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Biomedical subjects

P P Cook

Publications and source records attributed to P P Cook.

15 recordsLinked to original sources
PubMed2006

Effect of reduction in ciprofloxacin use on prevalence of meticillin-resistant Staphylococcus aureus rates within individual units of a tertiary care hospital.

Previous studies have shown a correlation between fluoroquinolone use in hospitals and rates of meticillin-resistant Staphylococcus aureus (MRSA) infection. This study examined the effect on MRSA infection rates within individual adult units of a tertiary care teaching hospital after instituting a programme to decrease ciprofloxacin use. Clinical specimens positive for S. aureus were determined on all adult inpatient units between 1 January 2004 and 31 December 2005. Units with >10 isolates of S. aureus per year were included in the analysis. Ciprofloxacin use, measured in defined daily doses per 1000 patient-days, was determined for each unit during the same time period. Ciprofloxacin use and MRSA rates for 2004 and 2005 were compared. In the 17 units studied, ciprofloxacin use decreased by 31.2% (P<0.0001). The MRSA rate in these units decreased from 59.6% to 54.2% (P=0.122). There was a correlation between ciprofloxacin use and the MRSA rate within these units (r=0.70; 95% confidence interval -0.01-0.94; P=0.053). Within individual units, there was a variable response. In seven of the units, there was an increase in the MRSA rate despite a reduction in ciprofloxacin use, suggesting that other factors (length of stay, infection control and community-acquired MRSA) may have contributed. Although many factors are associated with high MRSA rates, ciprofloxacin use appears to be a contributing factor. Reducing the use of ciprofloxacin may be a means of controlling MRSA in the hospital setting.

Anti-Infective Agents↗
PubMed1998

Unilateral adrenal mass due to Mycobacterium kansasii in an AIDS patient.

Infection with Mycobacterium kansasii in patients with acquired immunodeficiency syndrome usually involves the lung or disseminated infection. We report a case of infection with M kansasii confined to the adrenal gland and possibly to an adjacent vertebral body that presented as a fever of undetermined origin.

Acquired Immunodeficiency Syndrome↗
PubMed1995

MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype.

Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha, and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.

Animals↗
PubMed1995

Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death.

Protein kinase C (PKC) modulates growth, differentiation and apoptosis in a cell-specific fashion. Overexpression of PKC-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-alpha cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G1 arrest that was accompanied by Cip1 expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-alpha cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-alpha cells that waned at higher concentrations. TPA-treated MCF-7-PKC-alpha cells accumulated in G2/M, did not express p53, displayed decreased Cip1 expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-alpha cells expressed gadd-45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression of gadd45 in a p53-independent fashion.

Apoptosis↗
PubMed1994

Effects of chronic phorbol ester treatment on protein kinase C activity, content, and gene expression in the human monoblastoid U937 cell.

Immediate and sustained signal transduction is involved in mediating phorbol ester-induced changes in growth and differentiation. Activation of protein kinase C (PKC) is the initial step in phorbol ester-induced signal transduction. By virtue of preferential down-regulation of individual isoforms and generation of proteolytically derived kinase activities, the signal transduced by sustained activation of this pathway may differ substantially from that generated initially upon application of the phorbol ester. To examine the effect of chronic phorbol ester-induced activation of this pathway, the relationship between PKC activity/content and AP-1 binding activity and gene expression was studied in the U937 cell. Phorbol ester-induced differentiation of the U937 cell into a monocyte/macrophage-like cell requires sustained activation of the PKC pathway. AP-1 binding activity was enhanced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and in a temporally dependent manner, with conversion of a high to low mobility band shift occurring after a 12-h exposure to TPA. After a 72-h exposure, AP-1 binding activity was maximally increased by 1 nM TPA and remained elevated to a similar degree even after treatment with 600 nM TPA. Enhanced AP-1 binding activity was dependent upon continuous exposure to TPA and was not secondary to differentiation. A 72-h treatment with one nM TPA maximally increased expression of c-jun, krox-24, and jun-B mRNA transcripts. Exposure to higher TPA concentrations decreased the content of these transcripts. Maximal expression of collagenase and plasminogen activator receptor transcripts required exposure to much higher TPA concentrations (100 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Modulation of protein kinase C-epsilon by phorbol esters in the monoblastoid U937 cell.

Expression of protein kinase C-epsilon was examined in the human monoblastoid U937 cell. This cell type contained the alpha, beta, and epsilon isoforms of protein kinase C (PKC). While PKC-epsilon content was slightly higher in the cytosolic than in the particulate fraction, the amount contained in the particulate fraction was higher than the alpha and beta isoforms which were predominantly localized to the cytosol. After an acute exposure to tetradecanoyl-13-phorbol acetate (TPA), PKC-epsilon translocated to the particulate fraction. Acute or chronic exposure to ionomycin did not alter content of the epsilon isoform. Longer exposures to TPA decreased PKC-epsilon in both cellular fractions. PKC-epsilon displayed a similar sensitivity to TPA-induced down-regulation as did PKC-beta while PKC-alpha was more resistant to this effect. After a 72-h exposure to 0.1 nM TPA, increases in the alpha and beta isoforms but not in PKC-epsilon were observed. However, 1,25-dihydroxy vitamin D3 and dibutyryl cyclic AMP which induce U937 differentiation enhanced PKC-epsilon expression.

Cell Differentiation↗
PubMed1992

Interleukin-3 induces translocation and down-regulation of protein kinase C in human platelets.

Protein kinase C (PKC) is a family of phospholipid-dependent kinases that is involved, along with calcium mobilization, in the activation of human platelets. Since interleukin-3 (IL-3) has been shown to act, in part, by activating PKC, we investigated the effect of IL-3 on PKC activity and content in human platelets. Exposure of platelets to 10 ng/ml of IL-3 was associated with a rapid (i.e., within 3 minutes) translocation of PKC activity and content from the cytosol to the membrane fraction. In addition, treatment with IL-3 effected a time-dependent down-regulation of PKC activity and content. We speculate that IL-3 may act as a modulator of PKC-dependent pathways in the human platelet.

Blood Platelets↗
PubMed1992

Effect of phorbol esters on protein kinase C-zeta.

Protein kinase C-zeta (PKC-zeta) is a member of the protein kinase C gene family which using in vitro preparations has been described as being resistant to activation by phorbol esters. PKC-zeta was found to be expressed in several cell types as an 80-kDa protein. In vitro translation of a full-length PKC-zeta construct also yielded as a primary translation product an 80-kDa protein. In the U937 cell, PKC-zeta was slightly more abundant in the cytosol than in the particulate fraction. Acute exposure of U937 cells to tetradecanoyl-phorbol-13-acetate (TPA), phorbol dibutyrate, mezerin, or diacylglycerol derivatives did not induce translocation of this isoform to the particulate fraction. Chronic exposure to 1 microM TPA failed to translocate or down-regulate PKC-zeta in U937, HL-60, COS, or HeLa-fibroblast fusion cells. To examine whether PKC-zeta was activated by TPA, PKC activity was evaluated in COS cells transiently over-expressing this isoform. In non-transfected cells, two peaks of phospholipid- and TPA-dependent kinase activity were observed. Eluting at a lower salt concentration was a peak of activity associated with PKC-alpha. PKC-zeta eluted with the second peak of activity and at a higher salt concentration. In transfected cells which expressed PKC-zeta at 4-10-fold over endogenous levels, there was only a slight increase in activity associated with the second peak. The activity and quantity of PKC-zeta did not strictly correlate. Treatment with TPA under conditions that did not alter PKC-zeta content abolished detection of the second peak of PKC activity eluting from the Mono Q column. Thus, PKC-zeta does not translocate or down-regulate in response to phorbol esters or diacylglycerol derivatives. However, for reasons discussed these studies do not resolve the issue of whether this isoform is activated by TPA.

Amino Acid Sequence↗
PubMed1989

Nosocomial Branhamella catarrhalis in a paediatric intensive care unit: risk factors for disease.

There have been few reports on Branhamella catarrhalis as a nosocomial pathogen, and no risk factors for nosocomial infection have been identified. We report 11 cases (mean age 22 months) of nosocomial Branhamella catarrhalis respiratory tract infection in a paediatric intensive care unit (PICU) over a two-year period. There were 2 cases of pneumonia and 9 cases of bronchitis. Branhamella catarrhalis was the sole isolate recovered in 6 cases and was associated with other respiratory pathogens in 5 cases. A case-control study with two age-matched controls per patient (mean age 24.1 months) was undertaken to identify potential risk factors for infection; risk factors identified were the presence of an endotracheal tube (p less than 0.02) and frequent endotracheal tube suction (p less than 0.05). Five of 6 tested strains from PICU patients produced beta-lactamase. DNA preparations of 4 B. catarrhalis isolates from PICU patients revealed no plasmids. B. catarrhalis should be considered a potential nosocomial pathogen.

Boston↗