972 fragment, although devoid of the kinase activity, exerted a stimulatory effect on the ATPase activity of dephosphorylated myosin (Vmax = 7.36 +/- 0.44-fold, Km = 1.06 +/- 0. 20 microM, n = 4). When the N-terminal 39 residues of the fragment were deleted from the fragment, the resultant fragment, Met-816-Glu-972, lost the stimulatory activity. We synthesized the Ala-777-Ser-815 peptide that was deleted from the fragment and confirmed its stimulatory effect of the peptide (Vmax = 3.03 +/- 0. 22-fold, Km = 6.93 +/- 1.61 microM, n = 3). When this peptide was further divided into Asp-777-Met-795 and Ala-796-Ser-815 peptides, the stimulatory activity was found in the latter. We confirmed that the myosin phosphorylation did not occur during the experiments with the above fragments and peptides. Therefore, we suggest that phosphorylation is not obligatory for smooth-muscle myosin not to be active.

Animals↗
PubMed1999

A novel frameshift mutation in the McLeod syndrome gene in a Japanese family.

We report a novel mutation in the XK gene (XK) in a Japanese patient with McLeod syndrome. A 50-year-old man showed progressive muscular atrophy, choreic movement, elevated level of serum creatinine kinase, and acanthocytosis. The expression level of all the Kell antigens in erythrocyte was decreased and molecular analysis revealed a single-base (T) deletion at the nucleotide position 1095 in XK. This deletion caused a frameshift in translation, leading to a premature stop codon at the amino acid position 408. We conclude this single-base deletion causes defective Kx protein, which is responsible for the McLeod phenotype in this patient.

Amino Acid Transport Systems, Neutral↗
PubMed1999

Carbonylated proteins in aging and exercise: immunoblot approaches.

Protein carbonyls were studied in aging and exercise by immunoblot followed by one- or two-dimensional polyacrylamide gel electrophoresis using antibodies against 2,4-dinitrophenylhydrazones. Proteins of rat kidneys exhibited significant age-related increase in the amount of carbonyl while those of the brain and liver did not. Major carbonylated proteins in the kidney included serum albumin. In nematodes in which protein carbonyls increased with age, one of the carbonylated proteins was identified as vitellogenin, an egg-yolk protein. A possible biological significance of this protein present in abundance even after egg-laying stages is discussed in terms of protection against oxidative stress. Exhaustive exercise induced significant increase in the carbonylation of selected but unidentified proteins in the lung. This oxidative stress might be caused by xanthine oxidase in this tissue and hypoxanthine derived from ATP-depleted muscles. Exercise at high altitude caused higher carbonylation of the skeletal muscle proteins, most notably a protein likely to be actin, than that at sea level but no significant difference was observed in lipid peroxidation. These studies emphasize the value of immunoblot analysis of tissue protein carbonyls in a variety of situations where oxidative stress is likely involved.

Aging↗
PubMed1999

Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicals.

It is generally accepted that the oxidation of pentadiene structures of polyunsaturated lipids by lipoxygenase (LOX) is regio- and enantio-specific, while the free radical-mediated lipid peroxidation gives stereo-random racemic products. It was confirmed that the oxidation of human low density lipoprotein (LDL) by 15-LOX from rabbit reticulocytes gave phosphatidylcholine (PC) and cholesteryl ester (CE) hydroperoxides regio-, stereo- and enantio-specifically. 15-LOX also oxidized human plasma to give specific PC and CE hydroperoxides in spite of the presence of high concentrations of antioxidants. More CE hydroperoxides were formed than PC hydroperoxides from LDL, but the reverse order was observed for plasma oxidation. The S/R ratio of the hydroperoxides decreased during long time incubation but remained significantly larger than one, while free radical-mediated oxidation of LDL and plasma gave racemic products.

Animals↗
PubMed1999

Comparison of gene structures and enzymatic properties between two endoglucanases from Humicola grisea.

We have cloned two endoglucanase genes (egl3 and egl4) from a thermophilic fungus, Humicola grisea. The coding region of the egl3 gene was interrupted by an intron of 56-bp, and the deduced amino acid sequence of the egl3 gene was 305 amino acids in length and showed 98.4% identity with Humicola insolens EGV. The coding region of the egl4 gene was also interrupted by an intron of 173-bp, which contains 34 TTC repeated sequence units, and the deduced amino acid sequence of the egl4 gene was 227 amino acids in length and showed 61.5% identity with H. grisea EGL3. The typical hinge and the cellulose-binding domain were observed in the C-terminal region of EGL3, but they were not observed in EGL4. In the 5' upstream region of both genes, there were a TATA box or its similar sequence, CAAT motifs, and 6-bp sites which are identical or similar to the consensus sequence for binding a catabolite repressor CREA in Aspergillus nidulans. The egl3 and the egl4 genes were expressed in Aspergillus oryzae, and the translation products were purified. The fusion protein, EGL4CBD, which consists of a catalytic domain of EGL4 and the C-terminal region of EGL3, was also constructed and produced by A. oryzae, and purified. These enzymes showed relatively high activity toward carboxymethyl cellulose (CMC) and could not hydrolyze p-nitrophenyl-beta-D-glucoside and p-nitrophenyl-beta-D-cellobioside. The positive effect of substituting the C-terminal region of EGL4 with that of EGL3 was observed in the hydrolysis of CMC.

Amino Acid Sequence↗