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Biomedical subjects

F Tanaka

Publications and source records attributed to F Tanaka.

At least 91 records · Page 5Linked to original sources
PubMed1999

Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue.

A 20-year-old Japanese female needed frequent hospitalization due to premenstrual exacerbation of hereditary coproporphyria (HCP). Intranasal buserelin acetate, a gonadotropin-releasing hormone analogue, was given to suppress her menstrual cycles. Her porphyric symptoms subsided dramatically as she became amenorrhoeic. Urinary excretion of porphyrin derivatives fell significantly. She has been free from recurrent attacks, but suffers a minor porphyric attack once in 5 years. However, borderline osteopenia secondary to hypoestrogenism has been noted. Although these analogues are potent in suppressing estrogen-induced porphyric symptoms, due precautions should be taken to avoid bone demineralization in the long-term use.

Adult↗
PubMed1999

Functional morphometry of the striatum in Parkinson's disease on three-dimensional surface display of 123I-beta-CIT SPECT data.

UNLABELLED: The purpose of this study was to evaluate whether striatal morphology on a three-dimensional surface display of 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (123I-beta-CIT) SPECT data can be used as a diagnostic index for Parkinson's disease. METHODS: We studied 11 patients with mild Parkinson's disease and 21 age-matched controls. Triple-head SPECT scans were acquired for 30 min at 20 h after injection of 123I-beta-CIT. We measured the vertical height of the caudate head (H) and the length of the long axis of the striatum (L) on the three-dimensional surface display generated from SPECT data. The morphometric index of the striatum was defined as L/H. The power of L/H to discriminate Parkinson's disease and control groups was evaluated by discriminant function analysis and was compared with that of region of interest (ROI)-based 123I-beta-CIT binding measurements (V"3) and their ratios. RESULTS: The mean L/H ratios (ipsilateral/contralateral) to the most affected limbs were (33%/45%) lower in the Parkinson's disease group compared with the control group, respectively. All other ROI-based measures confirmed that dopamine transporter reductions were most severe in the contralateral posterior putamen (a 68% reduction in V"3). In 1 patient with a subsequent clinical diagnosis of drug-induced parkinsonism, all SPECT measures were normal. The contralateral putamen contributed most to the discriminatory power, and the contralateral L/H showed the best discriminatory power of all SPECT measures. CONCLUSION: These results suggest that striatal morphology on a three-dimensional display of 123I-beta-CIT SPECT data provides information of diagnostic significance for Parkinson's disease. This morphometry can be done without requiring technically demanding ROI analysis, and thus this technique may be suitable for routine clinical use.

Carrier Proteins↗
PubMed1999

[Somatic mosaicism of expanded CAG trinucleotide repeat in the neural and nonneural tissues of Machado-Joseph disease (MJD)].

The tissue-specific pattern of somatic mosaicism in Machado-Joseph disease (MJD) was reviewed. In the MJD central nervous system (CNS) tissues, the pattern of CAG repeat mosaicism in the mutant allele was similar among various portions except cerebellar cortex which had slightly smaller CAG repeat tracts. Among nonneural tissues, the muscle exhibited a lesser degree of CAG instability, while the liver, kidney and colon displayed a greater diversity of extra bands and more extended major band compared to CNS. Thus, mitotic turnover may contribute largely to the tissue-specific pattern of mosaicism in MJD, but other unknown cell specific factors should be taken into consideration for the understanding the mechanism of somatic mosaicism in CAG repeat diseases.

Animals↗
PubMed1999

[Somatic mosaicism of CAG repeats size in the nervous system of dentatorubral-pallidoluysian atrophy (DRPLA)].

The somatic mosaicism of CAG repeat expansion in the neural tissues of a dentatorubral-pallidoluysian atrophy (DRPLA) was reviewed. The size of the major bands of the expanded allele was significantly smaller in the cerebellar cortex, however no significant difference was recognized in other regions of neuronal tissues. This showed that severity of neuropathological involvement in DRPLA is not parallel to the size of the expanded allele, indicating somatic mosaicism doesn't explain the selective neurodegeneration in DRPLA. The mechanism underlying the somatic mosaicism remains unknown. However, somatic CAG instability, cell division and some tissue specific factors may closely relate to the occurrence of the somatic mosaicism.

Anticipation, Genetic↗
PubMed1999

[Somatic mosaicism of expanded CAG trinucleotide repeat in spinal and bulbar muscular atrophy (SBMA)].

The CAG repeat in spinal and bulbar muscular atrophy (SBMA) is relatively stable in mitotic and meiotic processes as compared with other CAG repeat diseases. Previous reports indicate that SBMA does not manifest somatic mosaicism. However, detailed analysis in various tissues from 20 SBMA including 4 autopsied patients revealed the presence of the tissue-specific pattern of mosaicism. The prominent somatic mosaicism was observed in the cardiac and skeletal muscles, which are predominantly composed of postmitotic cells, and in the skin, prostate, and testis. The central nervous system (CNS) tissues, liver, and spleen showed smallest mosaicism. Such tissue-specific pattern of somatic mosaicism in SBMA is not explained by cell composition with different cell turnover rates. Other cell specific factors are likely more important for the somatic mosaicism in SBMA.

Humans↗
PubMed1999

Electrocochleographic evaluation of hearing loss in acoustic neuromas.

OBJECTIVE: This study aimed to clarify the pathophysiology involved in the cause of hearing impairment due to acoustic neuromas (AN) with electrocochleograph (ECoG). STUDY DESIGN: The study design was a retrospective case study. SETTING: This study was conducted in a tertiary referral center. PATIENT: Thirty-four patients diagnosed as having AN by magnetic resonance imaging between 1988 and 1995. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The authors made a comparison between the patients' ECoG findings and the size of their tumors as determined by magnetic resonance imaging and a pure-tone audiometry (PTA). The disparity between the threshold of PTA and the detective threshold of compound action potential (CAP) or that of the cochlear microphonics (CM) was calculated. When the threshold of the PTA was worse than the detective threshold of the CAP or the CM, the disparity was regarded as indicating a hearing loss of retrocochlear origin. RESULTS: There was no correlation found between tumor size and the detective threshold of CAP or CM. Disparity was found to correlate with tumor size. CONCLUSIONS: These findings seem to indicate that retrocochlear damage in AN increases parallel to the growth of the tumor and that retrocochlear damage can be detected by the ECoG before surgery.

Adult↗
PubMed1999

Identification of human cytochrome P-450 isoforms involved in metabolism of R(+)- and S(-)-gallopamil: utility of in vitro disappearance rate.

Isoforms of cytochrome P-450 (CYP) involved in the metabolism of gallopamil enantiomers were identified by measuring the disappearance rate of parent drug from an incubation mixture with human liver microsomes and recombinant human CYPs. Mean (+/- S.D.) intrinsic clearances (CL(int)) of R(+)- and S(-)-gallopamil in human liver microsomes were 0.320 +/- 0.165 and 0.205 +/- 0.107 ml/min/mg protein, respectively. These values were highly correlated with the 6beta-hydroxylation activity of testosterone, a marker substrate of CYP3A4 (r = 0.977 and 0.900 for R(+)- and S(-)-gallopamil, respectively, p <.001). Ketoconazole and troleandomycin, selective inhibitors of CYP3A4, and polyclonal antibodies raised against CYP3A4/5 markedly reduced the CL(int) of gallopamil enantiomers in human liver microsomes. Among the 10 recombinant human CYP isoforms, CYP3A4 exhibited the highest CL(int) of gallopamil enantiomers, and CYP2C8 and CYP2D6 also exhibited appreciable activity. When the contribution of CYP3A4 to the total metabolic clearance of gallopamil enantiomers in human liver microsomes was estimated by relative activity factor, the mean (+/- S.D.) contributions were 92 +/- 18 and 68 +/- 19% for R(+)- and S(-)-gallopamil, respectively. These values were comparable to the rates of immunoinhibition by antibodies raised against CYP3A4/5 observed in human liver microsomes. The present study suggests that CYP3A4 is a major isoform involved in the overall metabolic clearance of gallopamil enantiomers in the human liver, and that the present approach based on disappearance rate may be applicable to identify major isoforms of CYP involved in the metabolism of a drug in human liver microsomes.

Cytochrome P-450 Enzyme System↗
PubMed1998

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers.

Our recent linkage study of urethane-induced pulmonary adenomas in SMXA RI strains of mouse revealed two host resistance genes, Par1 (chromosome 11) and Par3 (chromosome 12). The map positions of Par1 and Par3 correspond to human 17q11-23 and 14q11-24, based on synteny between mouse and human. In this study, we examined the loss of heterozygosity (LOH) in these two homologous human chromosomal regions in 30 primary lung adenocarcinoma samples with matched normal DNA. Using 15 highly polymorphic markers, two commonly deleted regions were identified on human chromosomes 14 and 17, respectively. At 17q21, nine (53%) of 17 informative tumors showed LOH between D17S588 and D17S518. On the other hand, at 14q11-12, seven (32%) of 22 informative tumors showed LOH at loci between D14S261 and D14S80. Subsequently, we examined 25 squamous cell carcinomas (SQ) and 24 small cell carcinomas (SCC). At 14q11-12, six (38%) of 16 informative SQ and five (42%) of 12 informative SCC showed LOH. In contrast, at 17q11-23, one (7%) of 15 informative SQ and two (14%) of 14 SCC showed LOH. Therefore, the gene on 17q seemed to affect selectively adenocarcinomas, whereas the other gene on 14q, all three types of lung carcinomas. These observations indicate that a comparative genetic analysis provides a promising approach to survey genes involved in multifactorial process of human lung carcinogenesis.

Carcinoma, Small Cell↗
PubMed1998

A structural basis for transition-state stabilization in antibody-catalyzed hydrolysis: crystal structures of an abzyme at 1. 8 A resolution.

The three-dimensional structure of a catalytic antibody, 6D9, has been solved as a complex with a transition state analog. The structure was determined from two different crystal forms, and was refined at a resolution of 1.8 A. The antibody 6D9, which was induced by immunization with the phosphonate transition state analog 3, hydrolyzes a prodrug of chloramphenicol monoester 1 to generate the parent drug 2. The kinetic studies have shown that the antibody is catalytic by virtue of the theoretical relationship between the affinity for the transition state and the catalytic efficiency (kcat/kuncat=KS/KTSA). The crystal structure makes it possible to visualize the theoretical relationship. A side-chain (Nepsilon) of HisL27D is placed in a key position to make a hydrogen bond to the phosphonate oxygen of the transition state analog with a distance of 2.72 A, suggesting a hydrogen bond to the oxyanion developing in the transition state of the hydrolysis. There are no catalytic residues, other than the histidine, around the phosphonate moiety. In addition, in the antibody-hapten complex, the hapten bears a folded conformation and the two stacked aromatic rings are buried deep in the antigen-combining site through aromatic-aromatic interaction with TrpH100I and TyrH58. The conformation of the bound hapten suggests that the antibody binds the substrate to change the conformation of the ester moiety to a thermodynamically unstable E-form, thereby making it easy for the substrate to reach the transition-state during catalysis. These observations reveal that the catalytic mechanism is explained purely on the basis of the stabilization of the transition state. The refined high resolution structures reported here are envisaged to have an impact on the understanding of other hydrolytic antibodies, since their haptens share some unique features with the hapten used in this study.

Antibodies, Catalytic↗
PubMed1998

Differential temporal expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha and gp130) in injured peripheral nerves.

The mRNA expression of the neuropoietic cytokines, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptor components (CNTFRalpha, LIFRbeta, IL-6Ralpha and gp130) was examined in peripheral nerves after two different types of injury, crush and transection. The CNTF mRNA expression levels decreased after injury and remained low in the transected model, but recovered in 4 weeks in the crushed model. The LIF mRNA rapidly increased after damage and returned gradually to control levels. The IL-6 mRNA expression increased rapidly within 1 day after injury but dramatically decreased soon after. The CNTFRalpha mRNA levels gradually increased after nerve injury. LIFRbeta was expressed in the intact nerve and decreased slightly after injury. The IL-6Ralpha expression was observed faintly in the intact nerve and increased significantly soon after injury. There was also an increase in the expression of gp130. Although the temporal expression of these neuropoietic cytokines and receptors was extremely different, their pattern was similar between the crushed and transected models, except for CNTF. These results suggest that the expression of the ligands and receptors are differentially regulated after peripheral nerve injury, implying that each cytokine and signal transduction system has entirely distinctive functions in neuronal regeneration and repair.

Animals↗
PubMed1998

Characterization of soluble artificial proteins with random sequences.

The structural and catalytic properties of two soluble random proteins, RP3-42 and RP3-45, of 141 amino acid residues were investigated. Although no marked secondary structure was detected by CD spectrum, sedimentation equilibrium and small-angle X-ray scattering studies showed that they form an oligomeric structure and are as compact as the molten globule. The random proteins have low but distinct esterase activity; the values of the second-order rate constant for the hydrolysis of p-nitrophenol were 0.78 and 1.39 M(-1) s(-1) for RP3-42 and RP3-45, respectively. The differences in the properties of the random and the native proteins are discussed from the evolutionary point of view.

Amino Acid Sequence↗
PubMed1998

Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. To study AR protein expression in normal and SBMA individuals, we used several antibodies that recognize AR protein, and analyzed neural and nonneural tissues by immunohistochemistry and western blotting. Both the normal and the mutant AR proteins were widely distributed, predominantly, but not exclusively, in the cytoplasm of neurons regardless of the pathological involvement, and predominantly in the nuclei of the nonneural tissues in both normal and SBMA individuals, with different expression levels of AR protein among different tissues. In the motor neurons of SBMA patients, there were AR-immunoreactive ubiquitinated nuclear inclusions that were detected by antibodies that recognize a small portion of the N terminus of the AR protein. Absence of other immunoreactive AR epitopes within the inclusion may be due to altered AR configuration, or masking of AR epitopes by other proteins, or proteolytic cleavage of the AR. Our data show that, in addition to the normal cellular distribution of the AR protein, mutant AR-bearing nuclear inclusions are present in SBMA.

Aged↗
PubMed1998

Nonneural nuclear inclusions of androgen receptor protein in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. Nuclear inclusions of the mutant AR protein have been shown to occur in the spinal motor neurons of spinal and bulbar muscular atrophy (Li M, Kobayashi Y, Merry D, Tanaka F, Doyu M, Hashizume Y, Fischbeck KH, Sobue G: Nuclear inclusions in spinal and bulbar muscular atrophy. Ann Neurol 1998 (in press)). In this study, we demonstrate the tissue-specific distribution, immunochemical features, and fine structure of nuclear inclusions of spinal and bulbar muscular atrophy. Nuclear inclusions were observed in affected spinal and brainstem motor neurons, but not in other, nonaffected neural tissues. Similar nuclear inclusions occurred in nonneural tissues including scrotal skin, dermis, kidney, heart, and testis, but not in the spleen, liver, and muscle. These inclusions had similar epitope features detectable by antibodies that recognize a small portion of the N-terminus of the AR protein only, and they were ubiquitinated. Electron microscopic immunohistochemistry showed dense aggregates of AR-positive granular material without limiting membrane, both in the neural and nonneural inclusions. These findings indicate that nuclear inclusions of AR protein are present in selected nonneural tissues as well as in neurons that degenerate in spinal and bulbar muscular atrophy, suggesting that a common mechanism underlies in the formation of neural and nonneural nuclear inclusions.

Aged↗
PubMed1998

Lewis Y antigen expression and postoperative survival in non-small cell lung cancer.

BACKGROUND: In contrast to other Lewis blood group-related antigens, Lewis Y antigen (LeY) has not been fully investigated in non-small cell lung cancer. METHODS: To assess the significance of LeY expression, 236 patients with completely resected pathologic stage 1-3a were reviewed with immunohistochemical analysis. RESULTS: LeY expression was positive in 179 patients (75.8%). In poorly differentiated cancer, percentage of LeY-positive patients was lower than in moderately to well-differentiated cancer (67.2% versus 81.2%, p = 0.028). Five-year survival rate of LeY-positive patients was 78.2%, significantly higher than that of LeY-negative patients (59.7%, p = 0.001). Combined with p53 status, differences in survival proved to be marked; 5-year survival rate of patients with positive LeY expression and without aberrant p53 expression, was as high as 83.3%, whereas that of patients with negative LeY expression and with aberrant p53 expression was only 38.4% (p < 0.001). Multivariate analysis confirmed that LeY expression was a significant independent factor to predict better survival. CONCLUSIONS: LeY expression is a significant prognostic factor related to grade of cancer differentiation.

Adolescent↗
PubMed1998

Auditory and visual event-related potentials and flash visual evoked potentials in Alzheimer's disease: correlations with Mini-Mental State Examination and Raven's Coloured Progressive Matrices.

We investigated possible correlations among neurophysiological examinations [auditory and visual event-related potentials (A-ERPs, V-ERPs), and flash visual evoked potentials (F-VEPs)] and neuropsychological tests [Mini-Mental State Examination (MMSE) and Raven's Coloured Progressive Matrices (RCPM)] in 15 subjects with probable or possible Alzheimer's disease (AD) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The P300 latency of A-ERPs was correlated with the scores of MMSE but not with those of RCPM. The P300 latency of V-ERPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was not correlated with the P300 latency of A-ERPs but was correlated with the P300 latency of V-ERPs. The close relationship among V-ERPs, F-VEPs and RCPM suggests that these examinations at least partly reflect the functions of visual association areas in AD. Furthermore, discrepancy between P300 latency by A-ERPs and V-ERPs suggests that the mechanism responsible for P300 generation is not identical between these two stimulus modalities.

Aged↗
PubMed1998

Advantage of post-operative oral administration of UFT (tegafur and uracil) for completely resected p-stage I-IIIa non-small cell lung cancer (NSCLC).

OBJECTIVE: Although adjuvant therapy after surgery for non-small cell lung cancer (NSCLC) has been reported to be ineffective, it has been recently reported in prospective randomised studies conducted by two different groups in Japan that oral administration of a 5-fluorouracil (5-FU) derivative drug, UFT (a combination drug of tegafur and uracil) can improve the post-operative survival [The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). Eu J Surg Oncol 1995;21:69-77; Wada, H., Hitomi, S., Teramatsu, T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. J Clin Oncol 1996;14:1048-1054]. To examine the efficacy of UFT as post-operative adjuvant therapy, a retrospective study was performed. METHODS: A total of 655 consecutive patients who underwent complete tumor resection for pathologic stage I-IIIa, NSCLC at the Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University between 1976 and 1992 were retrospectively reviewed. As post-operative adjuvant therapy, UFT was administrated to 98 patients (UFT group), and was not administered to the other 557 patients (Control group). RESULTS: The 5-year survival rate of the UFT group was 76.5%, which was significantly better than that of the Control group (5-year survival rate: 58.6%, P = 0.005). Stratified with pathologic stage, the efficacy of UFT was seen in the p-stage I disease (5-year survival rate: 88.6% for the UFT group, 72.0% for the Control group, P = 0.013) and in the p-stage IIIa, pN2 disease (5-year survival rate: 54.3% for the UFT group, 37.5% for the Control group, P = 0.037). Multivariate analysis of the prognostic factors also revealed the efficacy of UFT (P = 0.004, 95% confidence interval of relative risk: 0.325-0.840). Post-operative intravenous chemotherapy or radiation therapy did not prove to be significant factors affecting the prognosis. CONCLUSIONS: Efficacy of oral administration of UFT as post-operative adjuvant therapy for completely resected NSCLC was proposed. To confirm the efficacy, a prospective randomized study for a more homogenous patient group is needed.

Administration, Oral↗
PubMed1998

Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA).

The CAG trinucleotide repeats in mRNAs for the responsible genes of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and X-linked spinal and bulbal muscular atrophy (SBMA) were examined in various neural and nonneural tissues of affected individuals. The tissue-specific variation of expanded CAG repeat alleles were apparent for mRNAs of all three genes. The expanded CAG repeats of the mRNA were shorter in the cerebellum than in other regions of the central nervous system in DRPLA and MJD, but not in SBMA, and were longer in the liver and colon in MJD. Transcripts of the responsible genes with expanded CAG repeats were detected in all tissues studied, and the tissue-specific variation in the CAG repeat size of the mRNA did not correlate with the tissue-specific severity of pathological involvement in these diseases.

Adult↗