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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 109 records · Page 6Linked to original sources

Different drug sensitivity in two neuroblastoma cell lines established from the same patient before and after chemotherapy.

Drug resistance is one of the major impediments to the treatment of advanced neuroblastoma. Two neuroblastoma cell lines established from the same patient before (KP-N-AY) and after (KP-N-AYR) chemotherapy are described. Both cell lines were established from bone-marrow metastases of a 2 1/2-year-old patient with stage IV neuroblastoma. Chromosomal analysis, catecholamine assessment and the surface membrane phenotype of these cell lines confirmed that the tumors were of neuroblastoma origin. Compared with the KP-N-AY cell line, the KP-N-AYR line had decreased N-myc amplification but increased N-myc expression. An in vitro sensitivity test using a clonogenic assay showed the KP-N-AYR cell line to be 3.0-fold resistant to adriamycin and 2.7-fold resistant to cis-platinum as compared with the KP-N-AY cell line. The expression of the multi-drug-resistance gene (MDR1) was not observed in either cell line by the ribonuclease protection assay. The KP-N-AY cell line revealed only faint MDR1 RNA by the polymerase chain reaction, whereas the KP-N-AYR cell line had no expression of the MDR1 gene. The level of glutathione-S-transferase-pi was significantly higher in the KP-N-AYR cell line than in the KP-N-AY cell line. These findings suggest that the development of clinical drug resistance may be associated with the enhanced glutathione-S-transferase-pi activity but not with MDR1 gene expression.

Antigens, Surface

Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model.

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r = 0.88) but was poorly correlated with labelled antibody uptake (r = 0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

Animals

Identification of an A-factor-dependent promoter in the streptomycin biosynthetic gene cluster of Streptomyces griseus.

A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is a microbial hormone controlling streptomycin (Sm) production, Sm resistance and sporulation in Streptomyces griseus. In order to identify A-factor-dependent promoters in the Sm biosynthetic gene cluster, a new promoter-probe plasmid with a low copy number was constructed by using an extremely thermostable malate dehydrogenase gene as the reporter. Of the three promoters in the Sm production region that includes strR, aphD and strB, only the promoter of strR, which codes for a putative regulatory protein, was found to be directly controlled by A-factor. This was also confirmed by S1 nuclease mapping. The region essential for its A-factor-dependence was determined to be located 430-330 base pairs upstream of the transcriptional start point. Increase in the copy number of the strR promoter region did not lead to a corresponding increase in the total promoter activity, probably due to titration of a putative activator which binds to the enhancer-like region and controls the expression of the strR promoter. This putative activator is apparently distinct from the A-factor-receptor protein. The aphD gene, which encodes the major Sm resistance determinant, Sm-6-phosphotransferase, was transcribed mainly by read-through from the A-factor-dependent strR promoter; this accounts for the prompt induction of Sm resistance by A-factor.

4-Butyrolactone

Asymptomatic isolated microhaematuria: natural history of 136 children.

In a mass screening programme, 251 children with isolated microhaematuria were detected. Of these 251 children, 115 were excluded from the study because of microhaematuria secondary to a specific cause. The remaining 136 children were diagnosed as having asymptomatic isolated microhaematuria (ASH). Of these 136 children, 23 had evidence of urinary abnormalities in their family members. Red blood cell casts were evident in 31 children at their initial visit or during the follow-up period. Ten children had one or more episodes of macrohaematuria during the study. Renal biopsy was performed in 19 children because of indications of glomerular disease, and 13 of these 19 children had mild to moderate glomerulonephritis. None of these 136 children developed hypertension or renal impairment after a mean period of 7.4 years (range 6-13 years). Thirty-five children had normal urinary findings within 6 years of their initial visit, and 100 have had persistent microhaematuria without proteinuria throughout the follow-up period. The other child had microhaematuria with proteinuria greater than 1 g/m2 per day at the end of the study. This study suggests that the prognosis of ASH is good, and that renal biopsy is not indicated for children with ASH.

Adolescent

Aseptic meningitis in children: correlation between fever and interferon-gamma level.

We studied the correlation between interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in cerebrospinal fluid (CSF) and clinical/laboratory findings in children with aseptic meningitis. In 19/27 patients (70%), the CSF IFN level was high at initial diagnosis, and reduced to a low or undetectable level during the convalescent phase (5-14 days later) of the disease. There were no differences in IL-1 beta and TNF-alpha levels between the acute and convalescent phase of the patients. The serum IFN-gamma levels in the patients, which were simultaneously examined were undetectable in the acute phase. When we compared the clinical/laboratory findings between the 29 patients with detectable CSF IFN-gamma level and the 21 patients with an undetectable CSF IFN-gamma level in the acute phase, the former demonstrated higher body temperature (P less than 0.01), and higher cell number and protein level in the CSF (P less than 0.05) than the latter. On the other hand, there were no significant differences in the duration of meningeal signs, the titre of C-reactive protein, and the peripheral leucocyte count between the two groups. By the Spearman's rank sum test, the CSF IFN-gamma levels correlated more definitively with the severity of febrile episode (maximal body temperature, duration of fever and body temperature at the first lumbar tap), and the cell number and protein level in the CSF. These results suggest that IFN-gamma produced in the inflamed intrathecal space may be associated with the pathogenesis of aseptic meningitis, especially the production of fever.

Child

Moebius syndrome with central hypoventilation and brainstem calcification: a case report.

Moebius syndrome (MS) is described in an infant with central hypoventilation and brainstem calcification. The patient had limb defects and bilateral paralysis of the 6th, 7th, 9th, 10th, and 12th cranial nerves. Mechanical ventilation was continued from birth because of shallow spontaneous respiration. Computed tomography revealed brainstem atrophy and four small calcifications restricted to the dorsal portion of the pons and medulla. Prenatal brainstem injury such as ischaemia may have caused MS and central hypoventilation.

Abducens Nerve

Detection of multidrug-resistant protein, P-glycoprotein in childhood leukaemia and lymphoma.

Flow cytometric detection of surface P-glycoprotein, a multidrug-resistant gene product, with a monoclonal antibody, MRK 16, was performed on cells obtained from 18 children with leukaemia and lymphoma. Of 18 patients examined, 1 with malignant lymphoma at relapse showed a significant increase in P-glycoprotein-positive cells and a strong resistance to chemotherapy. Overexpression of P-glycoprotein in a case with B-cell type malignant lymphoma was confirmed by immuno-precipitation and Northern hybridization analysis. The present study suggests that an increased expression of surface P-glycoprotein might be involved in multidrug resistance at least in a certain case of childhood leukaemia and lymphoma.

ATP Binding Cassette Transporter, Subfamily B, Mem

Tumor necrosis factor in the cerebrospinal fluid of children with central nervous system leukemia.

To clarify the role of cytokines in cerebrospinal fluid (CSF) in the pathogenesis of central nervous system (CNS) leukemia, three cytokine activities, interleukin 1 (IL-1)-beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, and their correlations with other laboratory studies of the CSF were analysed in 23 children with acute leukemia. These patients were classified into three groups: group A (n = 8)--patients with overt CNS leukemia, group B (n = 5)--patients with CNS leukemia in remission, group C (n = 10)--patients without CNS disease. IFN-gamma in the CSF was undetectable in these 23 patients. There was no difference in IL-1-beta levels among the three groups. However, TNF-alpha levels were significantly higher in group A than in group B, and higher in group B than in group C. By Kendall's rank sum test, high TNF levels in CSF correlated with high CSF leukemic cell counts and low sugar levels. In two patients with overt CNS leukemia, the TNF level in the CSF decreased gradually with intrathecal chemotherapy. These results indicate that TNF released from stimulated cells in the cerebrospinal space may induce CNS leukemia-related symptoms or alter laboratory parameters measured in the CSF. TNF levels in CSF may also prove useful in diagnosing early CNS involvement in children with acute leukemia.

Acute Disease

The late waves of brainstem auditory evoked potentials in children with cerebrovascular diseases.

We examined brainstem auditory evoked potentials (BAEPs) in 28 children with cerebrovascular diseases and 38 normal control subjects and investigated the neuroanatomic correlations of the late waves (VI and VII) of the BAEPs. The patients included 19 patients with moyamoya disease and 9 with other cerebrovascular accidents. Wave VI was more consistently seen (only missing in 2 cases, 5%-2 ears, 3%) than wave VII (missing in 26 cases, 68%-40 ears, 53%) in the control group. Absent, depressed or prolonged wave VI correlated well with cerebral lesions involving internal capsule and basal ganglia, while wave VII had a less significant correlation with any cerebral lesions in children with cerebrovascular diseases.

Adolescent

Cytogenetic and cellular characteristics of a human embryonal rhabdomyosarcoma cell line, RMS-YM.

A human tumour cell line, designated RMS-YM, was established from a childhood rhabdomyosarcoma. The monolayer cells were polygonal, round or spindle-shaped. The cells became multilayered and formed many focal piles when confluent. RMS-YM became stable with a doubling time of about 30 h and has been maintained for 104 passages to date. Tumourigenicity of the cells was confirmed by heterotransplantation into nude mice. Morphological features were similar to those of the primary tumour, and myofibrils were found by electron microscopy. The expression of desmin and human myoglobin, and high levels of striated muscle system specific enzymes were recognised. Chromosomal analysis revealed possible gene amplification in the form of homogeneously staining regions. Oncogene analysis was performed on the primary tumour and the cell line, but neither N-myc nor N-ras genes were amplified, nor were Ki-ras, Ha-ras or N-ras genes mutated at the 12th, 13th and 61st codons. The RMS-YM cell line may provide a system to identify novel genes which are amplified in rhabdomyosarcoma.

Animals

Well-differentiated hepatocellular carcinoma showing intrahepatic neural invasion: autopsied case.

An autopsied case of well-differentiated hepatocellular carcinoma (HCC), showing neural invasion into the portal tract of the liver, a hitherto undescribed lesion, is reported. The patient, a 68-year-old man, had had treatment for HCC over nine years, comprising surgical resection, transcatheter arterial embolization, transportal venous embolization and percutaneous ethanol injection to nodules of the HCC. At autopsy, many HCC nodules (less than 7 cm in diameter) were found in the liver. In one of them, carcinoma cells infiltrated the medium-sized protal tract among the regenerative nodules and some of these carcinoma cells further invaded nerve fibers. Although the majority of the HCC nodules showed ischemic necrosis, the infiltrating carcinoma cells in the portal tract were viable, suggesting the biological behavior and/or blood supply of these infiltrating carcinoma cells to be different.

Aged

The role of intrahepatic portal venous stenosis in the formation and progression of hepatolithiasis: morphological evaluation of autopsy and surgical series.

Recently, it has been suspected in animal models that a decrease in portal blood flow plays a role in the formation and progression of hepatolithiasis. To find whether this hypothesis is applicable to humans, we examined histologically the intrahepatic portal venous and arterial systems in normal livers (n = 13), extrahepatic biliary obstruction (n = 18), intrahepatic biliary sludge and microcalculi (n = 18, most of which were associated with biliary obstruction and might represent pathogenesis of an early developmental stage of hepatolithiasis), and fully developed hepatolithiasis composed of calcium bilirubinate stones (n = 30). A scoring method was employed to quantify portal stenosis, portal phlebosclerosis, arterial stenosis, and parenchymal atrophy. We found that these vascular changes were significantly more severe in hepatolithiasis than in biliary sludge and microcalculi, or in extrahepatic biliary obstruction. There were no significant differences in the vascular changes except for arterial stenosis between the latter two. There is a positive correlation between vascular stenosis and parenchymal atrophy. These findings suggest that portal venous stenosis deteriorates during the progression of hepatolithiasis. We could not find direct evidence that portal venous stenosis is an initial lesion followed by the formation of hepatolithiasis. The vascular changes may be caused by an inflammatory extension of cholangitis and may deteriorate, causing parenchymal atrophy during the progression of hepatolithiasis.

Aged

Selective necrosis of encapsulated malignant lesion within atypical adenomatous hyperplasia of the liver following transarterial embolization. A report of two autopsy cases.

We report here the morphology of two nodules of atypical adenomatous hyperplasia (AH), a preneoplastic or early developmental stage of hepatocellular carcinoma (HCC), with a fibrously encapsulated malignant lesion occurring in two cirrhotic livers. The two patients had been treated for HCC by transarterial embolization. At autopsy, HCC nodules and several AH nodules were found in each case. Microscopically, two of the several AH nodules contained malignant lesions that showed selective coagulative necrosis: the hepatocytes of the nonmalignant parts of the two AH nodules were viable. The malignant lesions within the atypical AH nodules were surrounded with a fibrous capsule, and the majority of HCC nodules were necrotic; AH nodules themselves, except for malignant lesions, were viable. This suggests to us that there are differences in blood supply between the malignant lesions and surrounding tissue of atypical AH: malignant lesions within atypical AH may be supplied mainly by arterial blood, whereas nonmalignant areas of atypical AH may be dually supplied by both arterial and portal blood. Alternatively, it may be that the malignant lesions in atypical AH are more susceptible to hypoxia caused by transarterial embolization.

Adenoma

Carcinoma of the colon in children: a case report and review of 41 Japanese cases.

We report a case of sigmoid colon carcinoma in a 14-year-old girl. She had been suffering from several nonspecific abdominal symptoms for about 1 year before a definite diagnosis was made. While undergoing an operation, the main tumor was found to be unresectable. She died of Candida-induced septicemia on the 26th day after the operation. There have been 40 cases of colon carcinoma reported in the Japanese literature in patients 15 years of age or younger. We reviewed the 40 Japanese cases along with our case, and compared these to other children and adult studies. The prognosis is quite unfavorable in children because of the poor histological character and the delayed diagnosis. Serum carcinoembryonic antigen measurement might be one means for early diagnosis.

Adolescent