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Biomedical subjects

C Block

Publications and source records attributed to C Block.

At least 55 records · Page 3Linked to original sources

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗

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↗