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Biomedical subjects

K Kuroda

Publications and source records attributed to K Kuroda.

At least 163 records · Page 9Linked to original sources

Implantation of IL-2-containing osmotic pump prolongs the survival of superantigen-reactive T cells expanded in mice injected with bacterial superantigen.

In the present study we investigated the mechanism of deletion of superantigen (sAg)-reactive T cells expanded in sAg-injected mice. In staphylococcal enterotoxin A (SEA)-injected mice, IL-2 activity in serum peaked at 1 to 3 h and the expression of IL-2R alpha-chain (IL-2R alpha) on SEA-reactive (V beta 3+, or V beta 11+) T cells peaked at 6 to 12 h after the injection. Expansion of V beta 3+ or V beta 11+ T cells peaked at 2 days after the injection when most of these T cells were IL-2R alpha negative, and IL-2 activity was not detected at all in serum, suggesting the involvement of IL-2 deprivation in the deletion of expanded T cells. Implantation of an osmotic pump containing human rIL-2 (IL-2 pump) prolonged the expanded states of V beta 3+ or V beta 11+ T cells in SEA-injected C57BL/6 mice and of V beta 8+ T cells in SEB-injected MRL +/+ and Fas Ag-defective MRL-Ipr/Ipr mice. Adult thymectomy did not change at all the effect induced by implantation of IL-2 pump. DNA fragmentation was blocked substantially in mice co-treated with SEA and IL-2 pump. In addition, CD4+ T cell blasts, obtained by in vitro stimulation with rIL-2 of splenic CD4+ T cells from mice co-treated with SEA and IL-2 pump, produced substantial amounts of IL-2 upon restimulation with SEA. These results indicate that deprivation of IL-2 is deeply involved in the deletion of expanded sAg-reactive T cells and their anergy induction in sAg-injected mice.

Animals↗

Involvement of transforming growth factor beta1 in autocrine enhancement of gelatinase B secretion by murine metastatic colon carcinoma cells.

We have reported previously that highly metastatic LuM1 cells derived from colon carcinoma colon 26 secrete larger amounts of gelatinase B than NM11 cells with poor metastatic potential, and that an increase in this gelatinase B secretion can be induced by autocrine factors (Hyup et A, Cancer Res., 54: 3611-3616, 1994). In the present study, a partial characterization was achieved by comparison of the autocrine factor preparation (fraction G) from serum-free medium conditioned with metastatic LuM1 cells with soluble factors known to stimulate gelatinase B secretion. Secretion of gelatinase B by LuM1 cells was augmented by tumor necrosis factor alpha, transforming growth factor beta1 (TGF-beta1), interleukin 1beta, or epidermal growth factor, and specific neutralizing antibodies abolished the induced increases. Platelet-derived growth factor and insulin-like growth factor 1 had no effect on gelatinase B secretion by LuM1 cells. The enhancement of gelatinase B secretion by fraction G was partially inhibited by the antibody to TGF-beta1. TGF-beta1 was detected in both active and latent forms in serum-free medium conditioned with LuM1 or NM11 cells, with the amount of TGF-beta1 higher in the former case. Gelatinase B secretion by LuM1 cells was enhanced by the addition of TGF-beta1 to the culture medium, but that by NM11 cells was not seriously affected, although the latter bound more of the factor. These results indicate the involvement of this growth factor in the autocrine stimulation of gelatinase B secretion by LuM1 cells. However, the autocrine factor effect was not fully explained by TGF-beta1 in the medium, and the involvement of some other unknown factor(s) was thus indicated.

Animals↗

Amorphization of Serpentine at High Pressure and High Temperature

Pressure-induced amorphization of serpentine was observed at temperatures of 200° to 300°C and pressures of 14 to 27 gigapascals with a combination of a multianvil apparatus and synchrotron radiation. High-pressure phases then crystallized rapidly when the temperature was increased to 400°C. These results suggest that amorphization of serpentine is an unlikely mechanism for generating deep-focus earthquakes, as the temperatures of subducting slabs are significantly higher than those of the rapid crystallization regime.

Journal Article↗

Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right- and left-sided colorectal cancer.

BACKGROUND: Epidemiologic and genetic studies suggest that cancer of the right and left sides of the bowel arise through different mechanisms. To investigate the molecular mechanisms, allelic loss of chromosome 17p, p53 mutations, and microsatellite instability were analyzed in colorectal cancer according to tumor site. METHODS: Using the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) method, mutations within exons 5-8 of the p53 gene were examined in 108 colorectal cancers including 30 right-sided and 78 left-sided colorectal cancers. Allelic loss of chromosome 17p was studied by restriction fragment length polymorphism analysis, and genetic instability was examined for replication error (RER) at three microsatellite loci on chromosomes 2p, 17p, and 17q. RESULTS: Allelic loss was observed in 61% (14 of 23 informative cases) of right-sided tumors and in 60% (26 of 43 informative cases) of left-sided tumors. PCR-SSCP analysis demonstrated that 63 of 108 tumors had a mutated p53 gene in exons 5, 6, 7, or 8. When comparing the frequency of mutation in each exon based on tumor site, the frequency of mutation in exon 8 in right-sided (2 of 18 informative cases) tumors was significantly lower than that observed in left-sided (17 of 45 informative cases) tumors. RER(+) was observed in 43% of right-sided tumors, whereas 24% of left-sided tumors were RER(+). Although the difference was not statistically significant, a trend was observed between RER(+) phenotype and tumor site. CONCLUSIONS: Our results suggest that the molecular mechanisms of colorectal carcinogens may differ between right- and left-sided tumors.

Alleles↗

Isolation and characterization of cDNA for DREF, a promoter-activating factor for Drosophila DNA replication-related genes.

DREF, a transcription regulatory factor which specifically binds to the promoter-activating element DRE (DNA replication-related element) of DNA replication-related genes, was purified to homogeneity from nuclear extracts of Drosophila Kc cells. cDNA for DREF was isolated with the reverse-transcriptase polymerase chain reaction method using primers synthesized on the basis of partial amino acid sequences and following screening of cDNA libraries. Deduced from the nucleotide sequences of cDNA, DREF is a polypeptide of 701 amino acid residues with a molecular weight of 80,096, which contains three characteristic regions, rich in basic amino acids, proline, and acidic amino acids, respectively. Deletion analysis of bacterially expressed DREF fused with glutathione S-transferase (GST-DREF) indicated that a part of the N-terminal basic amino acid region (16-115 amino acids) is responsible for the specific binding to DRE. A polyclonal and four monoclonal antibodies were raised against the GST-DREF fusion protein. The antibodies inhibited specifically the transcription of DNA polymerase alpha promoter in vitro. Cotransfection experiments using Kc cells demonstrated that overproduction of DREF protein overcomes the repression of the proliferating cell nuclear antigen gene promoter by the zerknüllt gene product. These results confirmed that DREF is a trans-activating factor for DNA replication-related genes. Immunocytochemical analysis demonstrated the presence of DREF polypeptide in nuclei after the eighth nuclear division cycle, suggesting that nuclear accumulation of DREF is important for the coordinate zygotic expression of DNA replication-related genes carrying DRE sequences.

Amino Acid Sequence↗

Conformational and stacking properties of 3'-5' and 2'-5' linked oligoribonucleotides studied by CD.

Comparative CD studies have been carried out to characterize the properties of 2'-5' and 3'-5' oligoriboadenylates and oligoribouridylates from dimer to decamer. The CD band of the 3'-5' oligoribonucleotides was larger than that of the 2'-5' oligoribonucleotides and increased with the increase in chain length, while the CD band of the 2'-5' oligoribonucleotides increased little beyond the dimer level. The CD analysis of the chain length dependency revealed that the 3'-5' oligoribonucleotides adopt mainly the base-base stacking interaction, while the base-sugar interaction is predominant in the 2'-5' oligoribonucleotides. The CD intensity of 3'-5' oligoribonucleotides decreased to a larger extent at elevated temperatures or in the presence of ethanol compared to that of the 2'-5' counterparts. Mg2+ or Mn2+ ion enhanced the magnitude of the CD of 3'-5' octariboadenylate, while a small decrease in the CD was observed by the presence of Mg2+ or Mn2+ ion to the 2'-5' octariboadenylate. The 3'-5' oligoribonucleotide is likely conformationally flexible and can form helical ordered structure with strong base-base stacking depending on changes in the environment such as temperature the presence of Mg2+ ion, or hydrophobicity of the solution.

Circular Dichroism↗

Temperature mapping using water proton chemical shift obtained with 3D-MRSI: feasibility in vivo.

This article discusses the applicability to a living animal of the temperature mapping method using the water proton chemical shift obtained with three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). There are several sources of error in obtaining the spectra with 3D-MRSI: signal noise, limitation in the frequency resolution due to the finite signal length, intravoxel inhomogeneity in the static magnetic field, and variation in the magnetic field due to the eddy current magnetic field. A spectral estimation method called phase deduction complex Lorentzian fitting (PD-CLF) was proposed. Numerical simulations demonstrated that this method reduces the error in the chemical shift to one third of that obtained with the simple frequency subtraction method that uses zero-padded first Fourier transformation (FFT). The temperature images obtained using 3D-MRSI with PD-CLF clearly visualized the changes and distribution of temperature in an anesthetized rat.

Animals↗

A case of cranial meningocele associated with Joubert syndrome.

Joubert syndrome was first reported in 1969 as a rare, recessive autosomal syndrome associated with neuropathological abnormalities of the cerebellum and brain stem, partial or complete aplasia of the cerebellar vermis, and presenting with episodic hyperpnea and apnea, oculomotor abnormalities, and psychomotor retardation. Having experienced one case of this syndrome with associated cranial meningocele, we report the clinical course, MRI features, and surgical findings, and discuss the relevant literature.

Brain Stem↗

Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas.

To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.

Adenomatous Polyps↗

[Indicators of social functioning and social participation in mentally ill participants in a public health rehabilitation programme: a one year follow-up study].

In order to investigate social functioning, a self-administered questionnaire was distributed to 66 participants (30 men and 36 women) in a group rehabilitation programme for the mentally ill at public health centers, and followed for 1 year to investigate their employability as an indicator of social participation. The survey included 20 items related to 5 aspects of daily life: diurnal routine, basic personal management, social activities, personal relationships, and management of illness. The major findings were as follows: 1. The group who had become employed showed significantly higher positive responses to questions concerning self-management such as conversation with others, consultation with others and when condition worsened than the unemployed group. Also the employed showed a tendency for higher positive responses to such items as cooking, keeping appointments, taking medicine, taking an active role in managing medications. 2. According to discriminant analysis by Hayashi's quantification method II, factors distinguishing 17 participants who had become employed within the year and those who remained unemployed included the following: ability to converse with others, taking an active role in managing medications, and ability to cook, male gender, co-residence with family, and a period of 3 years or less since hospital discharge. These results suggest that a public health rehabilitation program aimed at improving interpersonal skills, self-management of illness and other skills of daily living may be useful in helping the mentally ill participate socially.

Adult↗

Percentage of elderly and the use of welfare services at city welfare offices in Japan.

Japan's population is aging rapidly. As in other developed countries, the establishment of a system of care for the elderly, especially for those suffering from dementia, has become an urgent issue. As the role of welfare offices, which is to directly serve the people, has become increasingly important, the need to assess their use in terms of demographic factors has risen. With respect to demographic factors, this study analyses the use of the welfare services by the demented elderly at city welfare offices in Japan from 1987 to 1989. In December 1991, questionnaires were mailed to 670 city welfare offices nationwide, excluding those located in designated large cities and special wards in Tokyo. Four-hundred and thirty-seven (65.2%) of the offices responded. Offices located in areas with a relatively high percentage of elderly reported giving fewer counselling sessions and reported fewer people registered for or utilizing domiciliary welfare services than offices in areas with a relatively low percentage of elderly. The differences between the two areas in the total amount of counselling, counselling cases at the welfare office, and respite-care for 1989 and day-care service registration were significant. The Pearson's correlation coefficients for the percentage of elderly and these activities all showed negative values, except for home-help utilization in 1987 and 1989. Welfare offices in which the number of activities increased significantly over the 3 years examined in this study were more common in the areas where a committee for communication between medical and welfare sectors (hereinafter "liaison-committee") existed. Discriminant analysis suggests a correlation between the existence of a liaison-committee and the following variables: the percentage of the elderly living alone, the number of home-helpers per elderly, the capacity of day-care service per elderly and the number of surgeries per elderly. From the results, it is apparent that the welfare offices in areas with a high elderly percentage tended to have less activity. Today, municipalities with a high percentage of elderly in its population are particularly required to draw up plans for their health and welfare. The establishment of a network like a liaison-committee will enable the municipalities to achieve their goals.

Aged↗

Subclavian artery aneurysm associated with absence of the ipsilateral internal carotid artery.

A 48-year-old male presented with a rare subclavian artery aneurysm associated with absence of the ipsilateral internal carotid artery. The aneurysm was resected and replaced with a Gore Tex artificial graft. Computed tomography, angiography and cerebral blood flow findings suggest that defect of the right internal carotid artery occurred in the developmental stage. There was no past history of trauma, nor histological evidence of inflammatory or sclerotic changes in the aneurysmal wall. The two vascular lesions may have been influenced by a synchronous causative factor in his developmental stage.

Aneurysm↗

An inverse method to optimize heating conditions in RF-capacitive hyperthermia.

An inverse method to directly optimize the electrode configuration (positions, sizes, and driving voltages) for radio frequency (RF) capacitive hyperthermia was proposed. The main algorithm, based on the two-dimensional finite element method (2-D-FEM) solution of Laplace and bio-heat transfer equations, iteratively modified the individual boundary potentials around an object thereby making a calculated temperature distribution approach a target temperature distribution. A penalty function governed continuity and smoothness among the boundary potentials so that the optimized boundary potentials became attainable for two plate electrodes. Case simulations demonstrated the viability of the algorithm. For instance, in a computed tomography (CT)-based human abdomen model which had deep-and shallow-seated tumors, the optimized electrodes produced a temperature distribution suitable for heating the tumors; the average temperature differences between the tumors and normal tissues were 3.5 degree C for the deep-seated and 7.6 degree C for the shallow-seated tumors within 600 s of heating. A drawback with the present algorithm is that the choice of penalty coefficient and modification of the boundary potentials to coincide with the use of two plate electrodes are carried out manually. These procedures would be automated.

Algorithms↗

Leukocyte function-associated antigen-1-dependent adhesion of rat ascites hepatoma AH66F to mesentery-derived mesothelial cells.

Rat ascites hepatoma AH66F cells adhered better than AH130 cells to mesentery-derived mesothelial cells (M-cells), though both cells secreted Mr 92,000 matrix metalloproteinase on a gelatin zymogram with similar activity. AH66F cells expressed leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1), a ligand of LFA-1, on the cell surface, while AH130 cells had ICAM-1 alone. The adhesion of M-cells of AH66F cells was inhibited to the adhesion level of AH130 cells by anti-rat LFA-1 alpha -and/or beta-chain monoclonal antibody (mAb) and also by anti-rat ICAM-1 mAb. This is the first report to show the LFA-1-dependent adhesion of cells other than leukocytes, because AH66F cells did not express CD45, T cell-alpha beta receptor or Cd11b/c (Mac-1/p150,95). These results indicate that a part of the adhesion of AH66F cells to M-cells is due to LFA-1/ICAM-1 interaction, and we suggest that this characteristic feature of AH66F cells may be related to the malignant properties.

Animals↗

The iothalamate clearance in cats with experimentally induced renal failure.

Plasma iothalamate (IOT) disappearance rates were measured after a single-injection of IOT (113.8 mg/kg, IV) in cats with experimentally induced renal failure. The disappearance rates especially fitted into the one compartment model. The mean value of plasma disappearance rates of IOT in these cats with induced renal failure (2.16 +/- 0.240 x 10(-3) micrograms/ml/min) was markedly lower than that of clinically healthy cats (4.10 +/- 1.00 x 10(-3) micrograms/ml/min). These results demonstrate that IOT clearance is available for evaluation of renal function in cats.

Animals↗

Schwannoma arising from the intermediate nerve and manifesting as hemifacial spasm. Case report.

This 35-year-old man presented with left facial spasm that had persisted for 10 months. Microvascular decompression was performed to relieve the symptom. No responsible vessel could be identified during surgery, but a small mass seeming to arise from the intermediate nerve and compressing the seventh cranial nerve was removed. The histological diagnosis was Antoni-B type schwannoma. This unique case of schwannoma arising from the intermediate nerve was recognized by means of an operative microscope, and supports the idea that portions of the seventh nerve schwannoma originate from the components of the intermediate nerve.

Adult↗