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Biomedical subjects

A Nakamura

Publications and source records attributed to A Nakamura.

At least 235 records · Page 13Linked to original sources

Clinical characteristics of aged Becker muscular dystrophy patients with onset after 30 years.

To elucidate the clinical characteristics of aged patients with Becker muscular dystrophy (BMD), 4 patients with this disease who were over 50 years were examined. The ages at onset in all patients were later than 30 years. All were proven to have a deletion around exons 45-55 of the Duchenne muscular dystrophy (DMD) gene. Two patients became wheelchair bound in their 40s or beyond, while the other 2 (aged 73 and 69, respectively) were still able to walk at the time of examination. Three of 4 patients had no obvious hypertrophy in their calves, which is known to be one of the characteristic clinical features in the juvenile BMD patients. Serum creatine kinase levels were elevated in all patients, but not markedly (mean 444.8 +/- 230.3 U/l; normal value < 180 U/l). Dilated cardiomyopathy was clinically apparent in 2 patients. We emphasize that some BMD patients are free of muscular symptoms until their 50s and are still self-supporting in their 60s or 70s.

Age of Onset↗

Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus.

PURPOSE: To investigate the efficacy and feasibility of concurrent chemoradiotherapy for locally advanced carcinoma of the esophagus. PATIENTS AND METHODS: Fifty-four patients with clinically T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusion of fluorouracil 400 mg/m(2)/24 hours on days 1 to 5 and 8 to 12, 2-hour infusion of cisplatin 40 mg/m(2) on days 1 and 8, and concurrent radiation therapy 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/m(2)/24 hours for 5 days) and cisplatin (80 mg/m(2) on day 1). RESULTS: There were 21 patients with T4M0 disease, one with T2M1 LYM, 17 with T3M1 LYM, and 15 withT4M1 LYM. Forty-nine patients (91%) completed at least 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 leukocytopenia 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%. CONCLUSION: Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus.

Adult↗

Recent advances in neuropharmacology of cutaneous nociceptors.

Cutaneous nociceptors are peripheral receptive endings of primary sensory neurons activated by noxious stimuli. Nociceptors detect and signal the presence of tissue-damaging stimuli or the existence of tissue damage. In this short review, we will focus on the molecular mechanism of maintenance, activation, inhibition and sensitization in cutaneous nociceptors. Neurotrophic factors are essential to the development of nociceptors during embryogenesis. Recent evidences have indicated that nociceptors in the adult are maintained by either nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF). A selective activator of nociceptors is capsaicin, natural product of capsicum peppers. Recently, the receptor for capsaicin (the vanilloid receptor 1: VR1) has been cloned, identified and characterized. VR1 seems to play an important role in the activation and sensitization of nociceptors. In contrast, peripheral endogenous cannabinoids such as anandamide are novel candidates for mediators that inhibit the excitation of nociceptors. Intracellular messengers and the mechanisms of signal transduction in nociceptors have also been studied. Our recent findings provide evidences demonstrate that an activation of both cAMP- and cGMP-second messenger systems is required to induce the sensitization of nociceptors. Such emerging evidences reviewed here would make a significant contribution to further understanding of the molecular mechanism of nociceptors.

Animals↗

Nystatin effects on vacuolar function in Saccharomyces cerevisiae.

The effects of nystatin, a polyene antibiotic, was studied in Saccharomyces cerevisiae by isolating and characterizing nystatin-sensitive mutants. We isolated a number of nystatin-sensitive mutants by ethylmethane sulfonate mutagenesis. One of these mutants, the nss1 mutant, was characterized in detail. The mutant was sensitive to stresses such as high temperature or high concentrations of monovalent and divalent cations. The nss1 mutants showed severe vacuolar protein sorting and vacuolar morphology defects. The nss1 mutant was demonstrated to have a mutational lesion in the known VPS16 gene, which is essential for vacuolar protein sorting in S. cerevisiae. All of the vacuolar deficient mutants (vps11, vps16, vps18, and vps33) were sensitive to nystatin. Nystatin was found to cause extensive enlargement of the vacuole in wild-type S. cerevisiae cells. These results are discussed with special reference to the vacuolar function of S. cerevisiae.

Alleles↗

Isolation and characterization of the actin gene from the cellulolytic fungus Humicola grisea and analysis of transcription levels of actin and cellulase genes.

An actin gene was isolated from the cellulolytic fungus Humicola grisea. The gene structure, which has 5 introns in the coding region, is similar to those of the so far cloned fungal actin genes. But there are some differences in intron sizes and codon usage. Transcription levels of actin and cellulase genes were also investigated.

5' Untranslated Regions↗

Biochemical characterization of a putative cytokinin-responsive His-kinase, CKI1, from Arabidopsis thaliana.

His-Asp phosphorelays are evolutionary-conserved powerful biological tactics for intracellular signal transduction. Such a phosphorelay is generally made up of "sensor histidine (His)-kinases", "response regulators", and "histidine-containing (HPt) phosphotransmitters". Results from recent intensive studies suggested that in the higher plant Arabidopsis thaliana, His-Asp phosphorelays may be widely used for propagating environmental stimuli, such as phytohormones (e.g., ethylene and cytokinin). In this study, we characterized, in vitro, the putative cytokinin-responsive CKI1 His-kinase, in terms of His-Asp phosphorelays. It was demonstrated for the first time that the receiver domain in this sensor exhibits a strong phosphohistidine phosphatase activity toward some Arabidopsis HPt phosphotransmitters (AHP1 and AHP2), suggesting the functional importance of the receiver domain for a resumed interaction of the sensor His-kinase with other His-Asp phosphorelay components.

Arabidopsis↗

Transcriptional regulation of the Bacillus ohbensis cyclodextrin glucanotransferase gene in B. subtilis.

The expression of the cyclodextrin glucanotransferase (CGTase) gene (cgt) of Bacillus ohbensis, when introduced into an alpha-amylase-defective strain of B. subtilis on a multicopy plasmid, pHY300PLK, was induced in the presence of starch and was subject to catabolite repression by glucose as well as in the original strain, B. ohbensis. We constructed a cgt'::'lacZ translational fusion to study the expression in B. subtilis, and this construct was confirmed to be subject to both starch induction and catabolite repression. In order to define the region involved in the regulation of the cgt gene, a series of cgt'::'lacZ gene with various lengths of deletion in the promoter region was constructed on pHY300PLK. DNA regions responsible for starch induction and catabolite repression by glucose could be separated in the deletion experiment. Primer extension analysis showed that the catabolite repression was controlled at the initiation of transcription, while the starch induction is likely to be controlled by a transcriptional termination-antitermination mechanism.

5' Untranslated Regions↗

Calcitonin induces 25-hydroxyvitamin D3 1alpha-hydroxylase mRNA expression via protein kinase C pathway in LLC-PK1 cells.

The biosynthesis of 1alpha, 25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) in renal proximal tubules. It was recently demonstrated that LLC-PK1 cells express CYP27B1 mRNA, which is regulated by intracellular cAMP but not vitamin D3. To clarify the effect of calcitonin on vitamin D3 metabolism in vitro, LLC-PK1 cells were incubated with hormonal factors, and expression of CYP27B1 mRNA was measured by quantitative reverse transcription-PCR. Calcitonin at 100 nmol/L significantly increased CYP27B1 mRNA expression by 24 h (271 +/- 21% of control). Incubation with calcitonin over a range of 1 micromol/L to 1 pmol/L resulted in a concentration-dependent increase in CYP27B1 mRNA levels. It is known that the calcitonin receptor has dual intracellular signaling pathways, via protein kinases A and C. Both 500 micromol/L 8-bromo-cAMP, a protein kinase A activator, and 100 nmol/L phorbol 12-myristate 13-acetate, a protein kinase C activator, increased CYP27B1 mRNA levels at 24 h (207 +/- 54 and 246 +/- 58% of control, respectively). However, calcitonin-induced CYP27B1 mRNA expression was only inhibited by the protein kinase C inhibitors staurosporine and calphostin C. The protein kinase A inhibitors Rp-cAMPS at 10 and 100 micromol/L and H-89 at 10 micromol/L had no effect on the action of calcitonin, in spite of cAMP-activation by calcitonin. The present data suggest that calcitonin upregulates CYP27B1 mRNA expression via the protein kinase C pathway in LLC-PK1 cells.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Cloning of porcine 25-hydroxyvitamin D3 1alpha-hydroxylase and its regulation by cAMP in LLC-PK1 cells.

The 25-hydroxyvitamin D3 1alpha-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B cDNA was cloned, and the effects of cAMP and vitamin D3 on the regulation of CYP27B1 mRNA expression in LLC-PK1 cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK1 cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 micromol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 micromol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1alpha,25(OH)2D3 had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D3 24-hydroxylase (CYP24) mRNA was markedly increased by 1alpha,25(OH)2D3. These findings suggest that LLC-PK1 cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

[Clinical study of parotid tumors: a 20 year statistical analysis of 633 cases].

During the 20 years from 1977 to 1996, 633 cases underwent excisions of parotid tumors (539 benign and 94 malignant) in the department of Otolaryngology of Kansai Medical University. The incidence of Warthin's tumors in the years from (1987 to 1996) was higher than that in the years from 1977 to 1986. On the other hand, the incidence of mucoepidermoid carcinomas was less than in previous reports. Tumors accompanied with spontaneous pain or facial nerve palsy and with invasion to both lobes frequently indicated malignancy. Facial nerve palsy caused by either benign or malignant tumors before operation showed no improvement after surgery. The incidences of facial nerve palsy (1.0% in benign, and 18.3% in malignant) and Frey's syndrome (17.8% in benign, and 18.3% in malignant) after surgery were lower than those in other reports of both benign and malignant tumors. Five-year mortality was 76.1%. All deaths that occurred five years after operation involved highly grade malignant tumors.

Adenolymphoma↗

[The role of mitochondria in apoptosis in U937 and Molt-4 cells: difference in order of mitochondrial membrane potential (delta psi m) reduction and interleukin-1 beta-converting enzyme (ICE) on signal transduction pathway in each cell type].

Time-course-analysis of two apoptotic events of DNA fragmentation and delta psi m reduction revealed that delta psi m reduction preceded DNA fragmentation in U937 and Molt-4 cells treated with etoposide (ETP). DNA fragmentation and delta psi m reduction were inhibited by N-acetylcysteine (NAC) in both cell lines treated with ETP. These findings suggest that DNA fragmentation was inhibited through maintenance of delta psi m. Z-Asp-CH2-DCB, interleukin-1 beta-converting enzyme (ICE) specific inhibitor, inhibited ETP-induced DNA fragmentation and delta psi m reduction in U937 cells. This suggests that activation of ICE is an earlier event than delta psi m reduction. On the other hand, in Molt-4 cells, Z-Asp-CH2-DCB inhibited ETP-induced DNA fragmentation but not delta psi m reduction, suggesting that delta psi m reduction occurs earlier than activation of ICE.

Apoptosis↗

Appearance in Japan of highly macrolide-resistant Escherichia coli producing macrolide 2'-phosphotransferase II.

Escherichia coli CU1, a clinical isolate recovered in Japan in 1997, was found to be highly-resistant to both 14-membered and 16-membered ring macrolide antibiotics. A crude extract prepared from strain CU1 inactivated 14-, 15- and 16-membered ring macrolides in the presence of ATP and the Rf value of inactivated oleandomycin was identical to that of oleandomycin 2'-phosphate. This suggested that strain CU1 produced the enzyme macrolide 2'-phosphotransferase [MPH(2')]. Substrate specificity of the crude enzyme from strain CU1 against 14-, 15- and 16-membered ring macrolides was basically similar to that of MPH(2')II from strain BM2506, differing in that the former more effectively inactivated roxithromycin and tylosin. Subsequent attempts were made to clone the novel mph gene encoding for MPH(2') in strain CU1. The mph gene carried by strain CU1 was located on nontransmissible plasmid DNA, designated pCU001. Its molecular weight, estimated by agarose electrophoresis, was approximately 57 kD. The DNA sequence of the cloned mph gene from the Japanese isolate CU1 was identical to that of mphB, which until now had only been recovered in France. The variance in the substrate specificity of MPH(2')II from each strain led us to speculate that other factors in the reaction affect the enzymatic inactivation activity.

Anti-Bacterial Agents↗

A case of 43-year-old fighter pilot with bronchial asthma.

A Japan Air Self-Defense Force (JASDF) fighter pilot with adult onset atopic bronchial asthma was successfully returned to flying status. This was against the common wisdom of most Japanese military flight surgeons. Bronchial asthma generally results in permanent disqualification from flying duties because of possible acute incapacitation during flight. This JASDF pilot was treated with inhaled medications, including beclomethasone, for 6 mo with suppression of all clinical symptoms. All medications were discontinued and the pilot was observed for another 7 mo before resumption of flying status. This aeromedical disposition was based on the thinking that his long asymptomatic period indicated bronchial inflammation was resolved, bronchial reactivity was improved, and thus the risk of exacerbation was reduced.

Adult↗

Distribution of thyrotropin releasing hormone receptor type 2 in rats: an immunohistochemical study.

OBJECTIVE: To investigate the organ distribution of thyrotropin releasing hormone receptor (TRHR) type 2 in rats by immunohistochemical method. METHODS: TRHR type 2 was identified immunohistochemically in the rat tissues using specific anti-TRHR antiserum raised in New Zealand white rabbits immunized with a conjugate of synthetic TRHR type 2 (5-23) with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. RESULTS: TRHR type 2 immunoreactivity was visualized in the central nervous system, anterior pituitary, gastric mucosa, Auerbach's and Meissner's nervous branch of the stomach, small intestine and colon, retina amd testis. Significant stain was detected in neural perikarya, axons and dendrites. When using antiserum preincubated with synthetic TRHR type 2(5-23) or anterior pituitary homogenates, no significant stain of anterior pituitary was detected. CONCLUSIONS: These findings suggest that TRHR type 2 is widely distributed and that the method used is valuable in studying the distribution of TRHR type 2 in rats.

Animals↗

[A peculiar MRI findings in a case with slowly progressive cerebral ischemia caused by internal carotid artery stenosis possibly due to fibromuscular dysplasia].

A 47-year-old man developed progressive muscular weakness in the left arm. MR images revealed low intensity signal lesions with ring enhancement by Gd-DTPA in right fronto-parietal lobes. At that time cerebral angiography was not performed because he refused. A tuberculin skin test showed strongly positive reaction and then administration of anti-tuberculous drugs was started. His symptom had remained stable for one year, but left facial palsy and dysarthria added about two years later. MR images revealed expansion of the lesions in right parietal lobe, adding cortical high intensity signal lesions with Gd-DTPA enhancement on T1-weighted images. Angiography disclosed tubular stenosis of right internal carotid artery at the portion of cervical to petrous segment and the local stenosis at right renal artery. These lesions were considered to be caused by fibromuscular dysplasia, but not atherosclerosis, because we could not find any atherosclerotic lesions in other arteries including right carotid bifurcation. His manifesting symptoms were ascribed to slowly progressive cerebral ischemia. And peculiar MRI findings in his early stage resembled those of inflammatory granulomatous diseases.

Arterial Occlusive Diseases↗

Purification and characterization of a glucuronyltransferase involved in the biosynthesis of the HNK-1 epitope on glycoproteins from rat brain.

The glucuronyltransferase involved in the biosynthesis of the HNK-1 epitope on glycoproteins was purified to an apparent homogeneity from the Nonidet P-40 extract of 2-week postnatal rat forebrain by sequential chromatographies on CM-Sepharose CL-6B, UDP-GlcA-Sepharose 4B, asialo-orosomucoid-Sepharose 4B, Matrex gel Blue A, Mono Q, HiTrap chelating, and HiTrap heparin columns. The purified enzyme migrated as a 45-kDa protein upon SDS-polyacrylamide gel electrophoresis under reducing conditions, but eluted as a 90-kDa protein upon Superose gel filtration in the presence of Nonidet P-40, suggesting that the enzyme forms homodimers under non-denatured conditions. The enzyme transferred glucuronic acid to various glycoprotein acceptors bearing terminal N-acetyllactosamine structure such as asialo-orosomucoid, asialo-fetuin, and asialo-neural cell adhesion molecule, whereas little activity was detected to paragloboside, a precursor glycolipid of the HNK-1 epitope on glycolipids. These results suggested that the enzyme is specifically associated with the biosynthesis of the HNK-1 epitope on glycoproteins. Sphingomyelin was specifically required for expression of the enzyme activity. Stearoyl-sphingomyelin (18:0) was the most effective, followed by palmitoyl-sphingomyelin (16:0) and lignoceroyl-sphingomyelin (24:0). Interestingly, activity was demonstrated only for sphingomyelin with a saturated fatty acid, i.e. not for that with an unsaturated fatty acid, regardless of the length of the acyl group.

Animals↗