Replacement of a tracheal defect with autogenous mucosa lined tracheal prosthesis made from polypropylene mesh

Reliable prosthetic or tissue grafts for the trachea have not, as yet, been developed for reconstruction of large, circumferential tracheal defects. Major limitations are anastomotic dehiscence and stenosis, attributed to the poor epithelialization and vascularization of the prosthetic graft. We have developed a new tracheal prosthesis that has a well vascularized and viable mucosa. The prosthesis consists of a Prolene mesh reinforced with polypropylene rings, and coated with gelatin. We lined the luminal surface of the prosthesis with transplanted autogenous oral mucosa, wrapped the prosthesis with greater omentum, and placed it in the peritoneal cavity for 2 weeks. Complete surgical resection and replacement of a segment (5 cm in length, 8 to 10 tracheal rings) of the thoracic trachea was then performed in nine adult mongrel dogs. The transplanted mucosa was well vascularized and maintained its normal histology in prereplacement analysis. Dogs with tracheal replacement regained their full activity and did not show any respiratory problems until sacrifice at 1, 2, and 6 months. After 6 months, the prostheses were completely incorporated by the host trachea in all dogs and confluent epithelialization was confirmed histologically from the upper to the lower anastomotic site of the prosthesis; furthermore, the transplanted mucosal cells had changed to ciliated columnar epithelium.     

Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 Effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy.

Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BMT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BMT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets.     

Development of a non-transformed human liver cell line with differentiated-hepatocyte and urea-synthetic functions: applicable for bioartificial liver

There is a need to develop human hepatocyte cell lines which retain both replicating capacity and highly differentiated functions to facilitate the development of an efficient bioartificial liver. The present study was undertaken to differentiate, using sodium butyrate, the actively replicating immortalized human liver cell line. The effects of butyrate on cell growth and cell cycle were analyzed, and the albumin synthesis, cytochrome P450 and ammonia-detoxifying activity of the butyrate-treated cells were measured. Butyrate treatment resulted in G2/M arrest of the cell cycle and polygonal changes in the cell morphology. Neither the control nor the butyrate-treated cells showed transformed characteristics. Butyrate treatment increased the amount of albumin secretion, cytochrome P450 activity, and the urea production rate of the cells. The present study provides non-transformed human hepatocytes, which can replicate unlimitedly and then restore differentiated hepatocyte-specific functions by butyrate, and therefore, have applications for the development of an efficient bioartificial liver.     

Giant-cell interstitial pneumonia in a gas station worker.

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.     

Analysis of antibody response to the measles virus using synthetic peptides of the fusion protein Evidence of non-random pairing of T and B cell epitopes

The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31–75; 111–145; 151–165; 191–215; 271–320; 421–440; 481–530) which include the major hydrophobic segment (111–145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides.     

Anaplasma phagocytophilum delay of neutrophil apoptosis through the p38 mitogen-activated protein kinase signal pathway

Human granulocytic anaplasmosis is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The bacterium avoids host innate defenses in part by infecting, surviving in, and propagating in neutrophils, as well as by inhibiting neutrophil apoptosis. However, the mechanisms of A. phagocytophilum survival in neutrophils and the inhibition of spontaneous apoptosis are not well understood. In this study, we demonstrated that antiapoptotic Mcl-1 protein (Bcl-2 family) expression is maintained and that inhibition of procaspase-3 processing occurs in A. phagocytophilum-infected human neutrophils. An evaluation of p38 mitogen-activated protein kinase (MAPK) showed evidence of increased phosphorylation with infection. Moreover, antagonism of p38 MAPK by the inhibitor SB203580 reversed apoptosis inhibition in live or heat-killed A. phagocytophilum-infected neutrophils. A role for the autocrine or paracrine production of antiapoptotic interleukin 8 (IL-8) expressed with A. phagocytophilum infection was excluded by the use of IL-8-, IL-8R1 (CXCR1)-, and IL-8R2 (CXCR2)-blocking antibodies. As previously demonstrated, the antiapoptotic effect was initially mediated by exposure to A. phagocytophilum components in heat-killed bacteria. However, an important role for active infection is demonstrated by the additional delay in apoptosis with intracellular growth and the refractory abrogation of this response by the p38 MAPK inhibitor 3 to 6 h after neutrophil infection. These results suggest that the initial activation of the p38 MAPK pathway leading to A. phagocytophilum-delayed neutrophil apoptosis is bypassed with active intracellular infection. Moreover, active intracellular infection contributes more to the overall delay in apoptosis than do components of heat-killed A. phagocytophilum alone.     

Determinants of private clinics' productivity: a comparison of city and county clinics in Korea

This study was designed to assess determinants of private clinics' productivity, and to compare city and county clinics in South Korea. We analyzed the revenue and patient data from all 9,212 private clinics in South Korea. This data was obtained from the Korean National Health Insurance Corporation, during the period between 1996 and 1999. We used a mixed model for repeatedly measured data. The following listed variables were used in our analysis: sex and age of physician, number of beds of clinics, competitiveness of medical institution, inhabitants'incomes, the proportion of elderly in the administrative unit, and time effects. Age, sex, number of beds, and specialty were found to be the most relevant determinants for the productivity of private clinics in both urban and rural settings, and number of clinics and beds per 100,000 and income of the administrative unit were found to be significant determinants, but only in city environments.     

Localized form of colitis cystica profunda--a case of occurrence in the descending colon.

An unusual localization of localized colitis cystica profunda in a 31-year-old man is described. The patient presented as anal bleeding and a protruding mass at the descending colon; the mass was polypoid and was made up of papillary epithelial hyperplasia with downward herniation of glands into the submucosa. Only one similar case involving a descending colon has been reported in the world literature.