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C Block

Publications and source records attributed to C Block.

At least 55 records · Page 3Linked to original sources
PubMed1996

Quantitative structure-activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo.

Binding of Ras to c-Raf-1 is a pivotal step of many mitogenic signalling pathways. Based on the recent crystal structure of the complex of Rap1A with the Ras-binding domain of Raf, mutations were introduced in c-Raf-1 and their effects on Ras/Raf binding affinity in vitro and Ras/Raf regulated gene expression in vivo were analysed. Our data reveal an empirical semilogarithmic correlation between dissociation constants and Raf-induced gene activity. The functional epitope that primarily determines binding affinity consists of residues Gln 66, Lys 84 and Arg 89 in Raf. This quantitative structure-activity investigation may provide a general approach to correlate structure-guided biochemical analysis with biological function of protein-protein interactions.

Amino Acid Sequence↗
PubMed1996

Ras/Rap effector specificity determined by charge reversal.

Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.

Amino Acid Sequence↗
PubMed1996

Employee injuries and convenience store robberies in selected metropolitan areas.

The number of robberies and robbery-related injuries to employees in convenience stores (C-stores) during 1992 or 1993 were estimated for selected metropolitan areas around Miami and Tampa, Florida; Atlanta, Georgia; Chicago, Illinois; Baltimore, Maryland; Boston, Massachusetts; Detroit, Michigan; Pittsburgh and Philadelphia, Pennsylvania; Charleston, Columbia, Greenville, and Spartanburg, South Carolina; and Arlington, Chesterfield, and Henrico counties, Virginia. Of the 1835 C-store robberies that occurred during 1992 or 1993 in all selected areas (excluding Atlanta and Chicago), there were 12 homicides of C-store employees; 219 nonfatal injuries of C-store employees; 1071 robberies in which there were no injuries but a weapon was used, displayed, or implied toward a C-store employee; and 132 robberies in which there was no injury and no weapon used, but an employee was struck, pushed, or shoved. Corresponding figures for the 238 robberies that occurred in Chicago during January to June 1993, and for which victim employment status was unknown (customer or employee) were three homicides, 53 nonfatal injuries, 120 attacks in which a weapon was used but there was no injury, and 57 attacks in which a person was struck, pushed, or shoved but there was no injury. The proportion of robberies that resulted in a homicide or injury to an employee varied among selected areas from .03 to .25. The proportion of homicides and injuries to an employee was. 14 or higher for target areas in Baltimore (.24), Detroit (.25), and Virginia (.14); the proportion to an employee or customer was .24 in Chicago. The conclusions from these data are that the risk of employee injury in C-store robberies was high in selected metropolitan areas. This underscores the need for effective robbery prevention programs to reduce injury. In addition, further research is needed to determine the effectiveness of prevention programs in the C-store industry and the application of these programs to other retail industries.

Commerce↗
PubMed1996

Limitations of paperless on-line reporting of diagnostic bacteriology culture results.

AIMS: To estimate the extent to which microbiology laboratory results made available on a computerised reporting system do not reach their intended destination. METHODS: Prospective observational study of 180 urine cultures submitted from patients seen at the accident and emergency department of a 250 bed university affiliated general hospital. Observations were made of: telephone requests for results; whether results were noted in patients' charts; and antibiotic administration to patients sent home. RESULTS: Results were requested/recorded for 73% of 37 patients admitted to hospital and for only 23% of 143 patients sent home (p < 1 x 10(-7)). Overall, results were more frequently recorded for patients with positive cultures (p = 0.04). When determined separately for admitted and discharged groups, this association was not shown. Three of 14 culture positive patients sent home and for whom results were not recorded received inappropriate therapy; 19 culture negative patients were given antibiotics. CONCLUSIONS: In view of the results, measures were instituted to ensure delivery of printed reports to the health care providers of patients not admitted from the accident and emergency department. Organisations operating computerised reporting systems in evolving health care settings must ensure that system design guarantees delivery of reports to all end-users. This will minimise therapeutic problems, reduce wastage of laboratory resources, and limit risks of litigation.

Bacteriology↗
PubMed1995

Switching to Rac and Rho.

Could the recent elucidation of the structure of the Rap-Raf complex have been the first glimpse of a universal arrangement between GTPase switches and kinase cascades, as a number of recent reports show that Ras is not unique in its ability to start a signalling 'chain reaction'?

Animals↗
PubMed1995

Shigella lipopolysaccharide antibodies in pediatric populations.

Shigellosis is the most common cause of bacterial dysentery. To study the specific immunity to the two major groups causing shigellosis, we assayed antibodies to lipopolysaccharide (LPS) by enzyme-linked immunoadsorbent assay to both Shigella sonnei and Shigella flexneri 2a serotypes in the following populations: (1) women immediately after delivery and their infants to assess the transfer of passive immunity by placenta and the presence of secretory antibodies in breast milk; (2) children of different ages; and (3) the kinetics of antibody production in pediatric patients, who had culture-proved shigellosis. The sera of these women showed variable concentrations of antibodies of all three isotypes to LPS of S. sonnei and S. flexneri 2a. These serotype-specific antibodies were not cross-reactive. Transfer of IgG anti-LPS across the placenta was significantly correlated with concentration of the specific antibody in the mother (S. sonnei, r = 0.96; S. flexneri, r = 0.84). Varying concentrations of anti-LPS IgA were present in colostrum, which was correlated with serum anti-LPS IgA titers in the case of S. sonnei (r = 0.44; P < 0.05) but not S. flexneri (r = 0.17). Healthy children between the ages of 6 months and 4 years in our population had undetectable or relatively low titers of anti-S. sonnei IgG. More children had detectable antibody titers to S. flexneri 2a than to S. sonnei. The relatively high concentrations of these natural antibodies are particularly noteworthy because there is a far lower incidence (< 10% of patients) with S. flexneri than with S. sonnei disease in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Meningococcal disease in the Israel Defense Force: epidemiologic trends and new challenges.

To determine recent trends in its epidemiology and the need to reconsider prophylactic interventions, meningococcal disease in the Israel Defense Force (IDF) from 1975 through 1993 was studied. All cases of meningitis or meningococcemia were included. A considerable increase in the number of cases has been observed since 1991, with serogroup C becoming predominant (76% of cases) since then. Serogroup Y was the second most frequent serogroup during this period, while serogroup B, predominant in the civilian population of Israel, was rare. Most cases occurred during the first 6 months of military service. Seasonality was important, with most of the cases occurring between December and March, although a small summer peak was also noted. Since 1992, three small clusters of meningococcal disease were encountered in the IDF, for the first time, with all cases caused by group C meningococci. In one cluster, the emergence of rifampicin resistance resulted in failure of chemoprophylaxis. The rise in group C and Y cases since 1991, and the occurrence of rifampicin resistance, necessitate considering meningococcal vaccines and new antimicrobial agents for prophylaxis.

Bacterial Vaccines↗
PubMed1994

Safety and immunogenicity of the oral E. coli K12-S. flexneri 2a vaccine (EcSf2a-2) among Israeli soldiers.

A double-blind placebo-controlled study was carried out on the safety and immunogenicity of the oral Shigella flexneri (EcSf2a-2) vaccine among Israeli soldiers. Sixty volunteers received the vaccine and 59 received placebo. Fifty-three were given the full vaccine regimen (four doses). Doses ranged between 4.1 x 10(8) and 1.1 x 10(9) c.f.u. Visits to the unit clinic for mild gastrointestinal symptoms were common after the first dose in vaccinees (13%) as compared with placebo recipients (5%), but the difference was not significant, p = 0.12. Similarly, there was no difference between the groups for either gastrointestinal or non-gastrointestinal complaints reported by questionnaire. The vaccine strain was excreted by 69% and 67% of the vaccinees one day after receiving the second and the fourth doses, respectively. As judged by antibiotic susceptibility, phage typing and restriction fragment length polymorphism (RFLP), the vaccine strain emerged as genetically stable after replication in human gut and shedding. There was neither bacteriological nor serological evidence of transmission of the vaccine from vaccinees to placebo recipients. Eighteen of 26 (69.2%) and 11 of 30 (36.7%) vaccinees had significant IgA secreting cell responses 7 and 21 days after the first dose, respectively. Significant IgA or IgG serum antibody response to S. flexneri 2a LPS was detected in 30% of the vaccinees. These results support further evaluation of EcSf2a-2 vaccine protective efficacy in field studies.

Administration, Oral↗
PubMed1994

Effect of corticosteroids on the maturation of neutrophil motility in very low birthweight neonates.

Neutrophil (PMN) chemotaxis and chemokinesis were longitudinally studied in a group of 17 neonates with birthweights between 750 and 1250 g. Five of the 17 neonates were treated with prenatal betamethasone to attempt to prevent hyaline membrane disease, six received postnatal dexamethasone in an effort to reduce bronchopulmonary dysplasia, three received both, and three were not treated with corticosteroids. The group of 17 neonates were tested on four separate occasions: (1-2, 3-4, 7-8, and 10-14 postnatal days). PMN chemotaxis and chemokinesis were determined using a standard micropore filter assay. A group of 36 adults was used as additional controls. There were no significant differences noted in PMN chemotaxis or chemokinesis for the corticosteroid vs the noncorticosteroid-treated groups. In the total group of 17 neonates, there was depression in PMN chemotaxis compared with adult values, which lasted at least through postnatal day 8. By day 13 to 14, PMN chemotactic values were similar to those of adults. In contrast, chemokinesis, was depressed during the initial 14 days (except for the first 2 postnatal days). These data suggest that perinatal corticosteroid administration does not affect PMN motility in newborn infants.

Betamethasone↗
PubMed1994

Epidemiology of pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel: a 3-year nationwide prospective study. Israeli Pediatric Bacteremia and Meningitis Group.

In a 3-year nationwide prospective study on pediatric meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis in Israel, 1258 invasive infections with a known focus were observed. Meningitis was found in 482 (38%): 56%, 16%, and 76% of all infections by H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. The incidence of meningitis during the first year of life was 67.1, 17.5, and 9.5/100,000 for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively, and in children < 5 years old it was 18.5, 5.3, and 5.2. Extrapolated for a population in which 100,000 live births occur yearly, 2097 hospital days were required. The case fatality rate was 2.2%, 5.9%, and 6.3% for H. influenzae type b, S. pneumoniae, and N. meningitidis, respectively. Boys were affected significantly more often than girls, but mortality was higher among girls. On the basis of the observed serotypes and age distribution, even with optimal vaccine development in the next 5 years, it is not likely that > 50% of all cases will be prevented.

Age Distribution↗
PubMed1994

Effects of cadmium on nuclear protein kinase C.

Cadmium is a carcinogen whose genotoxicity is only weak. Besides its tumor-initiating capacity, cadmium may be tumor-promoting, since it interferes with several steps of cellular signal transduction. We have investigated effects of cadmium(II) on protein kinase C (PKC), which is a key enzyme in the control of cellular growth and differentiation. Tumor-promoting phorbol esters cause an activation and translocation of PKC from the cytosol to the plasma membrane and to the nucleus of mammalian cells. In mouse 3T3/10 T 1/2 fibroblasts, cadmium(II) potentiated the effect of phorbol ester on nuclear binding and activation of PKC. Furthermore, in a reconstituted system consisting of rat liver nuclei and rat brain PKC, cadmium stimulated the binding of the enzyme to a 105-kDa protein. We propose a model in which cadmium(II) substitutes for zinc(II) in the regulatory domain of PKC, thus rendering the putative protein-protein binding site exposed. Further work is required to elucidate the potential role of the nuclear PKC binding protein(s) in the control of cell proliferation.

3T3 Cells↗
PubMed1994

Cryptococcus neoformans vertebral osteomyelitis.

A 67-year-old previously healthy woman presented with low back pain of 2 months duration and daily fever of 39 degrees C for 3 weeks. CT scan showed a lytic lesion in the third lumbar vertebra and a small right lower lobe lung infiltrate with mediastinal lymphadenopathy. Culture of material obtained from open biopsy of the vertebra grew Cryptococcus neoformans var. neoformans, which was also demonstrated on histology. Cryptococcal antigen was detected in the patient's serum. Treatment with amphotericin B (1000 mg total dose) and oral 5-fluorocytosine, resulted in complete recovery and resolution of the chest X-ray findings with a follow-up of 2 years. Since this case, as well as most of the previously described cases of cryptococcal osteomyelitis, were in normal hosts, cryptococcal osteomyelitis should be considered in the differential diagnosis even in a normal host, and therefore, prior to possible invasive diagnostic procedures, cryptococcal antigen in the serum should be determined.

Aged↗
PubMed1993

[Acanthamoebic keratitis].

Acanthamoebic keratitis is still a rare infection. It occurs in contact lens-wearers, especially when saline is prepared at home from contaminated tap water. There are periods of remission, and occasionally misleading findings resembling those of herpetic keratitis, which make the diagnosis difficult. The isolation of the acanthamoeba is not easy and special culture media are required. Early recognition and aggressive therapy with antiamebic medication and epithelial debridement, often in conjunction with penetrating keratoplasty, are needed. We describe the clinical course, laboratory diagnosis and treatment of 3 patients with acanthamoebic keratitis, 2 men aged 20 and 25, respectively and a women aged 42.

Acanthamoeba Keratitis↗
PubMed1993

Re-emergence of meningococcal carriage on three-year follow-up of a kibbutz population after whole-community chemoprophylaxis.

A long-term study was conducted to determine the rate of re-emergence of throat carriage of meningococci in a semi-closed kibbutz community after the administration of chemoprophylaxis to all its members. Serotype B:4 was selected as marker organism since it was isolated from a fatal case and was the most frequently occurring strain (80%) among serogroup B isolates, which themselves comprised 54% of all meningococci. The carriage rate among Israeli residents (volunteer workers were analyzed separately) before treatment was 6.6% (49/748) overall, with 4.3% group B strains. Three weeks after treatment, in most cases with rifampicin (whereby three persistently positive persons were retreated with minocycline), no meningococci were recovered. Six months later, 1.9% of a population sample aged < or = 30 years were positive, while before treatment and one and three years later, 9.4%, 8.6% and 4.6% respectively were positive in this age group. Serotype B:4 comprised 81.3% of group B strains before prophylaxis, 5.3% after one year, and 28.6% after three years, thus possibly re-establishing itself as the single dominant serotype. The marked suppression of carriage after mass chemoprophylaxis appeared to last at least six months, with the meningococcal population being re-established within a year.

Adolescent↗
PubMed1993

Inconsistency of a model aimed at predicting bacteremia in hospitalized patients.

Clinical prediction rules can help physicians determine the necessity for blood cultures in specific patients and/or in whom empiric antibiotic treatment should be administered. Before adopting a prediction rule its validity must be evaluated in different settings. We revealed independent predictors of true bacteremia and developed a risk score based on them in one group of adult hospitalized patients (n = 474; derivation set). An attempt was made to validate this risk score in a second group of in-patients at the same hospital (n = 438; validation set). The derivation set included 540 blood culture episodes and the validation set 516. A blood culture episode was defined as one or more of all blood specimens withdrawn for culture from one patient over one 24 hour period. Independent multivariate predictors of true bacteremia were: temperature of 39 degrees C or higher, current immunosuppressive therapy, serum alkaline phosphatase > 100 IU and hospitalization in an intensive care unit. In the low risk group, defined by the absence of the said predictors, the rates of true bacteremia were 5.1 and 4.6% for the derivation and validation sets, respectively. As raised temperature is the main clinical feature guiding physicians to suspect bacteremia, we examined the probability of true bacteremia in patients with a temperature of less than 38 degrees C and found it to be 5.6% in the two sets. The model identified high risk subset patient groups demonstrating true bacteremia in 38% of all episodes in the derivation set and the comparatively low rate of 12.1% (p < 0.01) for the validation set.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Forty years of meningococcal disease in Israel: 1951-1990.

Meningococcal disease accounts for approximately 20% of cases of bacterial meningitis in Israel. During the period 1951-1990, the annual incidence of meningococcal disease rarely exceeded two cases per 100,000 persons and was generally higher among non-Jews (largely the Arab population) than among Jews; there were some notable peaks of disease activity during 1963-1967, 1975, and 1987-1988. The highest incidence was among infants and young children, with a slight male predominance. The main period of disease activity was from January to April, but an unusual secondary peak in July coincided with the onset of peak summer temperatures. Monthly disease frequencies were significantly correlated with relative humidity. Incidence rates varied between regions and were lower in cities than in smaller settlements. Overall case-fatality rates decreased to approximately 11% for the period 1981-1990. Outbreaks were infrequent and tended to be small. Meningococci of serogroup B have dominated since the mid-1970s. Group A meningococci were isolated significantly more commonly from Arabs (26.26%) than from Jews (1.03%; P < .000001). The frequency with which group A organisms occurred among clinical isolates appeared to follow a more or less cyclical pattern.

Adolescent↗