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Biomedical subjects

N Araki

Publications and source records attributed to N Araki.

At least 73 records · Page 4Linked to original sources
PubMed1998

Photosensitive dermatitis caused by pyridoxine hydrochloride.

Few photosensitive reactions caused by pyridoxine hydrochloride have been reported. There have been no reports of detailed photosensitivity studies on patients who have developed photosensitivity from pharmacologic doses of pyridoxine. Two patients with pyridoxine photosensitivity are described. Photopatch tests were positive for pyridoxine hydrochloride. The minimal erythematous dose (MED) for UVA decreased after the intravenous injection of pyridoxine hydrochloride in both patients. Normal controls gave negative results in photopatch tests for pyridoxine hydrochloride and phototest for vitamin B complex containing pyridoxine hydrochloride. On the basis of these results, we believe both patients had a photoallergic reaction to pyridoxine hydrochloride.

Dermatitis, Photoallergic↗
PubMed1998

The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas.

Neurofibromatosis type 2 (NF2) protein, also known as merlin or schwannomin, is a tumor suppressor, and NF2 is mutated in most schwannomas and meningiomas. Although these tumors are dependent on NF2, some lack detectable NF2 mutations, which indicates that alternative mechanisms exist for inactivating merlin. Here, we demonstrate cleavage of merlin by the ubiquitous protease calpain and considerable activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway.

Base Sequence↗
PubMed1998

Extended HLA haplotypes in Japanese homozygous typing cells.

We have defined extended HLA haplotypes including the HLA class II genes, the non-HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)n microsatellite repeats within the NOTCH4 gene between DRA and 21OH in 33 Japanese HLA homozygous typing cells (HTC). These conserved haplotypes characterized by unique linkage might be maintained as a result of functional co-operation among them in the antigen presentation pathway. These HTCs can be served as an original and ethnic-specific standard panel, providing useful genetic markers in haplotypic diversity, disease association, and anthropology studies.

HLA Antigens↗
PubMed1998

Fluorometric measurement of intracellular pH in vivo in feline cerebral cortex during ischemia and reperfusion.

Intracellular acidosis has been considered to play an pivotal role in the progression of neuronal damage after cerebral ischemia. However, continuous measurement of the intracellular potential of hydrogen (pH) has not been done during and after ischemia. We measured temporal changes in intracellular pH in the feline cerebral cortex in vivo during and after ischemia using a novel fluorescent pH probe, 2',7'-biscarboxyethyl carboxyfluorescein (BCECF). A closed cranial window was installed in the left temporal skull. BCECF acetoxymethyl ester was superfused over the cortex, hydrolyzed and trapped in cortical cells. Intracellular pH was measured utilizing excitation light at 507 nm and fluorescent light at 550.5 nm. Focal cerebral ischemia for 60 minutes was induced by means of middle cerebral artery occlusion. Intracellular pH in the severely ischemic group became significantly acidic (p < 0.01) during ischemia and the acidosis persisted for at least 30 minutes after recirculation. The pH change was not significant in the mildly ischemic group. The severity of ischemia was determined based on the mean transit time, which was calculated from the hemodilution curve obtained by bolus injection of saline. The extent of ischemia was further confirmed pathologically (p < 0.01). The above results suggest that intracellular acidosis resulting from severe ischemia persists even after recirculation.

Animals↗
PubMed1997

Mutations of p53 tumor-suppressor gene in angiosarcoma.

Transgenic mice deficient for the p53 gene were reported to frequently develop angiosarcoma (AS), suggesting that alterations in the gene are associated with tumorigenesis of AS. However, little is known about genetic changes, including p53 gene alterations, in human AS because of its rarity. We analyzed p53 mutations on paraffin-embedded specimens from 33 patients with AS by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by direct sequencing. Age of patients ranged from 18 to 91 (median 70) years, with a male to female ratio of 1.5:1. Sites of tumor were the head in 13 patients, the trunk in 4, the extremities in 4, the heart in 4, bones in 2 and others in 6. PCR-SSCP revealed aberrant mobility shifts of bands in 17 cases: 11 in exon 5, 5 in exon 7 and 4 in exon 8. Direct sequencing on these 17 cases revealed a total of 20 mutations. The frequency of p53 mutations was different by site of tumors: 7 of 13 in head, all 4 in extremities, 2 of 4 in heart and none of 4 in trunk. Our findings suggest that occurrence of p53 mutation is a major pathway for development of human AS.

Adolescent↗
PubMed1997

Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells.

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Physiological aspects of the catabolism of non-enzymically glycated proteins were studied in vivo and in vitro. AGE-modified BSA (AGE-BSA) was a mixture of high-Mr (cross-linked), monomeric and low-Mr (fragmented) AGE-BSA. After intravenous administration in rat, all three fractions of AGE-BSA accumulated extremely rapidly and almost exclusively in liver. Uptake in liver endothelial, Kupffer and parenchymal cells accounted for approx. 60%, 25% and 10-15% respectively of hepatic elimination. Both cross-linked and monomeric AGE-BSA were efficiently taken up and degraded in cultures of purified liver endothelial and Kupffer cells. Endocytosis of AGE-BSA by these cells was inhibited by several ligands for the scavenger receptor. Although 125I-Hb was not endocytosed in vitro, 125I-AGE-Hb was effectively endocytosed by a mechanism that was subject to inhibition by AGE-BSA. Endocytosis of N-terminal propeptide of type I procollagen, a physiological ligand for the scavenger receptor, was effectively inhibited by AGE-Hb and AGE-BSA. We conclude that AGE-modification renders macromolecules susceptible for elimination via the scavenger receptor of both liver endothelial and Kupffer cells.

Animals↗
PubMed1997

Neoadjuvant chemotherapy for pediatric osteosarcoma patients.

BACKGROUND: Since the first trial for chemotherapy in children with osteosarcoma in 1977, the survival rate has gradually improved. Currently, more than 60% of all patients are cured, mainly because of the introduction of intensive chemotherapy using doxorubicin, high dose methotrexate, and cisplatin. The increased survival rates have promoted efforts to improve the quality of survival through the use of limb salvage surgery rather than amputation. Improvements in chemotherapeutic efficacy should result in a more favorable outcome and better function of the affected limb. The current study evaluated factors that influence chemotherapy so that a higher survival rate could be obtained. METHODS: Three chemotherapy regimens comprised of doxorubicin, high dose methotrexate, cisplatin, and ifosfamide were retrospectively analyzed in 67 pediatric osteosarcoma patients. Twenty-three patients were treated with chemotherapy comprised of high dose methotrexate and doxorubicin (OOS-A regimen), 25 were treated with OOS-A with the addition of cisplatin (OOS-B), and 19 were treated with OOS-B with the addition of ifosfamide (OOS-C). RESULTS: The OOS-A regimen was poorest in terms of survival (40.6%) compared with the OOS-B (67.5%) and OOS-C regimens (72.5%) (P < 0.001). There was no significant difference in survival between the OOS-B and OOS-C regimens. In the OOS-B regimen, patients who received a higher relative dose intensity showed a better prognosis. CONCLUSIONS: These findings show that doxorubicin, high dose methotrexate, and cisplatin are the most potent drugs and suggest that it is more important to maintain the dose intensity of the regimen to improve survival rather than add a new drug.

Adolescent↗
PubMed1997

Tumor size as a prognostic indicator of histologic grade of soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Tumor size is one of the independent factors affecting prognosis of patients with soft tissue sarcoma (STS). We evaluated the significance of tumor size in combination with tumor depth in each histologic grade. METHODS: A total of 162 adult patients with localized STS in the extremities and trunk were selected. Patient ages ranged from 15 to 84 (median 46.5) years with a male-to-female ratio of 1.19. Histologic grade of tumors was low in 53 cases, intermediate in 51, and high in 58. Two types of categorization were set, and their significance in predicting the prognosis of patients in each grade was evaluated. In the first category (intermediate grade), tumors were dichotomized at 10 cm: Group A comprised patients with deeply seated tumors measuring > 10 cm; Group B comprised patients other than those in Group A. In the second category (high grade), tumors were dichotomized at 5 cm: Group C comprised patients with deeply seated tumors measuring > 5 cm; Group D comprised patients other than those in Group C. RESULTS: Categorization was not useful in the prognosis of low grade tumors. In the intermediate grade group, the 5-year-survival rate of Group B patients (78%) was higher than in Group A patients (59%) (P < 0.05), showing that dichotomization at 10 cm was useful. In the high grade group, the 5-year survival rate in Group C patients (32%) was lower than in Group D patients (56%), showing that dichotomization at 5 cm was useful. CONCLUSIONS: These findings show that tumor size for the prognosis of patients with STS differs according to each histologic grade.

Adolescent↗
PubMed1997

Histological localization of advanced glycosylation end products in the progression of diabetic nephropathy.

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Adult↗
PubMed1997

Skeletal metastases from soft-tissue sarcomas. Incidence, patterns, and radiological features.

We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and 1995 to study the incidence, distribution, time of appearance, and radiological findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a mean period of 18.6 months after admission. The incidence of skeletal metastases differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma, dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show higher incidences. The regional bones close to the primary tumour were affected in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%). Radiologically, the metastatic bony lesions predominantly showed osteolytic changes, and there were pathological fractures in 21 of 44 lesions.

Adolescent↗
PubMed1997

Influence of local recurrence on the prognosis of soft-tissue sarcomas.

We have investigated the significance of local recurrence on survival in 173 patients with localised soft-tissue sarcomas of the limbs and of the trunk. The overall survival rates at five and ten years were 75.2% and 68.0%, respectively. After definitive surgery at our hospitals, there was local recurrence in 25 patients (14.5%). After inadequate operations elsewhere, there was a higher incidence of late local recurrence (28.3%), in comparison with those with primary tumours treated by us (9.0%), or patients referred to us immediately after inadequate surgery elsewhere (10.2%). Because of small numbers these differences in the survival rates were not statistically significantly different. Univariate survival analysis showed that local recurrence after definitive surgery (p = 0.006) together with the histological grade (p = 0.0002), the size of the tumour (p = 0.002), its depth in relation to deep fascia (p = 0.003), and the surgical margin (p = 0.0001) were the significant prognostic factors. Local recurrence at the initial presentation did not affect survival. Multivariate analysis showed that local recurrence after definitive surgery also lost its apparent prognostic significance.

Adolescent↗
PubMed1997

[Neurofibromatosis type 2 (NF2)].

Neurofibromatosis type 2 (NF2) is an autosomal dominantly inherited disorder, strongly associated with development of benign intracranial tumors, including bilateral vestibular schwannomas and meningiomas. The NF2 gene located on the human chromosome 22q12 was recently cloned, and the protein it encodes (termed merlin/schwannomin) was found to be strikingly similar to the moesin-ezrin-radixin (MER) family of cytoskeleton-associated proteins. Mutations of NF2 gene have been found not only in the NF2 patient but also in NF2-related sporadic tumors such as acoustic schwannomas and meningiomas, suggesting that the NF2 gene functionally acts as a tumor suppressor gene. To elucidate the biological function of merlin, we have detected five merlin binding cellular proteins. The N-terminal region of merlin, the entire merlin-ezrin-radixin-moesin (MERM) homology domain, was found to be essential for binding to all five proteins. Since most reported NF2 mutations in the region were determined to be necessary for binding, the mutations probably impair binding. The majority of NF2 mutations are nonsense mutations or frameshifts that resulted in premature termination of merlin. The lack of these interactions caused by such mutations of NF2 gene may affect the cellular signals, resulting in benign intracranial tumors in NF2 patients.

Chromosomes, Human, Pair 22↗
PubMed1997

Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia.

Ten years of experience in lower limb lengthening achieved in 35 patients with achondroplasia and seven patients with hypochondroplasia is reported. A uniform method of callus distraction (callotasis) was used in all cases, although the order of lengthening of each bone differed among the cases. The mean age of the patients at the time of first operation was 14.5 years; at followup, the mean age was 18.8 years. The mean lengthening achieved in the femur was 7.2 cm (range, 4.5-12 cm) and in the tibia 7.1 cm (range, 4.5-13 cm). More lengthening was achieved in the more recent cases. The function of lengthened limbs, evaluated by physical strength tests, was better at followup than before lengthening in the growing children, although the mechanical axes of the lengthened bones were not necessarily in correct alignment.

Achilles Tendon↗
PubMed1996

Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway.

To clarify roles of intermediate metabolites of the glycolytic pathway and the polyol pathway in nonenzymatic glycation under physiological conditions, we incubated bovine serum albumin with intermediates of both pathways in the micromolar range as well as with 20 mmol/l glucose, and observed the formation of advanced glycation end products (AGEs). We found that triose phosphates, glyceraldehyde, and a novel polyol pathway-related metabolite, fructose 3-phosphate along with its breakdown product, 3-deoxyglucosone were extremely potent glycating agents that at nearly physiological concentrations on incubation with albumin produced substantial amounts of AGEs as early as 24 hours, while 20 mmol/l glucose afforded trace amounts of AGEs after two week incubation. The results along with the previous evidence of the increased level of intermediates in diabetic states may suggest that the intermediate metabolites rather than glucose contribute to enhanced glycation in diabetic tissues, inspite of the much lower concentrations compared with glucose.

Animals↗
PubMed1996

Brain nitrite production during global ischemia and reperfusion: an in vivo microdialysis study.

Nitric oxide (NO) is considered to be associated with the pathogenesis of cerebral ischemic injury. In the present study, NO production was continuously monitored employing in vivo microdialysis. A microdialysis probe was inserted into the stratum. Levels of the major NO metabolite, NO-2, in the dialysate were determined using the Griess reaction. Rats were subjected to global cerebral ischemia produced by occlusion of both common carotid arteries together with induced hypotension. Cerebral ischemia induced a decrease in NO production, which was interrupted by a transient increase in NO synthesis. This increment was abolished in the presence of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), suggesting that NO synthase activity is transiently activated during ischemia. Following reperfusion, NO synthesis was enhanced. To our knowledge, this is the first report concerning the continuous temporal profile of NO production during global cerebral ischemia and reperfusion.

Animals↗
PubMed1996

Nitric oxide regulates NMDA-induced dopamine release in rat striatum.

We investigated the effect of nitric oxide (NO) on N-methyl-D-aspartate (NMDA)-induced changes in levels of dopamine (DA) and its metabolite in the striatum using in vivo microdialysis. Local administration of 1mM NMDA into the striatum significantly augmented DA release in the striatum. Simultaneous administration of -5mM N(G)-nitro-L-arginine methyl ester (-NAME), a NO synthase inhibitor, into the striatum significantly potentiated NMDA-induced DA release. This effect of L-NAME was completely reversed in the presence of 50mM L-arginine (L-Arg). Administration of 1 mM NMDA significantly decreased the levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect of NMDA was not affected by concurrent administration of L-NAME. This study provides in vivo evidence for the involvement of NO in NMDA-induced DA release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Correlation of in vivo nitric oxide and cGMP with glutamate/glutamine metabolism in the rat striatum.

We have examined how the suppression of endogenous production of nitric oxide (NO) in the striatal tissue affects release of glutamate (GLU) and glutamine (GLN) in pentobarbital-anesthetized male Sprague-Dawley rats. For the quantitative measurement of tissue NO production and amino acid release, an in vivo assay system for extracellular nitrite (NO2-) and amino acids was employed using an in vivo microdialysis technique. An NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) in concentrations ranging between 4-40 mM was perfused into the rat striatum using the assay system. Tissue NO production was found to be inversely proportional to the L-NAME concentration. L-NAME likewise decreased striatal levels of GLU and GLN. Furthermore, tissue NO production showed a positive correlation with GLU (R = 0.62, P < 0.02) and GLN (R = 0.86, P < 0.001) concentrations. Exogenous application of NO and cGMP by intrastriatal perfusion with 0.1-2.5 mM hydroxylamine and 0.4-10 mM 8-bromo-cGMP, respectively, increased striatal GLU release in a dose-related manner. Hydroxylamine reduced GLN release, and 8-bromo-cGMP showed a tendency to decrease GLN. In conclusion, striatal GLU/GLN metabolism is a function of the tissue concentration of NO. Normal endogenous concentration of NO causes GLU to be released at a consistent basal level, and enhanced tissue NO production facilitates GLU release via pathways including cGMP formation. We hypothesize that NO may suppress GLN formation by astrocytes.

Animals↗