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Biomedical subjects

N Ishii

Publications and source records attributed to N Ishii.

At least 19 recordsLinked to original sources

The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous-cell carcinoma.

The frequencies of mutations in the p53 tumor-suppressor gene and ras proto-oncogenes were investigated systematically in surgically resected oral squamous-cell carcinomas (SCCs) using single-strand conformation polymorphism (SSCP) and/or dot-blot hybridization analysis of DNA fragments which had been amplified by the polymerase chain reaction (PCR). p53 gene mutations, within the region of exons 5 to 8, were detected in 17 out of 27 (63%) tumor specimens. The role of p53 mutations in cell-line establishment was investigated. p53 gene mutations were detected in 5 out of 6 tissue samples from which cell lines were established and in 4 out of 5 specimens from which cell lines could not be established, suggesting that the presence of p53 gene mutations is not by itself sufficient for cell-line establishment. Tumor samples were also analyzed for point mutational activation of the ras proto-oncogenes. One out of 30 (3%) tumors showed an activating point mutation in codon 12 of H-ras, this being consistent with reports from Europe and USA but not with any from India. Compared to frequencies of the other genetic changes so far reported for oral SCC, the p53 mutations have been observed most often to undergo genetic change. p53 gene mutation is thus intimately involved in the genesis of oral SCC and consequently should be useful as a marker for the diagnosis of this neoplasm.

Adult

Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product.

BACKGROUND: Expression of nucleoside diphosphate (NDP) kinase, which is highly homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential in human breast cancer. PURPOSE: The present study was conducted to clarify the association of NDP kinase expression with metastatic potential in human hepatocellular carcinoma. METHODS: The immunohistochemical expression of NDP kinase was analyzed in 30 patients with histopathologically proven hepatocellular carcinoma. These patients included nine with distant metastases and 21 without distant metastases. Tissue specimens were reacted with rabbit anti-rat NDP kinase antibody and stained by the biotin-streptavidin complex method. The relative staining intensities were evaluated by comparing primary tumor sites with adjacent nontumorous liver tissue or with metastatic sites, RESULTS: The expression of NDP kinase in primary sites in patients with distant metastases was significantly less intense than that in patients without distant metastases (P = .018). NDP kinase was expressed significantly less intensely in metastatic sites than in primary sites (P = .005). The intensity of NDP kinase expression did not statistically correlate with tumor size or number of lesions in the liver, histopathological classification of tumor, associated liver diseases, hepatitis virus markers, or tumor markers. CONCLUSION: These results suggest that the reduced expression of NDP kinase is closely associated with distant metastatic potential in hepatocellular carcinoma. IMPLICATIONS: It is possible that both NDP kinase and the nm23 gene product may be active in the progression and differentiation of tumor cells and that their reduced expression induces a high metastatic potential in tumor cells. Studies using Northern blotting or in situ hybridization should be planned to confirm our findings.

Adult

Cloning of the gamma chain of the human IL-2 receptor.

A third subunit, the gamma chain, of the human interleukin-2 receptor (IL-2R) was identified, and a complementary DNA clone encoding this member of the cytokine receptor family was isolated. The gamma chain is necessary for the formation of the high- and intermediate-affinity receptors, which consists of alpha beta gamma heterotrimers and beta gamma heterodimers, respectively. The IL-2R on murine fibroblastoid cells can be internalized after binding IL-2 only if the gamma chain is present; alpha and beta are insufficient for internalization. Thus, the gamma chain is an indispensable component of the functional IL-2R.

Amino Acid Sequence

Enhanced DNA synthesis in rat hepatoma cells by conditioned media from Kupffer cells incubated with supernatants of tumor necrosis factor-alpha-pretreated hepatocytes.

The effects of tumor necrosis factor-alpha (TNF-alpha) on DNA synthesis in AH66 rat hepatoma cells and rat hepatocytes were analysed by means of [3H]thymidine incorporation. DNA synthesis in AH66 cells was suppressed when AH66 cells were directly incubated with TNF-alpha. When primary culture of rat Kupffer cells was incubated with hepatocyte conditioned media pretreated with TNF-alpha (0-200 U/ml), and AH66 cells were then treated with these hepatocyte/Kupffer cell-conditioned media, TNF-alpha used in the pretreatment caused a dose-dependent increase in DNA synthesis in AH66 cells with a maximum effect amounting to a more than 10-fold increase. In contrast, DNA synthesis in primary culture of rat hepatocytes was not stimulated by the TNF-alpha-pretreated hepatocyte/Kupffer cell conditioned media. These results suggest that TNF-alpha-mediated hepatocyte-Kupffer cell interaction selectively promotes proliferation of rat hepatoma cells.

Animals

Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity.

The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.

Carcinoma, Hepatocellular

Structure of holo-chaperonin studied with electron microscopy. Oligomeric cpn10 on top of two layers of cpn60 rings with two stripes each.

A structural model of holo-chaperonin, known as a protein-folding control protein comprising 60 kDa (cpn60) and 10 kDa polypeptides (cpn10), is proposed based on the electron microscopic images of holo-chaperonin from Thermus thermophilus and cpn60 from Paracoccus denitrificans. Isolated Paracoccus cpn60 shows very similar images to those of Escherichia coli tetradecameric cpn60, a seven-membered ring in the top view and a rectangular shape with four stripes in the side view. However, a small number of half-thick rectangles with two stripes are also seen which indicates that a single cpn60-heptamer ring has two stripes parallel to the plane of the ring. Thermus holo-chaperonin shows a bullet-like shape in the side view, and antibody against cpn10 binds only to the round side of the bullet. We conclude that a single cpn60-heptamer ring with two stripes stacks into two layers, and a cpn10 oligomer binds to one side of the layers.

Amino Acid Sequence

Improved procedure of complex demodulation and an application to frequency analysis of sleep spindles in EEG.

Complex demodulation is a local version of harmonic analysis that enables the amplitude and phase of particular frequency components of a time series to be described as functions of time. The paper presents a computational procedure involving complex demodulation with interpolation of data in the frequency domain. A computational procedure comprising repeated use of complex demodulation is also presented. This is used to estimate the optimum choice of the demodulating frequency which considerably influences the measurement of the instantaneous amplitude and phase of the underlying process. The usefulness of this procedure is verified by computer simulation. An example of applying this procedure to the estimation of the centre and the instantaneous frequencies of sleep spindles in the EEG (electroencephalogram) is presented. By using the procedure developed here, several partially overlapping sleep spindles are detected and correctly separated. The paper also presents an approach to separating and analysing transient time series (such as overlapping sleep spindles) by using an accurate frequency processing technique.

Computer Simulation

Electrical stimulation of pelvic floor musculature by percutaneous implantable electrodes: a case report.

A forty-year-old man with reflex urinary incontinence due to spinal cord injury was treated with electrical stimulation of the pelvic floor musculature. In this case we employed percutaneous implantable electrodes and an external pulse regulator. After 4 weeks of stimulation incontinence was improved and urodynamically maximum cystometric capacity increased from 220 ml to 350 ml. Our method is easy and not invasive. This technique can be an alternative for the electrical stimulation for urinary incontinence.

Adult

IgG subclass-containing cells around the lymph follicle in the human intestine.

The authors previously reported the ring-like distribution of IgG-containing cells around the lymph follicle in both the small and large intestine. In the present study, the distribution of IgG subclass-containing cells around the lymph follicle was examined in both the small and large intestine, including Peyer's patches, by the indirect immunoperoxidase staining method. A ring-like distribution of IgG subclass-containing cells was observed in 14 out of 21 lymph follicles including 4 Peyer's patches (66.7%) in the terminal ileum, and 4 out of 7 (57.1%) in the large intestine. The percentages of IgG1-, IgG2-, IgG3-, and IgG4- containing cells around the lymph follicle in the terminal ileum were 27.6 +/- 11.6%, 51.9 +/- 15.4%, 16.5 +/- 10.2%, and 4.0 +/- 3.1%, respectively, and those in the large intestine were 22.9 +/- 15.4%, 47.4 +/- 14.9%, 11.2 +/- 4.1%, and 18.5 +/- 7.7%, respectively. Thus, among the IgG subclasses, IgG2-containing cells showed the most frequent ring-like distribution around the lymph follicle. The IgG2 predominance around the lymph follicle in the intestine was markedly different from reported IgG1 predominance in the lamina propria in the large intestine. This difference in IgG subclass distribution may suggest different origins of the IgG subclass-containing cells in the lamina propria and in areas around the lymph follicle.

Adolescent

Expression of MHC class II antigens (HLA-DR, -DP, and -DQ) on human gastric epithelium.

Class II antigen expression on gastric epithelium was investigated using an immunoperoxidase method in relation to the degree of inflammatory cell infiltration in the lamina propria. Sixty-six biopsy specimens from 43 patients with chronic gastritis were examined. The frequency of HLA-DR expression in specimens with cell infiltration was 94%, while that in specimens without cell infiltration was 24%. There was significant difference in the frequency of HLA-DR expression between the two groups (P less than 0.01). HLA-DR was most intensely expressed in the glandular neck portion. The frequency and extent of class II antigen expression on gastric epithelium with cell infiltration were in the following order: DR greater than DP greater than DQ. The extent of DR and DP, but not DQ expression generally paralleled the degree of cell infiltration. Intestinal metaplasia was found in 13 specimens. In the area of intestinal metaplasia, epithelial class II staining was absent except for one specimen. These results suggest that the respective genes of three class II antigens are regulated by different mechanisms and that an immunological mechanism plays a role in the pathogenesis of gastritis.

Epithelium

A correlation between IgG class antibody production and glomerulonephritis in the murine chronic graft-versus-host reaction.

A graft-versus-host reaction (GVHR) was induced in (B10 x DBA/2)F1 (BDF1) and (BALB/c x A)F1 (CAF1) murine recipients by injection of their parental or B10.D2-derived spleen cells. The incidences of glomerulonephritis and autoantibody production were then correlated. All of the BDF1 mice that received DBA/2 spleen cells (termed DBA/2----BDF1) and 33% of the CAF1 mice that received BALB/c spleen cells (BALB/c----CAF1) developed glomerulonephritis. However, in other combinations (B10.D2----BDF1, A/J----CAF1) no significant glomerular lesions were observed. An analysis of antibodies by ELISA revealed that the groups with renal disease showed a significant polyclonal elevation of IgG class antibodies, including autoantibodies (anti-DNA, anti-MRBC, and NTA) and a conventional antibody (anti-TNP-KLH). No significant IgG class antibody production was observed in the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important in the development of glomerulonephritis in GVHR. Other factors also appear to be involved. Only 33% of BALB/c----CAF1 developed glomerulonephritis, even though a level of IgG class antibody production was comparable to that observed in DBA/2----BDF1 in which 100% showed severe glomerulonephritis.

Animals

UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans.

The unc-6 gene is required for the guidance of pioneer axons and migrating cells along the body wall in C. elegans. In mutants, dorsal and ventral migrations are disrupted, but longitudinal movements are largely unaffected. The gene was tagged for molecular cloning by two independent transposon insertions. Based on genomic and cDNA sequencing, the gene encodes a novel laminin-related protein, UNC-6 (591 amino acids). The N-terminus is homologous to the N-termini (i.e., domains V1, V-1, V-2, and V-3) of laminin subunits, while the C-terminus is a unique domain. We propose that UNC-6 is a component of an extracellular matrix cue that guides dorsoventral migrations on the epidermis.

Amino Acid Sequence

Effects of adenosine on canine penile erection.

We investigated the hemodynamic effects of intracavernous injection of adenosine on canine penile erection. In all ten dogs studied, adenosine induced a dose-dependent increase of intracavernous pressure (ICP). Adenosine (0.67 to 15 micrograms/kg., B.W.) increased arterial blood flow by 83 to 325 percent above baseline levels and also increased venous resistance, which resulted in a full erection (ICP = 80 to 140 cm. H2O) for one to 7 minutes. The repeatability of the adenosine effect was confirmed in eight dogs. We found that adenosine, by virtue of its smooth muscle relaxation properties, can induce a dose-dependent increase of ICP and cause a full erection in dogs.

Adenosine

A case of congenital trichofolliculoma.

A case of congenital trichofolliculoma on the right cheek of a 3-month-old boy is reported. Trichofolliculoma usually appears in middle age; it is unusual in childhood. This is the first reported case of congenital trichofolliculoma.

Cheek

Malignant Langerhans cell tumour.

We report the case of a 49-year-old woman suffering from a malignant neoplasm of Langerhans cells (LC), documented by immunohistochemical and ultrastructural analysis, and review the literature to examine and characterize the clinical and laboratory features, therapy, and prognosis of malignant neoplasms of LC. Langerhans cell histiocytosis is now regarded as a disorder of immune regulation or an inflammatory process, rather than as a malignant neoplasm. Although LC share certain features in common with ordinary histiocytes or interdigitating dendritic cells, they also differ significantly from these cells in other respects. Therefore, we propose designating a malignant neoplasm of LC 'malignant Langerhans cell tumour' and that it should be considered as a separate entity from Langerhans cell histiocytosis or other malignant histiocytoses.

Antigens, CD

Histopathological study of focal dermal hypoplasia (Goltz syndrome).

We report a case of focal dermal hypoplasia, or Golz syndrome in a 13-year-old girl. The patient presented with a variety of cutaneous defects, including atrophy-like depressions, striations, a verrucous papilloma, and lipomas. Histopathological examination showed deposits of fat cells or adipose tissue in the dermis, which were subepidermal, mid-dermal, perivascular, or involved the whole dermis. These findings indicate that the adipose tissue in the dermis is a result of dermal dysplasia and not hypoplasia.

Adolescent

Crohn's disease associated with diffuse lymphoid hyperplasia of the large intestine: a possible role of the lymph follicle in HLA-DR antigen expression on epithelium.

A 14-year-old girl diagnosed as Crohn's disease had lymphoid hyperplasia throughout the large bowel. Biopsy specimens from the lymphoid hyperplasia demonstrated non-caseous granulomas within the lymph follicles. An immuno-histochemical study of biopsy specimens showed that HLA-DR antigens were expressed on epithelium close to the lymph follicle, which was observed in all specimens containing the lymph follicle. This case provides evidence for the importance of the lymph follicle in the etiopathogenesis of Crohn's disease by demonstration of non-caseous granulomas within the lymph follicle and expression of HLA-DR antigens on epithelium close to the lymph follicle.

Adolescent

Aberrant expression of GM1 on lymph node cells of MRL/Mp-lpr/lpr mice: influences on the autoreactivities of anti-asialo GM1 antibodies.

Although changes in surface carbohydrate expression of abnormally expanded MRL/Mp-lpr/lpr (MRL/lpr) lymph node (LN) cells have previously been described, the composition and function of glycolipids present on these cells as well as the spectrum of specificity of anti-carbohydrate antibodies reactive with these cells remains obscure. Analysis of antibodies to a panel of 22 carbohydrate structures using a liposome immune lysis assay (LILA) showed that, except for anti-asialo GM2 (GA2) antibodies, marked reduction of antiglycolipid antibody levels was observed in sera from 4-mo-old MRL/lpr mice compared with these from MRL/Mp(-)+/+ (MRL/+) mice. Absorption experiments revealed that both anti-asialo GM1 (GA1) and globoside antibodies had binding capacity to MRL/lpr LN cells. To elucidate the glycolipid profiles of MRL/lpr LN cells, glycolipids were extracted from LN cells of both MRL/lpr and MRL/+ mice and analysed. A 30-fold elevation of GM1 was found in MRL/lpr LN cells compared with MRL/+ LN cells. From the results of LILA using GA1/GM1 mixed liposomes, aberrantly expressed GM1 inhibited the classical complement pathway but did not interfere with the binding of anti-GA1 antibodies to liposomal GA1. These findings suggest that a drastic GM1 increase on MRL/lpr LN cells would inhibit the action of anti-GA1 antibodies and complement on the cell surface. This may explain the escape of these cells from an activated self directed immune response.

Animals