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Biomedical subjects

A Mikata

Publications and source records attributed to A Mikata.

At least 37 records · Page 2Linked to original sources

Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.

Adult↗

Reappraisal of the relationship between immunoglobulin heavy chain gene rearrangement and Epstein-Barr virus infection in Reed-Sternberg cells of Hodgkin's disease.

We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.

Adolescent↗

Monoclonality of B-cell lineage in primary pulmonary lymphoma demonstrated by immunoglobulin heavy chain gene sequence analysis of histologically non-definitive transbronchial biopsy specimens.

Immunoglobulin heavy chain (IgH) gene rearrangements were amplified in transbronchial lung biopsy (TBLB) specimens taken from five patients with primary lymphoma of the lung in whom the diagnosis was established by surgical specimens. By histopathological analysis of TBLB specimens, only two of the five cases were diagnosed as lymphoma, the other three cases being classified as equivocal due mainly to low levels of cellular atypia and to artefactual distortion. All five TBLB specimens, as well as the subsequent surgical specimens, showed a sharp monoclonal band of IgH gene rearrangement on electrophoresis of polymerase chain reaction (PCR) products. By contrast, three surgical biopsy specimens from cases of lymphoid interstitial pneumonia (LIP) showed smear polyclonal bands. No clonal rearrangements were detected in six non-neoplastic controls, including five cases of chronic bronchitis and one of sarcoidosis. The PCR products of three of the lymphoma cases were sequenced from both TBLB and surgical specimens. In all three cases, there was dominant expression of a particular rearrangement, assumed to be tumour-derived. In each case, the major clones derived from the TBLB and the surgical specimen were identical. In both lymphoma and LIP cases, more frequent usages of JH4 and JH6 were evident. The diagnosis of lymphoma can be confirmed on TBLB specimens by use of this technique.

Adult↗

Interleukin-6 (IL-6) production in carcinoma of the cervix.

Interleukin-6 (IL-6) is a pleiotropic cytokine that is not only a mediator in major immunologic reactions but also a growth factor of keratinocytes. We studied the IL-6 secretion in vitro of 15 human cell lines derived from both squamous cell carcinoma (SCC) and adenocarcinoma of the uterine cervix. Four of the eight well differentiated SCC secreted a large amount (> 1500 pg/48 h/10(6) cells) of IL-6 in nude mice. In contrast, poorly differentiated SCC cell lines and all of the 7 adenocarcinoma cell lines secreted a small amount (< 500 pg/48 h/10(6) cells of IL-6). The expression of IL-6 mRNA of the cell lines correlated well with their IL-6 secretion potential. However, the expression of IL-6 receptor did not correlate with the IL-6 secretory potential. We also studied the IL-6 secretion of freshly isolated normal squamous epithelium and of dysplastic epithelium. In culture, two normal squamous epithelia secreted a large amount (> 2000 pg/48 h/10(6) cells), whereas 8 dysplasia epithelia secreted an extremely small amount (< 10 pg/48 h/10(6) cells). About one-third of patients with SCC had a raised serum IL-6 value. IL-6 production may help to differentiate between SCC and adenocarcinoma of the uterine cervix. IL-6 regulation seems to change in the course of SCC carcinogenesis.

Adenocarcinoma↗

Ileocolic intussusception in adult due to malignant lymphoma in the cecum with intramural metastasis.

A rare adult case of intussusception caused by malignant lymphoma of the cecum with intramural metastasis is reported. The patient was a 24-year-old man. Ileocolic intussusception was diagnosed by characteristic findings on abdominal computed tomography. Endoscopic examination revealed a massive protuberant tumor, 3 cm in diameter, and a semipedunculated polyp, 1 cm in diameter, in the cecum, which had caused the ileocolic intussusception. Endoscopic biopsy specimens failed to yield a definitive diagnosis histologically, but right hemicolectomy with lymph node dissection was performed. On histologic examination of the surgical specimens, both the tumor and the polyp were diagnosed as diffuse lymphoma of medium-sized cell type, and no lymph node involvement was found. The patient responded well to surgical and chemotherapeutic treatment, and has had no recurrence of malignant lymphoma in the 2 years since the surgical treatment. This was a very rare case of an intussusception in an adult patient due to malignant lymphoma in the cecum with intramural metastasis and without lymph node involvement.

Adult↗

HLA-DR antigen expression in colorectal carcinomas: influence of expression by IFN-gamma in situ and its association with tumour progression.

The authors attempted to investigate the host's immune response against colorectal carcinoma through the expression of HLA-DR antigen on carcinoma cells (Ca) on normal epithelia immediately adjacent to carcinoma (AN) in relation to tumour progression. The expression of HLA-DR antigen on Ca and on normal epithelia, both on AN and those 5-10 cm removed from the carcinoma (RN), were examined immunohistochemically. mRNAs of cytokines, IFN-gamma and TNF-alpha, were detected by reverse transcription-polymerase chain reaction (RT-PCR) in both carcinoma and remote normal tissues. The expression of HLA-DR antigen on AN was significantly increased compared with RN. Patients with tumours showing HLA-DR staining both in Ca and AN were in less advanced Dukes' stages (Dukes' A or B) compared with those without the stain. Furthermore, the expression of HLA-DR antigen in normal mucosa coincided significantly with the existence of IFN-gamma mRNA. Detection in carcinoma tissues of IFN-gamma mRNA that leads to the induction of HLA-DR antigen on AN could be an indicator of a host's immune response to carcinoma. These in vivo observations might be clinically applicable to the prediction of patients' immune responsiveness to carcinomas.

Adult↗

Third complementarity determining region sequence analysis of low-grade bronchus-associated lymphoid tissue lymphoma: genotypic analysis reveals heterogeneity in maturation.

It has recently been suggested that autoimmunity may play a role in the pathogenesis of low-grade mucosa-associated lymphoid tissue lymphomas, but precise genotypic analysis of antigen binding sites of low-grade bronchus-associated lymphoid tissue (BALT) lymphomas has not been reported. We analyzed the third complementarity determining region (CDR3) in eight cases of low-grade BALT lymphoma by 2-step PCR and sequencing analysis. All cases showed a distinct monoclonal band (about 100 base pairs) on electrophoresis. In seven cases, a single major CDR3 sequence was identified with five to nine clones among 10 vector clones being identical; and in the remaining case, two major sequences were obtained, with four clones among nine vector clones being identical. Findings suggestive of the autoimmunity of low-grade BALT lymphoma were obtained: (1) VHDJH rearrangements in seven of the eight lymphoma cell clones were potentially functional; (2) genotypically, two lymphoma cell clones showed 60 to 74% homology with G6 positive lymphocyte clones; and (3) five lymphoma cell clones showed 61 to 71 % homology with lymphocyte clones derived from fetal liver or cord blood. In one case, the N-D-N length of the neoplastic clone was very short and lacked N nucleotides at the D-JH junction. Therefore, our study demonstrates genotypic heterogeneity in maturation in low-grade BALT lymphoma.

Adult↗

[Ureteral malacoplakia: a case report].

Malacoplakia is a condition which occurs most often in the urogenital system, but ureteral malacoplakia is rare. A case of ureteral malacoplakia is presented. The patients was a 54-year-old woman admitted to our hospital with high fever as the chief complaint. Laboratory data suggested urinary tract infection. Escherichia coli were isolated from the urine. Ultrasonography indicated left hydronephrosis and excretory urography showed reduced function of the left kidney. From retrograde pyelography, obstruction of the left distal ureter was indicated. A ureteral carcinoma was suspected and nephroureterectomy was thus carried out. The histopathological diagnosis was malacoplakia. The patient is in good health without any indication of the disease at 1 year 9 months following surgery.

Female↗

Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.

Adenocarcinoma↗

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Adolescent↗

Investigation of EB virus and cytomegalovirus in rapidly progressive interstitial pneumonitis in polymyositis/dermatomyositis by in situ hybridization and polymerase chain reaction.

In polymyositis/dermatomyositis (PM/DM), a rapidly progressive interstitial pneumonitis (RPIP) which is a fatal complication of unknown etiology has received increasing attention. We have encountered 9 RPIP cases among 150 PM/DM cases in the past 10 years. To investigate the pathogenic role of viruses in RPIP, we examined lung specimens from patients with RPIP in PM/DM for the presence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) using polymerase chain reaction (PCR) and in situ hybridization (ISH). We analyzed 21 specimens from RPIP in PM/DM (n = 9), collagen diseases (n = 6; 4 had interstitial lung disease), and controls (n = 6). EBV was frequently detected in RPIP (7/9 by PCR 3/9 by ISH), but was also detected in other collagen diseases of the lungs. In lung specimens from both patients with RPIP in PM/DM and those with collagen diseases, EBV was significantly detected (13/15 by PCR, 5/15 by ISH, P < 0.005) compared to controls (1/6 by PCR, 0/6 by ISH). CMV was detected by ISH in 2 RPIP patients but in none of he others, though by PCR CMV was detected equally in the three groups studied. These findings indicate that a direct involvement of EBV or CMV in RPIP of PM/DM is unlikely, although it is possible that an immune response to latent viruses or viral products in PM/DM may have a role in the pathogenesis of the RPIP.

Adult↗

Restricted V beta gene usage of tumour-infiltrating T lymphocytes in primary gastric malignant B-cell lymphoma.

Ten cases of primary gastric malignant lymphoma (PGL) were investigated by immunohistochemical and molecular genetic analysis. These cases were diagnosed histopathologically as follicular small cleaved cell type (1 case), diffuse small cleaved cell type (3 cases) and diffuse large cell type (6 cases) based on the WF (Working Formulation) classification. Seven cases classified as small cleaved or diffuse large cell type belong to low (4 cases) or high (3 cases) grade MALT lymphoma according to Isaacson's classification. All PGL belonged to B lineage cells according to immunohistochemical study and immunoglobulin rearrangements. Rearrangements of TCR beta chain genes were observed in four of the ten cases. The possibility that the TCR beta rearrangements were caused by tumour-infiltrating T-cells (TILs) was supported by the following observations: the tumours did not show T- and B-cell biphenotype, TCR beta exhibited functional VDJ rearrangement and V beta usage pattern was not a neoplastic type. Analysis of the repertoire of the TCR beta chain in TILs revealed a common usage of V beta 2 in the above four cases, and furthermore, predominant usage of a particular beta chain composed of V beta 2-D beta 2.1-J beta 2.3 was observed in one of the four cases. These results indicate that the TILs of PGL have a restricted TCR repertoire.

Adult↗

Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.

To study the effect of localised secretion of chemokines on tumour growth, the genes for human (hu) interleukin 8 (IL-8), hu-MCP-1 (MCAF), hu-MIP-1 alpha (LD78), murine (mu)-MCP-1 (JE), mu-MIP-1 alpha or mu-MIP-2 were introduced, via mammalian expression vectors, into Chinese hamster ovary (CHO) cells, and the ability of transfected cells to form tumours in vivo was evaluated. The production of hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha by transfected clones did not influence the growth rate in vitro, but drastically suppressed tumour growth when injected subcutaneously (s.c.) into nude mice. However, clones transfected with hu-MCP-1, mu-MCP-1 or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with clones transfected with vector alone. Histological examination of the site of injection of CHO clones transfected with hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activity when released, even at low doses, at the tumour site, which may be mediated by recruitment and targeting of neutrophilic granulocytes to chemokine-releasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.

Amino Acid Sequence↗

Immunoglobulin gene analysis of cutaneous pseudolymphoma by polymerase chain reaction.

Polymerase chain reaction (PCR) was used to amplify the V-D-J region of the immunoglobulin heavy chain gene from DNA extracted from the formalin fixed, paraffin embedded skin of 3 cases of pseudolymphoma. The products were electrophoresed and observed under ultraviolet light after ethidium bromide staining. Specimens of two cases showed smears of polyclonal amplified DNA. The specimen of one case (Case 3), however, showed a single band with a smear. The presence of monoclonality in B lymphocyte populations may suggest the possibility of low grade malignancy of pseudolymphoma or transformation to malignant lymphoma in the future.

Adult↗

Epstein-Barr virus genomes in Hodgkin's disease and non-Hodgkin's lymphomas.

Seventeen of 40 cases of Hodgkin's disease (HD) and eight of 46 non-Hodgkin's lymphomas (NHL) were associated with Epstein-Barr virus (EBV) infection, judged by the EBER-1 in situ hybridization (ISH) method. Approximately 40% incidence in HD was comparable to previous reports. Young children and elderly HD patients were more prone to be found EBV positive. Fourteen of 17 HD and two of 8 NHL cases with positive EBER-1 ISH were also positive on LMP-1 immunostaining. EBV might have a role in lymphomagenesis in these cases. The fact that 7 of 8 EBV-related NHL were peripheral T cell lymphoma indicates the necessity of a larger-scale survey on this subject. As the present study revealed four cases with positive LMP-1 immunostaining but negative EBER-1 ISH (1 HD, 3 NHL), LMP-1 alone should not be regarded as a tool to prove EBV infection.

Adolescent↗

T cell-rich B cell lymphoma bearing Epstein-Barr virus in tumor cells: a case of IBL-T-like lesion following Lennert's lesion.

A case of T cell-rich B cell lymphoma (TCRBCL) with Epstein-Barr virus (EBV) infection in tumor cells is reported. A 50 year old male developed right cervical lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many scattered Hodgkinoid atypical cells with Lennert's lesion. After partial remission following chemotherapy, the lymph nodes enlarged again, and a second biopsy in February 1991 showed an IBL-T-like lesion. Only a small number of Hodgkinoid atypical cells were still observed. After apparently, complete remission, the lesion soon recurred and the patient died in November 1992. Immunohistochemically the Hodgkinoid cells were positive for L26, but negative for LN2, LN3, UCHL-1, MT1, lysozyme, Ber-H2 and Leu-M1. Reactivity for immunoglobulins showed false-positive because of polyclonal staining. IgH monoclonality was detected by the polymerase chain reaction method in the first biopsied specimen, and by Southern blotting in the second biopsied snap-frozen specimen. Monoclonal TCR beta rearrangement was not detected. The Hodgkinoid atypical cells were positive for EBV-encoding RNA by in situ hybridization, and LMP-1 by immunostaining. Occasionally, EBV-bearing immunoblastic, medium sized, or small lymphocytic cells were also observed. This case indicates the possibility that EBV is related to the pathogenesis of TCRBCL.

Blotting, Southern↗

Jh gene sequence analysis in a patient with Waldenström's macroglobulinaemia with subsequent development of immunoblastic lymphoma.

A case of Waldenström's macroglobulinaemia with subsequent development of immunoblastic lymphoma in a 69 year old man is reported. Plasmacytoid lymphocytes were initially observed in both peripheral blood and bone marrow smears. Lymph node biopsy was interpreted as malignant lymphoma, diffuse mixed cell type compatible with Waldenström's macroglobulinaemia. Complete remission resulted on combined treatment with prednisolone and melphalan. Four years later, lymphadenopathy recurred and biopsy revealed the development of an immunoblastic lymphoma. Initially, this lymphoma was thought to be the malignant transformation of Waldenström's microglobulinaemia, because both tumours produced IgM (kappa light chains). Sequencing of immunoglobulin heavy chain genes ofWaldenström's macroglobulinaemia and immunoblastic lymphoma cells, however, revealed different Dh and Jh usage between the two, indicating the independent nature of the two haematological malignancies. These results indicate that clonality of primary and secondary tumours should be determined not by phenotypic, but by genotypic analysis.

Journal Article↗