Activation of multiple protein kinases by interleukin-1.
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Animals↗
Biomedical subjects
B L Brown
Publications and source records attributed to B L Brown.
Interleukin-1 beta induces the synthesis of adenylyl cyclase in Swiss 3T3 fibroblasts and MG-63 osteosarcoma cells.
In this study, the longer term (> or = 6 hours) effect of interleukin-1 beta on adenylyl cyclase activity was investigated in Swiss 3T3 and MG-63 cells. No change was evident after 6 hours but after 1, 7 or 15 day incubations a significant increase in basal (1.5- 2 fold) and NaF-stimulated (2-4 fold) adenylyl cyclase activity was observed in interleukin-1 beta pre-treated cell membranes compared with non pre-treated controls. The response to forskolin, a direct stimulus of adenylyl cyclase, was also significantly enhanced, indicating that the effect of interleukin-1 beta was targeted to the enzyme itself. This action of interleukin-1 beta was blocked by co-incubation with cycloheximide, an inhibitor of protein synthesis, which demonstrated that de novo protein synthesis was required. It is concluded that interleukin-1 induces the expression of adenylyl cyclase in 3T3 and MG-63 cells, leading to enhanced activation by NaF and forskolin.
3T3 Cells↗
Fasting for less than 24 h induces cytochrome P450 2E1 and 2B1/2 activities in rats.
Cytochrome P450 (CYP) 2E1 activity is induced after 24 h of fasting but no information is available for shorter fasting periods. We investigate the induction of CYP 2E1, 2B1/2 and 1A1 in young adult male F344 rats after 8, 16 and 24 h of fasting compared to control. Liver microsomes were analyzed for the following enzyme activities: p-nitrophenol hydroxylase (PNP) for CYP 2E1, pentoxyresorufin-O-dealkylase (PROD) for CYP 2B1/2 and ethoxyresorufin-O-deethylase (EROD) for CYP 1A1. After each fasting interval, the activities per mg microsomal protein for PNP and PROD increased but the activity of EROD remained unchanged. Western blots for CYP 2E1 and CYP 2B1 showed increases comparable to the PNP and PROD activities, respectively. On a whole organ basis, increases were found for PNP and PROD activities, while decreases were found for EROD activity and total microsomal protein. The results are consistent with an induction of CYP 2E1 and CYP 2B1/2 activities after as little as 8 h of fasting.
Animals↗
Adjunctive treatment of cranial base malignacies.
The indications for skull base tumor surgery have increased in recent years primarily because of improving surgical techniques and adjunctive treatment modalities. In this article we review current and future adjunctive treatment for cranial base malignancies. Surgically clear tumor margins are often difficult to achieve in skull base surgery because of unacceptable morbidity to surrounding structures. Current phase I and II trials of adjunctive radiation and chemotherapy are discussed. Future advances in radiation therapy and chemotherapy are introduced.
Brain Neoplasms↗
The mitogenic action of recombinant basic FGF in Swiss 3T3 cells is independent of early diradylglycerol production and downregulatable protein kinase C activity.
In this study we have investigated the requirement for phosphoinositide metabolism, diradylglycerol (DG) production and protein kinase C (PKC) activation in recombinant basic fibroblast growth factor (rbFGF)-mediated reinitiation of DNA synthesis in Swiss 3T3 cells. We have assessed the involvement of PKC activation in rbFGF-induced DNA synthesis by two approaches; enzymic inhibition by H7 and down-regulation by prolonged phorbol-ester treatment. In both conditions we observed that rbFGF was able to sustain a significant component of its mitogenic response, therefore denying an exclusive role for the activation of downregulatable and H7-sensitive PKC isoforms in rbFGF-induced reinitiation of DNA synthesis. Moreover, we have found no evidence for diacylglycerol accumulation in response to rbFGF by 3T3 cells. In previous studies, we observed that rbFGF caused a moderate and slow accumulation of total inositol phosphates. This effect was significant only after a 60 min incubation. It is our contention that rbFGF, in our culture system, does not exert a direct effect on phosphoinositide metabolism.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Stimulation of arachidonic-acid release from Swiss 3T3 cells by recombinant basic fibroblast growth factor: independence from phosphoinositide turnover.
In this study we have attempted to characterize the mechanism of recombinant bovine basic fibroblast growth factor (rbFGF)-induced release of arachidonic acid from prelabelled Swiss 3T3 fibroblasts. Recombinant bFGF caused the release of [3H]arachidonic acid from metabolically labelled cells in a dose- and time-dependent manner. This effect was maximal with 10 ng rbFGF/ml and became significant after a 30-min incubation. Although rbFGF was able to cause a modest increase in total inositol phosphate accumulation, an examination of the time-course of the latter effect revealed that enhanced [3H]arachidonic-acid release could not have been derived from phosphoinositide metabolism. Evidence suggesting that rbFGF-induced release of [3H]arachidonic acid was being mediated via a PLA2 pathway was obtained by pharmacological antagonism using mepacrine, a putative PLA2 inhibitor. Moreover, treatment of cells with neomycin failed to attenuate rbFGF-mediated release of [3H]arachidonic acid. Chelation of extracellular calcium by EGTA was found to abrogate rbFGF-induced liberation of [3H]arachidonic add. Down-regulation of protein kinase C (PKC) by prolonged treatment of cells with the phorbol ester, PMA, was observed to have no effect on the action of rbFGF on [3H]arachidonic add release from Swiss 3T3 fibroblasts. While rbFGF was found to cause the indomethacin-sensitive production of prostaglandin E2 (PGE2) in a dose-dependent manner, this effect was independent of rbFGF-induced reinitiation of DNA synthesis. Clearly, the effect of rbFGF on cellular DNA synthesis was being mediated independently of PGE2 biosynthesis. We discuss the potential importance of the PLA2-signalling pathway in the mechanism of action of fibroblast growth factors.
3T3 Cells↗
Internal clock and memory processes in animal timing.
Temporal control of behavior was investigated within the framework of an internal clock model. Pigeons were exposed to signaled fixed-interval 30-s trials mixed with extended unreinforced (baseline) trials. On unreinforced break trials, the signal was interrupted for a period of time after trial onset. In Experiment 1, comparisons between the peak time obtained on baseline and on break trials produced peak time shifts that were longer than those expected if the clock had stopped during the break but shorter than if the clock had reset. In Experiment 2, systematic manipulations of duration and location of breaks produced peak time shifts that were nonlinear functions of break duration and that varied linearly with break location. The obtained peak times were more consistent with a continuous memory decay model than with the stop-retain or the reset hypotheses.
Animals↗
Fractured clavicle in the neonate: a retrospective three-year review.
A hospital-based case-controlled study was undertaken to determine maternal and neonatal characteristics associated with fractured clavicle. A total of 11,604 consecutive vaginal deliveries of liveborn infants in vertex presentation at the Mount Sinai Hospital from 1988 to 1990 were reviewed. Maternal and neonatal characteristics were compared for the neonates with and without a diagnosis of a fractured clavicle. Compared to controls, mothers of neonates with a fractured clavicle were more likely to be nulliparas or primiparas, to have had an operative vaginal delivery, and to have been delivered by an attending as opposed to a resident physician. The fractured clavicle group also had a longer gestational age, greater birthweight, and higher frequency of macrosomic infants. After controlling for maternal parity, type of delivery and infant birthweight, experience of the delivering physician, and gestational age at delivery were not significantly different. Fracture of the clavicle in the neonate is related to maternal parity, mode of delivery, and infant birthweight but not to the level of experience of the delivering physician.
Adult↗
The assessment of frequency estimates of Hae III-generated VNTR profiles in various reference databases.
The likelihood of occurrence of 1964 Hae III-generated target DNA profiles was estimated using fixed bin frequencies from various regional and ethnic databases and the multiplication rule. The databases generally were from the following major categories: Black, Caucasian, Hispanic, Oriental, and American Indian. It was found that subdivision, either by ethnic group or by U.S. geographic region, within a major population group did not substantially affect forensic estimates of the likelihood of occurrence of a DNA profile. As expected, the greatest variation in estimates for within-group estimates was among American Indian databases. Because the greatest variation in statistical estimates occurs across-major population groups, in most cases, there will be no unfair bias applying general population database estimates. Therefore, based on empirical data, there is no demonstrable need for using alternate approaches, such as the ceiling approach, to derive statistical estimates. The current practice of using general population databases and the multiplication rule provides valid estimates of the likelihood of occurrence of a DNA profile.
Bias↗
Evaluation of Hinf I-generated VNTR profile frequencies determined using various ethnic databases.
Concerns have been raised about hypothetical problems arising from the use of statistics for determining the likelihood of occurrence of DNA profiles for forensic purposes. A major contention is that reference databases based on subgroups of a major population category rather than on general (or major) population groups, might yield large differences in the estimated likelihood of occurrence of DNA profiles. This hypothetical issue is based on the assertion by some people that the differences among subgroups within a race would be greater than between races (at least for forensic purposes). To evaluate the effects of the above concern the likelihood of occurrence of 615 Hinf I-generated target DNA profiles was estimated using fixed bin frequencies from various ethnic databases and the multiplication rule. Based on the data in this study, differences in allele frequencies at a particular locus do not have substantial effects on VNTR profile frequency estimates when subgroup reference databases from within a major population group are compared. In contrast, the greatest variation in statistical estimates occurs across-major population groups. Therefore, the assertion, by some critics that the differences among subgroups within a race would be greater than between races (at least for forensic purposes), is unfounded. The data in the study support that comparisons across major population groups provide valid estimates of DNA profile frequencies without forensically significant consequences. The data do not support the need for alternate procedures, such as the ceiling principle approach, for deriving statistical estimates of DNA profile frequencies.
Black People↗
Double-blind; placebo-controlled trial of piperacillin prophylaxis in preterm membrane rupture.
OBJECTIVE: We attempted to test whether antibiotic therapy prolongs pregnancy in preterm premature rupture of membranes, because preterm premature rupture of membranes is frequently associated with chorionic-decidual infection. STUDY DESIGN: Women with preterm premature rupture of membranes and a singleton gestation at 24 to 34 completed weeks were randomized to receive either piperacillin 3 gm or placebo intravenously every 6 hours for 72 hours and were managed conservatively until spontaneous delivery, chorioamnionitis, or fetal distress. RESULTS: Between January 1987 and January 1992, a total of 75 patients were randomized to receive piperacillin (n = 38) or placebo (n = 37). There were no differences between the piperacillin group and the placebo group in mean gestational age at randomization (30.2 +/- 3 vs 30.3 +/- 2.9 weeks). However, a greater number of patients had pregnancy prolonged beyond 7 days (42.1% vs 10.8% p = 0.005) and the mean latency period was significantly prolonged (11.4 +/- 18.8 vs 6.1 +/- 13.6 days, p = 0.001) in the piperacillin group compared with the control groups. CONCLUSIONS: Use of intravenous piperacillin for 72 hours in preterm premature rupture of membranes significantly prolongs the latency period between membrane rupture and delivery.
Adult↗
OSHA regulations demand strict documentation, compliance.
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Confidentiality↗
A system for documentation of pharmacist interventions with incorporation into performance and quality improvement plans.
Budgetary constraints have compelled hospital administrators to take a more discerning look at the role of the pharmacist within the healthcare team. In 1991, financial difficulties and hospital-wide cutbacks at Northern Michigan Hospital resulted in the loss of pharmacy personnel. Consequently, the department has increasingly found it necessary to document the clinical activities of the pharmacists and their potential effect on patient care. To document therapeutic interventions, two forms specific to this activity were developed. These forms allowed evaluation of both the quantity and quality of interventions. The authors realize it is essential for pharmacists to not only maintain, but to continually update their knowledge base to be prepared for the future. A staff development program was developed to help meet the educational needs of the pharmacists. This article describes how therapeutic interventions were integrated into the quality improvement and performance plans to help motivate staff to continually improve their pharmacy practice skills at this institution.
Clinical Pharmacy Information Systems↗
Advanced abdominal pregnancy complicated by bilateral ureteral obstruction. A case report.
A case of term abdominal pregnancy is reported. The patient was followed throughout pregnancy, but the diagnosis was made only at the time of laparotomy for elective cesarean section. The report exemplifies the ease with which the diagnosis of abdominal pregnancy can be overlooked and stresses the importance of considering this diagnosis in cases of high maternal serum alpha-fetoprotein. The management of the placenta is also discussed. In this case the retained placenta was managed successfully without intervention despite the unusual complication of bilateral ureteral obstruction. Additionally, the biochemical activity of the placenta was assessed by following the progressive decline of serum human chorionic gonadotropin over time.
Adult↗
Bradykinin stimulates the production of prostaglandin E2 and interleukin-6 in human osteoblast-like cells.
The effect of bradykinin (BK) on proteinase activity, prostaglandin synthesis, and the production of interleukin-6 (IL-6) was investigated in cultures of human osteoblast-like cells. Bradykinin had no effect on stromelysin activity and plasminogen activator activity produced by human osteoblast-like cells. However, BK stimulated the production of prostaglandin E2, an effect that was markedly enhanced by pre-incubation with recombinant interleukin-1 alpha (rhIL-1 alpha), but was apparently unaffected by BK receptor antagonists types 1 and 2. Bradykinin stimulated the intracellular accumulation of total inositol phosphates suggesting that its effects were mediated by stimulation of phosphoinositide metabolism. Bradykinin within the dose range of 10(-11)-10(-5) M also significantly stimulated the production of IL-6. Bradykinin may, therefore, mediate a variety of responses in bone under both physiological and pathological conditions.
Bradykinin↗
The regulation of connective tissue metabolism by vasoactive intestinal polypeptide.
Immunohistochemical studies have confirmed the innervation of bone with neuropeptidergic neurons containing vasoactive intestinal polypeptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). In this study, we report effects of VIP on connective tissue cell metabolism. VIP stimulated PGE2 production in human articular chondrocytes, human osteoblast-like cells and human synovial cells, however, stromelysin production was unaffected. VIP also stimulated cAMP production in human osteoblast-like cells, but not in human articular chondrocytes or synovial cells. These findings are suggestive of a role of VIP in connective tissue cell metabolism which may contribute to the inflammatory processes of arthritis.
Cartilage, Articular↗
Effect of the GABAA agonist muscimol on prolactin secretion from human prolactin-secreting adenomas and GH3 rat pituitary tumour cells.
The effect of muscimol, a specific potent GABAA receptor agonist, on prolactin release from human prolactin-secreting tissue was investigated using a perifusion system. Perifusion studies on normal rat anterior pituitary tissue, which has identical GABA receptors to those found in normal human pituitary glands, show that muscimol has a specific biphasic effect on prolactin release. This is characterized by an initial transient stimulation (222.3 +/- 21.6% of basal) lasting for 5-10 min followed by a more prolonged inhibitory phase (63.9 +/- 3.1% inhibition of basal). Five human prolactin-secreting adenomas were studied, and in none of the tumours could a biphasic response be demonstrated. One of the prolactin-secreting adenomas had a blunted inhibitory response, but the other 4 showed no inhibitory effect of muscimol on prolactin release. Muscimol had no significant effect on basal or thyrotropin-releasing-hormone (TRH)-stimulated prolactin secretion from GH3 rat pituitary tumour cells. These studies suggest that the GABAergic effect on prolactin secretion is absent or altered in both rat and human prolactin-secreting tumour cells.
Adult↗
Maxillary removal and reinsertion for improved access to anterior cranial base tumors.
Portions or all of the maxillae are oftentimes removed solely to provide access to certain cranial base tumors rather than because they are involved directly with disease. The purpose of this report is to describe an approach that involves removal of one or both maxillae to improve tumor exposure with subsequent reinsertion as free bone grafts which are stabilized with titanium craniofacial fixation plates. The titanium permits postoperative imaging studies and radiotherapy. Eleven patients ranging from 10 to 69 years of age have undergone 12 operations using this technique for resection of 4 benign and 8 malignant tumors at The Ohio State University. Seven of the 8 patients with malignancies underwent postoperative radiation therapy. There have been no permanent complications and no evidence of bone resorption in this group after follow-up of up to 15 months.
Adolescent↗