The effect of FK 506 on peripheral blood T-lymphocyte subsets in orthotopic liver transplant patients.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Konno.
Explore the source record for details and available documents.
On fourteen volunteers with Japanese cedar pollinosis, nasal lavage and the determination of nasal airway resistance (NAR) were carried out periodically for twelve hours after an antigen challenge using antigen disk. The percentage of EG2 positive eosinophils, the number of activated eosinophils (EG2 positive eosinophils) and the amount of ECP in each sample of nasal lavage fluid were determined. 1. The percentage of activated eosinophils increased during the late phase compared with that before the challenge and during the early phase. The number of activated eosinophils and the amount of ECP increased during both phases, but more markedly during the late phase. 2. The number of activated eosinophils and the amount of ECP were compared between the group with late phase response and that without a marked late response. Both the number of activated eosinophils and the amount of ECP showed a tendency to increase in the positive group. 3. There was a statistically significant correlation between the percentage of increase in NAR and the number of activated eosinophils. The correlation coefficient during the late phase was considerably higher than in the early phase. From these findings, the increased number of activated eosinophils observed during the late phase response is assumed to have a significant relationship with increased NAR and also the hyperreactivity of nasal mucosa.
This report describes the development of hyperplasia of both the thymus and the peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats do not show age-related thymic involution, but rather develop thymic hyperplasia with advancing age. This thymic growth is expansile and there is no infiltration of the surrounding tissues. Because the enlarging thymus occupies the thoracic cavity, most of the rats die of respiratory failure by the age of 24 months. Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and the large number of proliferating lymphocytes. The hyperplastic epithelial cells are bizarre in shape and strongly positive when stained with Th-3 monoclonal antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes within the hyperplastic thymus are similar to those seen in young rats of other species. The high level of T-cell emigration from the thymus to the periphery appears to persist throughout life, since the percentage of normal splenic T-cells also increase with advancing age and exceed 70% of the total by 24 months of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial cells can be prevented by hypophysectomy.
Mice fed a 40% restricted diet until 1 year of age showed a 35% drop in body weight and markedly lower weights in the central lymphoid organs such as spleen and thymus than those of unrestricted mice. In contrast, the percentage of splenic Thy 1.2+ T cells was dramatically increased by dietary restriction. Splenic Ly 1+ T cells were also increased in the restricted mice. Spleen cells of the restricted mice revealed significantly higher responses not only in macrophage (MP)-dependent responses such as concanavalin A response and mixed-lymphocyte reaction but also in MP-independent T cell responses to recombinant interleukin 2 even at 1 year of age. These results strongly suggest that dietary restriction causes an enrichment of Thy 1.2+ T cells in spleen and augments the functions of T cells in mice.
Explore the source record for details and available documents.
To elucidate relationship between disease progress and immunologic alteration in feline immunodeficiency virus (FIV) infection, we classified naturally infected cats into clinical stage groups using the working criteria modified from those for human immunodeficiency virus (HIV) infection. Among the five distinct stages described for HIV infection, the three phases; asymptomatic carrier (AC), AIDS related complex (ARC), and acquired immunodeficiency syndrome (AIDS), were evaluated for concanavalin A (Con A)-induced lymphocyte blastogenic activities by using glucose consumption assay. There was a significant decrease of lymphocyte response in AC phase. The loss of response became marked as the disease progressed to ARC and AIDS, with an almost complete loss of mitogen response in AIDS phase. In addition to the loss of a lymphocyte function, AIDS in FIV infection was characterized by marked emaciation, anemia or pancytopenia, and postmortem evidences of opportunistic infections and lymphoid depletion.
A WKA rat fetus fibroblast (WFB) was transfected by several oncogenes including EJras (activated H-ras), polyoma middle T (PyMT), v-src, c-myc, and adenovirus type 12 E1A-E1B. We analyzed the expression of the transformation-associated cell surface antigens on WFB by developing monoclonal antibodies. One of the WFB transformation-associated cell surface antigens, recognized by monoclonal antibody 067, was constitutively expressed only on two (W31 and W70) of ten WFB-EJras-transformed clones. This antigen could not be detected on parental WFB cells as well as ten WFB-PyMT transformant clones. Furthermore, it was not expressed on several clones of partially transformed WFB-v-src and WFB-adeno E1 transfectants or nontransformed WFB-c-myc transfectants. Monoclonal antibody 067 could form an immunoprecipitate with an approximate molecular weight of 67,000 which was composed of a single polypeptide chain. It was also shown that the expression of this antigen could be enhanced by cyclic AMP or cholera toxin treatment of W31; treated cells also showed a phenotypic reversion to the nonmalignant growth characteristics of the parental WFB. Moreover, the expression of this antigen could be induced on the WFB-EJras transformants such as W14, which do not constitutively express this antigen, by treatment of these agents. Furthermore, the expression of antigen was enhanced by heat and superoxide treatment on W31. These data suggest that the monoclonal antibody 067-defined molecule is a novel transformation-associated cell surface antigen that could be induced by heat shock or other physiological stress.
Primary squamous cell carcinoma of the parotid gland is a rare tumor. Histological and ultrastructural features of a primary squamous cell carcinoma arising in the right parotid gland is presented. Light microscopically the tumor consisted of poorly differentiated squamous cell nests. PAS reaction was negative. Ultrastructurally the tumor cells were oval or spindle shaped and the cytoplasmic processes were frequently found. The majority of the tumor cells contained numerous intermediate filaments in their cytoplasm. No secretory granule was found. The desmosomes were well developed. It is known that mucoepidermoid carcinoma may be often misdiagnosed as squamous cell carcinoma. These findings can enable us to distinguish primary squamous cell carcinoma from mucoepidermoid carcinoma of the parotid gland.
In order to clarify the relationship between cold temperatures and the progression of hypertension, a prospective epidemiological study was carried out in a cold area of Hokkaido, Japan. We analysed the findings in 909 subjects, who were followed up for 8 years (1977 to 1985). The difference between the mean blood pressure in winter and in summer in the first year was significantly and positively correlated with the difference between the mean blood pressure in the first and in the eighth year. The winter/summer difference was significantly higher in the group with progressive hypertension than in the other groups. The pressor response to exposure to cold was significantly greater in hypertensives, and tended to be higher in borderline hypertensives compared with normotensives. From these results, we conclude that a cold environment might increase the inhabitants' blood pressure levels, and the difference between a subject's blood pressure in winter and summer may predict future hypertension.
A case of peliosis hepatis in a 52-year-old woman with unusual involvement of the spleen and lymph nodes is described. The initial sign was intraperitoneal hemorrhage from the splenic lesion, recessitating splenectomy. The hepatic lesion, which was first noticed during the operation, rapidly progressed and eventually resulted in hepatic rupture with fatal intraperitoneal hemorrhage. Serial sections treated by silver impregnation revealed degeneration and dissolution of the fine reticulin framework in the involved organs, suggesting the possible morphogenesis of the peliotic lesion. The patient had no history of any underlying disorders or of medication with steroids.
In the period 1983 to 1985, 66 patients presented to six Japanese university hospitals with squamous cell carcinoma of the maxillary sinus. Using self-administered questionnaires, a case-control study was conducted to examine history of nasal diseases, occupational exposures, and other possible risk factors for this disease. For each patient, two controls were selected from the general population, matched to the patient by sex, age (+/- 5 years), and district of residence. A history of chronic sinusitis was associated with a 2.3-fold increase in risk (p = 0.05). A high relative risk was also observed in males with an occupational history of woodworking or joinery, particularly when these jobs involved sanding or lathing practices (RR = 7.5, p = 0.02). No association between cigarette smoking and maxillary sinus cancer was observed in this study and no evidence was found that indoor air pollution in the home is involved in cancer development.
Acetylcholine receptors (AchRs) at the neuromuscular junctions of the cat posterior cricoarytenoid muscle (PCA muscle) were demonstrated by using erabutoxin b (Eb) which has a curare-like action. Eb is one of the short-chain neurotoxins which is obtained from Laticauda-semifasciata. At the light microscopic level, the localization of the neuromuscular junctions was detected on the muscle fiber by rhodamine-labeled Eb (TMR-Eb) under a fluorescein microscopy. For the electron microscopy horseradish peroxidase-labeled Eb (HRP-Eb) was used. After incubation with HRP-Eb conjugate the tissue was fixed in a mixture of paraformaldehyde and glutaraldehyde, then embedded in Epon. The reaction products were largely restricted to the postsynaptic membrane at the neuromuscular junction. Acetylcholinesterase (AchE) activity was also demonstrated electron microscopically by Karnovsky's and Lewis' methods respectively. The reaction products were localized at the subneural apparatus of the neuromuscular junction. Both these results were compared.
The purpose of this study is to clarify the role of peptide leukotrienes (LTs) on the onset of characteristic hyperreactive nasal symptoms of nasal allergy by observing the time course of the correlation among degrees of nasal symptoms, and by observing the amount of chemical mediators and the number of inflammatory cells in the nasal lavage fluid after nasal antigen challenge in subjects with Japanese cedar pollinosis during off season. Sneezing was terminated within 10 minutes and nasal discharge within 2 hours. However, time course change of the percent increase of nasal airway resistance showed dual response consisting of immediate and late phase responses. The peak of the former was seen at 30 minutes and the latter was at 7 hours after provocation. The significant increase of eosinophils in the nasal lavage fluid was observed during both the immediate and the late phase responses, but during the late phase response, the increase was more prominent. Basophilic cells definitely increased during the late phase response. The amount of LTs in the nasal lavage fluid increased significantly during both the immediate and the late phase responses. In contrast, the level of histamine increased significantly only during the immediate phase response. Considering that LTs, especially LTD4, has potent and persistent effect on causing swelling of nasal mucosa, LTs may play important role in causing nasal obstruction during both the immediate and the late phase responses after antigen challenge. On the other hand, the role of histamine may be confined to cause the hyperreactive nasal symptoms during the immediate phase response.(ABSTRACT TRUNCATED AT 250 WORDS)
It is generally accepted that abnormal autonomic responsiveness may contribute to the pathogenesis of hyperesthetic rhinitis. Histologically, in the nasal mucosa, cholinergic fibers are found close to blood vessels, but are particularly numerous around the glands. Adrenergic fibers are found mainly around the vascular structures. Physiological and pharmacological studies demonstrate that parasympathetic hypersensitivity causes hypersecretion, and sympathetic hyposensitivity causes vasodilatation. alpha 1-adrenergic receptor function is dominant for this vasodilatation. Using radioligand binding techniques, it has been found that there is an increased number of muscarinic cholinergic receptors and a decreased number of alpha 1- and beta-adrenergic receptors in patients with nasal allergy, while the binding affinities do not change. In this report, using radioligand binding techniques, we investigated the relationships between the number of receptors and the degree of the hyperreactive nasal symptoms in patients with hyperesthetic rhinitis. The results are as follows. 1. The number of muscarinic cholinergic receptors of human nasal mucosa in patients with hyperesthetic rhinitis was related significantly (P less than 0.01) to the degree of hypersecretion induced by methacholine and frequency of blowing nose estimated from allergy diary. 2. There was no relationship between frequency of sneezing and the number of muscarinic cholinergic receptors. 3. The number of alpha 1-adrenergic receptors was related significantly (P less than 0.05) to the degree of swelling of nasal mucosa induced by methoxyamine. Judging from these results, it was assumed that pathogenesis of hyperreactive nasal symptoms may be associated at least partially to the changes of number of autonomic nerve receptors in the nasal mucosa.
The key point in this study was that the cell surface antigens in the events of transformation were analyzed using the same clonal-derived nontransformed cell and various oncogenes. WKA rat fetus-derived fibroblast line, WFB, showed the strict non-transformant phenotypes. Transfection of EJras and polyoma middle T oncogenes into WFB resulted in the acquisition of tumorigenicity in vitro and in vivo. The newly expressed cell-surface antigens on some transformants were analyzed using four monoclonal antibodies (Moabs) (#109, #061, #081 and #067) that were produced after immunization of BALB/c mice with EJ-ras-transformed WFB clone, W31 and W14. #109 recognized a glycoprotein composed of a single polypeptide chain with 86 KD. This antigen was also expressed in the FJ ras transformants of Fisher rat fetus-derived 3Y1 fibroblast, FTL43 rat T lymphoma, SP56 rat gliosarcoma, and ca. 16th-day embryo. #061 could react with WFB transformants, but not with fetus. Furthermore, these two antigens are expressed on TGF-beta-stimulated WFB. However, #109 but not #061 is expressed on PDGF-stimulated WFB, indicating that #109 expression does not require the transforming process. It is also indicated that these two antigens act as target structures in the Natural killer (NK) cytotoxicity assay. #081 could react with WFB transformants but not with FTL43, SP56 and 3Y1 ras transformants, suggesting a limited expression of #081 defined antigen on WFB transformants. #067 reacted with W31 but not with W14. This antigen is expressed on 5 clones out of approximately 40 highly tumorigenic WFB ras transformed clones. We also analyzed the expression dynamics of these TAAs during the morphological reversion of W31 to parental WFB using cAMP analogues such as dibutylic cAMP. The data indicated that, although W31 cells were reversed morphologically to WFB, the level of #109 antigen expression was not changed. #061 and #081 defined antigens were reduced by cAMP treatment for 4-5 days. However, it is of interest that #067-defined antigen expression was greatly enhanced during the morphological reversion of W31 to WFB by cAMP. This was also true when W31 was treated with 1% FCS for 5 days and heat shock, suggesting that this antigen is a heat shock-related protein.
A series of seven patients with squamous-cell carcinoma that arose in the area of an old scalp burn is presented, and the patient's profiles, surgical procedures and results are reviewed. In six patients, burn scar of the scalp caused by direct exposure to fire in their infancy was a pathogenesis underlying the development of the malignancy, and the time interval was estimated to be an average of 53 years. In five patients there was evidence of intracranial invasion of the carcinoma involving the dura mater and cerebral parenchyma, as revealed by neuroradiological examinations and surgery. All patients were treated by extensive excision of the lesion, and to cover defects of the scalp and cranium, a variety of reconstructive techniques were used involving advancement, transposition or free latissimus dorsi musculocutaneous flaps combined with microvascular anastomosis. Radiochemotherapy was undertaken additionally in some patients either before or after surgery. Complete excision was accomplished in two patients, in whom the carcinoma was found localized within the layer of the scalp or in the depth of the periosteum. The survival time in these patients ranged from 73 to 87 months. In contrast, incomplete resection was performed in the remaining five patients, in whom the dura mater had been invaded with simultaneous involvement of the middle part of the superior sagittal sinus. The outcome resulted in poor prognosis, and all the patients except one died in 9 to 24 months after surgery due to continuous growth of the tumor in the intracranial cavity. Therefore, total resection facilitated by early detection prior to intracranial invasion is mandatory for successful treatment of such scalp carcinomas.
An extremely unique case of a liver tumor occurring in a 70-year-old man is documented in this article. The primary tumor was well encapsulated by a thick, connective capsule and was histologically composed of two distinct elements, i.e., a common hepatocellular carcinoma (HCC) and a rhabdomyosarcoma. Metastasis of HCC was only seen in the left adrenal gland, whereas intrahepatic metastatic foci as well as tumor thrombi occluding the portal vein branches were composed exclusively of rhabdomyosarcoma. The possibility that the rhabdomyoblastic component might have come from the preexisting HCC by way of metaplastic proliferation is discussed.
A WKA rat fetus-derived fibroblast cell line WFB showed strict nontransformant phenotypes in vitro such as anchorage dependency of cell growth in soft agar, contact inhibition, and serum dependency on the monolayer cell culture. Transfection of 6.6-kilobase EJras oncogene into WFB resulted in the acquisition of tumorigenicity in vitro and in vivo. The cell surface antigen that is moderately or highly expressed on these WFB transformants, designated as W14 and W31, was analyzed using monoclonal antibody 109 that was produced after the immunization of BALB/c mice with W31. Moab 109 recognized a glycoprotein with a molecular weight of 36,000 composed of a single polypeptide chain with 5.4 isoelectric point value. This antigen was highly expressed on WFB EJras and polyoma middle T-DNA transformants, but was undetectable or at the best only faintly recognized on WFB parental cells, transfectants of WFB with c-myc, and normal thymus, liver and kidney of WKA adult rats. It was also clearly expressed on the EJras transformants of Fisher rat fetus-derived 3Y1 fibroblast, but very faintly on parental 3Y1. Furthermore, this antigen was detected on some rat T-lymphoma and gliosarcoma lines. However, it was undetectable on EJras transformants on NRK-49F rat kidney cells and NIH3T3 and BALB3T3 mouse cells. In addition, this antigen appeared on the cell surface of concanavalin A-activated WKA rat lymphocytes and WKA rat on the 16th day of embryo but not on the 8th. These results suggested that the cell surface antigen detected by Moab 109 was clearly unrelated to the ras oncogene product p21 that was highly expressed on EJras-transformants of WFB or 3Y1 cells. Furthermore, it was shown that W14 and W31 cells but not parental WFB cells were susceptible to rat splenic NK cells that were induced by poly(I-C) treatment. Pretreatment of these W14 or W31 cells with Moab 109 could block the NK cell activity against W14 and W31. These data suggest that this antigen may act as one of the NK target structures, and plays an important role as a tumor antigen on the host tumor surveillance, since the antigen was expressed (a) on the cell surface after the cell transformation or enhanced DNA synthesis of some particular cells, and (b) in the W31 tumor developing progressively in the syngeneic rats.