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Biomedical subjects

K Ikeda

Publications and source records attributed to K Ikeda.

At least 163 records · Page 9Linked to original sources

The value of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls.

This study was conducted to assess the diagnostic potential and pitfalls of performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We retrospectively analyzed 1,012 aspirated samples obtained from 806 thyroid nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had been surgically treated, 152 (67%) of which were histologically diagnosed as malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a diameter of less than 5mm (73%, P = 0.10); either calcified (77%, P = 0.043) or benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate diagnosis was 16%, the false negative rate was 13%, and the positive malignancy rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008, and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy was improved to 81% by repeating the procedure. These findings indicated that repeated aspiration may be a simple and effective method of improving the diagnostic potential of FNAC.

Adenocarcinoma, Follicular↗

Inter-laboratory comparison of DNA preservation in archival paraffin-embedded human brain tissue from participating centres on four continents.

DNA extracted from formalin-fixed and paraffin-embedded brain tissue is known to contain as yet ill-characterized inhibitors of the PCR process. As part of a project that aims to clarify the role of mitochondrial DNA sequence variation in human neurodegenerative diseases using DNA from various ethnic backgrounds, we have investigated factors that influence the preservation of archival DNA and its suitability for PCR. In this study, neuropathological tissue samples were analysed that had been routinely processed in 18 international centres on four continents. Following DNA extraction, PCR amplification of mitochondrial and nuclear DNA sequences was performed with and without additional purification of the template DNA. In addition, the DNA used for PCR was analysed by HPLC. Phosphate-buffered formalin proved to be a superior fixative compared with unbuffered aldehyde: DNA extraction resulted in greater yields, the molecular weight of the isolated DNA was higher and PCR was more successful. PCR inhibitors were identified as (1) high concentrations of small (<300 bp) DNA fragments that competitively compete with template DNA and (2) contaminants of the DNA template solution including denatured protein that cannot be completely removed by phenolic extraction. HPLC analysis did not reveal significant qualitative differences between DNA isolated from fresh-frozen tissue samples and DNA recovered from formalin-fixed, paraffin-embedded brain tissue. The fact that DNA could be amplified from the majority of tissue specimens in this study suggests that rare diseases and diseases where ethnic background plays an important role can be sampled for genetic polymorphism analysis on a global scale using archival neuropathological collections.

Alzheimer Disease↗

Postoperative delirium and melatonin levels in elderly patients.

BACKGROUND: Melatonin, a hormone produced in the pineal gland, is involved in circadian rhythms and the sleep-wake cycle. Postoperative delirium is encountered frequently in elderly patients after major surgery; whether changes in the pattern of melatonin secretion are associated is unclear. METHODS: Plasma samples were obtained every 2 hours from 19 patients without delirium and 10 with delirium after major abdominal surgery. Postoperative delirium was determined using the Confusion Assessment Method in the Practice Guideline of the American Psychiatric Association. RESULTS: All patients without delirium showed nearly identical preoperative and postoperative melatonin secretion for 24 hours, although peak values were significantly lower in patients more than 80 years old (7.2 +/- 2.3 pg/mL) than in patients younger than 80 years (24.4 +/- 4.1 pg/mL, P = 0.022). Patients with delirium showed two different abnormal postoperative patterns: in 5 patients without complications, melatonin levels were lower than preoperative values (11.0 +/- 5.8 versus 6.5 +/- 4.2 pg/mL, P = 0.079); and in 5 patients with complications, melatonin levels were markedly increased (21.1 +/- 4.5 versus 58.8 +/- 12.4 pg/mL, P = 0.043). CONCLUSIONS: Abnormal melatonin secretion may be involved in postoperative sleep disturbances, which triggered delirium in elderly patients.

Abdomen↗

Dihydroxynortropane alkaloids from calystegine-producing plants.

Three dihydroxynortropanes, 2alpha,7beta-dihydroxynortropane, 2alpha,3beta-dihydroxynortropane, and 3alpha,7beta-dihydroxynortropane, were isolated from calystegine-producing plants in the families Convolvulaceae and Solanaceae. 2alpha,7beta-Dihydroxynortropane was isolated from six species in the Convolvulaceae whereas only Calystegia soldanella contained it and 2alpha,3beta-dihydroxynortropane. Although neither of these were detectable in three species tested in the Solanaceae, 3alpha,7beta-dihydroxynortropane was, however, isolated from Duboisia leichhardtii.

Alkaloids↗

Evaluation of quantitative measurements of hepatitis C virus RNA to predict sustained response to interferon by genotype.

Hepatitis C virus (HCV) virus load is one of the most important predictive factors for the outcome of interferon (IFN) therapy. Recent technological advances have allowed a more precise measurement of HCV load. However, the exact cutoff values that could be used to predict the outcome of IFN have not been established for each assay. Five recent quantitative assays were evaluated for the measurement of HCV (Amplicor monitor ver 1.0, Amplicor monitor ver 2.0 (GT), Amplicor monitor ver 2.0 (Cobas), Quantiplex branched DNA amplification (bDNA) ver 2.0 and HCV core protein level by enzyme immunosorbent assay) in 209 consecutive patients with chronic hepatitis C, who received IFN therapy. The results of the two second generation Amplicor monitor tests (GT and Cobas) showed the best correlation (r = 0.930), but the other tests also showed relatively good correlations (r = 0.646-0.925). Each method predicted the effect of IFN with comparable predictive efficacy, ranging from 77.0 to 80.8%. Receiver operating characteristic (ROC) curve analysis showed that Amplicor monitor ver 2.0 and bDNA ver 2.0 are superior in predicting the response in genotype 2a. The best cutoff value for predicting the response to IFN was different by genotype, which should be considered in selecting candidates for IFN treatment.

Adult↗

Cognitive decline in schizophrenics with Alzheimer's disease: a mini-review of neuropsychological and neuropathological studies.

Cognitive decline in elderly schizophrenic patients is an important clinical symptom, but it is often difficult to analyze in detail due to the patient's original residual psychotic symptoms. In this article, the authors provide neuropsychological and neuropathological research information about cognitive decline in elderly schizophrenic patients, especially with reference to Alzheimer's disease (AD). Neuropsychological and neuropathological reports about cognitive impairments are reviewed. The effect of long-term antipsychotic medication upon cognitive function is also discussed. As a result, it is apparent that elderly schizophrenic patients often show cognitive impairments, however, such impairments do not have the characteristics of progressive degenerative illnesses such as AD, and the speed of their progress is very slow. Neuropathological studies have shown that AD brain pathology appears no more frequently among schizophrenic patients than in the normal population. Since making a diagnosis of AD means that the progressive deterioration not only of cognitive function, but also of physical ability, paralleling the degeneration of the central nervous system, can be expected within a few years and appropriate care will be required. One should be very cautious in adding a diagnosis of AD to elderly schizophrenic patients with cognitive impairments.

Alzheimer Disease↗

The distribution of PIG-A gene abnormalities in paroxysmal nocturnal hemoglobinuria granulocytes and cultured erythroblasts.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia that is characterized by a deficiency of glycosylphosphatidylinositol-anchored membrane proteins due to phosphatidylinositol glycan-class A (PIG-A) gene abnormalities in various lineages of peripheral blood cells and hematopoietic precursors. The purpose of our study was to clarify the distribution of PIG-A gene abnormalities among various cell lineages during differentiation and maturation in PNH patients. The expression of CD16b or CD59 in peripheral blood granulocytes or cultured erythroblasts from three Japanese PNH patients was analyzed using flow cytometry. PIG-A gene abnormalities in both cell types, including glycophorin A(+) bone marrow erythroblasts, were examined using nucleotide sequence analysis. The expression study of PIG-A genes from each patient was also performed using JY-5 cells.Flow cytometry revealed that the erythroblasts consisted of negative, intermediate, and positive populations in Cases 1 and 3 and negative and intermediate populations in Case 2. The granulocytes consisted of negative and positive populations in all three cases. DNA sequence analysis indicated that all the PNH cases had two or three types of PIG-A gene abnormalities, and that a predominant clone with an abnormal PIG-A gene was different in granulocytes and erythroblasts from Cases 2 and 3. Expression studies showed that all the mutations from the patients were responsible for the null phenotype.PIG-A gene abnormalities result in deficiencies of glycosylphosphatidylinositol-anchored proteins in PNH erythroblasts and granulocytes. The distribution of predominant PNH clones with PIG-A gene abnormalities is often heterogeneous between the cell types, suggesting that a clonal selection of PIG-A gene abnormalities occurs independently among various cell lineages during differentiation and maturation.

Adult↗

Administration of granulocyte colony-stimulating factor induces hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function of peripheral blood monocytes.

OBJECTIVE: The incidence and severity of acute graft-vs-host disease after allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are not greater than those after conventional bone marrow transplantation despite infusion of more than one log greater number of donor T cells in PBSC. It has been postulated that monocytes from G-CSF-mobilized donors suppress alloreactivity of donor T cells. MATERIALS AND METHODS: We investigated the phenotype and function of monocytes in normal individuals receiving 10 microg/kg of G-CSF for 4 days. RESULTS: Monocytes were phenotypically and functionally different after G-CSF administration from steady-state monocytes. They were characterized by an increased CD14(+)CD16(+) subpopulation, reduced expression of HLA-DR, and diminished ability to produce tumor necrosis factor-alpha and interleukin-10 to lipopolysaccharide, compared with steady-state monocytes. These alterations were not replicated by culturing monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In addition, the antigen-presenting function of G-CSF-mobilized monocytes was impaired. CONCLUSION: Hyporesponsiveness of G-CSF-treated monocytes to lipopolysaccharide with regard to tumor necrosis factor-alpha production, together with impaired antigen-presenting function, may be responsible for the unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC transplantation.

Antigen Presentation↗

Distribution of protein motors along the lateral wall of the outer hair cell.

The outer hair cell (OHC) plays an important role in the normal functioning of the cochlea, and cochlear amplification is believed to be based on OHC electromotility. This electromotility putatively arises from a conformational change of molecules, i.e., 'protein motors', which would be distributed along the plasma membrane. Although it has been assumed that protein motors are distributed in a restricted area of the plasma membrane, details of such distribution remain unclarified. In this study, first, in order to understand the difference in the stiffness along the cell axis, the local deformation of the OHC in response to hypotonic stimulation is analyzed by measuring the displacement of microspheres attached randomly to the lateral wall of the cell. As a result, the stiffness is expected to be constant throughout the region except in the apical part of the cell, and the stiffness of the apical part is expected to be higher than that of the other regions. Then, the local elongation and contraction of the OHC in response to sinusoidal voltage stimulation are analyzed by measuring the displacement of the microspheres in the same way as in the case of the hypotonic stimulation. From the two measurements mentioned above, it is concluded that there are no motors in the apical and basal parts of the cell, and that the motors are equally distributed along the cell lateral wall in the middle part of the cell.

Animals↗

Genetics of Epstein-Barr virus infection.

Epstein-Barr (EBV) virus is a member of the human herpesvirus family. EBV is the etiologic agent of acute infectious mononucleosis and is closely associated with the genesis of Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. EBV is also implicated in a variety of other diseases, such as X-linked lymphoproliferative syndrome, T-cell non-Hodgkin's lymphoma, Hodgkin's disease, and NK-cell granular lymphoproliferative disorder. Recently, lymphoepithelial carcinoma of the stomach, gastric carcinoma, pyothorax-associated lymphoma, and smooth muscle tumors were also recognized as EBV-associated diseases. It is therefore important to review the genetics and immunological response of EBV infection. In this review we summarize the genetics of EBV, immunological responses and clinical findings of EBV-associated diseases, which would help us to understand the pathophysiology of EBV-associated disease and develop specific treatments.

Epstein-Barr Virus Infections↗

Precise emission probabilities of gamma-rays of 159Gd.

Measurement of emission probabilities for principal gamma-rays of 159Gd with 4pibeta(ppc)-gamma(HPGe) coincidence apparatus has given precise values as indicated by uncertainties of about 1%. Improved certainties are seen when comparing the present results with emission probabilities evaluated in Nuclear Data Sheets (Helmer, 1994, p. 72) for which the uncertainties are about 24%. The improvement resulted in precise decay scheme parameters of the nuclide.

Journal Article↗

Randomized controlled clinical trial of lymphoblastoid interferon-alpha for chronic hepatitis C.

Objective: Most of chronic hepatitis C patients with HCV-genotype 1 and a high virus load fail to eradicate the HCV-RNA by the interferon (IFN) or IFN/ribavirin therapy. But in these patients, IFN is often effective with regard to normalization of alanine aminotransferase (ALT). We had therefore the following two randomized controlled clinical trials to evaluate the effect of IFN which reduce ALT and maintain normalization of ALT. One approach (study 1) was to compare the efficacy of a 6 month course of three different dosages of recombinant IFN-alpha-2a in patients with chronic hepatitis C associated with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml. Another approach (study 2) was to make clear the significance of an additional 6 month course of IFN in patients who had biochemical response during the first 6 month course of IFN (study 1). Methods: (1) Study 1; 45 patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml were randomly assigned into three equal groups; group 1 was treated with 3 million units (MU), group 2 with 6 MU and group 3 with 9 MU. They were treated with IFN 3 times weekly for 6 months. Biochemical response was defined as normalization of ALT at the 6 month after initiation of IFN; (2) Study 2; Subsequently, of 23 patients with biochemical response by the first study, 22 were randomly assigned to two groups; patients in group A were continued to receive 3 MU of IFN-alpha-2a three times a week for an additional 6 months and patients in group B were discontinued IFN therapy. Results: (1) Study 1; One patient in group 1, three in group 2 and five in group 3 withdrew from IFN therapy because of IFN-related side-effects. Biochemical response was 10 (66.7%) patients of group 1,8 (53.3%) of group 2 and 5 (33%) of group 3 by the intention-to-treat (ITT) analysis. The biochemical response rate in group 1 was slightly higher than that in other two groups by the Cochran Armitage two-tailed test (P=0.066). With respect to serum HCV-RNA level, one patient in group 1, six patients in group 2 and four patients in group 3 became negative for HCV-RNA by reversed transcription nested-polymerase chain reaction (RT nested-PCR) at the end point of first 6 month course of IFN; (2) Study 2; The maintenance rate of ALT normalization was 88.9% (9/11) in group A and 11.1% (2/11) in group B. The maintenance rate of ALT normalization in group A was significantly higher than that in group B by the Fisher exact's test (P=0.0089). With respect to serum HCV-RNA level by RT nested-PCR, four patients in group A had negative HCV-RNA at the end of an additional IFN therapy. On the other hand, all the patients in group B had positive HCV-RNA at the same time. Conclusion: Our data suggested that a prolonged IFN therapy using a dose of 3 MU of IFN-alpha-2a is safe strategy to reduce ALT and to maintain ALT normalization in patients with HCV-genotype 1b and a high serum HCV-RNA level of more than 1 Meq/ml.

Journal Article↗

Reduced neuropeptide Y mRNA levels in the frontal cortex of people with schizophrenia and bipolar disorder.

To study the change of gene expression in the brain tissues of schizophrenia, we used the gene expression monitoring technology and compared two sets of pools each containing four RNA samples of frontal cortex that were randomly selected from the control or schizophrenia group. We found that the expression of two genes were commonly altered in four pairwise comparisons; the expression of DEAD-box protein p72 (p72) gene was increased and neuropeptide Y (NPY) gene expression was decreased in the schizophrenia group compared with the control group. To substantiate these results, we estimated their mRNA levels by the real time TaqMan method in the 15 samples of each frontal or temporal cortex of four matched groups of schizophrenia, bipolar disorder, major depression and normal controls. A statistically significant decrease was observed for NPY in the frontal, but not in the temporal cortex, in the schizophrenia group (P=0.003). A decrease was also observed in the frontal cortex of the bipolar disorder group (P=0.031). In contrast, p72 gene expression showed no significant difference among the four groups. In conclusion, by novel technology of DNA array and TaqMan PCR analyses, we found that neuropeptide Y mRNA levels were significantly reduced in the frontal cortex in both schizophrenia and bipolar disorder.

Journal Article↗

Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.).

New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.

Alkaloids↗

Glutathione content is correlated with the sensitivity of lines of PC12 cells to cisplatin without a corresponding change in the accumulation of platinum.

A study of the involvement of glutathione (GSH) in cellular resistance to cisplatin was performed using methylmercury-resistant sublines (PC12/TM series) of the PC12 line of rat pheochromocytoma cells. The seven clonal sublines of PC12 cells (PC12/TM, PC12/TM2, PC12/TM5, PC12/TM11, PC12/TM15, PC12/TM23, PC12/TM26) used in the study had intracellular levels of GSH that ranged from 8.7-39.9 nmol/mg protein. The intracellular level of GSH was significantly correlated (p < 0.01, r = 0.87) with the sensitivity to cisplatin of PC12 cells and the seven sublines. Among the seven sublines, PC12/TM cells contained the highest concentration of GSH and were the most resistant to cisplatin. Treatment of PC12/TM cells with L-buthionine-SR-sulfoximine, which reduced the level of GSH to that in the parental PC12 cells, significantly reduced the resistance of the cells to cisplatin. The amount of platinum accumulated by resistant PC12/TM cells after treatment with cisplatin was higher than that by sensitive PC12 cells. These results suggest that the intracellular level of GSH might be directly involved in the resistance to cisplatin of these cell lines. However, a high intracellular concentration of GSH does not appear to contribute to a decrease in the accumulation of cisplatin in these cells.

Animals↗

Inhibition of human parainfluenza virus type 1 sialidase by analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid.

Eleven novel analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) modified at the C-4 and C-9 positions were designed and tested for their ability to inhibit sialidase of human parainfluenza virus type 1 (hPIV-1). The analogs modified by the cyanomethyl, amidinomethyl, and thiocarbamoylmethyl groups at the C-4 position exhibited potent inhibition against hPIV-1 sialidase compared with Neu5Ac2en. The most effective compound was thiocarbamoylmethyl analog (4-O-thiocarbamoylmethyl-Neu5Ac2en). The activity of 4-O-thiocarbamoylmethyl-Neu5Ac2en causing 50% enzyme inhibition at a concentration of approximately 1.0x10(-5) M was 30-fold larger than Neu5Ac2en. While, the analogs of Neu5Ac2en modified by the azido and N-acetyl groups at the C-9 showed a decrease in inhibition of sialidase compared with the 9-hydroxy analogs. In addition, 4-O-thiocarbamoylmethyl-Neu5Ac2en strongly inhibited hPIV-1 infections of Lewis lung carcinoma-monkey kidney cells in comparison with Neu5Ac2en. The present findings would provide useful information for the development of anti-human parainfluenza virus compounds.

Animals↗

A case of persistent acute allograft glomerulopathy with long-standing stable renal function.

Acute allograft glomerulopathy (AAG) characterized by hypercellularity, enlargement of endothelial cells, infiltration of glomeruli by mononuclear cells and webs of PAS-positive material has been reported as an unusual but distinct form of acute rejection in kidney transplant recipients. We present a case of persistent AAG proven by serial biopsies. The patient was 53 years old when she received kidney transplantation from her mother. The immunosuppressants were methylprednisolone, azathioprine and FK506. She developed several acute rejections and received antirejection therapy. The patient transferred to our hospital 15 months after transplantation. Serum creatinine was 2.11 mg/dL. The level of serum creatinine was gradually elevated from 2.11 mg/dL to 3.09 mg/dL. Graft biopsy, performed 16.5 months after transplantation, represented prominent intraglomerular infiltration of mononuclear cells, segmental thickening of glomerular basement membrane (GBM) with double contour, grade 1 tubulitis, marked accumulation of mononuclear cells in peritubular capillaries and margination of mononuclear cells in a small artery. It was diagnosed as acute allograft glomerulopathy (AAG). Intravenous methylprednisolone pulse therapy, discontinuation of FK506 and administration of cyclosporin (CYA) resulted in decrease of serum creatinine. To evaluate histological evolution of AAG we performed two subsequent biopsies over 3 yr. Severe glomerulitis persisted as a prominent feature 8 months later and still existed 53.4 months after transplantation with decreased severity. The extent of GBM reduplication also decreased, but the percentage of glomerular sclerosis increased gradually. Multi-layering of basement membrane of peritubular capillary and interstitial fibrosis also increased. The prominence of infiltration of mononuclear cells in peritubular capillary was unchanged. At the last follow-up, i.e. 71 months after transplantation, her serum creatinine was 1.34 mg/dL. Neither proteinuria nor haematuria was observed. We consider that our immunosuppressive treatment has been successful so far, because the patient is still maintaining stable graft function since the transplantation over 6 yr ago. It is thus suggested that AAG per se probably has no influence on acute aggravation of graft function, but AAG and capillaritis in peritubular capillaries may cause an evolution of chronic allograft nephropathy, resulting in a slowly progressive deterioration of graft function.

Acute Disease↗

Machado-Joseph disease with retinal degeneration and dementia.

OBJECTIVES: To clarify the phenotypic varieties in Machado-Joseph disease (MJD). MATERIALS AND METHODS: We studied a 64-year-old man with ataxia, retinal degeneration and dementia neurologically, ophthalmologically and genetically. RESULTS: The patient noted dysesthesia of his hands at age 57 and later had memory disturbance. He had gait disturbance and needed a wheelchair at age 64. His total IQ was 61 on the WAIS-R. He had loss of central vision, ophthalmoplegia, hearing impairment, dysarthria, truncal and limb ataxia, sensory disturbance, and mild weakness of the extremities. Electrophysiologically he was suspected to have polyneuropathy. Brain MRI showed marked atrophy of the cerebellum and pons with mild cerebral atrophy. Ophthalmologic evaluation revealed multiple chorioretinal atrophy. Expanded CAG repeat numbers in MJD1 were 64. CONCLUSION: These findings indicate that the clinical features of MJD might cover a wider spectrum than previously expected, though it is possible that these complications, namely retinal degeneration and dementia, were incidental findings in this patient.

Brain↗