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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 271 records · Page 15Linked to original sources

Modulatory effects of interferon-gamma on the fibronectin receptor function of squamous cell carcinoma cells in vitro.

We previously showed that the in vivo invasion of a squamous cell carcinoma induced by the intradermal injection of tumor cells was significantly delayed after the IFN-gamma-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-gamma might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-gamma on the adhesion of Pam-T cells to ECM. The attachment of Pam-T cells to fibronectin (FN) was significantly higher than that to laminin (LN), collagen type I (COL I) or collagen type IV (COL IV) substrata. The attachment to FN was significantly enhanced specifically by the IFN-gamma-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-gamma. Neither IFN-alpha nor IFN-beta had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-gamma together with a neutralizable anti-IFN-gamma antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-gamma-treated Pam-T cells as well as non-treated cells to FN was blocked by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), but not by the control peptide Arg-Gly-Glu-Ser. Based on these results, we conclude that IFN-gamma specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.

Amino Acid Sequence↗

Immunohistochemical study of lepromin reaction in healthy adults.

Lepromin reaction was studied with immunoperoxidase techniques using monoclonal antibodies. The skin reactions were induced by injecting Mitsuda antigen into healthy adults without a family history of leprosy. Both early (48 hours) and late (3 weeks and 2 months) reactions were examined. In the late reaction, focal collections of epithelioid cells had formed, and not only T- but also B-lymphocytes were observed around the granuloma. CD1a+ cells were also confirmed to have increased in the late reaction.

Antigens, CD↗

Examination of HTLV-I integration in the skin lesions of various types of adult T-cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern blot analysis.

The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has been proposed by clinical studies. We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions. We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly. In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes. We also demonstrated the time course study in one patient. Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL.

Adult↗

Characterization of cutaneous infiltrates in MRL/lpr mice monitored from onset to the full development of lupus erythematosus-like skin lesions.

The skin is a primary site injured in lupus erythematosus (LE), but it is still controversial whether the injury is due to cells of the mononuclear infiltrate and which immunocompetent cells play the major role in the development of cutaneous LE. To better characterize the role of immunocompetent cells, we performed an immunohistochemical examination of these cells in LE-like skin lesions in MRL/Mp-lpr/lpr (MRL/lpr) mice. Skin lesions in 60 female MRL/lpr mice were monitored from onset to full development. Skin specimens from each stage were stained for epidermal Ia+ Langerhans cells (Ia(+)-LC), for Thy-1+ dendritic epidermal cells (Thy-1+DEC), and for the phenotype of the mononuclear cell infiltrates. The numbers of Ia(+)-LC and Thy-1+DEC were decreased markedly in the skin lesions at the later stage. However, the numbers of Ia(+)-LC were increased significantly in the central portion of lesions at an early stage and in the peripheral portion of lesions later. L3T4+ cells were predominant, and the L3T4/Lyt-2 ratio was high in dermal infiltrates at an early stage. With advancing stage, the L3T4/Lyt-2 ratio gradually decreased in dermal infiltrates, whereas the Thy-1.2/Lyt-2 ratio in lymph nodes was reversed. L3T4+ cells were especially predominant in dermal infiltrates under the epidermis with increased numbers of Ia(+)-LC. This immunohistochemical analysis of a mouse model of cutaneous LE revealed changes in immunocompetent cell populations with the evolution of skin lesions, and we conclude that Ia(+)-LC and Thy-1+DEC, as well as L3T4+ and Lyt-2+ cells, may play pathogenic roles in the development of skin lesions.

Animals↗

Regional development of Langerhans cells and formation of Birbeck granules in human embryonic and fetal skin.

The regional development of Langerhans cells (LC) and the formation of Birbeck granules (BG) were examined in human embryonic and fetal skin. Samples were obtained from multiple anatomic sites and stained with anti-CD36, anti-CD1a, and anti-HLA-DR antibody as well as Lag antibody specifically reactive to BG and some vacuoles of human LC. In the first trimester, CD36+ dendritic epidermal cells were identified before the appearance of CD1a+ cells and Lag+ cells. Some of the former co-expressed HLA-DR antigens but not CD1a antigens. In the second trimester, regional variations in LC development were observed. Epidermal LC of palms and soles reached a peak in number in the first trimester but were rarely detected after 18 weeks estimated gestation age (EGA), whereas, in other regions, their number increased with age. In the second trimester, CD1a+ cells and Lag+ cells were also identified in the epidermis, although Lag+ cells appeared later than CD1a+ cells. The Lag+ cells until 17 weeks EGA showed a variety of staining intensities and immunoelectron microscopy revealed that they contained various amounts of Lag-reactive BG. Flow cytometric analysis showed that relative amounts of Lag antigens in LC increased during the second trimester and that fetal LC of 18 weeks EGA expressed the same amounts of HLA-DR, CD1a, and Lag antigens as did adult human LC. In the dermis, in the second trimester, numerous CD36+ cells and HLA-DR+ cells were found, whereas CD1a+ cells and Lag+ cells were rarely detected. Taken together, it is suggested that HLA-DR+ dendritic cells acquire CD1a+ antigens first and then form BG after migration to the epidermis and that fetal LC are phenotypically mature in the second trimester.

Antigens, CD↗

Superoxide dismutase activity of murine ultraviolet radiation-induced fibrosarcoma cell strains.

The average superoxide dismutase (SOD) activity of seven cell strains from mouse skin fibrosarcoma induced by ultraviolet (UV) irradiation was 5.78 +/- 0.81 (mean +/- SE) unit/mg protein, while that of seven normal mouse skin fibroblasts was 5.36 +/- 1.58. Although tumor cells have been previously reported to exhibit reduced SOD activity, the present study demonstrates that there is comparable SOD activity between tumor cells and normal cells of the same tissue origin.

Animals↗

Oral contraceptive-induced lupus erythematosus in a Japanese woman.

A case of oral contraceptive-induced lupus erythematosus (LE) was reported. Erythematous skin lesions were noticed on hypothenor sites of palms and acral sites of pedes. Abnormal laboratory findings included an elevated ESR, CRP and weakly positive anti-nuclear antibodies. Skin biopsy specimens from involved skin showed Clq deposits at the dermo-epidermal junction. LE-like symptoms were considered to be induced by oral contraceptives, because her symptoms disappeared after the oral contraceptives were discontinued.

Adult↗

Lowered Cu, Zn-superoxide dismutase activity in human malignant skin tumors.

We examined Cu, Zn-superoxide dismutase (SOD) activities of fifteen malignant skin tumors (four malignant melanomas, three squamous cell carcinomas, four Bowen's diseases, two basal cell epitheliomas, one sebaceous epithelioma, and one extramammary Paget's disease) and compared them with those in adjacent normal tissues of the same patients. Though there were some individual differences, all the SOD activities in tumor tissues were significantly lower than those in adjacent normal tissues of the same subjects. The average SOD activity in tumor tissues was 12.01 +/- 2.17 unit/mg protein, while that of normal tissues was 17.62 +/- 2.85. These findings agree with previous reports from various other organ tumors.

Aged↗

Purpuric cutaneous manifestations in mitochondrial encephalomyopathy.

A six-month-old boy with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome developed repeated crops of purpuric macules on his soles and palms, which were histologically identified as hemorrhage into the dermis without inflammatory infiltrates. Transmission electron microscopy of the skin eruptions revealed various stages of endothelial degeneration in the dermal capillaries associated with consequent extravasation of erythrocytes. The degenerative change was characterized by swollen and vacuolated mitochondria which showed disintegration of their cristae. These morphological changes in the mitochondria of the endothelial cells resembled those seen in skeletal muscle fibers. Similar changes were also noted in other tissues of the skin, such as the axons of myelinated peripheral nerves and some of the keratinocytes in the epidermis. Although these fine structural features are difficult to differentiate from artifacts, abnormal mitochondria could result in functional disturbance particularly in the tissues that require relatively high kinetics, and thus contribute the symptoms of myopathy, encephalopathy, acidosis and stroke-like episodes.

Brain↗

Histochemical detection of burn-induced lipid peroxidation in sebaceous glands of rat skin.

Increased lipid peroxide levels both in skin and serum have been reported after cutaneous thermal injury. However, it still remains unclear where lipid peroxides are produced at the site of burned skin. In the present study, a histochemical method using cold Schiff's reagent was applied in order to detect the localization of lipid peroxide. Schiff positivity was detected in sebaceous glands, and the extent of positivity seemed to correlate with the serum lipid peroxide levels. These results may suggest that lipid peroxides produced in sebaceous glands after thermal injury enter the blood stream and are partially responsible for the elevated serum lipid peroxide levels.

Animals↗

Morphological characterization of hemangiomatous tumors derived from a novel murine vascular endothelial cell line (F-2).

Hemangiomatous tumors were induced in Balb/c nude mice by inoculating F-2 cells (5 x 10(6)) from a novel tumorigenic murine endothelial cell line which had been established and maintained in our laboratories. These tumors were morphologically investigated in the course of development. Subcutaneous hemorrhage was observed at the inoculation site within 12 hours after the injection of F-2 cells, followed by development of skin tumors of various sizes at the same sites. They were dome-shaped, glossy surfaced, black, soft tumors. Mice finally died of massive blood loss due to internal and/or external hemorrhage (on day 10-77). Light microscopically, F-2 cells formed aggregates immediately after inoculation and then branched into a network of channels and cysts containing erythrocytes. Thereafter, spongiform structures composed of various sizes of cysts appeared with subsequent formation of a single large blood-filled cyst lined by one or two layers of thin cells. Under an electron microscope, F-2 cells, possessing large amounts of cytoplasm, formed narrow spaces which were occasionally incomplete with ambiguous basal lamina at the early stages. However, later, in large cysts, they became attenuated, tightly connected, and produced complete lumen surrounded by a basal lamina. Immunohistological demonstration of H-2 K, D antigen showed that tumors induced by F-2 cells mainly consisted of the inoculated F-2 cells. These results indicate that F-2 presents a good experimental system for investigation of vascular endothelial cell tumorigenesis and differentiation.

Animals↗

Characterization of the lymphoproliferative diseases in the skin by DNA analysis.

Various samples from lymphoproliferative diseases in the skin were analyzed by Southern blotting technique with probes from the T cell receptor gene, immunoglobulin genes, and human T cell leukemia virus-I genome. Samples were taken from 10 mycosis fungoides (MF) patients, 1 parapsoriasis en plaque patient, 10 Adult T cell leukemia/lymphoma (ATL) patients, 1 cutaneous T cell lymphoma (CTCL) patient, 4 lymphomatoid papulosis (LP) patients, 4 B cell lymphoma patients, and 2 actinic reticuloid (AR) patients. In MF, the monoclonality of the T cells became detectable first in the skin when plaques develop to tumors then in lymph nodes, and finally in the blood lymphocytes, indicating this disease develops from local (skin) malignancy to systemic malignancy. In parapsoriasis en plaque, no monoclonality was detected in any sample. We could distinguish cutaneous ATL from the carrier state by detecting the T cell monoclonality and HTLV-I integration with these probes. One patient with CTCL showed detectable T cell monoclonality; 1 out of 4 patients with LP did the same. Four samples from patients with B cell lymphoma revealed detectable monoclonal rearrangement of immunoglobulin heavy and light chain genes. In AR, no monoclonality was detected in any sample. From these data, we conclude that DNA analysis is useful in determining the monoclonality, cell origin, and distribution of monoclonal cells from skin samples.

Antibodies, Monoclonal↗

Adaptational changes of MHC gene expression and isozyme transition in cardiac overloading.

Distribution of cardiac myosin heavy-chain (MHC) isozymes is regulated during development by hemodynamic change and hormonal stimuli. To understand the evolution of cardiac hypertrophy and the underlying processes, the interaction between acute or chronic cardiac over-loading and serum thyroid hormone levels was studied. Biochemical, physiological, and pathological studies were performed using coarctated (Coa) rats with or without administration of thyroid hormone (Thy) and on sham-operated (Sham) rats and normal rats with or without administration of Thy. The results showed that 1) although serum Thy levels in Coa and Sham rats were nearly the same at all timing points, a significant induction of beta-MHC mRNA and isozyme occurred in Coa rats; 2) in Coa rats where Thy was administered, there was no increase in beta-MHC mRNA and isozyme as seen in Coa rats, and this level was nearly the same as in Sham rats, whereas serum Thy levels were significantly high, as in the normals with administration of Thy; and 3) 77 days after surgery, the hypertrophy was completed, judging from pathological findings at this time, and beta-MHC mRNA and isozyme reached similar levels in all groups, except for the normals with administration of Thy. These results demonstrate the following: 1) the MHC isoform transitions induced by pressure overload are not induced by decreases in serum Thy levels, and the regulation of MHC gene expression is responsive to other triggers in addition to Thy; and 2) the first adaptational process of the heart to hemodynamic overload is the MHC isoform transition, and the second adaptational process of that is the hypertrophy itself.

Adenosine Triphosphatases↗

Nucleotide deletion resulting in frameshift as a possible cause of complete thyroxine-binding globulin deficiency in six Japanese families.

Complete T4-binding globulin deficiency (TBG-CD) is inherited in an X-linked fashion. A nucleotide substitution has been shown to cause this hereditary condition in caucasians of French Canadian origin. Heterogeneity in molecular mechanisms for TBG-CD has also been reported. Genomic DNA from a Japanese male exhibiting TBG-CD was subjected to polymerase chain reaction, and the generated DNA fragments were sequenced. A single nucleotide deletion was found in the first base of the codon for amino acid 352 of the common-type TBG molecule. This mutation causes a frameshift in translation and premature termination. Compared with common-type TBG, the mutated polypeptide results in 1) 22 different amino acids on its carboxy-terminus, 2) a 22-amino acid truncation, and 3) the absence of a potential N-linked glycosylation site. These alterations may lead to profound changes in the secondary and tertiary structures of the molecule. To ascertain the presence of this nucleotide deletion in the genomic DNA of affected subjects, a mutated primer was designed which together with the nucleotide deletion produced a new endonuclease restriction site in the polymerase chain reaction fragment. Results revealed the presence of the mutation in genomic DNA of the subject, and his mother was shown to have both mutant and normal alleles. The same mutation was also detected in five other unrelated families carrying TBG-CD. This mutation may be frequent in Japanese subjects with TBG-CD.

Amino Acid Sequence↗

A putative mouse oocyte maturation inhibitory protein from urine of pregnant women: N-terminal sequence homology with human nonsecretory ribonuclease.

A putative mouse oocyte maturation inhibitory protein was purified from a urine preparation from pregnant women by Sephadex G-100 gel filtration and reverse-phase chromatography on the basis of inhibitory activity of polar body formation of denuded mouse oocytes in culture. Amino terminal sequence analyses showed that residues 5 to 15 of this protein were identical to residues 1 to 11 of human nonsecretory ribonuclease. Furthermore, residues 1 to 4 of this protein were identical to residues -4 to -1, corresponding to part of a signal peptide region of eosinophil-derived neurotoxin, whose mature sequence is identical to nonsecretory ribonuclease. These results indicate that the protein purified as a putative mouse oocyte maturation inhibitory protein from the urine of pregnant women may be a product of an peculiar processing of a nonsecretory ribonuclease precursor.

Amino Acid Sequence↗

[Secondary malignant tumors of the temporal bone. A histopathologic study and review of the world literature].

Metastatic involvement of the temporal bone by malignant tumors is considered to be rare. The actual incidence of metastatic temporal bone tumors, however, is probably much higher than suggested by reports in the literature. The reason for this is that histologic studies are rarely performed on temporal bones in routine postmortem examinations of patients with possible metastatic disease. Also, in patients with multiple metastatic lesions, otologic complaints and signs may often be overshadowed by other more disabling symptoms. Twelve temporal bones were histopathologically examined from 6 patients who had metastatic temporal bone disease from various primaries and the results obtained in our present series of 6 cases were: 3 cases of hematogenous dissemination from a distant primary (a hepatic cell carcinoma, a bronchogenic squamous cell carcinoma, and an adenocarcinoma of unknown primary); 2 cases of direct invasion from adjacent head and neck tumors (squamous cell carcinomas of the eyelid and hypopharynx); and one case of diffuse metastatic leptomeningeal carcinomatosis (a transitional cell carcinoma of the renal pelvis). Among these, to our knowledge either hepatic cell carcinoma or renal pelvis carcinoma metastatic to the temporal bone has not been reported previously in the world literature. We reviewed the previously published reports of metastatic temporal bone tumors and found that there were 212 reported cases cited in the literature and that the most common sites of origin in order of frequency were breast, lung, pharynx, kidney, and prostate. Our temporal bone study and literature survey reveal that there are three distinct routes of tumor spread from the primaries to the temporal bone: 1) hematogenous dissemination from a distant primary, 2) direct neoplastic extension from adjacent areas, and 3) diffuse metastatic leptomeningeal carcinomatosis (DMLC). Our study also indicates that in most cases temporal bone symptoms appeared late in the course of disease, but in some cases the otologic symptoms were an initial sign of tumor, which was particularly conspicuous in the cases of DMLC. In the cases of hematogenous dissemination, the metastatic lesion tends to be overlooked or undiagnosed because occult metastases are relatively common or, when symptomatic, the otologic symptoms often resemble the features characterized by a severe form of mastoiditis. In the cases of direct neoplastic invasion, on the other hand, recognition of temporal bone involvement is usually simple since the primary disease is quite evident. Although metastatic temporal bone malignancies are rare, otologist should always be aware of existence of this disease entity in clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗