Dietary effect on blood pressure.
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Blood Pressure↗
Biomedical subjects
K Dyer
Publications and source records attributed to K Dyer.
Development of a universal connectivity and data management system.
Point-of-care testing (POCT) is an increasingly popular method of delivering laboratory testing. Management of POCT is challenging given the variety of devices, locations, and staff that need to be coordinated to ensure quality results and meet regulatory guidelines. Electronic capture and transfer of data are preferred for managing POCT, but there is currently no standard method of connecting different devices. Johns Hopkins Medical Institutions (JHMI) developed a common data management system with interfaces to all of its POCT devices. All POCT data are collected in one database and analyzed in a similar fashion. Where data were once collected by carrying laptops to each nursing unit, the POCT devices can now connect directly to the database over the Internet. Algorithms have been created to automate the data analysis and review process. Over the several years that this software has been used, JHMI has experienced improved quality, accuracy, and management of its POCT program. The labor saved by increased automation of data review is refocused on enhancing the performance and scope of the program. Current connectivity and analysis algorithms have future application to remote consultation, management of home self-monitoring patients, and examination of real-time data.
Academic Medical Centers↗
Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock.
Interleukin-6 (IL-6) is produced within multiple tissues and can be readily detected in the circulation in resuscitated hemorrhagic shock (HS). Instillation of IL-6 into lungs of normal rats induces polymorphonuclear neutrophilic granulocyte (PMN) infiltration and lung damage, while infusion of IL-6 into the systemic circulation of rats during resuscitation from HS reduces PMN recruitment and lung injury. The current study was designed to determine whether or not IL-6 makes an essential contribution to postresuscitation inflammation and which of the two effects of IL-6, its local proinflammatory effect or its systemic anti-inflammatory effect, is dominant in HS. Wild-type and IL-6-deficient mice were subjected to HS followed by resuscitation and death 4 h later. IL-6-deficient mice subjected to HS did not demonstrate any features of postresuscitation inflammation observed in wild-type mice, including increased PMN infiltration into the lungs, increased alveolar cross-sectional surface area, increased PMN infiltration into the liver, increased liver necrosis, increased signal transducer and activator of transcription 3 activation, and increased nuclear factor-kappaB activity. These findings indicate that IL-6 is an essential component of the postresuscitation inflammatory cascade in HS and that the local proinflammatory effects of IL-6 on PMN infiltration and organ damage in HS dominate over the anti-inflammatory effects of systemic IL-6.
Animals↗
A question of space: options for the restorative management of worn teeth.
The prevalence of tooth surface loss has increased in recent years. The essence of management is an effective preventive regime; however, in many instances restoration may also be necessary. A number of strategies is available for creating sufficient space to enable restoration and several techniques for restoration known. This article reviews the significance of the vertical dimension of occlusion and describes the restorative management of a patient affected by severe tooth wear.
Adult↗
Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway .
BACKGROUND: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates growth and differentiation of various types of malignant tumors, including prostate carcinomas. The levels of IL-6 are elevated in sera of patients with metastatic prostate cancer. In this study, we evaluate the role of IL-6 in the growth regulation of prostate cancer cells. METHODS: Expression of IL-6 and its receptors in human prostate cancer cells was measured by ELISA and RT-PCR. The effects of IL-6 on cell growth were evaluated by ectopically expressing IL-6 cDNA into IL-6-negative LNCaP human prostate cancer cells. Stat3 DNA binding activities were analyzed by electromobility shift assay and supershift assay. RESULTS: Expression of IL-6 was detected in the androgen-insensitive prostate cancer cell lines (i.e. , TSU, PC3, and DU145), but not in the androgen-sensitive LNCaP cell line. IL-6 receptors, including both IL-6-specific receptor alpha chain and gp130 signal transducer, are expressed in all human prostate cancer cell lines (i.e., LNCaP, TSU, PC3, and DU145). Overexpression of IL-6 by ectopically expressing IL-6 into IL-6-negative LNCaP human prostate cancer cells significantly increased clonogenic ability and cell proliferation in vitro compared to the IL-6-negative parental LNCaP cells and the antisense controls. This growth stimulation by IL-6 was accompanied by activation of the Stat3 signaling transduction pathway. CONCLUSIONS: IL-6 is an autocrine growth factor for LNCaP human prostate cancer cells; the effects of IL-6 on prostate cancer cell growth are mediated through the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway.
Antigens, CD↗
Distinct effects of systemic infusion of G-CSF vs. IL-6 on lung and liver inflammation and injury in hemorrhagic shock.
Production of pro-inflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) occurs at multiple tissue sites in hemorrhagic shock (HS), resulting in elevated circulating plasma levels. The current study was designed to test the hypothesis that circulating G-CSF and IL-6 contribute to polymorphonuclear neutrophilic granulocyte (PMN)-mediated inflammation and organ injury in HS. Sprague-Dawley rats were subjected to decompensated HS (mean arterial blood pressure = 40 mm Hg for 2.5 h), followed by resuscitation with lactated Ringer's solution with or without G-CSF (3 microg/kg) or IL-6 (3 microg/kg). Animals were killed 4 h after resuscitation, and their lungs and livers were assessed quantitatively for PMN infiltration, organ injury, and activation of NF-kappaB and signal transducer and activator or transcription (STAT) 3. Infusion of G-CSF during resuscitation increased PMN infiltration into the lungs by 2.4-fold (P < 0.01) compared with animals resuscitated with lactated Ringer's solution alone. Increased PMN infiltration was accompanied by interstitial edema and pneumocyte swelling, resulting in a 42% increase in lung alveolar wall cross-sectional surface area (P < 0.01) and a 3.7-fold increase in Stat3 activity (P < 0.01). G-CSF infusion did not affect PMN infiltration into the liver and was accompanied by a 68% decrease in focal hepatocellular necrosis (P < 0.01). Infusion of IL-6, in contrast, dramatically decreased inflammation and injury in both the lung and liver; the anti-inflammatory effects of IL-6 may be mediated, in part, by down-modulation of nuclear factor (NF)-kappaB activity. Thus, circulating G-CSF and IL-6 have opposing effects on PMN recruitment and injury in the lung in HS while both protect against hepatic necrosis. The beneficial effect of these cytokines on liver injury in HS appears to be independent of PMN recruitment.
Animals↗
Synaptophysin immunoreactive axonal swelling in p-bromophenylacetylurea-induced neuropathy.
A single intraperitoneal dose of 300 mg/kg of p-bromophenylacetylurea (BPAU) induced progressive distal neuropathy in rats, prominently involving peripheral nerves and long central nervous system myelinated tracts such as the fasciculus gracilis and spinocerebellar pathways. Clinical signs assessed using a Functional Observational Battery (FOB) and in-cage observation included weakness and deficits in motor and sensory integration, definitively noted on post-dosing day 7. The signs were more pronounced upon repetition of the FOB on post-dosing day 12. The neuropathological substrate of these signs was a progressive axonopathy with regional swelling, leading to Wallerian-like degeneration of affected myelinated fibers. Immunocytochemical staining for synaptophysin revealed often striking increase in immunoreactivity for this synaptic vesicle glycoprotein in swollen and otherwise injured axons. Such accumulations were considered consistent with interruption of anterograde (and possibly retrograde) fast axonal transport systems secondary to toxicant-induced nerve fiber breakdown.
Animals↗
Comparison of second-messenger responses to muscarinic receptor stimulation in M1-transfected A9 L cells.
A9 L cells stable transfected with m1 muscarinic receptors were stimulated with the full agonist carbachol and with the partial agonist pilocarpine. The EC50 values and maximal activation from PI hydrolysis, calcium mobilization, membrane hyperpolarization, cell proliferation and arachidonic acid release were compared. Pilocarpine was approximately half as effective in eliciting PI hydrolysis, calcium mobilization and arachidonic acid release, but was almost as effective as carbachol in the other assays. These findings suggest that the intracellular signals leading to receptor-mediated cell proliferation and to membrane hyperpolarization are amplified, and that therefore these assays are not suitable for determining whether a compound is a partial agonist.
Animals↗
Muscarinic receptor-mediated inhibition of mitogenesis via a protein kinase C-independent mechanism in M1-transfected A9 L cells.
Previous studies have shown that activation of various PI-coupled receptors stimulates DNA synthesis in some cells, and inhibits DNA synthesis in others. In order to study this effect further, we measured carbachol-mediated [3H]thymidine incorporation in m1-transfected A9 L cells and in m1-transfected CHO cells, and found that carbachol profoundly inhibited DNA synthesis in both cell lines. This carbachol response was observed whether the cells were grown in the presence or in the absence of serum. The half-maximal value for carbachol-mediated inhibition of [3H]thymidine incorporation was 5.73 +/- 1.15 microM in m1-transfected A9 L cells. Pre-treatment of m1-transfected A9 L cells with the protein kinase C inhibitors staurosporine, sphingosine or phorbol 12-myristate 13-acetate-induced down-regulation did not prevent the carbachol inhibition of DNA synthesis, thereby demonstrating that this effect is not mediated via protein kinase C. Inhibition of [3H]thymidine incorporation was significant at 2 h, but not at 1 h of carbachol treatment. Recovery of [3H]thymidine incorporation following carbachol activation was also studied by blocking the receptor with atropine following carbachol stimulation. Following this treatment, cells needed at least 3 h to recover normal [3H]thymidine incorporation. Taken together, the kinetics of this response suggest that it is not mediated directly by a second messenger which typically has much more rapid kinetics.
3T3 Cells↗
Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells.
Loss of telomeres has been hypothesized to be important in cellular senescence and may play a role in carcinogenesis. In this study, we have measured telomere length in association with the immortalization and transformation of human cervical and foreskin epithelial cells by the human papillomavirus type 16 or 18 E6 and E7 open reading frames. By using a telomeric TTAGGG repeat probe, it was shown that the telomeres of precrisis normal and E6-, E7-, and E6/E7-expressing cells gradually shortened with passaging (30 to 100 bp per population doubling). Cells that expressed both E6 and E7 went through a crisis period and gave rise to immortalized lines. In contrast to precrisis cells, E6/E7-immortalized cells generally showed an increase in telomere length as they were passaged in culture, with some later passage lines having telomeres that were similar to or longer than the earliest-passage precrisis cells examined. No consistent association could be made between telomere length and tumorigenicity of cells in nude mice. However, of the three cell lines that grew in vivo, two had long telomeres, thus arguing against the hypothesis that cancer cells favor shortened telomeres. Our results indicate that arrest of telomere shortening may be important in human papillomavirus-associated immortalization and that restoration of telomere length may be advantageous to cells with regard to their ability to proliferate.
Animals↗
Comparative evolution of mipafox-induced delayed neuropathy in rats and hens.
Adult male Long-Evans rats and White Leghorn hens were given 30 mg/kg mipafox ip. Administration of this organophosphorus ester resulted in > or = 89% inhibition of brain and spinal cord neurotoxic esterase activity in both species 4 hr after dosing. Our sequential, comparative study of the bilateral mipafox-induced neuropathy in the medulla and cervical spinal cord in hens and rats demonstrated that the rats had well-developed, vacuolar axonopathic lesions in the fasciculus gracilis by post-dosing day 7. Severely affected rats with such lesions were noted through day 21, but not subsequently (days 28 and 35). The hen had a slower developing, but more severe, consistent and longer lasting neuropathy than the rat. In these birds, lesions in the medulla and rostral cervical spinal cord levels were more extensive, involving large regions of both the spinocerebellar tracts and fasciculus gracilis. Neuropathic changes, including myelinated fiber axonopathy and Wallerian-like degeneration, were prominent from days 14 - 35 in hens, and were associated with prominent gliosis in the later stages.
Animals↗
Effects of choice making on the serious problem behaviors of students with severe handicaps.
This study assessed the impact of choice making on the serious problem behaviors of 3 students with severe autism and/or mental retardation. In the context of within-subject reversal designs, the results showed consistently reduced levels of problem behaviors (e.g., aggression) when the students were given opportunities to make choices among instructional tasks and reinforcers. Additional data showed no systematic differences in the rate of correct responding between the two conditions. The results are discussed in relation to the continuing search for effective, nonintrusive solutions to the occurrence of serious problem behavior.
Autistic Disorder↗
Retinal pigment epithelium cells can influence endothelial cell plasminogen activators.
Endothelial cells from both human retinal microvessels (HME) and fetal bovine aortic endothelium (FBAE) were grown in aggregate cultures alone, or with either retinal pigment epithelium (RPE) cells or fibroblasts. The levels of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in the conditioned media of the various aggregate types were measured. High PA levels were detected in the conditioned medium of pure endothelial cell aggregates (equal to 140% and 124% of urokinase control for HME and FBAE, respectively), and high PAI levels were associated with pure RPE aggregates (inhibiting 93% of the urokinase control). The conditioned medium of pure fibroblast aggregates had very low levels of either PA or PAI. When RPE cells were aggregated with FBAE or HME cells into mixed (heterogenous) aggregates, the PA measured in the conditioned medium was equal to 22% and 30% of the urokinase control, respectively. The PA level in the conditioned medium of mixed fibroblast-FBAE cell aggregates was higher, 104% of the control, and the difference was statistically significant (P less than 0.001). Co-incubation of pure RPE aggregates with pure FBAE aggregates or with pure HME aggregates resulted in PA activity in the conditioned medium that was equal to 110% and 96% of the control, respectively. The PA level found when pure FBAE cell aggregates were co-incubated with pure fibroblast aggregates was higher, 134% of the control, and the difference was statistically significant (P less than 0.001). Our results indicate that RPE cells can reduce endothelial cell PA, probably through both direct contact between the cells and PAI production. Fibroblasts did not have this influence on endothelial cell PA.
Analysis of Variance↗
Congenital rubella syndrome in the United States, 1970-1985. On the verge of elimination.
The National Congenital Rubella Syndrome Registry, a passive surveillance system, and the Birth Defects Monitoring Program, a newborn hospital discharge data set, are used to monitor the incidence of congenital rubella syndrome in the United States. Reports to the registry contain clinical and laboratory data which allow cases to be classified into six categories according to the likelihood of having congenital rubella syndrome. The monitoring program records newborn discharge diagnoses, without detailed information, of a nonrandom sample of about one fourth of the births in the United States annually. To evaluate the two systems and to estimate the actual incidence of congenital rubella syndrome, the authors collected hospital discharge summaries on all cases as reported by the monitoring program from 1970-1985 and classified them by the registry criteria. Of the 392 cases reported to the monitoring program during 1970-1985, 24% (n = 93) could be classified as confirmed or compatible compared with 79% (n = 415) of the 526 cases reported to the registry (rate ratio = 3.3; 95% confidence interval (CI) 2.9-3.8). Diagnosis of congenital rubella syndrome was made during the neonatal period for 68% (263 of 389) registry cases for whom such data were available. When the Lincoln-Peterson capture-recapture method of estimating population size for independent surveillance systems was used, an estimated 1,064 confirmed and compatible cases (95% CI 668-1,460) diagnosed during the neonatal period occurred during 1970-1979, for an average of 106 cases per year. During 1980-1985, an estimate of 122 neonatal confirmed and compatible cases (95% CI 8-236) occurred, for an average of 20 cases per year. A downward secular trend in the incidence of congenital rubella syndrome beginning in 1980 was observed. The registry detected 22% of all neonatal confirmed and compatible cases, the monitoring program detected 8%, and the two systems combined detected a total of 28%. The results indicate that congenital rubella syndrome may be on the verge of elimination in the United States.
Age Factors↗
Prosodic aspects of motherese: effects on gaze and responsiveness in developmentally disabled children.
This study was conducted to examine the effectiveness of using voice tones (prosody) typical of "motherese" (O. K. Garnica, 1977, in C. E. Snow & C. A. Ferguson (Eds.), Talking to Children: Language Input and Acquisition, pp. 63-88, Cambridge: Cambridge Univ. Press) on responsiveness and eye gaze in children with severe handicaps. Specifically, two conditions, "motherese" and "conversational" voice tones, were compared. The current study presents data from naturalistic observations of six children, and controlled experimental manipulations with four children. The results of the naturalistic observations in Study 1 suggested a positive relationship between the use of voice tones typical of "motherese" and responsiveness and eye gaze. Further analysis using an alternating treatments design in Study 2 revealed similar results. Specifically, the use of prosody associated with "motherese" showed increased levels of eye gaze when compared to the use of "conversational tones." The results suggest the importance of considering normal development in analyzing social and teaching interactions between teachers and severely handicapped children.
Adolescent↗
The competition of autistic stereotyped behavior with usual and specially assessed reinforcers.
This study was conducted to empirically assess a reinforcement theory of stereotyped behavior. Six students with autism were first presented with tasks, and no contingent reinforcers were provided for correct responding. Then, contingent reinforcers that were typically used with the students (usual reinforcers) were presented in a multiple baseline across subjects design. Three of the students evidenced decreases in stereotypy and increases in responding in the presence of usual reinforcers. The other three students required external suppression of stereotypy before increases in responding were shown. For these students, usual reinforcers and specially assessed reinforcers were then compared. The specially assessed reinforcers resulted in decreases in stereotypy and increases in responding and subjective measures of responsiveness. The results were discussed in terms of supporting a competing reinforcement hypothesis, such that powerful external reinforcers will successfully compete with and suppress reinforcers provided by stereotypy.
Adolescent↗
Developmental influences in teaching language forms to individuals with developmental disabilities.
The purpose of this experiment was to test the assumption that the sequencing of language goals for individuals with developmental disabilities should be based on the normal developmental sequence. In a series of two studies, phonetic sounds and syntactic structures representing different levels of normal development were taught to individuals with developmental disabilities. The results showed that (a) the majority of earlier emerging forms were acquired in fewer trials, (b) there was never an instance when the later emerging form was acquired and the earlier emerging form was not, and (c) the majority of earlier emerging forms were correctly produced at higher levels than the later emerging forms during probe sessions conducted 6 months after training. The results are discussed in terms of their implications for the development of language curricula for individuals with developmental disabilities.
Adolescent↗
The influence of child-preferred activities on autistic children's social behavior.
One of the characteristics of autistic children is severe social avoidance behavior. We assessed whether the type of activity (child-preferred vs. activities that were arbitrarily determined by an adult) engaged in during an interaction was correlated with the amount of social avoidance behaviors these children exhibit. Results revealed a negative correlation between appropriate child-preferred activities and social avoidance behavior. Additional analyses revealed that (a) social avoidance behaviors could be manipulated within a reversal design, and would predictably decrease when the children were prompted to initiate appropriate child-preferred activities; and (b) these procedures could be used to teach children to initiate child-preferred activities in community settings, resulting in reductions in social avoidance responses even after the therapist's prompts were completely removed. These data suggest that the manipulation of task variables may influence the severe social unresponsiveness that is characteristic of autistic children.
Adolescent↗