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Biomedical subjects

C Fujii

Publications and source records attributed to C Fujii.

At least 19 recordsLinked to original sources
PubMed2001

An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2.

Individual vulnerability to reactive intermediates and oxidative stress accompanying metabolism of endogenous toxic compounds in the brain may promote the development of PD. Phase II detoxification enzymes such as glutathione S-transferase M1 (GSTM1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH):quinone oxidoreductase 2 (NQO2) are important as cellular defenses against catecholamine-derived quinones and the oxidative stress that arises as a consequence of their metabolism. We conducted a study of the potential association between idiopathic Parkinson's disease and polymorphisms of GSTM1, NQO1, and NQO2. DNA samples from 111 unrelated outpatients with idiopathic PD and 100 unrelated healthy volunteers were analyzed. GSTM1 deletion polymorphism exhibited no positive association with PD (P = 0.596, odds ratio: 1.135), although GSTM1 were grouped into three genotypes (deletion/deletion, deletion/nondeletion, and nondeletion/nondeletion). In addition, polymorphism of the NQO1 gene caused by a C to T substitution in exon 3 presented no association with PD (P = 0.194, odds ratio: 1.31). However, polymorphism in the form of an insertion/deletion (I/D) of 29 base pairs (bp) nucleotides in the promoter region of the NQO2 gene, which contains four repeats of the putative core sequence (GGGCGGG) of the Sp1-binding cis-element, did associate with PD. The frequency of the D allele was significantly higher in patients with PD than in controls (P < 0.0001, odds ratio: 3.463). Our data suggested that the deletion of 29-bp nucleotides in the promoter region of the NQO2 gene associates with the development of PD.

Aged↗
PubMed2001

Preoperative diagnosis of obturator hernia by computed tomography in six patients.

Obturator hernia is a rare condition, and the prognosis of patients with this condition is poor. A retrospective study was performed on six patients with obturator hernia between 1993 and 1998. They had been diagnosed preoperatively by computed tomography (CT). The initial CT scan of the abdomen, including the pelvic area, revealed an incarcerated bowel in the obturator foramen of all six patients. All patients underwent laparotomy on the day of admission. Resection of the small bowel was performed in three patients, and release of the small bowel was performed in the remaining three patients. There were no perioperative deaths. In elderly women who have evidence by abdominal plain X-ray studies of small bowel obstruction, we recommend performing CT scan of the abdomen, including CT scan of the pelvic area, for detection of obturator hernia.

Adolescent↗
PubMed2001

Difference in the way of macrophage recognition of target cells depending on their apoptotic states.

Dying cells are selectively eliminated from the organism by phagocytosis. Previous studies suggested the existence of some other phagocytosis marker(s) that function together with phosphatidylserine, the best-characterized phagocytosis marker. We obtained here a monoclonal antibody named PH2 that inhibited macrophage phagocytosis of late apoptotic or necrotic cells, but not of early apoptotic cells. On the other hand, phagocytosis of cells at any time during the process of apoptosis was inhibitable by phosphatidylserine-containing liposomes. Inhibition occurred even when target cells were preincubated with PH2 and separated from unbound antibodies. Moreover, PH2 bound to apoptotic cells at late stages more efficiently than to those at early stages, and it did not bind to normal cells unless their plasma membrane was permeabilized. These results suggest that the putative PH2 antigen is a novel phagocytosis marker that translocates to the cell surface at late stages of apoptosis, resulting in maximal recognition and engulfment by macrophages.

Antibodies, Monoclonal↗
PubMed2000

Cross-cultural traits for personality of patients with Parkinson's disease in Japan.

Recent studies suggest that Parkinson's disease (PD) is associated with particular personality traits. Using Cloningers's Tridimensional Personality Questionnaire (TPQ), Menza and colleagues [1993: Neurology 43:505-508] reported a possible association between PD and a reduced score in the novelty seeking (NS) dimension of the TPQ. We sought to determine whether this association, which was found in a study conducted in the United States, could also be found among Japanese PD patients. We performed personality assessments of 67 Japanese PD patients, using the TPQ test. The results suggest that Japanese PD patients have significantly lower scores in the NS dimension of the TPQ, as well as significantly higher harm avoidance (HA) scores, compared with matched control subjects. Furthermore, the PD patients undergoing treatment for depression using antidepressant drugs scored significantly higher in the HA dimension than PD patients who did not receive antidepressant drug treatment. Our results suggest that the high HA score, and the low NS score in the TPQ test observed in patients with PD, is a cross-cultural phenomenon, although the influence of depression, long-term treatment, and premorbid gene/environmental interactions may also affect these personality traits. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:1-3, 2000.

Aged↗
PubMed2000

Intravenous detergent poisoning.

CASE REPORT: In the literature regarding surfactant poisoning, the route of exposure has almost always been oral. We report a case in which about 40 mL of bath detergent for home use was self-injected. The primary pathophysiologic effects were relative hypovolemia and cardiac dysfunction. The patient experienced frequent ventricular tachycardia, acute renal failure, rhabdomyolysis, hemolysis, and coagulation dysfunction. Intensive care included the administration of antiarrythmial agents and hemodialysis. The patient survived and was discharged from our hospital without sequelae.

Acute Kidney Injury↗
PubMed2000

[Antidotes for poisoning and medication overdosage].

Supportive therapy is crucial in the treatment of severe intoxication. Furthermore, specific antidotes are available to neutralize or prevent the toxic effects of poisoning and overdosage. Recently it has become possible to determine the probable toxicity precisely by plotting plasma poison or drug levels. This is especially appropriate in severely intoxicated patients. We conclude that the screening of blood using special agents is the most important in the treatment of such patients at present.

Antidotes↗
PubMed1999

Association between polymorphism of the cholecystokinin gene and idiopathic Parkinson's disease.

Parkinson's disease (PD) is characterized by major alterations of neurotransmitter activity due to damage of the substantia nigra. Changes in neuropeptide concentration within the basal ganglia may play an important role in the putative dopaminergic-peptidergic interactions associated with the disease. Cholecystokinin (CCK) modulates the release of dopamine in the mesolimbic pathway and affects dopamine-related behavior. We analyzed genetic variations in the CCK gene, in both the coding and promoter region, in order to investigate the role of polymorphism in idiopathic PD. Four polymorphic sites of the CCK gene (-196G/A, -45C/T, 1270C/G, 6662C/T) were found in PD patients and controls. Complete linkage disequilibrium was observed between the -45 locus and the 1270 locus, and also a possible linkage disequilibrium was found between the -45 and -196 loci. A significant difference was found in the distributions of three identified genotypes at the -45 locus between 116 PD patients and 95 age-matched control subjects (chi2 = 7.95, p = 0.018, Bonferroni correction; p = 0.054). In addition, a significant difference was obtained amongst the three genotypic groups at the -45 locus when compared between PD patients who experienced hallucinations (n = 23) and those (n = 93) who did not (chi2 = 8.08, p = 0.018, Bonferroni correction, p = 0.126). Our data suggested that mutations at the -45 locus in the promoter region of the CCK gene may influence vulnerability to hallucinations in PD patients treated with L-dopa.

Age of Onset↗
PubMed1999

Essential tyrosine residues in 3-ketosteroid-delta(1)-dehydrogenase from Rhodococcus rhodochrous.

Tetranitromethane treatment of 3-ketosteroid-Delta(1)-dehydrogenase of Rhodococcus rhodochrous caused loss of the catalytic activity in a time- and concentration-dependent manner. Peptides (P-81) and (PN-83) were isolated from tryptic digests of the native and tetranitromethane-treated enzyme proteins, respectively. PN-83 was the nitrated form of P-81. The amino acid sequence was GGAPLIDYLESDDDLEFMVYPWPDYFGK (positions 97-124 of the dehydrogenase sequence). PN-83 showed a low yield of PTH-Tyr of position 116, i.e. less than 5% of that of P-81, and instead a high yield of PTH-3-nitrotyrosine. This indicated that tetranitromethane modifies Y-116 under the experimental conditions used. Mutation of Y-104, Y-116, and Y-121 to smaller amino acid residues, Phe, Ser, or Ala, significantly changed the catalytic activity of the dehydrogenase. All of the mutants contained FAD and exhibited the same spectrophotometric properties as those of the wild type enzyme. The K(m) values for 4-androstene-3,17-dione of the Y-104, Y-116, and Y-121 mutants changed to large values. The most drastic change was observed for Y116A. The K(d) values for 1,4-androstadiene-3,17-dione of the Y116 mutants changed to 1.5-2.6-fold larger values than that of the recombinant enzyme. The Y-121 mutant enzymes exhibited catalytic activities like those of the recombinant enzyme, but the catalytic efficiencies of Y121F and Y121A drastically decreased to 0. 014-0.054% of that of the recombinant enzyme. The present results indicate that Y-121 plays an important role in the catalytic function, and that Y-116 and Y-104 act on binding of the substrate steroid.

Amino Acid Sequence↗
PubMed1999

[Sepsis due to Salmonella Oranienburg--a case report].

A previously healthy 15-year-old female was admitted to our hospital complaining of nausea and vomiting. She did not complain of diarrhea. A physical examination revealed a lower right quadrant abdominal tenderness without rebound or spontaneous pain and a knocking pain of the costovertebral angle. A high fever, knocking pain of costovertebral angle, and urinary findings including Gram's stain, lead us to suspect a urinary tract infection, cefotiam was administered intravenously. Spiking fever with shaking chills continued for three days, and three sets of blood cultures were positive for Salmonella Oranienburg, but her urine culture was negative. Her history was taken again, revealing an intake of a processed squid product. The product was confirmed by the local public health center to be Salmonella Oranienburg. Finally food poisoning by Salmonella Oranienburg with sepsis was diagnosed. With cefotiam she became better and was discharged from the hospital on the 10th hospital day. During admission to the hospital she did not experience any diarrhea, and her stool culture was negative. Epidemics of Salmonella Oranienburg food poisoning are relatively rare in the literature. In Japan, one has arisen as a result of contamination of a processed squid product in March 1999. However, there have been no cases without so-called gastroenteritic symptoms (abdominal pain and diarrhea) who were previously healthy and developed sepsis caused by Salmonella Oranienburg, reported in Japan. Even in previously healthy patients, with an epidemic situation of non-typhoidal salmonellosis, salmonella sepsis must be ruled out. Among such cases, those who present with spiking fever and shaking chills should be given antibiotic therapy after taking appropriate cultures.

Adolescent↗
PubMed1999

[Relationship between ALDH2 genotypes and choice of alcoholic beverages].

There are obviously individual differences in the choice for many kinds of alcoholic beverages such as beer, wine, whisky, sake, cocktail and so on. It is generally believed that these differences are related to acquired preferences in taste and smell, in addition to life style. However, the basis of these acquired preferences is not yet understood. It has been shown that around half of Japanese show a marked sensitivity to alcoholic beverages because of aversive reactions due to a catalytic deficiency in ALDH2 isozyme. Therefore, differences in ALDH2 genotypes may possibly influence the choice of alcoholic beverages because the individuals possessing the ALDH2*2 gene may prefer the alcoholic beverages containing lower concentrations of alcohol. A large population survey (320 males, 132 females) was conducted using questionnaires to investigate the relationship between ALDH2 genotypes and the choice of alcoholic beverages. Individuals with the homozygote of ALDH2*1 generally showed more preference for alcoholic beverages containing a higher concentration of alcohol than those with the heterozygote or the homozygote of ALDH2*2. It was noted that the latter groups preferred whisky and water, and sweet cocktails. Also, the choices for beer, whisky, and sake were significantly different between both genders. Our data suggested that individuals with ALDH2*2 prefer beverages with lower concentrations of alcohol due to an aversive reaction after drinking, and that there are obvious gender differences in the consumption as well as the choice for many alcoholic beverages.

Adult↗
PubMed1999

A novel polymorphism (-357 G/A) of the ALDH2 gene: linkage disequilibrium and an association with alcoholism.

BACKGROUND: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. METHODS: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. RESULTS: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2*2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2*1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A chi2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (chi2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. CONCLUSION: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.

Adult↗
PubMed1999

[Preliminary evaluation of the effect of an attenuation correction method in myocardial perfusion SPECT].

We propose a method to assess an attenuation correction method in myocardial perfusion SPECT. Three types of images are obtained: one resulting from a classic acquisition and filtered back-projection (classic), and those resulting from acquisition with a transmission source and an iterative reconstruction, with (music) or without (hybrid) the attenuation correction factored in to compare the three types of images and classify them as normal or abnormal, a three dimensional inter-patient quantitative comparison method was used. Differences were computed as fractions of the myocardial volume in which density differences are significant by population standards. In 7 cases the cumulative difference between prone and supine in hybrid images was 124 and 45 in music images. In 10 cases the cumulative difference between classic vs music images was 279, and between classic and hybrid 86. The AC changed 4/12 cases from abnormal to normal. The attenuation correction effect was concentrated on the septal and inferior walls, but neither exclusively nor evenly among patients. The attenuation correction effectively minimizes attenuation effects by a factor of 2.7, due to a correction of at least 69%. The correction has a small but substantial effect on the results.

Female↗
PubMed1998

Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum.

Chromosome 2 of Plasmodium falciparum was sequenced; this sequence contains 947,103 base pairs and encodes 210 predicted genes. In comparison with the Saccharomyces cerevisiae genome, chromosome 2 has a lower gene density, introns are more frequent, and proteins are markedly enriched in nonglobular domains. A family of surface proteins, rifins, that may play a role in antigenic variation was identified. The complete sequencing of chromosome 2 has shown that sequencing of the A+T-rich P. falciparum genome is technically feasible.

Amino Acid Sequence↗
PubMed1998

Complete genome sequence of Treponema pallidum, the syphilis spirochete.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Bacterial Proteins↗
PubMed1998

A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells.

Wild-type and several mutant human manganese superoxide dismutases (Mn-SODs) were produced in a baculovirus/insect cell system and characterized. The enzymatic activity of a homogenate of Sf21 cells, infected with baculovirus carrying wild-type Mn-SOD and grown in the conventional medium, was indistinguishable from that of control cells, but was augmented by supplementation with Mn2+. The protein produced was largely imported into the mitochondria, as judged from the enrichment in the mitochondrial fraction, the mobility of the protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the results of N-terminal processing, which was confirmed by sequencing of the purified enzyme. However, a significant amount of precursor was also detected by an antibody raised against the human Mn-SOD signal peptide. While both Mn2+ and Fe3+ stimulated Mn-SOD accumulation within mitochondria, the active form was produced in the presence of submillimolar Mn2+ only. Amino acid substitutions at a signal peptide-cleavage site, His-Ser-Leu4 to Pro-Met-Va14, in the mature Mn-SOD prevented the processing of the precursor protein, and thus resulted in the accumulation of the precursor protein within mitochondria, as judged on immunostaining with an anti-Mn-SOD antibody. Mutant Mn-SODs with a truncated signal peptide or carboxyl region (8, 13, and 42 amino acid residues in the mature form) were barely solubilized, even with a nonionic detergent, and exhibited no activity, suggesting inappropriate folding of these mutant SODs. They were also susceptible to proteolytic degradation, while the wild-type and precursor forms were resistant. Thus, the baculovirus/insect cell expression system appears to be adequate for the analysis of mitochondrial import using intact cells as well as for the large scale production of active Mn-SOD.

Amino Acid Sequence↗
PubMed1998

3-Ketosteroid-delta1-dehydrogenase of Rhodococcus rhodochrous: sequencing of the genomic DNA and hyperexpression, purification, and characterization of the recombinant enzyme.

The gene encoding 3-ketosteroid-Delta1-dehydrogenase from Rhodococcus rhodochrous was cloned and sequenced. The gene (ksdD) consists of 1,536 nucleotides and encodes an enzyme protein of 511 amino acid residues. The amino terminal methionine residue was deleted in the mature protein. The amino acids involved in the flavin binding site are conserved in the dehydrogenase sequence. The deduced amino acid sequence is highly homologous to that from Arthrobacter simplex but less so to that from Pseudomonas testosteroni. Upstream of the gene was located a heat shock protein gene, dnaJ, and downstream, a gene of a hypothetical protein. The enzyme gene was ligated with an expression vector to construct a plasmid pDEX-3 and introduced into Escherichia coli cells. The transformed cells hyperexpressed the 3-ketosteroid-Delta1-dehydrogenase as an active and soluble protein at more than 30 times the level of R. rhodochrous cells. Purification of the recombinant 3-ketosteroid-Delta1-dehydrogenase from the E. coli cells by a simplified procedure yielded about 13 mg of enzyme protein/liter of the bacterial culture. The purified recombinant dehydrogenase exhibited identical molecular and catalytic properties to the R. rhodochrous enzyme.

Amino Acid Sequence↗
PubMed1998

Severe respiratory distress following sodium oleate ingestion.

CASE REPORT: Oleic acid and oleate are pulmonary toxins used to create laboratory models of acute respiratory distress syndrome, but there is little information on human toxicity. We report the intentional ingestion of 50 mL sodium oleate 20% by a 22-year-old woman with no symptoms for the first 2 days after ingestion. Her respiratory status deteriorated rapidly on day 3 progressing to acute respiratory distress syndrome (PaO2/FIO2 < 100 mm Hg) on day 4. Treatment with high-dose steroids and intensive respiratory support including high-frequency jet ventilation were associated with gradual but complete recovery by day 39. The delayed onset of symptoms suggested that the lung injury was due to the systemic circulation of oleate to the lungs rather than to direct aspiration. In oral poisoning by sodium oleate, the lung is the first and most lethally affected target organ in humans. This case demonstrates that ingestion of a relatively small amount of sodium oleate can cause delayed, progressively severe, lung injury.

Adult↗