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Biomedical subjects

J Adachi

Publications and source records attributed to J Adachi.

At least 55 records · Page 3Linked to original sources

Change in nitric oxide in humans due to application of a pneumatic tourniquet.

The nitric oxide profile produced by application of a pneumatic tourniquet was investigated in the plasma of 15 patients. Nitrite (NO2-) and nitrate (NO3-) plasma concentrations were measured simultaneously by high-performance liquid chromatography (HPLC). UV detection using the Griess reaction was done after the reduction of nitrate to nitrite. The plasma nitrate concentration 5 min after reperfusion was significantly higher than the concentrations before ischemia, immediately before reperfusion, and the next day. In contrast, there was no significant difference in the plasma nitrite concentrations before ischemia, immediately before reperfusion, 5 min after reperfusion, and the next day. These findings suggest that the generation of NO is important in ischemic reperfusion injury.

Adolescent↗

Increasing incidence of streptococcal impetigo in atopic dermatitis.

Streptococcal impetigo associated with atopic dermatitis has dramatically increased from 1989 to 1994 in outpatients visiting our hospital, totalling 174 cases. The most frequent causative agents were group A streptococci (Streptococcus pyogenes, 70.7%) followed by group G (19.5%) and group B (9.8%). Streptococcus was isolated singly in 28.2% of cases and in concomitant with Staphylococcus aureus (S. aureus) in 71.8%. Major clinical features of streptococcal impetigo, especially caused by group A streptococci, were non-bullous pustules with thick crusted ceiling. Impetigo caused by group G or B streptococci generally formed smaller sized pustules of fewer numbers. Impetigo was usually present, associated with severe eczematous lesions. Various degrees of fever were noticed in 32.8% (group A, 39.8%; group G, 17.6%; group B, 11.8%) during active stages. The lesions on the face often resembled Kaposi's varicelliform eruption in any group. Systemic antimicrobial agents were administered in 71.3% of cases and the remainder were treated with topical antibiotics (oxytetracycline hydrochloride) or disinfectants (povidone-iodine). Recurrence occurred within a month in 38.0% of cases treated with topical agents only and in 17.7% treated with systemic antimicrobial agents. Antimicrobial susceptibility tests and the results of treatment seem to indicate that cephems, as well as penicillins, are the first choice of treatment for streptococcal impetigo.

Adolescent↗

Phenotypic alterations of small cell lung carcinoma induced by different levels of wild-type p53 expression.

p53 induces both growth arrest and apoptosis in cancer cells. To clarify whether the level of p53 expression determines the response of small cell lung carcinoma (SCLC) cells, we assessed the effect of various p53 levels on a p53-null SCLC cell line, N417, using a tetracycline (Tc)-regulated inducible p53 expression system. Apoptosis was induced in SCLC cells with high p53 expression. Although low levels of p53 induced G1 arrest accompanied by p21 expression, cells with G1 arrest seemed to undergo apoptosis after further cultivation. Expression of exogenous p21 induced G1 arrest but not apoptosis in SCLC cells, suggesting that p53-mediated G1 arrest was induced through p21 expression. Moreover, high level of p53 expression down-regulated Bcl-2 expression in SCLC cells, while Bax was consistently expressed irrespective to the level of p53 expression. These results suggest that p53-mediated apoptosis and G1 arrest depend on level of p53 expression in SCLC cells and that the relative dominancy of Bax to Bcl-2 is involved in the induction of apoptosis by high level of p53 expression.

Apoptosis↗

Identification and characterization of families with aggregation of lung cancer.

BACKGROUND: To clarify genetic factors involved in the susceptibility to lung cancer, it is essential to identify families with lung cancer clustering and to characterize the mode of clustering. Since somatic mutations of the p53, RB and p16 genes occur frequently in lung cancer and the replication error phenotype is seen in a subset of lung cancer, it is possible that germ-line mutations of the p53, RB, p16 and mismatch repair genes influence the susceptibility to lung cancer. METHODS: In this work, cases with familial clustering of lung cancer were selected from 1068 families with primary lung cancer cases in analogy with the criteria for hereditary non-polyposis colorectal cancer (HNPCC). Cases with Li-Fraumeni syndrome, familial retinoblastoma, familial melanoma and HNPCC were also searched among these 1068 families. RESULTS: There were only four families (0.4%) in which more than three relatives were affected by lung cancer. Two successive generations were affected in 36 families (3.4%). Patients with lung cancer before the age of 50 were present in 165 families (15.5%). However, no family conformed to all three criteria. There was only one family with Li-Fraumeni syndrome and no family with familial retinoblastoma, familial melanoma and HNPCC. CONCLUSION: Familial aggregation of lung cancer is rare and germ-line mutations of the p53, RB, p16 and mismatch repair genes may not contribute greatly to susceptibility to lung cancer.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

Abnormality of very long-chain fatty acids of erythrocyte membrane in alcoholic patients.

Profiles of very long-chain fatty acids were studied in the erythrocyte membrane of five alcoholic patients. We identified three fatty acids as cis-16-pentacosenoic acid (C25:1), cis-17-hexacosenoic acid (C26:1), and hexacosenoic acid (C26:1), and hexacosanoic acid (C26:0) by gas chromatography-mass spectrometry. The ratios of C26:1/C22:0, C26:0/C22:0, C24:1/C22:0, and C24:0/C22:0 were increased. These findings suggest that active oxygen species or free radicals generated by chronic alcohol consumption in alcohol patients interrupt the peroxisomal beta-oxidation of fatty acids, because very long-chain fatty acids are mainly metabolized by the peroxisomal beta-oxidation system. This is the first study showing accumulation of very long-chain fatty acids in the erythrocyte membrane of alcoholic patients.

Alcoholism↗

Increased very long-chain fatty acids in erythrocyte membranes of patients with aceruloplasminemia.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. Our previous studies suggested that increased susceptibility to plasma lipid peroxidation secondary to iron accumulation may contribute to the pathogenesis in this disease. We now have identified increases in the very long-chain fatty acids cis-17-hexacosenoic (C26:1) and hexacosanoic (C26:0) acid in the erythrocyte membranes of three family members affected with aceruloplasminemia. All of them had elevated C26:1/C22:0 and C26:0/C22:0 ratios. These findings suggest that free radicals generated in persons with aceruloplasminemia may interrupt the peroxisomal beta-oxidation of fatty acids.

Apoproteins↗

Differentiation induced by RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line.

Multiple genetic alterations, including concurrent inactivation of RB and p53, occur frequently in several human cancers. To investigate the biological significance of RB and p53 gene inactivations, a wild-type RB or p53 cDNA expression vector regulated by tetracycline was introduced by stable transfection into an osteosarcoma cell line Saos-2, in which both the RB and p53 genes were inactivated. Induction of introduced RB expression resulted in suppression of cell growth, increased percentage of cells at the G0/G1 phase, and enlargement of the cells. Furthermore, activity of alkaline phosphatase was increased and expression of fibronectin was decreased, suggesting the induction of cell differentiation by RB expression. Induction of p53 expression also resulted in significant suppression of cell growth with slight accumulation of cells at the G0/G1 and G2/M phases. The cells were detached from culture dishes and the dead cell fraction increased. Furthermore, condensation of chromatin and DNA fragmentation were observed, suggesting the induction of apoptosis by p53. These results suggest that RB and p53 play different roles in carcinogenesis of osteoblast; RB inactivation releases cells from G0/G1 arrest and suppresses cell differentiation while p53 inactivation assists the cells to proliferate by repressing both apoptosis and cell cycle arrest at G0/G1 and G2/M.

Apoptosis↗

Very long-chain fatty acid pattern in crush syndrome patients in the Kobe earthquake.

Profiles of very long-chain fatty acid were studied in the erythrocyte membrane of healthy controls and four patients with crush syndrome caused by the Great-Hanshin Earthquake. The identities of cis-17-hexacosenoic acid (C26:1) and hexacosanoic acid (C26:0) were verified by gas chromatography-mass spectrometry (GC-MS). The ratios C26:1/C22:0, C26:0/C22:0, C24:1/C22:0, and C20:1/C22:0 also were elevated. These findings suggest that active oxygen species and/or free radicals generated by ischemia-reperfusion in the crush syndrome result in beta-oxidation disorders in peroxisomes.

Adult↗

Novel phylogeny of whales supported by total molecular evidence.

Given that the analysis of a single gene does not necessarily provide unambiguous phylogenetic information, it is important to scrutinize as many genes as possible. Using the maximum likelihood method, particularly suitable for a total evidence approach, we evaluated the phylogenetic information provided by the 12S and 16S rRNA, cytochrome b, and myoglobin sequence data in order to resolve one of the most debated phylogenetic questions: the relationships among the major groups of cetaceans. Our analysis strongly supports the hypothesis that sperm whales are closer to baleen whales than to dolphins.

Animals↗

Epicoprostanol found in adipocere from five human autopsies.

Adipocere formation is well known as a later postmortem change. We collected adipocere from five male victims which had been submerged under the sea or fresh water for 1 mon to 4 yr. Fresh subcutaneous fat of a male victim who died from a cerebral contusion was used as the control. The samples were homogenized, and the lipids were extracted with chloroform and methanol followed by injection into a gas chromatograph and a gas chromatograph-mass spectrometer. We detected hydroxy fatty acids (10-hydroxyoctadecanoic acid and 10-hydroxyhexadecanoic acid) as well as 10-ketooctadecanoic acid in adipocere, but not in the control. In addition, we found for the first time a cholesterol-related peak with a molecular ion of 388 in adipocere and identified it as epicoprostanol, suggesting not only oxidation but also reduction had occurred during the formation of adipocere. In addition, we showed the time-course of epicoprostanol accumulation. The relationship between the time of adipocere formation and the characteristic lipid composition is discussed.

Adipose Tissue↗

Allelotype and replication error phenotype of small cell lung carcinoma.

Allelotype and replication error (RER) phenotype analyses were performed to clarify the pathogenetic significance of inactivation of tumor suppressor genes and genomic instability in the genesis and progression of small cell lung carcinoma (SCLC). We examined 37 cases of SCLC for loss of heterozygosity (LOH) and microsatellite instability at 49 loci on all 39 nonacrocentric chromosomal arms. LOH was frequently (>70%) detected on chromosomes 3p (29/32, 90.6%), 5q (15/21, 71.4%), 13q (25/26, 96.2%), 17p (22/25, 88.0%), and 22q (24/33, 72.7%). Frequent LOH (>70%) on these loci was observed even among seven cases of stage I tumors. The incidence of LOH on all 39 nonacrocentric chromosomal arms was not significantly different between primary tumors and metastases. These results suggest that inactivation of multiple tumor suppressor genes accumulates relatively early during progression of SCLC and it may be responsible for clinically and biologically aggressive phenotype of SCLC. RER was observed in 6/37 (16.2%) of SCLC, however, RER at multiple loci was observed only in two cases. Therefore, it was indicated that genomic instability is uncommon, but might play a role in the genesis of a small subset of SCLC.

Alleles↗

p16INK4 expression is associated with the increased sensitivity of human non-small cell lung cancer cells to DNA topoisomerase I inhibitors.

Inactivation of p16INK4, an inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), may be essential for oncogenesis in non-small cell lung cancer (NSCLC). We examined the sensitivity of two clones of p16INK4-transfected NSCLC cell line with homozygous deletion of p16INK4, A549/p16-1 and 2, to DNA topoisomerase I (topo I) inhibitors. A549/p16-1 and -2 showed 7.7- and 9.1-fold increases in sensitivity to CPT-11 (11,7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin ), respectively, compared with A549 cells. Ectopic p16INK4-expressing cells also showed approximately 4.0-fold increase in sensitivity to SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of CPT-11, compared to the parent cells. The topo I-mediated DNA relaxation activities of ectopic p16INK4-expressing cells were approximately 5 times higher than those of the parent cells. Northern and western blot analyses indicate that these increased topo I activities of ectopic p16INK4-expressing cells were due to an elevated topo I mRNA level and an increase in topo I protein. The chemosensitivity to topo I inhibitors, topo I mRNA level, protein content and activity of a p16INK4 revertant, lacking functional p16INK4, tended to be restored toward those of the parental phenotype to some extent. These results suggest that p16INK4 expression is closely associated with the increased sensitivity of ectopic p16INK4-expressing NSCLC cells to topo I inhibitors. The up-regulation of topo I mRNA level, protein content and activity may be responsible for this hypersensitivity.

Antineoplastic Agents, Phytogenic↗

Evaluation of scratch movements by a new scratch-monitor to analyze nocturnal itching in atopic dermatitis.

Itching is very important in atopic dermatitis, but the details of itching or scratch movements, especially during sleep at night, have not yet been fully comprehended. We designed a new, simple device, the Scratch-Monitor (SM), to evaluate scratch movements at night and assessed the usefulness of this device by a comparison involving 26 patients and 17 healthy controls. The SM, a box weighing only 25 g with a pressure sensor on the bottom, is attached to the back of each hand under a cotton glove and records the number as scratch movements per minute in the case of more than three successive changes of pressure. The SM indicated that patients with atopic dermatitis scratched more frequently and suffered more severe sleep disturbance than healthy controls. Although the SM had several problems related to specificity and sensitivity, we conclude that the SM is a useful tool for evaluating nocturnal itching.

Adolescent↗

Osteoporosis clinical trials endpoints: candidate variables and clinimetric properties.

We reviewed evidence on endpoints used in osteoporosis clinical trials to assist in the development of a set of endpoints to be included in all trials. A MEDLINE search was conducted using the Cochrane Collaboration strategy for each endpoint. Additional published literature was obtained from content experts. A proposed list of endpoints was developed after consultation with experts in the field. Each endpoint was evaluated with respect to validity, reproducibility, redundancy, and feasibility. We classified the endpoints into 2 major categories: clinical health status outcomes and intermediate endpoints, and for each endpoint we present current evidence from the literature as pertains to defined methodologic criteria. Multiple endpoints have been used in osteoporosis clinical trials, and an agreement on a core set of measures needs to be evidence based with an emphasis on validity, reproducibility, and feasibility and to satisfy clinical credibility.

Biomarkers↗

[Effect of vacuum cleaning of room floors and bed clothes of patients on house dust mites counts and clinical scores of atopic dermatitis. A double blind control trial].

By a randomized double blind control trial we studied the effect of vacuum cleaning of room floors, mattresses and quilts for twelve months on clinical symptoms and laboratory data of atopic dermatitis patients. All patients used the identical new vacuum cleaners. Thirty patients (3-12 years of age) with relatively stable skin conditions were randomly allocated to either of the following two groups. In the monitor group we visited patient's home every three weeks and mite specialists cleaned drastically the room floors, mattresses and quilts and the patient continued to clean in the same way in-between. In the control group we visited similarly but the cleaning was made insufficiently which was also followed by the patient. But, at 2 occasions (the first and the last visits), cleaning was made drastically also in the control group. Thus the mite numbers were counted precisely at the start and the end of the experiment both in the monitor and control groups. Each patient was seen every six weeks by the same doctor and estimated of his symptoms using our unique scoring system (Fig. 1). At the start and the end of the study, total IgE and specific IgE antibodies to house dust mites in the serum were evaluated. The monitor group showed a tendency to count smaller number of mites than the control group after a year, when there was a significant difference only in quilts. However, a statistically significant decrease in the mite counts was observed only in room floors and not in mattresses and quilts both in the monitor and control groups (Fig. 2). Clinical scores after a year significantly improved only in the monitor group and not in the control group (Fig. 3). Serum IgE value and specific antibody titer to house dust mites were not changed significantly after the trial in both groups. As a conclusion, vacuum cleaning of the patient's room improved the clinical symptoms of atopic dermatitis but this could not be related to the reduction of house dust mite number.

Animals↗

Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 6. Use of bisphosphonates in the treatment of osteoporosis.

OBJECTIVE: To describe the mechanisms of action of bisphosphonates in the treatment of osteoporosis and compare bisphosphonate therapy with other treatments. OPTIONS: The bisphosphonates, etidronate, alendronate, clodronate, pamidronate, tiludronate, ibandronate and risedronate; combined bisphosphonates and estrogen; combined bisphosphonates and calcium supplements. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with bisphosphonate treatment. EVIDENCE: Relevant clinical studies and reports were examined with emphasis on recent controlled trials. The availability of treatment products in Canada was also considered. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Treatment with bisphosphonates may be an acceptable alternative to ovarian hormone therapy in increasing bone mass and decreasing fractures associated with osteoporosis. Compared with estrogens, bisphosphonates are bone-tissue specific, have equal or greater antiresorptive effect and have few side effects and no known risk for carcinogenesis. They also hold promise in treating male osteoporosis and steroid-induced bone loss. Prolonged, continuous treatment with etidronate may lead to impaired calcification of newly formed bone; therefore, etidronate is administered cyclically. This risk is not present in newer generations of bisphosphonates. RECOMMENDATIONS: Bisphosphonate therapies may be considered as an alternative to ovarian hormone therapy in postmenopausal osteopenic or osteoporotic women who cannot or will not tolerate ovarian hormone therapy. They should also be considered in treating male osteoporosis and steroid-induced bone loss. Combination therapy with estrogen may be effective, although more research is needed. Combination therapy with calcium supplements is recommended. Bisphosphonate therapies should be restricted to postmenopausal patients with osteopenia or established osteoporosis and are not yet recommended for younger perimenopausal women as prophylaxis.

Aged↗