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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 235 records · Page 13Linked to original sources

Localization of DNA in the condensed interphase chromosomes of Euglena.

The localization of DNA in the condensed interphase chromosomes of Euglena was determined by immunoelectron microscopy. Deposits of gold particles that coincided with the localization of DNA followed threads that corresponded to the chromatin fibers. The threads were 55-80nm in diameter and were assumed to be supersolenoids. The localization of gold deposits on chromosomes that had been sectioned in various directions suggested that the chromatin fibers coiled around the surface of chromosomes, with a wide central axial region of the chromosomes remaining free of DNA. These findings are discussed in relation to current models of chromosomal structure.

Animals

A human pancreatic islet inwardly rectifying potassium channel: cDNA cloning, determination of the genomic structure and genetic variations in Japanese NIDDM patients.

Ligand gated potassium channels, such as the ATP-regulated potassium channel, play crucial roles in coupling of stimuli to insulin secretion in pancreatic beta cells. Mutations in the genes might lead to the insulin secretory defects observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). We isolated a cDNA encoding a putative subunit of a ligand gated potassium channel from a human islet cDNA library. The channel, which we designated hiGIRK2, appeared to be an alternative spliced variant and a human homologue of recently reported mbGIRK2, KATP-2/BIR1. Transcripts were detected in human brain and pancreas, but not in other tissues including cardiac muscle. The sizes of transcripts in the pancreas differed from those in the brain, suggesting tissue-specific alternative splicing and possible isoforms. We then isolated human genomic clones, determined the complete genomic structure and localized the gene to chromosome 21 (21q22). The gene was comprised of four exons and the protein was encoded by three exons. The entire coding region of the hiGIRK2 gene was scanned by polymerase chain reaction-single strand conformation polymorphism analysis in 80 Japanese NIDDM patients. We found five nucleotide substitutions; three were silent mutations of the third base of codons, one in the first intron, 9 bases upstream of exon 2, and one in the 3'-untranslated region. We conclude that mutations in the gene encoding hiGIRK2, a (subunit of) ligand gated potassium channel, is not a major determinant of the susceptibility to NIDDM in Japanese.

Alternative Splicing

Interferon-alpha therapy for multiple hemangiomas associated with coarctation of the aorta.

We report a rare combination of multiple hemangiomas and coarctation of the aorta in a 2-month-old female infant who responded to interferon-alpha (IFN-alpha) therapy. The coarctation was repaired successfully with the use of an artificial graft. In patients with symptomatic hemangiomas that do not respond to steroid therapy, IFN-alpha therapy should be considered.

Antineoplastic Agents

IS431mec-mediated integration of a bleomycin-resistance gene into the chromosome of a methicillin-resistant Staphylococcus aureus strain isolated in Japan.

A methicillin-resistant Staphylococcus aureus (MRSA) strain B-26, isolated clinically in Hiroshima University Hospital, is resistant to bleomycin together with kanamycin. In the present study, we analysed the nucleotide sequence of the 5.1-kb HindIII fragment containing the bleomycin- and kanamycin-resistance genes, which were previously cloned [Bhuiyan et al. (1995) Appl Microbiol Biotechnol 43: 65-69] from the chromosomal DNA of MRSA B-26. The present study found that the DNA sequence contains the duplicated target sequence (GATTAGAT) consisting of 8 bp for transposase and the entire nucleotide sequence of the plasmid pUB110, together with the sequence of inverted repeats (16 bp), designated IR-r and IR-1 in IS431 mec. The 8-bp duplication sequence, produced by the transposable element, was first found by us. We proposed that bleomycin resistance in MRSA B-26 is attributed to the IS431 mec-mediated integration of pUB110 into the chromosome.

Bacterial Proteins

Disadvantages of muscle-sparing thoracotomy in patients with lung cancer.

At our institute patients with lung cancer had traditionally undergone lobectomy with mediastinal lymph node dissection using a standard posterolateral approach. The considerable morbidity associated with the standard posterolateral thoracotomy led us to investigate an alternative muscle-sparing approach. A prospective, randomized study of 30 patients with primary lung cancer (stage I or II) was performed to compare the following: operative field size, number of dissected lymph nodes, surgery time, postoperative pain, shoulder range of motion, and pulmonary function test results between patients who underwent either standard thoracotomy (SP group, n = 15) or the muscle-sparing thoracotomy (MS group, n = 15). The procedure should provide enough operative field size to access to mediastinum. Compared with the standard posterior thoracotomy, the muscle-sparing thoracotomy supplied a smaller operative field (218 +/- 31 versus 165 +/- 41 cm2) and required more surgery time (87 +/- 13 minutes) than the standard posterior thoracotomy (66 +/- 12 minutes). There were no significant differences in the number of dissected mediastinal lymph nodes. During the early postoperative days, pain and restriction of shoulder flexion were significantly less in the MS group than in the SP group. There were no significant differences in pulmonary function between the two groups. In terms of the operative field there is a marked disadvantage with the muscle-sparing incision compared with standard thoracotomy. The operative field is significantly smaller than with a standard thoracotomy, requiring more time to dissect the mediastinum; however, the pain is less and shoulder range of motion is superior to what is seen after standard thoracotomy during the early postoperative period. We conclude that there is no overall advantage to using the muscle-sparing incision in patients with lung cancer.

Female

Malignant neoplasms in the Japanese community of Hisayama: mortality and changing pattern during a 30-year observation period based on a consecutive autopsy series.

To obtain a relatively true mortality from malignant neoplasms, we studied the frequency of cancers in the different sites and the changing patterns of the frequency and sites over time among residents of the community of Hisayama, where an autopsy-based population survey (autopsy rate, 80%) has been conducted since 191. During the 30-year period from 1962 to 1991, we found 438 malignant neoplasms in 407 cases among 1,250 consecutive autopsies. Stomach cancer was not frequent in type of cancer, with 123 cases (9.8%), followed by lung cancer in 62 (5.0%), colorectal cancer in 42 (3.4%), liver cancer in 37 (3.0%), and pancreatic cancer in 30 (2.4%). We compared the mortality from cancers for both autopsy and nonautopsy cases (the proportional mortality) among three 10-year periods. The proportional mortality from all cancers, as well as for lung, colorectal, and liver cancers, showed an increase in recent years, while stomach and pancreatic cancer showed a decrease. These figures were nearly similar to the mortality statistics for the Japanese population as a whole except for the observed decreasing trend in mortality from pancreatic cancer.

Adolescent

Attenuation of cardiotoxicity of daunomycin using a complex with heparin.

Daunomycin (DM) is one of the most important antitumor agents. However, the cardiotoxicity of DM limits it's clinical use. We have made an ionic complex with heparin to decrease the cardiotoxicity. Cardiotoxicities of DM and DM-heparin complex were compared in hamsters. On the electrocardiogram (ECG), two of the four hamsters given DM showed the serious abnormality, bidirectional ventricular premature contraction, while the hamsters given DM-heparin or saline had no abnormalities. On pathological examination, cardiac tissue in hamsters given DM showed deposition of basophilic materials, mild eosinophilic change of myofibrils and microvascuolization, whereas no change was observed in hamsters given DM-heparin complex or saline. Acute toxic effects on survival rates and body weights were more profound in DM-infused mice than in DM-heparin-infused mice. DM and DM-heparin complex showed similar anticancer activity both in vivo and in vitro. Thus, the present study suggests that the DM-heparin complex may attenuate the cardiotoxicity of DM without affecting it's antitumor effect in humans.

Animals

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

Adolescent

Reference intervals for serum granulocyte colony-stimulating factor levels in children.

OBJECTIVE: To determine age-adjusted reference intervals for children for serum granulocyte colony-stimulating factor (G-CSF) levels. DESIGN: We determined the serum G-CSF levels of 168 disease-free children who were term neonates to 15 years of age with a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: The lowest values (5 ng/L) exceeded the detectable limit (1 ng/L) of this assay technique. The G-CSF levels were highest on the day of birth (mean +/- SD 147 +/- 146 ng/L); thereafter values decreased to 46 +/- 33 ng/L in the early neonatal period and to 23 +/- 10 ng/L in the late neonatal period. The G-CSF levels both on the day of birth and in the early neonatal period were significantly higher than in all older age groups. No significant differences were found among any of the age groups after 4 weeks of age. The G-CSF values were correlated with both blood leukocyte counts (r = 0.496, p < 0.0001) and neutrophil counts (r = 0.547, p < 0.0001). In children older than 4 weeks of age (n = 128), the 95% reference interval for G-CSF values was 5 to 42 ng/L. CONCLUSIONS: Our study in disease-free children revealed that change in serum G-CSF levels are age dependent and are correlated with neutrophil counts. Determination of reference intervals for the neonatal period requires further study.

Adolescent

Effect of cyclosporin analogues and FK506 on transcellular transport of daunorubicin and vinblastine via P-glycoprotein.

PURPOSE: P-glycoprotein-mediated transcellular transport of anticancer agents and the inhibitory effect of cyclosporin analogs and FK506 were investigated. METHODS: The transcellular transport of daunorubicin and vinblastine by monolayers of LLC-GA5-COL150 cells which overexpressed P-glycoprotein was measured in the presence and absence of cyclosporins or FK506. RESULTS: Cyclosporins and FK506 inhibited P-glycoprotein-mediated transport of daunorubicin and vinblastine in the order of cyclosporin D, dihydrocyclosporin D > cyclosporin A > FK506 > cyclosporin C, dihydrocyclosporin C. The intracellular accumulation of the anticancer agents was highly associated with the transporting function of P-glycoprotein. The inhibitory effect of cyclosporin D was concentration-dependent. The inhibitory effect of the modulators on P-glycoprotein was not correlated with the immunosuppressive activity, but was correlated with their lipophilicity. CONCLUSIONS: In the transcellular transport system, lipophilicity may be one of the determinants for the inhibitory effect of various multidrug resistance modulators on the P-glycoprotein-mediated transport.

ATP Binding Cassette Transporter, Subfamily B, Mem

Chronic myelomonocytic leukaemia with t(8;9)(p11;q34) in childhood: an example of the 8p11 myeloproliferative disorder?

We describe the case of a 10-year-old girl with chronic myelomonocytic leukaemia with the chromosomal translocation t(8;9)(p11;q34), who had developed tonsillar lymphoma as extramedullary involvement at the initial presentation. The cytogenetic study of the cells in both bone marrow and tonsils demonstrated t(8;9)(p11;q34), despite no malignant features in the bone marrow specimens. She developed acute leukaemic transformation 8 months after diagnosis during chemotherapy for lymphoma. Although etoposide reduced the number of blasts, t(8;9)(p11;q34)-bearing cells were not eradicated. Complete remission was obtained following an unrelated bone marrow transplantation. The clinical characteristics of this patient are similar to those of the patients with t(8;9)(p11;q34 or q32) or t(8;13)(p11;q11 or q12) reported previously. The unusual progression of the disease might be associated with the presence of (8;9)(p11;q34), suggesting a part in the 8p11 myeloproliferative syndrome.

Child

Temporoparietal sandwich technique in acute avulsion injury of the hand.

In degloving injuries of the hand, rehabilitation can be delayed due to poor wound healing and partial flap necrosis, if the avulsed tissue is sutured back primarily. By sandwiching a temoroparietal fascial flap between the avulsed flap and the tendons, rehabilitation can be started immediately, even if flap necrosis is present.

Accidents, Occupational

Successful treatment with ranimustine and carboplatin for recurrent intraocular retinoblastoma with vitreous seeding.

This is the first report of successful treatment of recurrent retinoblastoma with vitreous seeding by a combination of ranimustine (MCNU) and carboplatin. The patient was diagnosed with bilateral retinoblastoma at 3 years of age. Although he received photocoagulation and radiotherapy for the left eye after enucleation of the right eye, a recurrent tumor associated with vitreous seeding developed 6 years later. The child underwent chemotherapy with cyclophosphamide and nimustine hydrochloride (ACNU), and a transient decrease of tumor cells in the vitreous was seen. We then changed the chemotherapy regimen to MCNU (70 mg/m2/ day for 1 day) and carboplatin (400 mg/m2/day for 2 days). After five courses of this chemotherapy, the tumor in the vitreous completely disappeared. No recurrence has been observed for > 4 years. Side effects, including myelosuppression, general fatigue, and vomiting, were observed during the course of chemotherapy, but they were ameliorated with supportive therapy. Neither nephro- nor ototoxicity was observed. The patient has useful vision. These results warrant further study of this novel drug combination in patients with recurrent, or even primary, retinoblastoma.

Antineoplastic Agents

Bleed of and biologic response to triglyceride filler used in radiolucent breast implants.

Radiolucent breast implants filled with triglyceride oil have recently entered limited clinical trials. To investigate the questions of oil bleed and the fate of triglycerides that might escape from ruptured breast implants, experiments reported here used peanut oil labeled with radioisotopes so that it could be traced in the urine, feces, and organs of two groups of rabbits. In one experiment, 18 rabbits were implanted with peanut oil-filled implants labeled with tritium to determine whether triglycerides diffuse across silicone elastomer shells. In another experiment, 19 rabbits were injected with 14C-labeled peanut oil to study what might happen to the oil if an implant ruptures. At the end of the follow-up period, we measured radioisotope levels in tissue samples taken from the periprosthetic capsule or injection site of each rabbit, as well as from major organs and the subcutaneous fat on the dorsum opposite the experimental site. One experiment revealed that triglycerides do bleed across the implant shells. Tritium levels were highest in the implant capsule, the omentum, the aorta, and the subcutaneous fat on the nonexperimental side. In the experiment simulating implant rupture, 14C levels were above the background radiation count at the injection site and in the same tissue sites as in the bleed experiment. Both in vivo radiolabeling studies indicate that triglycerides freed from implants by means of bleed or rupture would be absorbed, metabolized, and either excreted or redistributed to the body's normal fat storage sites if they are not needed for energy. In a third in vitro experiment, triglyceride oil specimens were inoculated with various microorganisms associated with wound infections: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and diphtheroids. The data demonstrate that neutral triglycerides used as a breast implant filler do not support growth of common infection-producing bacteria and suggest that triglycerides may have bactericidal properties.

Adipose Tissue

Erythrocyte deformability in schizophrenic patients.

Erythrocyte deformability as a clinical indicator of microcirculatory disturbance was determined in the erythrocyte of 25 schizophrenic patients and of 18 normal controls. Schizophrenic patients had significantly lower erythrocyte deformability than did the normal controls (P < 0.001). This result suggests that microcirculation in schizophrenic patients is disturbed, and that this disturbance might be involved in the pathophysiological genesis of schizophrenia.

Adolescent