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ABSTRACT: The reason(s) why individual cytotoxic T lymphocytes (CTL) possess a fast-acting, perforin/granzyme-mediated, as well as a much slower, Fas ligand (FasL) -driven killing mechanism is not clear, nor is the basis for wide variations in killing activity exhibited by individual CTL, ranging from minutes to hours. We show that perforin expression among individual, conjugated CTL varies widely, which can account for the heterogeneity in killing speeds exhibited by individual CTL. Despite a 2-hr lag in FasL-based killing, CTL lytic action is enhanced when the two mechanisms operate in concert. This is explained by finding that the two pathways in fact are jump-started simultaneously with the lag in FasL lytic action reflecting pre-lytic caspase-8 activation and BH3-interacting domain (BID) cleavage. The complementary action of the two lytic pathways, co-expressed at varying levels among individual CTL, facilitates the lytic action of late-stage poor perforin-expressing CTL, ensuring optimal cytocidal action throughout the CTL response.
Immunology 06/2011; 133(2):190-6. · 3.32 Impact Factor
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ABSTRACT: Although CD8(+) cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8(+) CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8(+) T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8(+) cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8(+) CTL have two killing strategies.
Immunology 10/2009; 128(1):69-82. · 3.32 Impact Factor
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ABSTRACT: To determine the efficacy of intraurethral metal stents in preventing or eradicating urinary-tract infections (UTI) during the management of bladder outlet obstruction (BOO) by comparing the frequency and nature of the infections with indwelling-catheter-associated UTI.
The SAS relative-risk test was used to compare the risks of UTI in 76 patients with temporary urethral stents, 60 patients with BOO who had never been catheterized nor stented, and 34 patients with a permanent indwelling urethral catheter (PIUC). Infection was assessed 1 month after placement of the devices. Scanning electron microscopy (SEM) of the proximal and distal pieces of the stents removed from five patients with and five patients without UTI was carried out in a search for predisposing changes on the surfaces.
After insertion of the catheter, UTI developed in 79.4% of the patients who originally had sterile urine. However, after insertion of the stent, UTI developed in only 40.9% of the patients with sterile urine. In 21 (44.6%) of the catheterized patients who had infected urine, UTI was eradicated after stent insertion. The SEM analysis of the stents showed that a thick organic layer had formed only on the infected devices but with no sign of erosion.
Urinary infection is a significant problem in patients with PIUC but is significantly less frequent and less severe in patients with urethral stents. This advantage of stents over the conventional urethral catheter, in addition to their obvious convenience for the patient, make them good alternatives to reduce the risk of UTI.
Journal of Endourology 05/2006; 20(4):272-7. · 1.85 Impact Factor
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ABSTRACT: In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported.
European Journal of Internal Medicine 01/2005; 15(8):531-533. · 2.00 Impact Factor
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Yardena Siegman-Igra,
Rotem Levin,
Miriam Weinberger,
Yoav Golan,
David Schwartz,
Zmira Samra,
Hana Konigsberger,
Amos Yinnon,
Galia Rahav,
Nathan Keller, [......],
Michael Alkan,
Zvi Landau,
Julia Novikov, David Hassin,
Carlos Rudnicki,
Ruth Kitzes,
Shmouel Ovadia,
Zvi Shimoni,
Ruth Lang,
Tamar Shohat
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ABSTRACT: Listeria monocytogenes, an uncommon foodborne pathogen, is increasingly recognized as a cause of life-threatening disease. A marked increase in reported cases of listeriosis during 1998 motivated a retrospective nationwide survey of the infection in Israel. From 1995 to 1999, 161 cases were identified; 70 (43%) were perinatal infections, with a fetal mortality rate of 45%. Most (74%) of the 91 nonperinatal infections involved immunocompromised patients with malignancies, chronic liver disease, chronic renal failure, or diabetes mellitus. The common clinical syndromes in these patients were primary bacteremia (47%) and meningitis (28%). The crude case-fatality rate in this group was 38%, with a higher death rate in immunocompromised patients.
Emerging infectious diseases 04/2002; 8(3):305-10. · 6.17 Impact Factor
