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Biomedical subjects

S Kon

Publications and source records attributed to S Kon.

At least 37 records · Page 2Linked to original sources
PubMed1999

Case report of lymphoepithelioma-like carcinoma of the lung--lymphoid population consisting of cytotoxic T cells in resting state.

The present report describes a case of lymphoepithelioma-like carcinoma (LELC) of the lung and presents immunohistochemical and in situ hybridization (ISH) studies of the tumor. A 39-year-old Chinese woman, who was born in China and emigrated to Japan at the age of 29, suffered from a cough for 2 years and received a middle and lower lobectomy with mediastinal lymph node dissection after induction chemotherapy. The tumor consisted of undifferentiated carcinoma and areas of more differentiated squamous cell carcinoma with an intense lymphoid infiltrate. Serological studies and ISH studies showed EBV infection of the tumor. The immunophenotype of tumor-infiltrating T-lymphocytes (TITL) of the present case was examined immunohistochemically and was compared with that of an LELC case reported previously. Most CD3-positive T cells of TITL in both cases were labeled with both CD8 and TIA-1 but not with granzyme-B, indicating the TITL to be cytotoxic T lymphocytes (CTL) in the resting state. The lack of CTL activation at the tumor site might have been due to local inhibition of EBV-specific CTL responses such as T-cell anergy. Because the EBV-specific CTL derived from peripheral blood lymphocytes, in contrast to the TITL, may not be influenced by either tumor-produced suppressor factors or negative regulatory T cells, they may inhibit the hematogenous metastasis of EBV-positive LELC, possibly resulting in a better prognosis. Because LELC of the lung responded to preoperative chemotherapy in the present study, it may be useful for reducing the local tumor burden and facilitate subsequent local therapy, although the mechanism of chemosensitivity of LELC remains unknown.

Adult↗
PubMed1999

Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

[Lymphoepithelioma-like carcinoma of the lung].

Lymphoepithelioma-like carcinoma of the lung was diagnosed in a 39-year-old Chinese woman. In situ hybridization of Epstein Barr virus-encoded small nuclear RNA 1 (EBER 1) detected strong EBER 1 signals in the nuclei of tumor cell specimens from the patient. After polymerase chain reaction (PCR) amplification, electrophoresis identified the IR-1 region in this tumor as a positive sharp band, closely resembling Raji cells (Burkitt's cell line). The uniform and intense presence of EBER 1 in the tumor nuclei and the PCR products of EBV DNA in the tumor demonstrated that a high copy number of EB virus genome existed in the tumor, and indicated involvement of the EB virus in the pathogenesis of lymphoepithelioma-like carcinoma of the lung.

Adult↗
PubMed1998

Expression of carbohydrate antigens, p80NPM/ALK, cytotoxic cell-associated antigens, and Epstein-Barr virus gene products in anaplastic large cell lymphomas.

The expression of carbohydrate antigens, including sialyl Lewis X (SLEX) and BNH9 antigen, the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion protein (p80NPM/ALK), cytotoxic cell-associated antigens, and Epstein-Barr virus (EBV) gene products in CD30+ anaplastic large cell lymphoma (ALCL) was investigated by immunohistochemistry and in situ hybridization (ISH) methods. The expression of SLEX and BNH9 antigen in ALCL was examined using CSLEX1 and BNH9, which specifically react with SLEX and oligosaccharides (H and Y haptens), respectively. SLEX was expressed in seven of 12 ALCL and BNH9 was positive for five of 12 ALCL. With respect to the relationship between SLEX and BNH9 expression in ALCL, some ALCL expressed both antigens, which suggests that they might have an increased or preserved activity of glycosyltransferase that is responsible for the synthesis of the type I or type II core sequences, although other ALCL expressed either SLEX or BNH9. To detect p80NPM/ALK in ALCL, the sections were immunostained with an anti-p80 antibody. Three of 12 ALCL expressed the NPM/ALK-encoded p80 protein. All three ALCL positive for p80NPM/ALK expressed SLEX and two of them were stained with BNH9, which raised the possibility that p80 overexpression may be involved in the aberrant expression of type I or type II chains with varying degrees of fucosylation or sialylation. While the expression of cytotoxic cell-associated antigens such as CD8, CD56 and T cell intercellular antigen 1 (TIA-1) in ALCL was immunohistochemically examined, none of the 12 ALCL expressed CD56 and only one case expressed CD8. TIA-1 was expressed in seven of 12 ALCL. Four of five BNH9-positive cases expressed TIA-1, suggesting that BNH9-positive cases tended to have TIA-1. In situ hybridization studies using an EBV-encoded RNA-1 (EBER-1) probe were performed on 12 ALCL to detect EBV in the lymphoma cells. EBER-1 signals were detected in the small lymphocytes but not in the lymphoma cells of two ALCL. However, latent membrane protein 1 immunoreactivity was found in one case. These results appear to indicate that there is no strong association between EBV and ALCL.

Adolescent↗
PubMed1997

Detection of the CTG repeat expansion in congenital myotonic dystrophy.

Myotonic dystrophy (DM) is caused by an abnormal expansion of an unstable CTG trinucleotide repeat in the 3' untranslated region of mRNA encoding a putative serine/threonine protein kinase. We analyzed 59 patients with DM (28 congenital DM families: 27 families with maternal transmission and 1 paternal transmission) and 27 normal control subjects to evaluate their CTG repeat size between DM patients and the normal controls, and to search for a correlation between the clinical characteristics of congenital DM (CDM) and CTG repeat expansions. Analysis was on the basis of the Southern blot and polymerase chain reaction (PCR) methods, and by direct sequencing of PCR amplified CTG repeats. Analysis of intergenerational differences in the CTG repeat size for mother-child pairs showed a positive correlation (y = 1.0384x + 1265.2, r2 = 0.311). In addition to the strong parental bias, this group showed genetic anticipation. There was a significant correlation of the CTG repeat expansion with disease severity. The largest CTG repeat expansion (2,293 CTG repeats) on average belonged to the severe CDM group, and the smallest (129 CTG repeats) to the subclinical DM group. The mutant allele of an asymptomatic father in the paternally transmitted pedigree revealed 75 CTG repeats, demonstrating that he was a DM protomutation carrier.

Blotting, Southern↗
PubMed1997

Immunohistochemical detection of p21WAF1/CIP1 and p53 proteins in formalin-fixed paraffin-embedded tissue sections of squamous cell carcinoma of the skin.

Thirty-two cases of squamous cell carcinoma (SCC) of the skin were investigated as to the expression of p53 and p21 (WAF1/CIP1) using an immunohistochemical method. These cases were surgically resected or biopsied, tissue samples were then fixed in formalin and embedded in paraffin in the conventional way. Microwave heating was used for antigen retrieval. The primary monoclonal anti-p21 antibody and the monoclonal antibody against p53 were employed. The labeled-streptoavidin-biotin-peroxidase method was used for immunohistochemical staining. Of these, 30 cases showed overexpression of p53 staining, but normal epidermal cells were free of stain. p21 positive cells were detected faintly in the middle layer cells of normal epidermis. Of these, 30 cases showed overexpression of p21 staining. The staining pattern of p53 and p21 showed intratumoral heterogeneity in SCC. In general, there was the inverse relationship between p21 and p53 staining in tumors, namely p53 positive cells were p21 negative and vice versa. However, some of the tumor cells expressed both genes simultaneously. This study supports a hypothesis that p21 expression is regulated by p53, and that it is also regulated by an additional pathway(s) in SCC.

Antibodies, Monoclonal↗
PubMed1997

Isoflurane attenuates early neutrophil-independent hypoxia-reoxygenation injuries in the reperfused liver in fasted rats.

BACKGROUND: Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon. METHODS: The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured. RESULTS: Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion. CONCLUSIONS: The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.

Anesthetics, Inhalation↗
PubMed1997

Heat shock protein 70 messenger RNA reflects the severity of ischemia/hypoxia-reperfusion injury in the perfused rat liver.

OBJECTIVES: To determine whether ischemia-reperfusion and hypoxia-reoxygenation cause cellular damages and stress responses in an isolated perfused rat liver model. To determine whether the increased synthesis of stress protein messenger RNA reflects cellular injury. DESIGN: Prospective, controlled study. SETTING: Institutional laboratories. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Isolated rat livers with cell free perfusion were exposed to various periods of ischemia-reperfusion or hypoxia-reoxygenation. MEASUREMENTS AND MAIN RESULTS: We measured hepatic oxygen consumption and alanine aminotransferase leakage from liver during perfusion. We analyzed the gene expression of heat shock protein 70, a major stress protein, of the liver by Northern blotting after perfusion. The expression of heat shock protein 70 messenger RNA augmented as the reperfusion period increased. The expression level after graded ischemia or hypoxia significantly correlated with the calculated hepatic oxygen debt (r2 = .737; p < .001; n = 21), or with the accumulated alanine aminotransferase leakage from the liver (r2 = .509; p < .001; n = 21). CONCLUSIONS: These results suggest that the accumulation of heat shock protein 70 messenger RNA reflects the severity of ischemia-reperfusion and hypoxia-reoxygenation injuries, and that a stress response in reperfusion can be triggered without formed elements of blood.

Alanine Transaminase↗
PubMed1997

A possible case of eccrine poroma arising in seborrheic keratosis with partial intermediate malignancy and tumor of the follicular infundibulum.

An eighty-year-old woman presented with a eccrine poroma that appeared to have arisen in a seborrheic keratosis lesion on the right side of her abdomen. The tumor consisted of a brownish, flat, elevated lesion with an eroded nodule at its periphery. Histopathological analysis of the flat, elevated lesion revealed benign basaloid and squamoid cells that showed acanthotic upward proliferation, suggesting a seborrheic keratosis. The eroded nodule showed irregular proliferation of slight atypical squamoid cells with, in parts, ductal structures in the upper dermis, suggesting that it was an eccrine poroma with partial intermediate malignancy. In addition to the eroded nodule, an occult tumor clinically accompanied the seborrheic keratosis. Histopathology of the occult tumor revealed fenestrated columns and cords of pale epithelial cells attached to the base of the seborrheic keratosis lesion, which was diagnosed as a tumor of the follicular infundibulum. Although reports of seborrheic keratosis transforming into a sweat gland tumor are rare, the present case suggests that seborrheic keratosis may develop into benign or malignant adnexal tumors, including sweat gland and follicular tumors. Thus, seborrheic keratosis should be considered as a possible precursor of adnexal tumor.

Aged↗
PubMed1997

Trichoblastoma with rippled-pattern.

The following is a case study of a 36-year-old Japanese man with a trichoblastoma which exhibited a rippled-pattern on the left temporal region of the scalp. The histological findings of the tumor revealed lobular aggregations composed of immature follicular basaloid cells, lobules of squamous eddy-like foci of incomplete keratinization or small keratinous cysts, and multiple papillary mesenchymal bodies similar to hair germ. Interestingly, a rippled-pattern of basaloid cells and hyalinized matrixes resembling the Verocay bodies of neurilemmoma was also observed. We propose that the rippled-pattern of the basaloid cells and hyalinized matrices is caused by the characteristic stromal induction of trichoblastoma.

Adult↗
PubMed1997

Two cases of basal cell carcinoma arising in seborrheic keratosis.

The present study reports two cases of basal cell carcinoma arising in seborrheic keratosis. The first case is a seventy-three-year-old female who presented with a blackish nodule arising from a pigmented lesion on her chest. Histopathological analysis of the nodule and the pigmented lesion revealed a basal cell carcinoma with hair follicular differentiation and an acanthotic seborrheic keratosis, respectively. The second case is a seventy-year-old female with a blackish nodule arising from a pigmented lesion on her back. Histological analysis of the nodule revealed an atypical basaloid cell mass surrounded by a seborrheic keratosis lesion. In addition to the coexisting seborrheic keratosis with the basal cell carcinoma, a basaloid follicular hamartoma that showed multiple hamartomatous hair follicles or small cysts replaced by a branching cord or lace-like network of basaloid cells surrounded by fibrovascular stroma was identified. We concluded that both cases presented a rare combination of a seborrheic keratosis which underwent a malignant change to basal cell carcinoma. It appears that both basal cell carcinomas and seborrheic keratosis may derive from a similar source: pluripotential cells of either the epidermis or hair follicle epithelium.

Aged↗
PubMed1997

A case of pigmented dermatofibrosarcoma protuberans (Bednar tumor).

The present paper reports a 67-year-old male with pigmented dermatofibrosarcoma protuberans (Bednar tumor) on his right shoulder. The lesion had recurred twice. Clinically, the lesion was a reddish-brown, exophytic, multilobular, firm nodule with an irregular surface, which measured 6.4 x 4.2 cm. Histologically, the proliferated fibroblasts showed a cartwheel pattern and stained positively with CD34, similar to those of a common dermatofibrosarcoma protuberance. However, many melanin-bearing cells that were positive for the S-100 protein were found intermingled among the tumor cells. Based on these findings, we concluded that the clinical manifestations, level of malignancy, and cytological features, as well as the exception of melanin-bearing dendritic cells associated with pigmented dermatofibrosarcoma protuberans, suggest a common dermatofibrosarcoma protuberans. This supports the hypothesis that pigmented dermatofibrosarcoma protuberans is a pigmented variant of dermatofibrosarcoma protuberans. Thus, this type of tumor is not benign, but is an intermediate malignant tumor.

Aged↗
PubMed1997

Pigmented epidermal cyst.

A 58-year-old Japanese woman with a pigmented epidermal cyst on the upper arch of the right external ear is described. The blue appearance of the cyst was striking and uncommon in Japanese. Histologically, abundant melanin pigment was observed in the keratinous mass of the cavity, and epithelial cells showed epidermoid keratinization. Increased numbers of melanocytes in the basal layer, large globular cells of melanocytic origin in the spinous layer, and hair-germ-like aggregates of basaloid cells and melanocytes were also observed. The blue clinical appearance is probably due to the rich melanin granules in the cyst, keratinous mass, keratinocytes, and hair-germ-like structures.

Ear, External↗
PubMed1997

Effects of volatile anesthetics on the calcium ionophore A23187-mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Alterations in intracellular calcium homeostasis have been implicated in heptic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium. The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr-fasted male Sprague-Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion-aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively. All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 microM. None of the anesthetics significantly influenced the A23187-induced enhancement of net lactate production. Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.

Anesthetics, Inhalation↗
PubMed1997

Detection of the mutation in facioscapulohumeral muscular dystrophy patients.

The gene responsible for facioscapulohumeral muscular dystrophy (FSHD) was mapped to chromosome 4q35 by linkage analyses. Recently, the probe p13E-11 derived from the cosmid clone 13E, which has been mapped to 4qter, detected a polymorphic EcoRI fragment, usually greater than 28 kb in normal individuals. In sporadic and familial FSHD patients, a specific shorter fragment, usually smaller than 28 kb, was found to cosegregate with FSHD. Two FSHD patients are presented here. Patient 1 is a sporadic case of FSHD with healthy parents. He had a de novo mutation identified by Southern blot analysis using the above-mentioned probe. Patient 2 is a typical familial FSHD patient clinically and histologically. A rearranged and shortened EcoRI fragment was identified by molecular analysis. Southern blot analysis using the probe p13E-11 also indicated a rearranged EcoRI fragment in both patients.

Alleles↗
PubMed1997

Detection of numerical chromosomal aberrations in malignant melanomas using fluorescence in situ hybridization.

To evaluate the numerical chromosomal aberration in malignant melanoma, we have applied fluorescence in situ hybridization (FISH) with repetitive DNA probes specific for chromosomes 1, 6, 7, 9, 10, and 17 on 24 fresh malignant melanomas (primary: 14, metastatic: 8). We defined a tumor that had copies with more than 3 spots as chromosomal gain. Chromosomal copy number gain was found in 40.9% of the cases for chromosome 7, 27.2% for chromosome 6, 27.2% for chromosome 17, 22.7% for chromosome 9 and 10, and 4.5% for chromosome 1. Monosomy was found in 54.5% of the cases for chromosome 10, 36.5% for chromosome 9, 27.2% for chromosome 6, 22.7% for chromosome 17, and 18.1% for chromosome 1 and 7. The most frequent numerical alterations were seen in chromosomes 6, 7, 9 and 10. Gain of chromosome 6 and 7 and/or losses of chromosome 9 and 10 may play an important role in the tumorigenesis and development of malignant melanomas.

Adult↗