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Biomedical subjects

D Raveh

Publications and source records attributed to D Raveh.

At least 55 records · Page 3Linked to original sources

Th1 and Th2 cytokines cooperate to stimulate mannose-receptor-mediated phagocytosis.

The mannose receptor is a macrophage surface receptor that mediates both endocytosis and phagocytosis. Previous work has demonstrated that the prototypical Th2 cytokine, interleukin-4 (IL-4), increases both cell-surface receptor expression and mannose receptor-mediated endocytosis, whereas the prototypical Th1 cytokine, interferon-gamma (IFN-gamma), decreases both surface expression and endocytosis. In many aspects of the immune response, Th1 and Th2 cytokines oppose each others' actions. We demonstrate that IL-4 and IFN-gamma alone and together enhance mannose receptor-mediated phagocytosis, despite opposing effects on cell-surface mannose receptor expression and endocytosis. Thus these usually antagonistic cytokines cooperate in increasing mannose receptor phagocytic function. The cooperative effect of these cytokines is not observed for Fc receptor-mediated phagocytosis. The Th2 cytokine IL-13 exerts similar effects to IL-4. Our results suggest that Th1 and Th2 cytokines may act in concert at sites of inflammation to enhance mannose receptor-mediated phagocytosis of microorganisms.

Animals↗

Murine macrophage mannose receptor promoter is regulated by the transcription factors PU.1 and SP1.

The mannose receptor (MR) is a transmembrane protein that functions primarily as a phagocytic receptor for a wide range of microorganisms. Its expression appears to be restricted to tissue macrophages and Langerhans cells. To gain an understanding of the regulation of the gene, we have isolated the 5' flanking sequence of the murine MR gene and have analyzed a 536-bp sequence upstream of the ATG start site for transcriptional activity. This sequence lacks a TATA box but contains an initiator (Inr) consensus element overlapping the single transcriptional start site. Transcription factor binding sites contained within this sequence include PU.1, Sp1, ETS, GATA, and MYB motifs. Serial 100-bp deletions of this promoter fragment fused to a luciferase reporter gene showed various patterns of activity when transfected into different cell types. In myeloid cells, sequence elements upstream of bp -300 appeared to have a silencing effect on promoter activity. Of the four potential PU.1 binding sites contained within the fragment, one site (at -164) bound the PU.1 factor most strongly, whereas the adjacent PU.1 site (at -177 bp) bound PU.1 to a lesser degree. Mutations of these sites decreased transcriptional activity but did not abolish it. However, promoter activity was abrogated when both the -164 bp PU.1 site and the adjacent -177 bp PU.1 site were mutated. In addition, mutation of the Sp1 site also significantly reduced promoter activity. Cotransfection studies in Drosophila Schneider cells indicated that PU.1 and Sp1 may function synergistically in transactivating the murine MR. This study indicates that MR gene expression is regulated in part by the interaction between the ubiquitously expressed factor Sp1 and the lymphoid/myeloid factor PU.1 and provides a basis for studying the regulation of this gene.

Animals↗

Legionella feeleii pneumonia and pericarditis.

Legionella feeleii pneumonia has been described in seven cases, three of them being immunocompromised. We describe a case of L. feeleii pneumonia and pericarditis in a healthy man. Epidemiological survey was not conclusive. To the best of our knowledge, there have been no previous descriptions of pericarditis caused by this organism.

Humans↗

Tetracycline derivatives, alternative treatment for nocardiosis in transplanted patients.

Nocardiosis is a rare infection in patients with immunosuppression following transplantation. Thus far, treatment with sulfa derivatives, when combined with immunosuppressive agents, has been shown to carry an unacceptably high rate of toxic effects. Therefore, the possibility of using an alternative antimicrobial treatment was investigated. The treatment of disseminated Nocardia infection with doxycycline or minocycline in patients after either kidney, bone marrow or liver transplantation was investigated retrospectively. Three patients were treated at The Hadassah University Hospital in Jerusalem. Antibiotic treatment with tetracyclines was administered for one to 14 months at a dose of 100 to 600 mg/d. Additional seven patients were reviewed from previous published reports. Nine out of the ten treated patients had an uneventful recovery. One non-compliant patient died of disseminated nocardiosis. In conclusion, the favorable outcome of the patients treated with minocycline for Nocardia infection which developed after transplantation, suggests that this antibacterial agentis is both effective and safe. These data support the recommendation that tetracycline derivatives may be considered as an alternative treatment for Nocardia infections in transplanted patients.

Adult↗

Emergence of drug-resistant tuberculosis in Jerusalem: ten-year retrospective review.

Drug-resistant tuberculosis (TB) has emerged as a worldwide problem. The annual incidence of TB has increased in Israel in the last decade, mainly due to successive waves of immigration. Few data are available on drug-resistant TB in Israel A 10-year retrospective review was conducted on all patients who had been infected with culture-proven Mycobacterium tuberculosis and had been admitted to our hospital. Forty-seven patients had culture-positive TB; 27 (57%) were male, 20 (43%) were female; mean age (+/- SD) was 56 +/- 23 years. Twenty patients (43%) had pulmonary TB. Three patients (6.4%) had single-drug resistance; 4 patients (8.5%) had multi-drug resistance. Six of the seven patients (86%) with drug-resistant TB had been diagnosed after 1990. Six of the 20 patients (30%) with pulmonary TB had drug-resistant organisms. Six of the 7 patients (86%) with drug-resistant TB had pulmonary infection, as compared to 15/40 (37%) of the patients with drug-susceptible TB (p < 0.001). Six of the 7 patients (86%) with drug-resistant TB had a history of TB. Fifteen percent (14.9%) of all new cases diagnosed with TB in our hospital in the last 10 years had drug-resistant M. tuberculosis. Thirty percent of patients with pulmonary TB had drug-resistant organisms. Drug-resistant TB has evidently emerged in Israel and poses a serious clinical and social threat. A strong case for directly-observed treatment in Israel should be made, especially since the incidence of TB here is still small.

Adolescent↗

Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study.

The purpose of this study was to examine coagulase-negative staphylococcal infections in bone marrow transplantation (BMT) patients with central vein catheters by investigating incidence, clinical relevance, risk factors, methicillin resistance, clinical impact of initial empiric antimicrobial therapy without vancomycin, and management of documented catheter-related infections. A 5-year prospective study was conducted with daily evaluation of 242 BMT patients during hospitalization, including clinical assessment and blood culture via the Hickman/Broviac catheter. If fever or infected appearance occurred, peripheral blood cultures or exit site cultures, respectively, were done. Results showed a septicemia incidence of 7.0%, including in 6 patients following colonization, in 1 patient with tunnel infection, in 1 patient with thrombophlebitis, in 1 patient with exit site infection, and in 8 patients with septicemia of unknown origin. Total colonization incidence was 7%, with colonization only in 11 patients who had 16 episodes; incidence of exit site infection was 3.7%. Age > or = 18 years was the only identified risk factor for developing staphylococcal infection (P = 0.03). Despite a methicillin resistance rate of 45% and omission of vancomycin from the routine initial empiric antimicrobial regimen, the clinical course of coagulase-negative staphylococcal infections was relatively benign. A single patient, who experienced marrow rejection, died on day +31 with septicemia and only one patient experienced microbiological failure with recurrent colonization. Bacteria grown in both aerobic and anaerobic bottles were more likely true bacteremia than contaminant (P = 0.03). We conclude that the hazard of coagulase-negative staphylococcal infection does not mandate inclusion of a glycopeptide in the initial empiric antimicrobial regimen in BMT patients, even during febrile neutropenia. Hickman/Broviac-related staphylococcal infections, except for tunnel infection or thrombophlebitis, can usually be treated successfully without removing the catheter.

Adolescent↗

Klebsiella bacteraemia: community versus nosocomial infection.

In the period 1988-1993, 241 patients had Klebsiella bacteraemia at our medical centre. The annual number of patients with positive blood cultures increased from 306 in 1988 to 622 in 1993, representing a 4.5-6% positivity rate of drawn cultures. After E. coli, Klebsiella was the leading cause of Gram-negative bacteraemia. During this period, the absolute number of Klebsiella bacteraemia increased from 25 in 1988 to 84 in 1993; this represents a true increase in Klebsiellaa bacteraemia, from 6-7% of positive cultures in the late 1980s to 12-13% in more recent years. There were 210 cases with K. pneumoniae and 31 with K. oxytoca. A representative sample of 80 records was retrieved and subdivided into two groups: community-acquired Klebsiella bacteraemia (CAKB) vs. hospital-acquired Klebsiella bacteraemia (HAKB). Urinary tract infection was the underlying source of 58% of CAKB vs 28% of HAKB (p < 0.01); pneumonia occurred significantly more often in HAKB (25%) than in CAKB (7%) (p < 0.01). In HAKB, as compared to CAKB, serious manifestations of illness were more common, e.g. shock (65% vs. 37%, p < 0.046) and respiratory failure (45% vs. 20%, p < 0.046). Overall mortality was 32%, 22% of patients with CAKB died vs. 42% of those with HAKB (p < 0.05). Multiple drug resistance was very common: only 57% of all Klebsiella strains were susceptible to gentamicin, 66% to ceftriaxone, 70% to ciprofloxacin, and 83% to amikacin. The susceptibility rates of Klebsiella spp isolated from patients with HAKB were significantly lower (p < 0.001). Sepsis due to multiple-drug-resistant Klebsiellaa has become frequent, carrying significant morbidity and mortality. Restriction of broad-spectrum antimicrobials in the hospital and the community as well as implementation of infection control measures are needed to contain this problem.

Aged↗

Oral tuberculosis following autologous bone marrow transplantation for Hodgkin's disease with interleukin-2 and alpha-interferon immunotherapy.

A patient with Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Six months later while receiving interleukin (IL)-2 and alpha-interferon immunotherapy, he developed a painful lesion in his oral cavity with a fistula in the buccal area. Excision biopsy disclosed necrotizing granulomatous inflammation with acid-fast bacillus. The patient received a 9-month course of isoniazide, rifampin and pyrazinamide, and recovered. The possible pathophysiological mechanism is discussed.

Adjuvants, Immunologic↗

Identification of the heterothallic mutation in HO-endonuclease of S. cerevisiae using HO/ho chimeric genes.

HO-endonuclease initiates a mating-type switch in the yeast S. cerevisiae by making a double-strand cleavage in the DNA of the mating-type gene, MAT. Heterothallic strains of yeast have a stable mating type and contain a recessive ho allele. Here we report the sequence of the ho allele; ho has four point mutations all of which encode for substitute amino acids. The fourth mutation is a leucine to histidine substitution within a presumptive zinc finger. Chimeric HO/ho genes were constructed in vivo by converting different parts of the sequence of the genomic ho allele to the HO sequence by gene conversion. HO activity was assessed by three bioassays: a mating-type switch, extinction of expression of an a-specific reporter gene, and the appearance of Canr Ade- papillae resulting from excision of an engineered Ty element containing the HO-endonuclease target site and a SUP4 degrees gene. We found that the replacement of the fourth point mutation in ho to the HO sequence restored HO activity to the chimeric endonuclease.

Alleles↗

Infections caused by Pseudomonas pickettii in association with permanent indwelling intravenous devices: four cases and a review.

Permanent indwelling intravenous devices (PIIDs) have become increasingly prevalent in the past decade. These devices offer the advantage of long-term and convenient venous access, but their not-infrequent colonization by bacterial or fungi can lead to bloodstream infection with or without sepsis. We describe a series of four patients with PIIDs who became infected with Pseudomonas pickettii, and we review the properties of this unusual organism and the clinical presentation of the infections it causes.

Adult↗

Ganciclovir for the treatment of disseminated CMV disease without pneumonia in allogeneic T-lymphocyte depleted bone marrow transplantation.

Treatment with ganciclovir was assessed in 13 patients who underwent allogeneic T-lymphocyte depleted bone marrow transplantation (BMT) for a variety of malignant hematological disorders and subsequently developed severe cytomegalovirus (CMV) disease without pneumonia. The manifestations of CMV disease appeared on days 23-105 (median 51) post BMT, and included gastrointestinal symptoms, weight loss, fever, disturbed liver function, leukopenia and thrombocytopenia. Ganciclovir was administered for 14 days, without the addition of intravenous immunoglobulins. Following therapy, the clinical manifestations subsided in most of the patients, while leukopenia, thrombocytopenia and liver dysfunction resolved in about half of the patients. One patient who experienced recurrent CMV disease responded to a second course of ganciclovir. Poor response to ganciclovir treatment was observed in 2 of the 3 patients with grade 4 graft-versus-host disease (GVHD). Our experience suggests that a 2-week course of ganciclovir may be effective in BMT recipients who develop severe CMV-associated disease without lung involvement, especially when there is no concomitant severe GVHD.

Adolescent↗

Sexual behavior of homosexual and bisexual men attending an HIV testing clinic in Jerusalem 1986/7-1990.

We investigated whether the sexual practices of homosexual and bisexual men attending the Jerusalem AIDS Clinic had changed between 1986/7 and 1990. The responses of a group of 79 homosexual and bisexual men to a questionnaire in 1986/7 were compared to the responses of a group of 37 homosexuals/bisexuals in 1990. Consistent yet statistically insignificant differences in sexual behavior between the 1990 and 1986/7 groups were observed: More individuals were using condoms (53% vs 36% respectively), and at an earlier age. The practice of anal sex was less common (48% vs 67% respectively) and that of oral sex more common (46% vs 27% respectively). These differences were not confounded by the level of education between the two groups. Analyzed separately for homosexuals and bisexuals, the increase in condom use was more noticeable among homosexuals compared with bisexuals, while the decrease in anal sex was greater in bisexuals compared with homosexuals. These results may indicate a trend towards safer sexual behavior in this at risk population, but further studies are needed to support or refute these observations.

AIDS Serodiagnosis↗

Effects of lovastatin therapy on LDL receptor activity in circulating monocytes and on structure and composition of plasma lipoproteins.

The effect of lovastatin therapy on LDL-receptor activity in fresh monocytes and on the structure and composition of lipoproteins was determined in 9 patients with familial hypercholesterolemia (FH) and 8 patients with non-familial hypercholesterolemia (NFH). Lovastatin reduced LDL-cholesterol levels by 34.8 and 47.5%, respectively, in the 2 groups of patients, and plasma apo B levels by 33.3 and 42.5%. LDL receptor activity in fresh monocytes increased by 53% and 86% respectively. HDL-cholesterol and plasma apo A-I levels increased only in the NFH group, by 10.2 and 7.1%. Lipoproteins were separated by centrifugation on a zonal rotor. Except for the intermediate density lipoprotein (IDL) fraction, no changes were observed in the structure and composition of the various lipoproteins. The investigations thus demonstrated that lovastatin therapy is associated with a measurable and significant increase of LDL-receptor activity in circulating monocytes that may contribute to the lipid lowering action of the drug.

Apolipoproteins↗