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S Kon

Publications and source records attributed to S Kon.

At least 19 recordsLinked to original sources

Nasal T-cell lymphoma causally associated with Epstein-Barr virus: clinicopathologic, phenotypic, and genotypic studies.

BACKGROUND: The authors have previously demonstrated nasal T-cell lymphoma (NTL) associated with Epstein-Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified. METHODS: The study group consisted of 18 patients with NTL. The phenotype was determined by immunoperoxidase staining with various monoclonal antibodies. Genotypic study was done using Southern blot hybridization. The presence of EBV-encoded small nuclear early region (EBER) RNA and EBV DNA were determined by in situ hybridization. The expression of EBV-encoded nuclear antigen (EBNA) and latent membrane protein (LMP1) were identified by immunohistologic methods. Clonotypic analysis of EBV genomes was performed by Southern blot hybridization with EBV termini fragment probe. RESULTS: The clinical features of NTL were characterized as prolonged fever (16 patients), widespread dissemination into distant sites (13 patients), and poor prognosis with a median survival of only 6 months. EBER transcripts were identified in 16 of 18 patients. Monoclonal EBV genomes EBNA1 and LMP1 were also detected in all EBER-positive cases tested. All 18 patients expressed pan-T antigens such as MT1, CD45RO, and/or CD2. The rearrangements of T-cell receptor (TCR)-beta, -gamma, and/or -delta genes were shown in all 11 patients tested. The natural killer (NK) cell phenotype CD56 was expressed in all EBV-positive cases tested, and was not detected in EBV-negative cases. Seven EBV-positive cases expressed a TCR-delta chain with rearranged TCR-gamma or -delta genes whereas both EBV-negative cases corresponded to alpha beta T-cell lymphoma, which expressed a TCR-beta chain with a rearranged TCR-beta gene. CONCLUSIONS: These data suggest that EBV-positive NTL may be derived from the lineage of NK-like T-cells or gamma delta T-cells, and that EBV may play a role in lymphomagenesis. Therefore, we propose that NTL which has peculiar clinical and histologic features could be classified as a new lymphoma entity.

Adult

Neuronal localization of CD38 antigen in the human brain.

CD38 is a lymphocyte differentiation antigen which is involved in the cyclic ADP-ribose-mediated second messenger system. We provide immunochemical and immunohistochemical evidence for the expression of CD38 in the adult human brain. We used six polyclonal antibodies against synthetic CD38 polypeptides, in addition to four monoclonal antibodies already available. Brain CD38 was detectable by Western blotting after immunoaffinity purification of the brain extracts. Immunoperoxidase staining localized CD38 immunoreactivity to the perikarya and dendrites of many neurons, such as the cerebellar Purkinje cells, implying that CD38 is involved in the signal transduction within the central nervous system neurons.

ADP-ribosyl Cyclase

Modulation of protein kinase C produces glucose-dependent alterations in hemodynamics and metabolism in the perfused liver in fasted rats.

Protein kinase C (PKC) has been suggested to be involved in the regulation of hepatic blood flow and metabolism. To confirm the role of PKC, we studied the effects of active and inactive PKC modulators on hemodynamics and metabolism in the perfused rat liver. In addition, the influence of glucose concentration in the medium was studied. The liver was isolated from fasted Sprague-Dawley rats and perfused through the portal vein at a constant pressure of 12 cm H2O. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester for PKC, slightly decreased hepatic flow only when its initial concentration was raised to 20 microM. In contrast, 4 beta-phorbol 12,13-didecanoate, an active phorbol ester for PKC, at initial concentrations of 80 nM to 1.28 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and increased lactate production. HA-1004, a relatively inactive PKC inhibitor, at an initial concentration of 33 microM did not modify the effects of phorbol 12-myristate 13-acetate (PMA), a potent PKC activator. However, H-7, a relatively specific PKC inhibitor, at a concentration of 33 microM attenuated the effects of PMA. The effects of PMA were enhanced by an increase in n-glucose concentration from 10 to 25 mM but not by an increase in L-glucose concentration. These results suggest that modulation of PKC exerts glucose-dependent influences on hepatic flow and metabolism.

Animals

Incidence of latent infection of Epstein-Barr virus in lung cancers--an analysis of EBER1 expression in lung cancers by in situ hybridization.

To evaluate the presence of Epstein-Barr virus (EBV) in lung cancers of Japanese patients, 81 lung cancers were examined using a highly sensitive in situ hybridization (ISH) method, employing an antisense oligonucleotide probe for EBV-encoded small nuclear RNA-1 (EBER). EBER1 expression was demonstrated in one poorly differentiated squamous cell carcinoma associated with marked lymphoid stroma (PDSCC-LS), two well differentiated adenocarcinomas, and two moderately differentiated squamous cell carcinomas, but was not detectable in other lung cancers, including small cell carcinomas. Unlike lymphoepithelioma-like undifferentiated carcinoma (LELC) of the lung, the PDSCC-LS consisted of poorly differentiated cells with distinct cell borders and nuclei with a coarse chromatin pattern and some prominent nucleoli. Most of the cancer cells expressed intense EBER1 signals. Although small to moderate numbers of cells positive for EBER1 were present in two adenocarcinomas and two squamous cell carcinomas, EBER1 signals varied in intensity and number in these four cases. Although polymerase chain reaction (PCR) and Southern blot hybridization with a 32P-labelled probe internal to the primers were conducted to detect the EBV genome in 24 lung cancers, including five EBER1-positive cases, the genome was found to be positive in the five cases with EBER1-positive staining, including the PDSCC-LS, two adenocarcinomas and two squamous cell carcinomas, but not in the other cases. This study indicates that the morphological features of EBV-associated lung cancers are not restricted to the typical LELC type.

Adenocarcinoma

A case of superficial epithelioma with sebaceous differentiation.

Superficial epithelioma with sebaceous differentiation developed on the left cheek of a 58-year-old man over a three-year period. Biopsy of the lesion demonstrated plate-like lobules of basophilic basaloid cells with broad attachments to the overlying epidermis. Clusters of or solitary sebaceous cells were present within the lobules. Three tumor types were considered; a subtype of sebaceoma growing in the epidermis, an acanthotic seborrheic keratosis subtype with sebaceous differentiation, or a tumor of the follicular infundibulum with sebaceous differentiation.

Aged

Interphase cytogenetics of melanocytic neoplasms: numerical aberrations of chromosomes can be detected in interphase nuclei using centromeric DNA probes.

This study shows that fluorescence in situ hybridization (FISH) to thin sections cut from paraffin-embedded material can be used to distinguish between groups of melanocytic neoplasms and thus may be useful as an investigational and diagnostic tool. FISH with a probe for a repeated, alpha satellite sequence specific to chromosome 17 was used to investigate the chromosomal composition of dysplastic (or Clark's nevus) and Spitz's nevi and malignant melanomas. Hybridization was to thin (approximately 6 microns) sections cut from paraffin blocks. The number of signals per nucleus in normal diploid cells is expected to be less than 2 since the sections are thinner than one nuclear diameter. Keratinocytes and lymphocytes in these same sections showed 1-2 signals per nucleus with a mean of 1.2. Dysplastic nevi showed 1-4 hybridization signals per nucleus with a mean of 1.5. Spitz's nevi showed 1-2 signals per nucleus with a mean of 1.3. Melanomas showed 1-6 signals per nucleus with a mean of 2.1. We were thus able to use FISH to demonstrate differences in chromosome numbers between groups of benign and malignant melanocytic neoplasms. Technical improvements in the near future can be expected to result in more precise estimates of chromosomal number.

Centromere

Applications of DNA flow cytometry and fluorescence in situ hybridization using a chromosome-specific DNA probe on paraffin-embedded tissue sections of primary malignant melanomas.

We have applied DNA flow cytometric analysis to paraffin-embedded tissue sections of primary malignant melanomas. Conventionally, flow cytometric analysis of paraffin-embedded tissue sections has been done by the method of Hedley et al. We added ultrasound treatment to the method of Hedley et al. and a lower value of coefficient of variation was shown. Furthermore, a new technique, fluorescence in situ hybridization with a chromosome-specific repetitive DNA probe, was used for the analysis of chromosomal numerical aberrations in the same paraffin-embedded tissue sections. The DNA flow cytometric analysis showed that in 8 cases six primary malignant melanomas were of the aneuploid pattern and two cases of lentigo maligna (melanoma in situ) were of the diploid pattern. By fluorescence in situ hybridization, the two cases with the diploid pattern had spots/nucleus of 1.28 and 1.12, and those with the aneuploid pattern had spots/nucleus from 2.01 to 2.27. Only one nodular melanoma in an aneuploid case showed spots/nucleus of 1.71. These data indicate that fluorescence in situ hybridization with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of solid human tumors and may be useful for the study of tumor cell heterogeneity.

Adult

Structural analysis of the CD3 zeta/eta locus of the rat. Expression of zeta but not eta transcripts by rat T cells.

We analyzed the structure and pattern of expression of rat TCR zeta- and eta-chains to investigate if these components function in activation and development of rat T cells. The rat zeta cDNA contained the complete open reading frame coding for a polypeptide of 164 amino acids and the 5' and 3' noncoding sequences. Comparison of the amino acid sequence to those of mouse and human counterparts revealed a high degree of similarity, more than 85% homology among all three species except for the signal peptide, which was especially high in the cytoplasmic domain including the nucleotide binding site and the possible tyrosine phosphorylation sites. Furthermore, we determined the nucleotide sequences of a rat genomic eta-like sequence located in the 3' region of the rat zeta-gene. Although it showed a high level of nucleotide similarity to mouse and human counterparts, 90.4 and 78.9%, respectively, the deduced polypeptide was very short (only 28 residues) and markedly divergent from the mouse and human eta-specific polypeptides due to frameshift mutations. Transcription of rat zeta was shown to be highly restricted to T cells; abundantly in thymocytes and scarcely in peripheral T cells. Surprisingly, the rat eta transcript could not be detected in any rat tissues so far tested by Northern blot analysis and even by the sensitive reverse transcription-polymerase chain reaction method, whereas it was readily detected in mouse thymus. These findings suggest that the zeta-chain has conserved roles in the TCR assembly and TCR-mediated signaling. However, the eta-chain seems not to be indispensable because of its structural diversity among these three species characterized to date and the apparent lack of eta expression in the rat.

Amino Acid Sequence

Detection of Epstein-Barr virus DNA and EBV-determined nuclear antigen in angioimmunoblastic lymphadenopathy with dysproteinemia type T cell lymphoma.

Six cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like T cell lymphoma were analyzed by immunohistochemical staining, polymerase chain reaction (PCR) and Southern blot analysis. Five cases out of six showed gene rearrangements of the T cell receptor beta chain, indicating the existence of a clonal T cell proliferation. Epstein-Barr virus (EBV) DNA was detected in all six AILD type cases by PCR amplifying the sequence located in the internal repeat I, and confirmed by Southern blot hybridization, using a BamHI-W fragment as a probe. Detection of the EBV genome occurred more frequently as compared with other types of lymphoid disorders. Furthermore, EBV determined nuclear antigen (EBNA) was detected in UCHL-1 (CD45RO, pan-T cell marker) positive cells by immunostaining. These results suggest that a significant number of AILD type cases are T cell origin lymphomas and EBV infection may be relevant to the biological features of this type of lymphoma.

Adolescent

Multiple agminated juvenile melanoma arising on a hyperpigmented macule.

A case of multiple agminated juvenile melanoma (MAJM) arising on a hyperpigmented macule is reported. The patient, a 1-year-old boy, had 9 small nodules on an irregular, hyperpigmented macule on the right shoulder. Histologically, the nodules contained nests of spindle-shaped cells in their epidermis and at the dermoepidermal junction, and the hyperpigmented macule exhibited increased melanin granules in the basal layer and small nests of epithelioid cells. We concluded that MAJM on a hyperpigmented macule is the subtype of the nevus spilus.

Humans

Melanin repigmentation after gingivectomy: a 5-year clinical and transmission electron microscopic study in humans.

The epithelium-melanin unit is formed by the melanocytes and keratinocytes. There is little information available about the behavior of melanocytes after surgical injury. Five white patients with comparable gingival pigmentation underwent gingivectomy to remove bandlike melanin pigmentations for cosmetic reasons. Biopsy specimens were taken from gingivectomy sites and healing areas 2, 3, 6, 7, 15, 50, and 180 days and 1.5, 3, and 5 years after the procedure. Transmission electron microscopic study revealed melanocytes in the process of migration and undergoing mitosis 6 and 7 days postoperatively. These cells exhibited, in the 15-day specimens, renewal of their dendritic processes and the four different stages of melanosome development. Keratinocytes were devoid of pigmented material until 50 days postoperatively. Clinically, the intensity of the pigmentation varied among the patients. Two reached baseline coloration 1.5 years postsurgery, while three returned to baseline coloration by 3 years postsurgery. Thus, gingival resective procedures, if performed solely for cosmetic reasons, offer no permanent results. (Int J Periodont Rest Dent 1993; 13:85-92.)

Adult

[A case of sporadic and transient bradyarrhythmias in a patient with a glioma in the medulla oblongata].

In a 20-year-old female patient with a brain stem glioma in the medulla oblongata in association with paraplegia and respiratory paralysis, bradyarrhythmias such as sinus bradycardia and sinus arrest repeated sporadically and transiently, but soon subsided as radiotherapy was being delivered to the glioma in the medulla oblongata. The bradyarrhythmias were differentiated from sick sinus syndrome in their sporadic and transient character. The patient responded normally to atropine, isoproterenol, and phenylephrine. Parasympathetic nerve reflexes induced by Aschner's, Czermak's, and Valsalva's maneuvers and sympathetic nerve reflex induced by change of body position were within normal limits. Although EKG abnormalities associated with diseases of the central nervous system are frequently due to intracranial hypertension and/or irritation of the hypothalamus, the bradyarrhythmias in this patient were possibly due to vagus stimulation caused by the glioma in the medulla.

Adult

Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.

Adult

Tooth morphology following root resection procedures in maxillary first molars.

The Disto-Buccal root is the most commonly resected root in maxillary molars. This root resection procedure results in a unique environment dictated by the contours of the remaining roots and the residual furcation between them. Tooth morphology was evaluated in 50 extracted maxillary first molars after disto-buccal root resection. The following measurements were studied: 1) The maximum concavity (D) on the distal aspect of the resected molar; 2) the minimum mesio-distal dimension (d) of tooth structure between the two remaining roots; 3) the width (s) of the residual interradicular septum; and 4) the distance (p) from the pulp chamber floor to the root separation on the distal aspect of the resected molar. The mean measurements were (D) = 2.47 mm, (d) = 3.67 mm, (s) = 3.33 mm and (p) = 2.70 mm. The value of (p) was equal to or less than 3 mm in 86% of the teeth; this means that the distance from the finish line to the interradicular osseous peak is less than 2.04 mm (average biologic width), if the finish line is placed on solid tooth structure about 1 mm below the pulp floor. Six percent of the resected molars had an overall topography easily amenable to periodontal maintenance and restorative procedures with (D) less than 2 mm, (d) greater than 3 mm, (s) greater than 3 mm, and (p) greater than 3 mm. Poor root anatomy of the remaining roots after removal of the disto-buccal root in maxillary first molars may be considered as a contraindication for root resection procedures. Unfortunately, this poor topography can be ascertained only during the surgery and after removal of the disto-buccal root.

Dental Pulp Cavity

[Gene rearrangement analysis of conjunctival malignant lymphomas].

Specific DNA probes for genes encoding immunoglobulins (Ig) and the T cell receptor (TCR) are useful diagnostic tools in lymphoproliferative disorders. Gene rearrangement analysis was carried out in 2 cases of conjunctival lymphoid lesions. A 36-year-old man (case 1) had a 1-year history of left conjunctival tumor. A biopsy was performed and histopathological findings showed diffuse proliferation of small lymphocytes, but monoclonality was not revealed by immunophenotypic analysis. A right conjunctival lesion developed and five months later a biopsy of the left conjunctiva was performed again. A frozen sample was analyzed and immunoglobulin heavy chain gene rearrangement was found. A 53-year-old woman (case 2) had a 6-month history of bilateral conjunctival tumor. The first biopsy did not reveal monoclonality immunophenotypically. A second biopsy with a frozen specimen was analyzed and immunoglobulin heavy chain gene rearrangement was found. We diagnosed these two cases as B-cell lymphoma. We discuss the clinical value of gene rearrangement analysis as a diagnostic method for lymphoproliferative disorders.

Adult