Susceptibility of Neisseria meningitidis in Israel to penicillin and other drugs of interest.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
C Block
Publications and source records attributed to C Block.
14-Day continuous infusion of mitoxantrone in hormone-refractory metastatic adenocarcinoma of the prostate.
A dose-finding investigation was conducted with mitoxantrone administered as 14-day continuous infusions to patients with hormone-refractory metastatic adenocarcinoma of the prostate. Fifteen men participated in four dosage groups: mitoxantrone 1.0, 1.25, 1.4, and 1.5 mg/m2/day; a treatment cycle was defined as a dose of mitoxantrone given over 2 weeks, followed by 2 weeks of monitoring prior to the next course. The patients received 1 to 10 courses, with the majority receiving 1 to 3. The maximum tolerated dose was 1.25 mg/m2/day for 14 days of continuous infusion. Two patients discontinued treatment because of gastrointestinal effects. Most adverse clinical experiences were mild or moderate in intensity. A decrease in prostate-specific antigen (PSA) response was seen after one course in 6 of 14 patients who had PSA measurements. Stable disease was achieved in 40% of the evaluable patients, and some quality of life parameters improved. Further clinical trials with mitoxantrone are indicated in patients with prostatic cancer, especially in those who have had less previous treatment.
Adenocarcinoma↗
Nuclear protein kinase C and signal transduction.
Protein kinase C (pKC) is a family of enzymes, consisting of ten isoenzymes. Some of the members of the pKC family are not dependent on calcium for their activity and also do not bind diacylglycerol. Protein kinase C is either translocated to the nucleus or present endogenously. Both calcium-dependent as well as calcium-independent isoenzymes are located in the nucleus. Protein kinase C has specific functions in the events activated within the nucleus during signal transduction. Three lines of approach have been taken to discern the nuclear function of pKC: pathways of activation of cytosolic pKC regulating nuclear events; translocation of pKC to the nucleus from the cytosol, and activation of native pKC in isolated nuclei. Protein kinase C contains a nuclear targeting bipartite motif and has a role in the nuclear calcium signaling process. Targeting and binding of pKC to the sites of replicational and posttranscriptional activity may be one of the mechanisms of the pKC signaling process. Protein kinase C-mediated activation of nuclear phosphatases and dephosphorylation of target nuclear proteins are the areas where much less attention has been paid. Exploring these avenues may lead to new insights into the molecular mechanism of nuclear signal transduction.
Amino Acid Sequence↗
Role of cadmium in activating nuclear protein kinase C and the enzyme binding to nuclear protein.
Specific effects of cadmium on nuclear protein kinase C activity were found with 3T3/10T1/2 mouse fibroblast and rat liver nuclei. Treatment of the mouse fibroblasts in culture with 12-O-tetradecanoylphorbol-13-acetate resulted in the stimulation of nuclear protein kinase C activity in a "fixed" pool which is defined by its resistance to chelator extraction, whereas the chelator extractable enzyme activity, defined as the "labile" pool was unaffected. Cadmium was found to potentiate the effect of the phorbol ester, directed specifically to nuclei, since the particulate protein kinase C activity was not changed under similar treatment. In a reconstituted system consisting of rat liver nuclei and rat brain protein kinase C, cadmium stimulated the binding of the enzyme to a 105-kDa nuclear protein. The binding of a 105-kDa protein to protein kinase C is attributed strictly due to the cadmium effect, whereas a 50-kDa protein binding to protein kinase C was only enhanced by cadmium. We propose a mechanistic model, where cadmium substitutes zinc in the regulatory domain of protein kinase C rendering the putative protein-protein binding site exposed.
3T3 Cells↗
A bipartite nuclear targeting motif in protein kinase C?
Explore the source record for details and available documents.
Amino Acid Sequence↗
Enhancement of neonatal neutrophil motility (chemotaxis) with adult fresh frozen plasma.
We examined the effect of adult fresh frozen plasma (FFP) on neonatal neutrophil (PMN) motility (chemotaxis) using a micropore filter assay. Adult FFP was transfused into 13 neonates receiving FFP transfusion for suspected life-threatening sepsis. Blood was obtained from neonates before and after FFP transfusion for assessment of PMN chemotaxis. An increase in PMN chemotaxis was noted in 12 of the 13 neonates following FFP transfusion, with a mean percentage increase of 12 +/- 3% (p less than 0.01). PMN chemotaxis increased 13 +/- 2% (p less than 0.01) in four bacteremic infants and 11 +/- 5% (p = 0.06) in nine infants without bacteremia. Adult FFP transfusion may enhance impaired neonatal PMN motility and improve outcome from infection in newborn infants.
Adult↗
Effect of labor and delivery on neonatal polymorphonuclear leukocyte number and function.
The ability of the neonate to mount an adequate polymorphonuclear leukocyte (PMN) response, either quantitatively or functionally, is impaired. To assess whether neonatal PMN number and function are altered by labor and delivery, three groups of infants were studied: cesarean section without labor (10), cesarean section after labor (10), and vaginal delivery (11). PMN counts were higher in the groups undergoing labor (p less than 0.01) compared with the cesarean section without labor group. Similarly, the labor groups had evidence of complement activation (increased C3a desarg) compared with the cesarean section without labor group. No differences were noted between the groups in measures of PMN motility (chemokinesis or chemotaxis) or PMN degranulation (plasma lysozyme), suggesting that normal labor and delivery does not contribute to the general PMN dysfunction of the neonate.
Cesarean Section↗
Natural immunity to shigellosis in two groups with different previous risks of exposure to Shigella is only partly expressed by serum antibodies to lipopolysaccharide.
Explore the source record for details and available documents.
Adult↗
Reduction of transmission of shigellosis by control of houseflies (Musca domestica)
The effect of control of houseflies on the incidence of diarrhoea and shigellosis was evaluated in a prospective crossover intervention study at two military field bases several kilometers apart. In early summer, 1988, intensive fly control measures (mainly bait and trap strategy) were introduced on one base, while the other served as a control. After 11 weeks, as new cohorts arrived, the intervention was abruptly discontinued in the first base and instituted in the second for the next 11 weeks. The study was repeated the next summer. Overall, fly counts were 64% lower on the bases exposed to fly control measures (p = 0.024). Concomitantly, clinic visits dropped by 42% (p = 0.146) for diarrhoeal diseases and by 85% for shigellosis (p = 0.015), as did rates of seroconversion, by 76% (p = 0.024) for antibodies to Shigella and by 57% (p = 0.006) for antibodies to enterotoxigenic Escherichia coli. The findings indicate that houseflies, acting as mechanical vectors, transmit Shigella (and possibly enterotoxigenic E coli) diarrhoeal infections.
Adolescent↗
Detection and treatment of brucellosis by screening a population at risk.
Brucellosis presents a difficult diagnostic challenge in view of its protean manifestations, multiple organ involvement and variable clinical course. The purpose of the present study was to determine whether active screening of a population at risk, identified through index cases, would enhance the detection rate of brucellosis and improve treatment. During a 1-month period all 98 individuals sharing risk factors with 4 diagnosed symptomatic cases of brucellosis in one Bedouin town in southern Israel were approached and 86 agreed to undergo screening. Symptomatic brucellosis was found in 8 (9%) of the screened population and an additional 5 (6%) asymptomatic individuals were found to be seropositive. These 13 were followed for 12 months. All symptomatic cases were treated and cured. Of the 5 asymptomatic seropositive individuals 2 showed a further elevation of Brucella antibody titers. One became symptomatic, was treated and was cured. This screening program provided 53% of all reported cases from the Bedouin town during the entire year of the study. Screening a population at risk increased the detection rate of brucellosis and improved the treatment.
Adolescent↗
Prospective study of the association between serum antibodies to lipopolysaccharide O antigen and the attack rate of shigellosis.
A means for determining immune status against shigellosis would significantly improve the design and evaluation of interventional and other epidemiologic studies. Previous case-control studies have indicated the potential role of humoral antilipopolysaccharide antibodies. To test this proposition, 190 soldiers serving in a field unit were monitored prospectively for 2.5 months for shigellosis. Blood samples were taken at the beginning of the follow-up period and tested for serological evidence of prior exposure to Shigella sonnei and Shigella flexneri. The risk for acquiring S. sonnei shigellosis was 3.7 times higher for individuals lacking homologous antibodies (P less than 0.02). The risk for acquiring S. flexneri shigellosis was 2.4 times higher for individuals lacking antibodies, although a low attack rate for S. flexneri resulted in numbers too small to achieve statistical significance. While the importance of the serum antilipopolysaccharide antibodies in protection against the disease remains unclear, these findings demonstrate that they are strong markers of acquired immunity. Serological markers should be incorporated in epidemiologic studies of shigellosis and in the design and evaluation of future trials of potential anti-Shigella vaccines.
Antibodies, Bacterial↗
Two different zinc sites in bovine 5-aminolevulinate dehydratase distinguished by extended X-ray absorption fine structure.
The zinc coordination in 5-aminolevulinate dehydratase was investigated by extended X-ray absorption fine structure (EXAFS) associated with the zinc K-edge. The enzyme binds 8 mol of zinc/mol of octameric protein, but only four zinc ions seem sufficient for full activity. We have undertaken a study on four forms of the enzyme: (a) the eight-zinc native enzyme; (b) the enzyme with only the four zinc sites necessary for full activation occupied; (c) the enzyme with the vacant sites of (b) occupied by four lead ions; (d) the product complex between (b) and porphobilinogen. We have shown that two structurally distinct types of zinc sites are available in the enzyme. The site necessary for activity has an average zinc environment best described by two/three histidines and one/zero oxygen from a group such as tyrosine or a solvent molecule at 2.06 +/- 0.02 A, one tyrosine or aspartate at 1.91 +/- 0.03 A, and one cysteine sulfur at 2.32 +/- 0.03 A with a total coordination of five ligands. The unoccupied site in (b), obtained by taking the difference spectrum between the spectra from samples (a) and (b), is dominated by a single contribution of four cysteinyl sulfur atoms at 2.28 +/- 0.02 A. Spectra from samples (c) and (d) show only small changes from that of (b), reflecting a slight rearrangement of the ligands around the zinc atom.
Animals↗
An in-use evaluation of decontamination of polypropylene versus steel bedpans.
A prospective cross-over study in three different wards has demonstrated the lack of effect of two disinfectants compared with a detergent when added to the washing cycle of automatic bedpan washers that employ hot water centrally supplied at 60 degrees C. An unexpected and potentially important finding was that polypropylene pans were much more effectively cleaned and decontaminated than their stainless steel counterparts. The role, if any, of bedpans in the epidemiology of nosocomial infections remains a mystery. The continued absence of information clearly incriminating these ubiquitous devices in the transmission of potential pathogens, or of genes encoding antibacterial drug resistance, raises questions as to whether extensive efforts to achieve a high degree of decontamination of bedpans are necessary at all.
Cross Infection↗
Nasal carriage of Staphylococcus aureus: correlation with hormonal status in women.
In view of recent observations on hormone-microorganism interactions, a study of Staphylococcus aureus nasal carriage in relation to sex-hormone status was undertaken. Prospectively in 479 women attending a colpocytologic clinic, hormonal status was assessed by determining the karyopyknotic index (KI) on smears stained by the Papanicolaou method. Rates of S. aureus nasal carriage were 29.3% in premenopausal women and 21.9% in postmenopausal women (P not significant). Carriage rates were significantly higher (P = .026, chi 2 7.32) for women with high KIs (40.7%) than for those with intermediate and low KIs (27.03% and 25.1%, respectively). S. aureus nasal carriage also correlated independently and significantly with previous antibiotic use and the presence of insulin-treated diabetes mellitus. This preliminary observation confirms an association between levels of sex hormones as reflected by the KI and S. aureus nasal carriage rates.
Adolescent↗
Pefloxacin versus ceftazidime in therapy of soft tissue infections in compromised patients.
Soft tissue infections in compromised patients are frequently caused by Gram-negative organisms and particularly by Pseudomonas aeruginosa. These pathogens are effectively eradicated by pefloxacin as well as by ceftazidime. The effectiveness and safety of these two agents were compared in a prospective randomized study in 67 patients with soft tissue infections. Underlying conditions included malignant diseases, diabetes mellitus and chronic renal failure. The infections included: post operative infection, septic foot, soft tissue abscess and cellulitis. Thirty-three patients were treated with intravenous ceftazidime for a mean duration of ten days. More than half the 34 patients given pefloxacin were treated only orally for a mean period of 13 days. The clinical and bacteriological outcomes were similar in both groups. There was clinical cure or improvement in 26 pefloxacin cases and in 23 ceftazidime cases, failure in six pefloxacin cases and in seven ceftazidime and relapse in two pefloxacin and in three ceftazidime patients. The bacteriological responses were eradication in 23 pefloxacin cases and in 22 ceftazidime cases, persistence in five pefloxacin cases and in six ceftazidime cases, relapse in one pefloxacin case and in none of the ceftazidime group, reinfection in four pefloxacin cases and in three ceftazidime cases and there was one unassessed patient in the pefloxacin group and two in the ceftazidime group. Nausea and vomiting occurred in three patients and elevation of liver enzymes in another patient; all side effects were observed only in the pefloxacin treated patients. These results suggest that oral pefloxacin could offer an alternative to intravenous ceftazidime in half the compromised patients with tissue infections. However, adverse reactions due to pefloxacin administration should be watched for during such therapy.
Administration, Oral↗
Rapid screening of urine for bacteria and cells by using a catalase reagent.
Five hundred urine samples were tested for cells and bacteria by using a commercial dipstick, a catalase screening device, standard culturing, and chamber counts. The sensitivities of the catalase test were 83% for all samples and 97.6% for specimens containing significant numbers of leukocytes and bacteria. The catalase screening test is simple to perform and should prove useful for the detection of urinary tract infections.
Bacteriuria↗
Probing of active site residues of the zinc enzyme 5-aminolevulinate dehydratase by spin and fluorescence labels.
5-Aminolevulinate dehydratase from bovine liver requires Zn(II) for its activity and is inhibited by micromolecular concentrations of Pb(II). To elucidate the structure of the active site and its interactions between the active site and the metal binding site we labeled the active site for fluorescence studies and ESR spectroscopy. o-Phthalaldehyde reacted with active site lysyl and cysteinyl residues to form a fluorescent isoindole derivative. The fluorescence energy was independent of the deprivation of Zn(II) and of its substitution by the inhibitory Pb(II). For ESR-studies five iodoacetamide and four isothiocyanate pyrrolidine-N-oxyl derivatives with various spacer lengths were used to label the active site cysteinyl and lysyl residues, respectively. The ESR spectra of the modified enzyme preparations exhibited a significant immobilization of all labels, even with the longest spacers employed. Obviously the reactive cysteine is buried more than 12 A, and the active site lysine more than 11 A in a cleft of the enzyme structure. Zn(II) deprivation from the iodoacetamide spin-labeled enzyme caused a marked reversible increase in label mobility, whereas the Pb(II) substituted enzyme exhibited a smaller mobilization of the label. These results are interpreted by a model of the active site where the reactive cysteinyl and the lysyl side groups are close enough to be crosslinked by o-phthalaldehyde within a distance of 3 A. A structural role is assigned to Zn(II) in the enzyme, since Zn(II) deprivation does not alter the fluorescence of the isoindole derivative and increases the mobility of the cysteine-bound spin labels in the active site cleft.
Apoenzymes↗
Immunoglobulin M, A, and G antibody response to lipopolysaccharide O antigen in symptomatic and asymptomatic Shigella infections.
The antilipopolysaccharide antibody response in sera obtained from subjects involved in 10 outbreaks of shigellosis occurring in Israeli military field units was determined by an enzyme-linked immunosorbent assay and a passive hemagglutination test. Both tests were found to be sensitive and specific for the diagnosis of shigellosis. A significant antibody response was detected in 73 to 82% of the symptomatic and 48 to 60% of the asymptomatic subjects during the Shigella sonnei and Shigella flexneri outbreaks. Fifty percent of the symptomatic and none of the asymptomatic subjects showed a significant antibody response in the Shigella boydii outbreaks. An examination of the kinetics of the antibody levels over a 10-week period after the onset of disease revealed that immunoglobulin A (IgA) levels were highest 2 weeks after infection and had declined to initial levels within 2.5 months. In contrast, IgG levels at the late convalescent stage were half those measured at early convalescence, still being about twice as high as the initial titers. Although the IgM levels showed a pattern similar to that of IgA, their elevation at the early convalescent stage was less pronounced. We conclude that the detection of an increase in the level of the IgA fraction appeared to be the best indicator for recent symptomatic, as well as symptomatic, infections due to Shigella organisms.
Adult↗