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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 127 records · Page 7Linked to original sources
PubMed2001

[Clinical features of autosomal dominant spinocerebellar ataxias genetically unclassified into any known triplet-repeat diseases].

To clarify the clinical features of genetically unclassified autosomal dominant spinocerebellar ataxias (AD-SCAs) treated in our hospital, we retrospectively analyzed the clinical findings of patients who could not be molecularly classified into SCA types 1 through 3, 6 through 8, 12 and dentato-rubro-pallido-luysian atrophy (DRPLA). The clinical findings of 19 patients from 15 different families which form 14 percent of all patients with different types of AD-SCAs (136 patients, 105 families) were collected. Based on these, 17 patients from 13 families showed late-onset (mean age at onset: 46 years old) and slowly progressive truncal and limb ataxias of cerebellar origin. Some of them showed gaze-evoked nystagmus, increased deep reflexes without Babinski sign, tremor, mildly decreased vibration sense and mild rectourinary disturbances. All but one were still ambulatory after 15 years of their mean disease duration. An earlier disease onset in successive generations was observed in 8 families. Brain MRIs revealed cerebellar atrophy predominantly in the anterior vermis in all the patients and mild brainstem atrophy in only 3 patients. Although the clinical phenotype manifested by most of the genetically unclassified AD-SCAs is similar to that of SCA6, whether the phenotype is caused by expansion of triplet repeats or some mutations in a single gene or different mutations in various genes is still unclarified.

Adult↗
PubMed2001

Segmental bronchial atresia of the left upper lobe treated with segmental resection under video-assisted thoracic surgery.

We report our experience of segmental bronchial atresia managed with segmental resection under video-assisted thoracic surgery. A 23-year-old woman reporting a cough, dyspnea, and back pain underwent segmental resection in which a stapling device was used under video-assisted thoracic surgery. Her postoperative course was uneventful with minimal pain and a disappearance of preoperative symptoms after surgery. Once an accurate preoperative diagnosis can be established, video-assisted thoracic segmentectomy together with the use of a stapling device is considered to be feasible.

Adult↗
PubMed2001

[A case of renal cell carcinoma producing alpha-fetoprotein].

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition with only 11 cases reported in Japan to our knowledge. A 69-year-old man was admitted to our hospital for further examination of an incidental right renal tumor. Laboratory tests showed markedly increased serum level of AFP whereas both HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic resonance imaging imagings showed a right renal tumor but no tumor in liver, testis or lymph node. We performed right radical nephrectomy. Serum level of AFP declined within the normal range 7 weeks after nephrectomy according to its half-life curve. The tumor specimen was composed mainly of granular cells. Immunohistochemical examination of the tumor cells proved the presence of AFP in the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma in this case was presented.

Aged↗
PubMed2001

New genome type of adenovirus serotype 19 causing nosocomial infections of epidemic keratoconjunctivitis in Japan.

Twelve strains of adenovirus serotype 19, isolated from cases of epidemic keratoconjunctivitis in Japan in 1992, 1993, 1997, and 1998, were analyzed by DNA restriction analysis, using restriction endonucleases BamHI, BglI, BglII, EcoRI, HindIII, KpnI, PstI, SacI, SalI, SmaI, and XhoI. Among these 11 restriction endonucleases, EcoRI, PstI, SacI, and SmaI were discriminative enzymes, showing restriction patterns different from those reported previously for the prototype and the variant 19a. This new genome type was isolated in 1997 and 1998, when an increase of epidemic keratoconjunctivitis cases caused by adenovirus serotype 19 was observed for both sporadic and nosocomial infections. Strains from 1992 and 1993 showed restriction patterns similar to those of the worldwide reported variant 19a for all enzymes used. The changes detected in strains from 1997 and 1998 could be the reason for the recent epidemic.

Adenovirus Infections, Human↗
PubMed2001

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Adult↗
PubMed2001

[A case of untreated systemic lupus erythematosus presenting with listerial meningitis].

A fourty-year-old woman suffered from meningitis and sepsis of Listeria monocytogenes, after presenting with several early symptoms from systemic lupus erythematosus (SLE). Listeriosis often causes central nervous system infection with relatively high mortality rate. This infection commonly affects patients with predisposing factor, such as immunosuppression. According to the previous reports, all of the previous reports, all of listeriosis with SLE received immunosuppressive therapy. To the best of our knowledge, no case of listeriosis has ever been reported in SLE patients without medication to SLE, although most of the previously reported cases of listeriosis with collagen disease accompanied SLE. We presume that suppression of T cell-mediated immunity, which is characteristic of SLE, plays a role as a predisposing factor in listerial infection.

Adult↗
PubMed2001

Fatal buckwheat dependent exercised-induced anaphylaxis.

Cases of food-dependent exercise-induced anaphylaxis (FEA) caused by buckwheat have been rare. Clinical, laboratory, and autopsy findings are present on an 8-year old girl with FEA caused by Japanese buckwheat. The patient consumed buckwheat noodles called "zaru soba" and immediately thereafter swam vigorously. Approximately 30 minutes later, she complained of abdominal pain, vomiting, coughing, and chest discomfort. Another ten minutes later her consciousness level deteriorated and she experienced cardiorespiratory arrest. The heart beat was restored and she was admitted to the hospital. She never regained consciousness and expired after another arrest 13 days later. Her IgE level was high (2,840 IU/ml) and the IgE-radioallergosorbent test (RAST) score was 2 for soybeans, 3 for buckwheat, 2 for rice, and 3 for wheat. An exaggerated hematemesis that occurred immediately after hospital admission indicated an inflammatory condition of the digestive tract that was caused by buckwheat. Marked ulceration accompanied with hemorrhage and necrosis was noted at the ileum. Extensive hemorrhage involving the endotracheal pulmonary field and lymphocyte infiltration of the alveolar space likely appeared after the inflammation. The analysis of buckwheat-specific IgE antibody by immunoblotting showed 7 bands that reacted with the IgE of the patient's serum, 4 bands: 16, 20, 24, and 58 kDa, were specific to the patient as compared to subjects not allergic to buckwheat. A first case of fatal FEA by buckwheat is reported with reference to specific IgE.

Anaphylaxis↗
PubMed2000

CIRP2, a major cytoplasmic RNA-binding protein in Xenopus oocytes.

In an attempt to isolate mRNA-binding proteins we fractionated Xenopus oocyte lysate by oligo(dT)-cellulose chromatography. A 20 kDa protein was the major component of the eluate. cDNA cloning revealed that this protein is a Xenopus homolog of the cold-inducible RNA-binding protein (CIRP) which was originally identified in mammalian cells as a protein that is overexpressed upon a temperature downshift. This Xenopus protein, termed here xCIRP2, is highly expressed in ovary, testis and brain in adult Xenopus tissues. In oocytes it is predominantly localized in the cytoplasm. By biochemical fractionation we provide evidence that xCIRP2 is associated with ribosomes, suggesting that it participates in translational regulation in oocytes. Microinjection of labeled mRNA into oocytes followed by UV cross-linking of the oocyte lysate led to identification of two major RNA-binding activities. Immunoprecipitation of the RNA-binding proteins demonstrated that one is xCIRP2 and that the other contains FRGY2. FRGY2, which is one of the principal constituents of mRNA storage particles involved in translational masking of maternal mRNA, has an RNA-binding domain conserved to those of bacterial cold shock proteins. Possible implications of the highly abundant expression in oocytes of cold shock RNA-binding proteins of both eukaryotic and prokaryotic types are discussed.

Amino Acid Sequence↗
PubMed2000

Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor.

We report on the molecular, biochemical, and functional characterization of Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase inhibitor that is developmentally regulated and has anti-elastase properties. CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(-)(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated at 79%. CmPS-1 displayed no detectable inhibitory properties against chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with the piercing-sucking aphid, Myzus persicae, established a close correlation between the developmentally regulated increase in CmPS-1 within the phloem sap and the reduced ability of these insects to survive and reproduce on C. maxima. However, in vitro feeding experiments, using purified phloem CmPS-1, failed to demonstrate a direct effect on aphid survival. Likely roles of this novel phloem serpin in defense against insects/pathogens are discussed.

Amino Acid Sequence↗
PubMed2000

Daily melatonin injections entrain the circadian change of synaptic ribbon number in the pineal organ of the Japanese newt.

The effect of melatonin on the number of synaptic ribbons (SR) in the pineal photoreceptor cells was examined in the Japanese newt using electron microscopy. Under a light-dark cycle of LD 12:12 (lights on at 07:00), a subcutaneous injection of 10 microg of melatonin at two times during the day (at 11:00 and 11:30) did not increase the number of SR. However, daily injections of 10 microg of melatonin in constant darkness at 11:00 for 7 days did reset the phase of the circadian rhythm in SR number. The time of melatonin injection, corresponding to the onset of subjective night, preceded the daily increase of SR number. These data suggest that although melatonin does not directly increase the SR number, daily injections of melatonin can entrain the pineal circadian clock responsible for the circadian change in SR number.

Animals↗
PubMed2000

GroEL binds artificial proteins with random sequences.

Chaperonin GroEL from Escherichia coli binds to the non-native states of many unrelated proteins, and GroEL-recognizable structural features have been argued. As model substrate proteins of GroEL, we used seven artificial proteins (138 approximately 141 residues), each of which has a unique but randomly chosen amino acid sequence and no propensity to fold into a certain structure. Two of them were water-soluble, and the rest were soluble in 3 m urea. The soluble ones interacted with GroEL in a manner similar to that of a natural substrate; they stimulated the ATPase cycle of GroEL and GroEL/GroES and inhibited GroEL-assisted folding of other protein. All seven artificial proteins were able to bind to GroEL. The results suggest that the secondary structure as well as the specific sequence motif of the substrate proteins are not necessary to be recognized by GroEL.

Amino Acid Sequence↗
PubMed2000

Hydrophilic residues at the apical domain of GroEL contribute to GroES binding but attenuate polypeptide binding.

The GroES binding site at the apical domain of GroEL, mostly consisting of hydrophobic residues, overlaps largely with the substrate polypeptide binding site. Essential contribution of hydrophobic interaction to the binding of both GroES and polypeptide was exemplified by the mutant GroEL(L237Q) which lost the ability to bind either of them. The binding site, however, contains three hydrophilic residues, E238, T261, and N265. For GroES binding, N265 is essential since GroEL(N265A) is unable to bind GroES. E238 contributes to rapid GroES binding to GroEL because GroEL(E238A) is extremely sluggish in GroES binding. Polypeptide binding was not impaired by any mutations of E238A, T261A, and N265A. Rather, these mutants, especially GroEL(N265A), showed stronger polypeptide binding affinity than wild-type GroEL. Thus, these hydrophilic residues have a dual role; they help GroES binding on one hand but attenuate polypeptide binding on the other hand.

Adenosine Triphosphatases↗
PubMed2000

Structural analysis of the gene encoding RP58, a sequence-specific transrepressor associated with heterochromatin.

RP58, a sequence-specific transcriptional repressor sharing homology with the POZ domain of a number of zinc-finger proteins, is highly synthesized in brain and localized in condensed chromatin regions, suggesting a role in transcriptional repression in the central nervous system. In the present study, genomic clones of the human rp58 gene were isolated to determine the complete genomic organization. Sequence analyses indicated that the human rp58 gene encoding the functional protein is uninterrupted over its entire 4.2 kb length. Comparison of the human and mouse rp58 genes revealed that they share not only a high homology in the amino acid sequences of their encoded proteins, but also a high degree of structural similarity at the genomic level. RT-PCR analysis also demonstrated the existence of an alternatively spliced form of rp58 similar to the previously reported zinc-finger cDNA, C2H2-171. Chromosomal mapping by fluorescence in situ hybridization analysis allowed localization of the rp58 gene to human chromosome 1q44 ter, a genetic region associated with a number of human malignancies and neurological disorders.

Alternative Splicing↗
PubMed2000

A 38 kb segment containing the cdc2 gene from the left arm of fission yeast chromosome II: sequence analysis and characterization of the genomic DNA and cDNAs encoded on the segment.

A genomic 38 kbp segment on the c1750 cosmid clone containing the cdc2 gene, located in the left arm of chromosome II from Schizosaccharomyces pombe, was sequenced. The segment was found to have five previously known genes, pht1, cdc2, his3, act1 and mei4. Among 11 coding sequences (CDSs) predicted by the gene finding software INTRON.PLOT., four CDSs, pi007, pi010, pi014 and pi016, had considerable similarity to 40S ribosomal protein, glycosyltransferase, cdc2-related protein kinase and alpha-1, 2-mannosyltransferase, respectively. Another unusually huge open reading frame (ORF) (pi011), consisting of 2233 amino acids, existed, having significant homology to alpha-amylase, granule-bound glycogen synthase and the Sz. pombe YS 1110 clone product at the N-terminal, middle and C-terminal regions, respectively. All the predicted 11 CDSs were experimentally analysed by RACE PCR. The sequencing of the RACE products revealed that there were two small overlaps at the 3' untranslated regions (UTRs) between pi004 and pi005 (17 bp) and between pi007 and pi008 (2 bp). The distances between 5' end of the 5'UTR and the putative translation initiation codon varied from 10 to 302 nucleotides (nt) among the nine CDSs successfully analysed by 5'-RACE. The expression level of each CDS on this clone was determined. Among the 16 genes on this clone, the previously determined genes, pht1, cdc2, his3 and act1, were found to be most highly expressed. Finally, cDNAs of all the newly identified genes were detected by RACE, proving the actual expression of these genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AB004534.

Base Sequence↗
PubMed2000

Mechanism of damnacanthal-induced [Ca(2+)](i) elevation in human dermal fibroblasts.

Damnacanthal is a potent and selective inhibitor of p56(lck) tyrosine kinase in a variety of tissues. We have found, however, using the Ca(2+) microfluorimetry technique, that damnacanthal releases intracellular Ca(2+) stores and promotes Ca(2+) entry in human dermal fibroblasts. The effect of damnacanthal on the peak [Ca(2+)](i) values and the latent time to the peak was concentration-dependent. Damnacanthal releases Ca(2+) from thapsigargin-sensitive Ca(2+) stores, and the Ca(2+) stores responding to damnacanthal were overlapped with those of bradykinin. Damnacanthal-induced Ca(2+) entry was mediated by voltage-dependent and voltage-independent Ca(2+) channels. This effect of damnacanthal on intracellular Ca(2+) mobilization was also observed in cultured bovine coronary endothelial cells but not demonstrated in freshly isolated rat basilar smooth muscle cells. Our study suggests that damnacanthal increases intracellular Ca(2+) by releasing Ca(2+) from internal stores and promoting Ca(2+) entry. The relationship between the actions of damnacanthal on tyrosine kinase and intracellular Ca(2+) requires further investigation.

Animals↗
PubMed2000

Effect of electrostatic interactions on the binding of charged substrate to GroEL studied by highly sensitive fluorescence correlation spectroscopy.

The binding processes of GroEL with apo cytochrome c (apo-cyt c) and disulfide-reduced apo alpha-lactalbumin (rLA) in homogeneous solution at low concentration were analyzed by fluorescence correlation spectroscopy (FCS) with extremely high sensitivity. Although apo-cyt c, a positively charged substrate, was tightly bound to GroEL in both the absence and the presence of 200 mM KCl, the strength of the binding was changed with varying salt concentration. Results from experiments when two different salts (KCl or MgCl(2)) were titrated into a sample solution containing GroEL and apo-cyt c clearly showed that the binding strength decreased with increasing salt concentration. On the other hand, the binding affinity of GroEL for rLA, a negatively charged substrate, increased by adding of 200 mM KCl. These results indicate that electrostatic interactions substantially contribute to the binding interactions by manipulating the binding affinity of charged substrates.

Animals↗
PubMed2000

Restricted expression of an adenoviral vector encoding Fas ligand (CD95L) enhances safety for cancer gene therapy.

Gene transfer of Fas ligand (CD95L) using adenoviral vectors has been shown to generate apoptotic responses and potent inflammatory reactions that can be used to induce the regression of malignancies in vivo, but these vectors also cause significant hepatotoxicity that may limit their clinical utility. Here we describe an adenoviral vector encoding CD95L with restricted gene expression that reduces its toxicity in vivo. Preclinical efficacy and gene expression studies of lineage-restricted CD95L adenoviral vectors were performed. To enhance its cytotoxicity and reduce potential systemic effects, a noncleavable CD95L was made by deleting a segment containing the cleavage site (CD95L deltaQP). Higher CD95L expression of this mutant was observed on the tumor cell surface, together with a reduction in the release of soluble CD95L. This CD95L cleavage mutant was then expressed under control of a smooth muscle-specific promoter, SM22apha, and analyzed for its ability to suppress the growth of tumors of smooth muscle origin in vivo. Growth of human leiomyosarcomas but not gliomas was inhibited after ADV gene transfer into tumor-bearing immunodeficient mice. In contrast to viral promoters, in which mortality was uniformly seen after injection of 10(12) particles, no significant hepatic injury or systemic toxicity was observed in mice, and the maximum tolerated dose was increased > or = 10- to 100-fold. These findings suggest that restricted specificity of adenoviral CD95L gene expression enhances the safety of this approach for cancer gene therapy.

Adenoviridae↗