Punctuated equilibrium in scientific publishing.
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Periodicals as Topic↗
Biomedical subjects
E Rubinstein
Publications and source records attributed to E Rubinstein.
Non random activation of endogenous interleukin-2, (IL-2), IL-2 receptor alpha and IL-2 receptor beta genes after transfection of mouse fibroblasts with a cDNA for the alpha chain of the human IL-2 receptor.
Mouse fibroblasts do not ordinarily express components for the interleukin-2 receptor (IL-2R alpha, beta, and gamma). An analysis of these cells by reverse transcription followed by polymerase chain reaction, however, indicates the presence of transcripts specific for the IL-2R beta and gamma genes. Transfection of the cDNA for the alpha chain of the human IL-2R into LTK- mouse fibroblast cell line (L3 cells) leads, in long-term cultures, to the formation of transcripts of endogenous mouse IL-2, IL-2R alpha and beta genes, as detected by Northern blotting. Based upon the results of the binding of 125I-labeled IL-2 to the transfected cells, three IL-2-binding proteins of 55 kDa, 65 kDa and 75 kDa were expressed by the transfected cells. The 65-kDa and 75-kDa proteins bound IL-2 in the presence of monoclonal antibodies for the IL-2R alpha chain. These polypeptides assembled to form high-affinity IL-2R, as shown by Scatchard binding analyses. The receptors were functionally active, since the expression of H-2k major histocompatibility complex antigens on the surface membranes of L3 cells was enhanced by exposing the cells to IL-2. Activation of the IL-2 gene was also observed in long-term cultures of L alpha beta cells, another LTK- transfectant expressing the human IL-2R alpha chain. This type of gene activation was not observed in LTK- fibroblasts transfected with cDNA for human IL-2 or IL-2R beta genes. In L3 and L alpha beta cells, transcription of the endogenous IL-2 gene was suppressed by cyclosporin A and enhanced by cycloheximide. These data may have implications for gene therapy of cancer cells.
Animals↗
Prevalence of antibodies against hepatitis A virus among new immigrants in Israel.
Israel, located in a region endemic for hepatitis A virus (HAV), recently absorbed a large population of immigrants who came from the former USSR. To assess the risk of high morbidity in this population a serosurvey of HAV antibodies was undertaken. Serum samples were collected from 965 new immigrants, of whom 664 came from the European, non-endemic region, and 301 from the Asian and Caucasian endemic regions of the former Soviet Union. They were compared to 240 Israelis. Each population was divided into six age groups: 1-9, 10-19, 20-29, 30-39, 40-49, and 50 years of age and older. The Asian/Caucasian immigrants and the Israeli population were found to share similar characteristics. In both groups, antibodies to HAV (anti-HAV) were present in the 1-9-year-old age group and reached maximum prevalence (90% and 86.7%, respectively) in the 20-29-year-old age group. In contrast, among the European immigrants anti-HAV was first found in the 10-19-year-olds and peaked (93%) in the age group of 50 years and older. It is concluded that immigrants originating from the European part of the former USSR may require vaccination against hepatitis A.
Adolescent↗
Anti-platelet antibody interactions with Fc gamma receptor.
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Animals↗
Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group.
We compared ceftazidime monotherapy with ceftriaxone/tobramycin in a prospective, randomized clinical trial that included 580 patients with serious hospital-acquired infections. One-half of the patients had an underlying disease with a rapidly or ultimately fatal prognosis; 40% were nursed in intensive care units. Clinical response among patients with pneumonia (73% in the ceftazidime group vs. 65% in the ceftriaxone/tobramycin group), septicemia (73% vs. 59%), and complicated urinary tract infections (80% vs. 76%) showed that there were no significant differences in efficacy between the two regimens. Pseudomonas aeruginosa was the most prevalent pathogen and was effectively eradicated by both treatments. The odds of bacteriologic cure with either study regimen were equal. Mortality was similar in both treatment groups. Ceftazidime monotherapy was not associated with a higher incidence of development of resistance or superinfection. Both regimens were well tolerated; no patients receiving ceftazidime evidenced nephrotoxicity, compared with nine who received the combination. We conclude that ceftazidime may be used as monotherapy in the empirical treatment of patients with serious nosocomial infections.
Adult↗
Fungal endocarditis.
Fungal endocarditis has become an important infection associated with medical progress and a modern lifestyle. The most common organisms isolated from patients with fungal endocarditis are: Aspergillus spp.; Candida spp. and Torulopsis glabrata. Men are more frequently affected than women and predisposing factors include: previous cardiac surgery, antibiotic use and hyperalimentation, long-term i.v. catheters. Common clinical findings in patients with endocarditis include: fever, changing murmurs, peripheral emboli which are characteristically large and chorioretinitis. Characteristic laboratory findings are absent and positive blood cultures are obtained only in a relatively small number of patients. Characteristically, Aspergillus spp. almost never grow in blood cultures and must be isolated from removed emboli, from the diseased valve or from infected foreign bodies. Overall survival in patients with fungal endocarditis is rather poor, and hardly exceeds 50%. In general, a combined surgical-medical approach would yield the best results. New therapeutic modalities are needed in order to improve the prognosis of fungal endocarditis.
Endocarditis↗
Intestinal elimination of sparfloxacin, fleroxacin, and ciprofloxacin in rats.
The intestinal transepithelial elimination of sparfloxacin and fleroxacin was compared with that of ciprofloxacin in a rat model following a single parenteral administration of 25 mg of each of the antibiotics per kg of body weight. All three fluoroquinolones were eliminated through the small intestine. Ciprofloxacin was eliminated in the proximal jejunum at a rate of 1.97 +/- 0.70 micrograms/cm2, while the elimination rates of fleroxacin and sparfloxacin were 0.64 +/- 026 and 0.21 +/- 0.10 micrograms/cm2, respectively, over a 90-min collection period. In the ileum, the elimination rates of ciprofloxacin, fleroxacin, and sparfloxacin over the same period were 1.44 +/- 0.77, 1.00 +/- 0.33, and 0.41 +/- 0.26 micrograms/mc2, respectively. These data suggest that these fluoroquinolones undergo a transepithelial elimination process in the small intestine. This route of elimination may be important in the therapy of bacterial diarrhea.
Animals↗
Effect of allogeneic polymorphonuclear neutrophils on staphylococcal sepsis in mice.
The antibacterial and host-damaging properties of locally injected allogeneic polymorphonuclear neutrophils (PMN) were studied in vivo. Peritoneal PMN were obtained from donor mice 24 h after i.m. infection with sublethal (SD) and lethal (LD) dose of Staphylococcus aureus. These donor PMN were mixed with S. aureus and injected i.m. into normal recipient mice. Normal donor PMN and PMN obtained from SL-infected donor mice did not induce the mortality of SL-infected recipient mice but protected LD-infected recipients (5.8% mortality vs. 29.4%). PMN obtained from LD-infected donor mice caused ca. 77% mortality in SD-infected recipients. In survivors, during the first 3 h infection, serum tumor necrosis factor (TNF) concentrations were higher than those in nonsurvivors and then decreased. In contrast, TNF level in nonsurvivors continued to be increased until death. PMN from LD-infected donors had the highest spontaneous chemiluminescence response (CL), the shortest time of peak and the lowest level of intracellular CL against S. aureus. These donor PMN exhibited increased phagocytosis and decreased killing of S. aureus than that of PMN of SD-infected donor mice. Early stimulation of PMN functions such as bacterial internalization and respiratory burst may result in decrease of their tissue-damaging properties.
Animals↗
Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.
The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Severe necrotizing soft-tissue infections: report of 22 cases.
Twenty-two cases of severe necrotizing soft-tissue infections (SNSTIs), seen by the infectious disease service from 1983 to 1988 in a community teaching hospital, are described and compared with previously reported series. Clinical findings were distinguishable from cellulitis at the time of surgery in only 45% of the patients who had either necrosis, crepitus, vesicle or bullae, and/or an abnormal air pattern on x-ray studies. Patients with "cellulitis" were not less sick than patients with "necrosis" findings (ie, presence of shock, leukocytosis with left shift, fever, or anion gap). Despite the fact that all but one of the patients were seen by the infectious disease service preoperatively, and 55% underwent surgical intervention within 48 hours of admission, patient mortality (18%) was not better than some reported in earlier series. However, the epidemiology of SNSTI was different: in our series there were more diabetic patients (64%) and fewer postsurgical infections (14%). Among the diabetic patients, SNSTI developed more frequently at a site not related to peripheral vasculopathy or neuropathy. Abdominal wall involvement was 10 times more likely be diagnosed as cellulitis (5/8 vs 2/14 with involvement elsewhere, P < 0.02).
Adult↗
CD9 antigen is an accessory subunit of the VLA integrin complexes.
The CD9 antigen is a cell surface glycoprotein of unknown function which belongs to the tetraspans family. We demonstrate here, by precipitation, Western blotting and co-capping experiments, that this molecule is associated with a large fraction of beta 1 integrins in two cell lines, the pre-B cell line NALM-6 and the megakaryocytic cell line HEL. In HEL cells, CD9 antigen is only associated with VLA-4. In contrast, in NALM-6 cells, CD9 antigen is associated with both VLA-4 and VLA-5. On the other hand, only the beta 1 chain is co-precipitated with the CD9 antigen in transfected L cells. These data show that the CD9 antigen is associated with the beta 1 chain rather than with a particular integrin. CD9 monoclonal antibodies (mAb) did not modify the binding of HEL and NALM-6 cells to fibronectin, laminin or collagen. The association of CD9 antigen to VLA integrins is strengthened by the fact that both CD9 and anti-VLA mAb induce aggregation of the two cell lines and inhibit their migration in Transwell chambers. Because the aggregating effect, but not the inhibition of migration, is observed in CEM or CD9-transfected CEM cells, these two effects are likely to be mediated by different mechanisms.
Amino Acid Sequence↗
Treatment of severe infections caused by penicillin-resistant pneumococci. Role of third generation cephalosporins.
Penicillin resistance occurred soon after the discovery of penicillin, first in the test tube and subsequently in patients. The prevalence of invasive pneumococcal disease has been estimated to be as high as 15-18/100,000 in the elderly population and even higher in AIDS patients, children and the very old. While prevention with pneumococcal vaccine seems the most reasonable solution, under-utilization of the vaccine and an increase in the number of immuno-compromised individuals has limited the success of this approach. Streptococcus pneumoniae is conventionally classified as penicillin-susceptible (MIC < 0.125 mg/l), penicillin-intermediate (MIC 0.125-1.0 mg/l) and penicillin-resistant (MIC > or = 2 mg/l). In many countries, penicillin resistance in pneumococci is on the increase and in some areas penicillin intermediate and resistant isolates reach 60%. As a consequence, a switch of therapy from penicillin to other agents is mandatory in infections caused by penicillin-resistant strains. Benzyl-penicillin, however, can be used for most infections caused by penicillin-intermediate and all infections caused by penicillin-sensitive strains. Third generation cephalosporins, and in particular cefotaxime, are an optional alternative, particularly in view of their low MICs against penicillin-susceptible and -intermediate and some penicillin-resistant strains, and the easily achievable therapeutic concentrations in serum, pulmonary tissues and other compartments in which pneumococcal infections occur. Third generation cephalosporins have a high safety record and can be administered to children, pregnant women and the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
Cefotaxime↗
Human live anthrax vaccine in the former USSR.
The history of the development and use of the Soviet live spore human anthrax vaccine is described. Results of mass field trials on this vaccine following administration by scarification, by subcutaneous injection route or by aerosol exposure are presented. For the immunological assessment of these vaccinations a skin test with an original product 'Anthraxin' was used.
Anthrax↗
How interleukin-2 can affect human fibroblasts behaviour.
The alpha and beta chains of the Interleukin 2 receptor (IL2R alpha and IL2R beta) were detected at the surface of cultured fibroblastic cells by flow cytometry, using monoclonal antibodies (mAbs) directed against the IL2R alpha and the IL2R beta. These cells bound FITC-IL2 and this binding was inhibited by an excess of cold ligand and by mAbs recognizing the IL2 binding sites of the alpha and beta chains. Internalisation studies show that the fibroblastic IL2R/IL2 complex is internalized at 37 degrees C. By Northern Blot analysis we detected the presence of specific transcripts for the IL2R alpha and IL2R beta genes. Finally, the addition of exogenous IL2 specifically modified the surface expression of different antigens involved in the process of immunosurveillance. Indeed, IL2, at concentrations affecting the high affinity IL2R, caused the down regulation of ICAM-1 protein. IL2 also decreased the surface expression of the class I and class II HLA. By contrast, the use of IL2 concentrations which saturate the intermediate affinity IL2R beta caused the up regulation of the surface expression of the ICAM-1 protein. ICAM-1 is the natural ligand for the LFA-1 integrin expressed at the surface of lymphoid cells. ICAM-1/LFA-1 interactions favour homotypic and heterotypic cell-cell adhesion. Since human fibroblasts express an LFA-1 like molecule, we propose that in these cells IL2 can modify homotypic and heterotypic interactions acting on the surface expression of ICAM-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Line↗
The intestinal elimination of ciprofloxacin in the rat.
The transepithelial intestinal elimination of ciprofloxacin was studied in a rat model. Two jejunal and one ileal segment, along with their intact blood supplies, were isolated and continuously perfused. Following a single parenteral administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70, 1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered over 90 min from the proximal and distal jejunal loops and the ileal loop, respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in the entire small intestine. The rate of intestinal elimination related linearly to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were not accompanied by a concomitant increase in the eliminated fraction, suggesting a saturable transport process. Parenterally administered probenecid, amoxicillin, and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates did not alter transepithelial elimination. This pathway of elimination of ciprofloxacin may play an important role in curing intestinal infections.
Amoxicillin↗
Efficacy of combinations of doxycycline and rifampicin in the therapy of experimental mouse brucellosis.
Mice infected with Brucella melitensis were treated with doxycycline and rifampicin in daily dosages of: 1.5, 3 and 6 mg/kg separately and in combination, for a period of 14 days. Doxycycline alone in all dosages did not result in a cure rate superior to controls. A significant reduction in the viable count of B. melitensis recovered from the spleens of mice (which was the criterion for cure) was achieved with 6 and 3 mg/kg/day of doxycycline. Rifampicin at a dose of 6 mg/kg/day gave significantly better cure rates and reduction of mean viable counts of B. melitensis than untreated controls or doxycycline in similar doses. Low dose therapy with rifampicin (1.5 and 3 mg/kg) resulted in a further reduction in viable counts from spleens but with a cure rate no better than untreated animals. Rifampicin was more potent than doxycycline in all low dose regimens. When rifampicin was given in combination with doxycycline, the effect observed was similar to that of rifampicin alone. No synergy between rifampicin and doxycycline was demonstrable in the mouse model of brucellosis.
Animals↗
The inhibitory effect of fluoroquinolones on Coxiella burnetii growth in in-vitro systems.
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Animals↗
The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.
The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents.
Animals↗