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Biomedical subjects

Y Eishi

Publications and source records attributed to Y Eishi.

At least 37 records · Page 2Linked to original sources

Regulation of experimental autoimmune orchitis by the presence or absence of testicular antigens during immunological development in SCID mice reconstituted with fetal liver cells.

Severe combined immunodeficient (SCID) mice were immunologically reconstituted by the transfer of fetal liver cells (FLC) of BALB/c mice (SCID-FLC mice). In peripheral blood (PB) of SCID-FLC mice, B and T cells started to appear 2 and 5 weeks, respectively, after the transfer of FLC, and had attained normal levels by 7 weeks. Orchidectomy and transplantation of testis under the kidney capsule were conducted at various stages of immunological maturation, and the induction of experimental autoimmune orchitis (EAO) was performed after immunological maturation in SCID-FLC mice. The experimental system was used to establish that the presence of testicular antigens in the early stage of immunological development influences the induction of EAO; grade of EAO was reduced in the presence of the antigens, and enhanced in their absence. In other words, the existence of self tissue antigens in the early stage of immunological development was essential for proper establishment of tolerance to the self tissue. These findings suggested that the SCID-FLC mouse is a suitable model with which to analyse the interaction between self antigens and cells of the developing immune system, which is otherwise observed only in the fetal or perinatal stage in experimental animals.

Animals↗

Histological differentiation and basement membrane distribution in gastric adenocarcinomas.

To analyse the histological distribution of basement membranes (BM) in gastric adenocarcinomas, we produced a monoclonal antibody, BM909 (IgG 2b, kappa), which has been found useful for identifying the BM in routinely processed specimens. The BM 909 antibody was shown by ELISA to be negative against the three major BM components (type IV collagen, laminin and fibronectin). Gastric carcinomas from 78 patients including both differentiated and undifferentiated adenocarcinomas were classified into three types (tubular, trabecular, and isolated) based on the histological arrangement of the cancer cells. Histological distributions of the BM were also classified into four patterns (peritubular, peritrabecular, intratrabecular, and pericellular) based on the immunostaining results with the BM 909 antibody. Our results demonstrated a close relationship between these two parameters as follows: 1) the tubular type of gastric carcinomas showed a peritubular pattern of BM distribution in the differentiated adenocarcinomas; 2) The isolated type of gastric carcinomas showed a pericellular pattern of BM distribution in the undifferentiated adenocarcinomas; and 3) The trabecular type of gastric carcinomas showed either peritrabecular or intratrabecular patterns of BM distribution, in both differentiated and undifferentiated adenocarcinomas. In conclusion, we suggest that all gastric adenocarcinomas are accompanied by BM deposition regardless of the degree of histological differentiation.

Adenocarcinoma↗

Development of the immune system in severe combined immunodeficiency mice reconstituted with transferred fetal liver cells.

Severe combined immunodeficiency (SCID) mice were immunologically reconstituted by the transfer of fetal liver cells (FLC) from BALB/c (SCID-isoFLC mice) or C57BL/6 mice (SCID-alloFLC mice). The developmental process of the immune system in the peripheral blood (PB) was almost comparable between SCID-isoFLC and SCID-isoFLC mice. Analysis of the lymphoid organs and the PB from SCID-alloFLC mice indicated that slg+ B cells appeared and were distributed to the periphery within 2 weeks after the transfer of FLC. It was also suggested that precursor T cells entered the thymus before 4 weeks after the transfer, and were differentiated into mature CD4+ or CD8+ T cells which then migrated to the periphery by 6 weeks. All of mature lymphocytes in the periphery of the SCID-alloFLC mice were shown to express donor-type H-2 antigens. Additionally, in the SCID-isoFLC mice, cell-mediated immunity such as rejection against alloantigens was functioning from 6 weeks, and humoral immune function was suggested by the detection of cells generating antigen-specific antibodies. We discuss that development of the immune system in SCID mice receiving transferred FLC was comparable to that normally seen in the fetal and neonatal stages.

Animals↗

[Small cell carcinoma of the urinary bladder: a case report and review of the Japanese literature].

A 50-year-old man presented with asymptomatic gross hematuria which he had first noticed 3 months earlier. Clinical examinations revealed a non-papillary, broad-based tumor on the left lateral wall of the urinary bladder with a clinical stage of T3N0M0. The pathological diagnosis of a transurethral biopsy tissue specimen was small cell carcinoma. Neoadjuvant intraarterial infusion chemotherapy using cisplatin and adriamycin was initially administered but proved to be ineffective. Thus, we performed a radical cystectomy. The tumor tissue was apparently homogenous and composed of small cells arranged in sheets and solid patterns, and was staged to be pT3bR1L2V0N0. An electron microscopic study confirmed small cell carcinoma with neurosecretory granules. Postoperatively, 4 courses of adjuvant chemotherapy consisting of cisplatin, etoposide and ifosfamide were administered. The patient is alive without any evidence of tumor recurrence 26 months after the operation.

Antineoplastic Combined Chemotherapy Protocols↗

Contribution of immune response to the hepatic fibrosis induced by porcine serum.

To investigate whether hepatic fibrosis induced by porcine serum in rats is caused by an immune reaction to porcine serum, rats that were immunologically tolerant exclusively to porcine serum were subjected to the repeated injection of porcine serum over a long period. This porcine serum-tolerant group consisted of 15 Wistar rats that had been injected intraperitoneally with porcine serum twice a week from the first postnatal day for 18 weeks. The control group consisted of 16 Wistar rats, aged 8 weeks, that were injected intraperitoneally with porcine serum twice a week for 10 weeks. Livers were fixed and examined by light microscopy. The serum of each rat was subjected to indirect enzyme-linked immunosorbent assay (ELISA) to measure the level of antibody to porcine albumin. In addition, immunohistochemical staining for ED1 was performed on untreated normal and porcine serum-induced fibrotic rat livers to examine the distribution of macrophages and their precursors, the monocytes. All rats in the tolerant group showed an extremely low antibody level (x = 68.27 +/- 4.53), and none (0/15) developed hepatic fibrosis. The majority of rats in the control group showed a very high antibody level (x = 1242.19 +/- 201.15); 75 percent (12/16) developed hepatic fibrosis. Data indicate that, despite the prolonged, repeated injections of porcine serum, if an immune response to porcine serum does not occur, the rats do not develop hepatic fibrosis. The porcine serum-tolerant rats developed hepatic fibrosis after 4 weeks of CCl4 treatment, indicating that injection of porcine serum into neonatal rats did not cause anergy of fibrogenesis, thereby preventing the animal from developing hepatic fibrosis. In normal rat liver, ED1-positive cells, which include nearly all Kupffer cells, were located pre-dominantly in the periportal area. In fibrotic rat liver, ED1-positive cells aggregated prominently in the newly formed and advanced connective tissue septa developed mainly between the neighboring central veins, and in fibrotic parts of the liver capsule. Aggregation of ED1-positive cells was rarely observed in nonfibrotic parts of the liver capsule. The difference between normal and fibrotic rat liver in distribution of EDl-positive cells suggests an involvement of macrophages in fibrogenesis and septum formation. In conclusion, our study showed a significant contribution by the immune response to porcine serum antigens leading to porcine serum-induced rat hepatic fibrosis--processes in which macrophages may be important. This study may lead to an understanding of the mechanism responsible for this form of experimental hepatic fibrosis.

Animals↗

Reactive lymphoid hyperplasia of the liver characterized by an angiofollicular pattern mimicking Castleman's disease.

A case of reactive lymphoid hyperplasia of the liver exhibiting a characteristic angiofollicular pattern is reported. A hepatic nodular lesion was discovered by abdominal echography during clinical follow-up of abnormal liver function tests. It was diagnosed as hepatocellular carcinoma because of its hypervascularity when observed by angiography, and surgically resected. Grossly, the lesion was well-demarcated and measured 2 cm in diameter. Microscopically, the nodule was composed of lymph follicles with germinal centers, and the hyalinized inter-follicular space contained abundant hyalinized vasculature and plasma cells. The surrounding liver tissue exhibited chronic inflammation with some peculiar angiofollicular structures mimicking Castleman's disease. An immunohistochemical study revealed that the angiofollicular structure had the same characteristics as a lymph follicle with a germinal center, and that the plasma cells proliferating in the inter-follicular space had polyclonal immunophenotypes. These histological and immunohistochemical findings indicated that the angiofollicular structure observed was a kind of reactive lymph follicle, and that this hepatic lesion was reactive lymphoid hyperplasia rather than Castleman's disease or an inflammatory pseudotumor.

Aged↗

Shared amino acid motifs in T-cell receptor beta junctional regions of bronchoalveolar T cells in patients with pulmonary sarcoidosis.

To clarify the nature of the accumulated lung T cells of pulmonary sarcoidosis, we studied bronchoalveolar and peripheral blood (PB) lymphocytes from Japanese patients for expressed T-cell receptor beta-chain variable (TCR V beta) gene usage. Quantitative polymerase chain reaction technique revealed that the V beta repertoires of bronchoalveolar and PB T cells were heterogeneous. However, the bronchoalveolar lymphocytes from five out of 10 patients showed overrepresentation of T cells, with a few TCR V beta families, which varied among individuals, possibly reflecting a difference in the human leukocyte antigen (HLA) backgrounds. Nucleotide sequence analysis of third complementarity determining region (CDR3) segments in overrepresented V beta families demonstrated limited diversity of the transcripts. Two HLA-DR 12(5)+ individuals with overrepresented V beta 6 gene transcripts in the lungs shared a common amino acid motif within their CDR3. By contrast, non-overrepresented TCR V beta transcripts did not show clonal expansion, and the oligoclonal clones in the lung were not found in PB of the corresponding patient. These results showed that, at least in subsets of Japanese patients with pulmonary sarcoidosis, a limited number of T-cell clones are accumulated in the lung in response to a specific antigen. They may mediate an immune response to shape pathology of the disease.

Adult↗

Production of monoclonal antibodies directed to Hanganutziu-Deicher active gangliosides, N-glycolylneuraminic acid-containing gangliosides.

We have established three kinds of monoclonal antibodies against gangliosides containing N-glycolylneuraminic acid (NeuGc) by immunization of BALB/c mice with the purified gangliosides inserted into liposomes comprising Salmonella minnesota R595 lipopolysaccharides, and fusion of spleen cells with a mouse myeloma cell line. One monoclonal antibody, SHS-1, which was generated by immunizing mice with purified i-active ganglioside(NeuGc), reacted specifically with the i-active ganglioside(NeuGc) used as an immunogen. Structurally related gangliosides, such as GM3(NeuGc), sialosylparagloboside (SPG) (NeuGc), or I-active ganglioside(NeuGc), corresponding gangliosides [GM3 containing N-acetylneuraminic acid (NeuAc), SPG(NeuAc), i-active ganglioside(NeuAc), and I-active ganglioside(NeuAc)], other gangliosides, or neutral glycosphingolipid (GSL) were not recognized by the monoclonal antibody. These findings indicate that the SHS-1 monoclonal antibody may be specific for NeuGc-containing i-active ganglioside. On the other hand, the other two monoclonal antibodies, MSG-1 and SPS-20, which were generated by immunizing mice with purified ganglioside GM3(NeuGc) and SPG(NeuGc), respectively, showed cross-reactivity to structurally related gangliosides. The MSG-1 monoclonal antibody exhibited reactivity to ganglioside GM3(NeuAc). The SPS-20 monoclonal antibody also cross-reacted with SPG(NeuAc), i-active ganglioside(NeuGc), and i-active ganglioside(NeuAc). Neither MSG-1 nor SPS-20 reacted with corresponding gangliosides, other gangliosides, or neutral GSLs tested. Using the SHS-1 antibody specific for i-active ganglioside(NeuGc), we studied the expression of NeuGc-containing antigen in human colon cancer tissue. An NeuGc-containing glycoconjugate was detected in the colon cancer tissue.

Animals↗

Ultrastructural features of alveolitis in sarcoidosis.

Seventy-nine specimens of lung parenchyma from 61 patients with sarcoidosis were examined ultrastructurally with a focus on alveolitis, and they were compared with specimens of hypersensitivity pneumonitis (HP) and the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF). Lymphocytes and monocytes were frequently observed in the capillary lumina, and these cells and macrophages were found in the interstitium of the alveolar walls in the specimens with alveolitis of sarcoidosis and HP. Increases in the percentage of lymphocytes in BALF correlated with the degree of alveolitis. Swelling and bleb formation of the endothelium of alveolar capillaries and changes in the capillary basement membrane were commonly found and were significantly increased in the specimens with alveolitis. The frequency of bleb formation was significantly higher in alveolitis of sarcoidosis than in that of HP. However, the changes in alveolar epithelium were not significant in sarcoidosis. Microvascular changes in alveolitis are not specific for sarcoidosis, but they are observed in other interstitial lung diseases. These alterations may play an important role in the development of pulmonary sarcoidosis.

Adult↗

Paraneoplastic encephalo-myelo-ganglionitis: cellular binding sites of the antineuronal antibody.

The cellular binding sites of an antineuronal antibody were characterized in an autopsy case of the paraneoplastic encephalo-myelo-ganglionitis. A 61 year-old woman developed a subacute sensorimotor polyneuropathy and, later, multiple involvement of cranial nerves, disturbance of consciousness, and generalized seizure. An autopsy revealed a small cell lung carcinoma and neuropathological changes that included disseminated encephalitis, spinal anterior horn lesions, severe loss of dorsal root ganglion neurons, and secondary degeneration and loss of the nerve fibers in the spinal posterior column and peripheral nerves. The serum IgG from the patient contained antineuronal antibody(s) including an antibody to 35- to 37-kDa neuronal antigens called anti-Hu as demonstrated in Western blot. In immunohistochemical studies, the serum IgG immunostained neurons of the brains, spinal cords, and dorsal root ganglia of humans or rats. Confocal laser-scanning microscopy revealed binding of the patient's IgG in the neuronal nuclei and cytoplasm, but not in the nucleoli. In immunoelectron microscopic studies, immunolabelling with the IgG was found diffusely in the karyoplasm, excluding nucleoli, and in the cytoplasmic matrix between the cisternae of the reticulums, Golgi apparatus, and mitochondria. Encephalo-myeloganglionitis is a clinicopathological entity frequently associated with the presence of neoplasm and antineuronal antibody, however, the role of the antibody in the pathogenesis remains to be elucidated.

Autoantibodies↗

Transferrin receptor in oral tumors.

The transferrin receptor (TfR) appears in vigorously proliferating cells. We did an immunohistochemical study of TfR in oral tissues and a quantitative analysis by flow cytometry of TfR in a cancer cell line after an anticancer drug treatment. TfR was found in the parabasal and basal layers of the normal epithelium, but rarely in benign tumors. Generally, in the malignant tumors, the poor prognostic cases showed strong staining regardless of the differentiation of the tumor. In the flow cytometric analysis, the amount of TfR decreased according to the reduction of the proliferative ability of cancer cells. These results suggest that TfR expression may be useful as a prognostic marker.

Adult↗

[Seeking a causative agent of sarcoidosis].

Bacterial components (MDP and IT27 antigen), demonstrated in sarcoid granulomas, strongly suggest the causative agent of sarcoidosis to be derived from some bacteria but many kinds of bacteria are known to have these bacterial components. Our PCR detection of mycobacterial DNA could not demonstrate a significant contribution of M. tuberculosis to the pathogenesis. We then developed a monoclonal antibody to the causative agent by immunizing mice with a crude homogenate of the affected lymph nodes. Hybridized spleen cells were checked with ELISA and all the Ig-producing cell colonies were examined by immunostaining on paraffin sections of lymph nodes with sarcoidosis or tuberculosis. The established antibody (SG5) recognized some extrinsic antigens sequestrated in sarcoid granulomas, in a similar pattern of distribution to those of the bacterial component of MDP and the bacterial product of IT-27. Moreover, ELISA analysis of the SG5 antibody revealed a specific reactivity to culture supernatant of P. acnes. By the immunization of mice with a crude bacterial extract of P. acnes, we recovered one clone of hybridoma named PAB antibody, that possessed an identical reactivity to that of SG5 antibody, as far as examined by ELISA and immunohistochemistry. Furthermore, PCR detection of P. acnes DNA resulted in 92% (36/39) positive in the lymph nodes with sarcoidosis and 41% (12/29) in the control lymph nodes, with a significant difference (p < 0.001, by Fisher's Probability Test) between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization of HSP90 in rat brain.

1. In rats, HSP90 (90-kDa heat shock protein) was abundant in the brain compared with the liver and kidney. Immunohistochemical studies showed the presence of HSP90 in almost all neurons in the brain. 2. On immunoblotting using an anti-HSP90 antibody, HSP90 was present in a lower amount in the medulla oblongata and spinal cord. 3. In the pituitary gland, some of superficial cells of the anterior lobe adjacent to the middle lobe was specifically stained with anti-HSP90 antibody.

Animals↗

Basic fibroblast growth factor (bFGF) receptors decrease with luteal age in rat ovarian luteal cells: colocalization of bFGF receptors and bFGF in luteal cells.

Ovarian growth factors have been implicated in the development and differentiation of corpus luteum. We have characterized both high and low affinity receptors for basic fibroblast growth factor (bFGF) in luteal cells and tissue throughout the life span of corpus luteum using gonadotropin-treated rat luteinized ovaries. Additionally, we determined bFGF location in luteal tissue. High affinity (Kd, approximately 0.2 nM) and low capacity (approximately 500-6000 sites/cell, depending on luteal ages) [125I] bFGF-binding sites (mol wt, 140 kilodaltons, determined by affinity labeling) were found on luteal cells. [125I]bFGF binding to luteal cells and corpus luteum membranes progressively decreased in binding capacity without affecting binding affinity as the age of corpus luteum advanced. bFGF receptor (flg) mRNA in luteinized ovaries decreased with the luteal age similar to the [125I]bFGF binding. In contrast, low affinity binding sites, identified as heparan sulfate proteoglycans, which were immunohistochemically visualized around luteal cells, did not appear to change with luteal age. The signals for heparan sulfate proteoglycans that were found only in granulosa, but not theca-interstitial, cells of follicles became intense during folliculogenesis. The functionality of the bFGF receptors was shown by tyrosine phosphorylation of 16.5- and 18-kilodalton proteins in luteal cells with the antiphosphotyrosine antibody. Immunohistochemistry localized bFGF to steroidogenic luteal cells, and immunoblotting displayed larger molecular forms of bFGF in luteal cells. These results suggest that the bFGF receptors may be associated with the development and differentiation of corpus luteum in an autocrine manner.

Animals↗

Human autoantibody to Sertoli cells detected in healthy individuals.

Human autoantibody to Sertoli cells was detected in normal human sera. This IgM-type autoantibody was undetectable during the neonatal period and was found in 11.5% of 365 serum samples taken from adult healthy persons of both sexes. This human autoantibody to Sertoli cells exhibited quite the same target-organ specificity and multi-organ reactivity (salivary gland ductules, pancreatic intercalated duct, renal lower nephron, pituitary acidophilic cells) as those of the murine monoclonal autoantibody (IgM class) to Sertoli cells (TM-1: WHO registered code T43). The TM-1 monoclonal antibody could recognize testicular antigens with molecular weights of 67,000 and 23,000 in Sertoli cells, and had already been demonstrated capable of inducing murine experimental spermatogenic disturbance when administrated together with murine monoclonal autoantibody to seminiferous tubular basement membrane (TM-2: WHO registered code T44). These observations may suggest that human spermatogenic disturbance could be easily induced by the multi-organ reactive autoantibody to Sertoli cells even in healthy individuals under particular conditions where this autoantibody can be allowed to reach the target Sertoli cells across the barrier of seminiferous tubular wall by either autoantibody to seminiferous tubular basement membrane or other toxic damage.

Adolescent↗

Developmental expression of autoimmune target antigens during organogenesis.

A common factor existing among autoimmune target antigens was sought in association with their developmental expression during organogenesis. Autoimmunity against a certain organ was experimentally induced in rats by deliberate immunization with whole tissue extract of the respective organ. Histopathological changes in a target organ of the immunized rats were recorded, and tissue specificity of the raised autoantibodies was immunohistologically examined with tissue sections of normal adult rats. These immune sera were also reacted with tissue sections of a target organ in each stage of organogenesis, and the time of first expression of the target antigen was determined for each immune serum. As a result, induced autoantibodies were directed only to a limited number of tissue antigens, such as thyroid follicular antigens [gestation day 17 (17 GD)], salivary ductal antigens (18 GD), anterior pituitary antigens (21 GD), gastric parietal cell antigens (22 GD), neural myelin antigens (2 days after birth), retinal photo-receptor cell antigens (3 days after birth) and testicular germ cell antigens (4 weeks after birth). They were first expressed on the day indicated in parentheses. Comparing with the development of the immune system, which was monitored by demonstrating CD4- and/or CD8-positive cells in the developing thymus and spleen, a common feature of these potential autoimmune target antigens was found to be that they were expressed either in parallel with, or after, but never before, the development of the immune system. This observation might suggest why only a limited number of self antigens can be autoimmune target antigens among the enormously large number of antigen determinants existing in the whole extract of each organ.

Animals↗

Transferrin receptor expression in oral tumors.

Transferrin receptor expression in oral tumors was examined by staining with monoclonal antibody against the human transferrin receptor. The cells with positive reaction were recognized in the basal and parabasal layers of the normal epithelium. The staining was found in all the malignant tumors but not in the benign tumors. These results suggest that the immunohistochemical analysis of the transferrin receptor is useful for the diagnosis of oral malignant tumor in addition to the clinical and pathological examinations.

Antibodies, Monoclonal↗