Blood compatibility of surfaces modified by plasma polymerization

Tubular blood-contacting polymeric materials were modified by plasma polymerization and evaluated in the baboon with respect to their capacity to induce both acute and chronic arterial thrombosis. Polymer surface composition was determined by electron spectroscopy for chemical analysis. Steady-state arterial thromboembolism was initiated by introducing tubular segments into chronic arteriovenous shunts. Rates of platelet destruction induced by the test materials were calculated from 111In-platelet survival measurements. Nine plasma polymers based on tetrafluoroethylene, hexafluoroethane, hexafluoroethane/H2, and methane, when deposited on silicone rubber, consumed platelets at rates ranging from 1.1-5.6 x 10(8) platelets/cm2-day. Since these values were near the lower detection limit for this test system, the plasma polymers were considered relatively nonthrombogenic. Acute thrombus formation was initiated by inserting expanded Teflon (Gore-Tex PTFE) vascular grafts into the shunt system. 111In-platelet deposition was measured by scintillation camera imaging over a 1-h exposure period. Standard PTFE grafts (10 cm x 4 mm i.d.) accumulated approximately 1 x 10(10) platelets over this interval. While modification of PTFE grafts with a plasma polymer based on hexafluoroethane/H2 did not alter graft surface morphology, platelet deposition was reduced by 87% as compared to the controls (p less than 0.001). We conclude that both the surface chemistry and texture of prosthetic materials influence thrombogenesis. The method of plasma polymerization may be useful for assessing the importance of these variables independently and, perhaps, for minimizing certain adverse blood-material interactions.     

Immunohistochemical profile of primary sclerosing Iipogranuloma of the scrotum: Report of five cases

Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed Common histologicat features; a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophageimonocytes in the interstitium. lmmunahistochemistry disclosed the epithelioid cells and multinuclaated giant cells of the granuloma to be monocytetr in nature, as bath types of cells were positive for lyso-yme, α-1-antltrypin, α-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and 5–100 protein positive Langerhans-like cells were frequently found. 5100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.     

Hypoalbuminemia accelerates erythrocyte membrane lipid peroxidation in chronic hemodialysis patients

BACKGROUND: Persistent hypoalbuminemia is a long-term poor prognostic factor in chronic hemodialysis patients. PATIENTS AND METHODS: We investigated the correlation between the degree of peroxidation of erythrocyte membrane lipids, erythrocyte alpha tocopherol content, erythrocyte glutathione peroxidase activity and serum albumin concentration in twelve patients with uremia not undergoing hemodialysis and fifteen patients on maintenance hemodialysis. RESULTS: The glutathione peroxidase activity in erythrocytes was higher in patients of uremia not undergoing hemodialysis than in chronic hemodialysis patients. A significant negative correlation was observed between the erythrocyte alpha tocopherol content and the degree of erythrocyte membrane lipid peroxidation in chronic hemodialysis patients. There was a statistically significant difference in the degree of erythrocyte membrane lipid peroxidation between patients with chronic hemodialysis-associated hypoalbuminemia and chronic hemodialysis patients having normal serum albumin levels. CONCLUSION: This study suggested that serum albumin inhibits peroxidation of erythrocyte membrane lipids and that hemodialysis induces recovery of serum reductivity. We conclude that persistent hypoalbuminemia worsens the serum antioxidant activity in chronic hemodialysis patients and may contribute to increased oxidative cell damage.     

Differences of milk-transmitted murine mammary tumor virus (MMTV) among mouse strains.

To clarify the oncological differences of milk-transmitted Murine Mammary Tumor Virus (MMTV) in various strains, BALB/c mice were foster-nursed on C3H/He, GR, DDD, DDD/1-Mtv-2/Mtv-2 and FM strains and observed for the development and morphology of mammary tumors, followed by testing tumors for pregnancy dependence (PD) after transplantation. MMTV were different in tumorigenicity and morphology and PD of induced tumors among the mouse strains. These differences of MMTV appeared not to be parallel with the difference in specificity of superantigens which are encoded by MMTV on the previous report. Interestingly, host factors influenced the properties of MMTV produced by the same endogenous Mtv gene.     

Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion

Betacellulin (BTC), a member of the epidermal growth factor family, is expressed predominantly in the human pancreas and induces the differentiation of a pancreatic acinar cell line (AR42J) into insulin-secreting cells, suggesting that BTC has a physiologically important role in the endocrine pancreas. In this study, we examined the in vivo effect of recombinant human BTC (rhBTC) on glucose intolerance and pancreatic morphology using a new mouse model with glucose intolerance induced by selective alloxan perfusion. RhBTC (1 microg/g body wt) or saline was injected subcutaneously every day from the day after alloxan treatment. The intraperitoneal glucose tolerance test revealed no difference between rhBTC-treated and rhBTC-untreated glucose-intolerant mice at 2-4 weeks. However, glucose tolerance was significantly improved and body weight was significantly increased in rhBTC-treated mice compared with untreated mice at 8 weeks. Islet-like cell clusters, consisting mainly of beta-cells, were increased in the pancreas and were localized in contact with the ductal lining cells and sometimes with acinar cells. In conclusion, administration of rhBTC improved glucose tolerance in this mouse model by increasing beta-cell volume, primarily through accelerated neogenesis from ductal lining cells.     

Expression of GPIV and Naka antigen on monocytes in Naka-negative subjects whose platelets lack GPIV

Summary. The platelet antigen Nak^a was once considered to be a platelet-specific alloantigen and is carried on platelet membrane glycoprotein (GP) IV. Recent studies suggest that Nak^a-negative subjects lack platelet GPIV. GPIV is an important adhesive receptor and expressed on the surface of monocytes as well as of platelets. In the present study, flow cytometry was used to detect GPIV and Nak^a antigen on the surface of monocytes. Nak^a antigen was expressed on monocytes as well as on platelets in Nak^a-positive subjects ( n = 6) (P-GPIV-positive subjects). To our surprise, monocytes of Nak^a-negative subjects ( n = 7) (P-GPIV-negative subjects) having no anti-Nak^a antibody in their serum expressed GPIV and Nak^a antigen to almost the same degree as did the monocytes of P-GPIV-positive subjects. Competitive experiments using OKM5 (a monoclonal antibody against GPIV) and anti-Nak^a antibody showed that the epitope of anti-Nak^a antibody on monocytes was very close to that of OKM5. In two P-GPIV-negative subjects having anti-Nak^a antibody in their serum, GPIV and Nak^a antigen were not expressed on the surface of either monocytes or platelets. These results indicate that the GPIV molecules and Nak^a antigen are expressed on the surface of monocytes in the majority of P-GPIV-negative subjects, but that in a very few P-GPIV-negative subjects neither GPIV nor Nak^a antigen is expressed on the surface of their monocytes. We hypothesize that P-GPIV-negative subjects who carry neither GPIV nor Nak^a antigen on their monocytes produce anti-Nak^a antibody as a result of transfusion or pregnancy.     

Role of IL-16 in delayed-type hypersensitivity reaction

Interleukin (IL)-16 is a chemoattractant cytokine for CD4(+) leukocytes. Because delayed-type hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4(+) T cells can be chemoattracted by IL-16, we have investigated the involvement of IL-16 in the DTH reaction. Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an enzyme-linked immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing monoclonal antibody (mAb) against IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an antigen challenge, together with decreased infiltration of leukocytes including not only CD4(+) T cells but also CD8(+) T cells and macrophages into the DTH footpads. Decreased production of macrophage inflammatory protein 1alpha was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that IL-16 plays an important role in the recruitment of leukocytes-presumably including antigen-specific Th1 cells, which secrete cytokines and chemokines mediating the following hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the antigen-for the elicitation of DTH response. (Blood. 2000;95:2869-2874)     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.