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Biomedical subjects

K Kelley

Publications and source records attributed to K Kelley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain.

Interleukin-1beta plays an important role in mediating central components of the host response to peripheral infection such as fever and neuroendocrine activation by acting in the brain. The present study assessed whether interleukin-1beta produced in the brain is relevant to neuronal activation and the fever response induced by intraperitoneal injection of bacterial lipopolysaccharide. The distributions of Fos protein, interleukin-1beta protein and inducible nitric oxide synthase messenger RNA, used as an anatomical indicator of interleukin-1beta bioactivity, were compared in brains of animals killed 2, 4 or 8 h after lipopolysaccharide (250 microg/kg) or saline injection. Saline did not induce interleukin-1beta or Fos immunoreactivity in the brain. Interleukin-1beta positive cells were found 2 h after lipopolysaccharide injection in circumventricular organs. Fos immunoreactivity at this time-point was not found in circumventricular organs, but in parenchymal structures such as the nucleus of the solitary tract, paraventricular hypothalamus and ventromedial preoptic area. Fos expression did occur in circumventricular organs only 8 h after lipopolysaccharide injection. This late pattern of Fos expression coincided with the rise in body temperature and the induction of inducible nitric oxide synthase messenger RNA. These data show that after peripheral lipopolysaccharide administration interleukin-1beta is synthesized and bioactive in circumventricular organs. Interleukin-1beta may activate local neurons that induce fever and neuroendocrine activation via projections to the ventromedial preoptic area and the nucleus of the solitary tract.

Abdomen↗
PubMed1999

The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome.

We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number.

Adolescent↗
PubMed1999

Distinct ICAM-1 forms and expression pathways in synovial microvascular endothelial cells.

Human synovial endothelial cell (HSE) intracellular adhesion molecule-1 (ICAM-1) is upregulated maximally by synergy of tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). Such synergy is not as pronounced in human umbilical vein endothelium (HUVE). ICAM surface staining and ELISA detection reflected similar levels on HUVE and HSE cells, yet mRNA levels were much higher in HSE cells in response to TNF alpha/IFN gamma. To correlate protein and mRNA levels of ICAM-1, both cell types were permeabilized and stained with a monoclonal antibody against ICAM-1. HSE cells displayed a distinct vesicular cytoplasmic staining for ICAM while HUVE cells were devoid of such stained vesicles upon staining with the antibody. ICAM-1 immunostaining of HSE cytoplasmic vesicles appeared enhanced in cells treated with TNF alpha/IFN gamma and monensin, an endosomal processing inhibitor. Monensin inhibited HSE cell surface expression of ICAM-1 routinely up to 70%, while HUVE cell expression was unaffected. In addition, monensin also inhibited soluble ICAM-1 release from HSE cells while not effecting HUVE cells. Immunoprecipitation of ICAM-1 followed by gel electrophoresis indicated that HUVE and HSE cell ICAMs are expressed in cell-specific forms. These results define distinct forms and distinct secretory pathways for ICAM-1 in HSE cells and HUVE cells that indicate functional differences between these human endothelia.

Cells, Cultured↗
PubMed1999

Gender differences in the aerobic fitness levels of young African-American adults.

This study examines gender differences in the aerobic fitness levels of young African-American adults. Two hundred twelve African-American college freshmen (79 men, 133 women) completed the Houston Non-Exercise Test-Body Mass Index Model (HNET-BMI) questionnaire, a questionnaire designed to estimate maximum oxygen consumption (VO2max, mL kg-1 min-1) in adults. Using a three-point scoring system (below average, average, and above average), 100% of the men and 80% of the women were classified as having average or above average levels of VO2max. Statistical analysis revealed that more women than men had average or below average levels of aerobic fitness (chi 2 = 54.5; P = .0001). The results of this study suggest that a larger percentage of African-American women have lower levels of aerobic fitness compared with African-American men.

Adolescent↗
PubMed1998

Psychological readiness of black college students to be physically active.

Black students' psychological readiness to be physically active was examined in 212 1st-year students (79 men and 133 women) at a historically Black university in the South. The students responded to the Physician-based Assessment and Counseling for Exercise (PACE) survey, which asked students about current physical activity habits. More men (57%) than women (32%) were classified as being in the action stage. Approximately 37% of the men in the sample, compared with 63% of the women, were in the contemplation stage, and 6% of the men and 5% of the women were classified as precontemplators. The findings indicated that health professionals need to provide interventions aimed at increasing the physical activity of Black students, especially women.

Adolescent↗
PubMed1998

Dietary monounsaturated fatty acids promote aortic atherosclerosis in LDL receptor-null, human ApoB100-overexpressing transgenic mice.

In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the dietary content of monounsaturated fatty acids but not of polyunsaturated fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experimental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including fat as 10% of energy, with 5 different fatty acid enrichment patterns including the following: saturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant differences (ANOVA, P<0. 0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922)=cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol were also found in the trans and cis mono and sat groups, and triacylglycerol concentrations were also elevated in all groups. High density lipoprotein cholesterol concentrations were consistently low (20 to 50 mg/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl ester concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mono (34.6)>n-6 poly (18. 3)=n-3 poly (9.7)=commercial diet (7.8). Therefore, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis development, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group.

Analysis of Variance↗
PubMed1997

FDG-positron emission tomography and invasive EEG: seizure focus detection and surgical outcome.

PURPOSE: To study the value of [18F]2-deoxyglucose (FDG)-positron emission tomography when surface ictal EEG is nonlocalizing. METHODS: FDG-PET scans were performed in 46 patients with complex partial seizures (CPS) not localized by ictal surface-sphenoidal video-EEG (VEEG) telemetry. Interictal PET was performed with continuous EEG monitoring, and images were analyzed with a standard template. Forty patients subsequently had subdural and 6 had depth electrodes (invasive EEG, IEEG); 22 had bilateral implants. A focus was detected in 40, and 35 had temporal lobectomy based on IEEG localization. RESULTS: There was a close association between IEEG and PET localization (p < 0.01): 26 patients had relative unilateral temporal FDG-PET hypometabolism, all had congruent IEEG, and 18 of 23 were seizure-free after temporal lobectomy. Five patients had unilateral frontotemporal hypometabolism (3 of 5 were seizure-free), 1 had frontal hypometabolism, and 14 had no lateralized PET abnormality (4 of 7 were seizure-free). Patients who became seizure-free had significantly higher lateral temporal asymmetry index (AI). PET showed > or = 15% relative temporal hypometabolism (AI) in 12 of 22 patients with nonlateralized surface ictal VEEG and was capable of distinguishing between frontal and temporal foci in 16 of 24 patients with lateralized, but not localized, surface ictal video-EEG. CONCLUSIONS: FDG-PET provides valuable data in patients with unlocalized surface ictal EEG and can reduce the number of patients who require IEEG studies. Quantitation is necessary for optimal PET interpretation.

Brain↗
PubMed1996

Characterization of an insulin-like growth factor binding protein-5 protease produced by rat articular chondrocytes and a neuroblastoma cell line.

Both articular cartilage and the central nervous system are target organs for insulin-like growth factors (IGFs). We have previously described the hormonal regulation of IGF binding proteins (IGFBPs) in the conditioned media (CM) of rat articular chondrocytes and in a rat neuroblastoma cell line (B104). In the studies presented here, we have investigated the role of IGFBP-5 proteases in these complex systems. Proteolysis of [125I] IGFBP-5 was maximal after 2-3 h incubation with CM of either cell type and did not further increase, even with an incubation of 12 h. Assessment of the effect of pH on protease activity showed that proteolysis was active between pH 6 and pH 9, but not at more acidic pH. Among the various protease inhibitors, serine protease inhibitors [benzamidine (100 mM), aprotinin (1 mg/ml), PMSF (10 mM)] and metalloprotease inhibitors [EDTA (1 mM), 1,10-phenanthroline (10 mM)] were the most effective in inhibiting the proteolysis of IGFBP-5, whereas aspartic and cysteine protease inhibitors were ineffective. These results indicate that the IGFBP-5 protease in the conditioned medium of rat articular chondrocytes and B104 cells belongs to a family of serine-metallo proteases. Interestingly, divalent cations, such as Zn+2 (1 mM) and Ca+2 (10 mM) also inhibited the IGFBP-5 proteolysis. This effect was not observed with monovalent ions, such as Na+ and K+. We also examined the effect of IGFs on IGFBP-5 protease activity, and found that IGF-I and -II inhibited the proteolysis in cell-free conditioned medium, while des(1-3) IGF-I was less effective. The IGFs may act to protect [125I] IGFBP-5 from the proteases in the CM, although the precise mechanism remains unknown. Thus, IGFBP-5 protease activity produced by both rat articular cartilage and B104 cells is a serine-metallo protease, that is inhibited by divalent cations and in the presence of IGF.

Animals↗
PubMed1995

Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS.

To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain.

Animals↗
PubMed1995

The Patient Self-Determination Act. A matter of life and death.

The Patient Self-Determination Act (PSDA) is a federal law, and compliance is mandatory. It is the purpose of this act to ensure that a patient's right to self-determination in health care decisions be communicated and protected. Through advance directives--the living will and the durable power of attorney--the right to accept or reject medical or surgical treatment is available to adults while competent, so that in the event that such adults become incompetent to make decisions, they would more easily continue to control decisions affecting their health care. Without advance directives and the proper adherence to such directives, former President Richard Nixon and former First Lady Jacqueline Kennedy Onassis might still be alive today, in persistent vegetative states. This article examines the history of the act, its importance to each individual, the clinical, ethical and legal issues, and the role of health care professionals in effectively implementing and ensuring compliance of the PSDA.

Advance Directives↗
PubMed1994

A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells.

Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this antitumor agent.

Amino Acid Sequence↗
PubMed1994

Postictal behavior. A clinical and subdural electroencephalographic study.

OBJECTIVE: To examine postictal behaviors after temporal lobe complex partial seizures (CPSs) and to correlate these behavioral phenomena with side of origin and ictal spread pattern. DESIGN: Review language and other behavioral phenomena after seizures defined by subdural electroencephalography. SETTINGS: A surgical epilepsy center. PATIENTS: We studied postictal behavior following 65 CPSs in 18 patients with left hemisphere language dominance using subdural electrode recordings. INTERVENTION: Subdural electrodes. MAIN OUTCOME MEASURES: Language function, affect, orientation, and postictal automatisms. RESULTS: Following the CPS ictal discharge, the mean interval for initial nonreflexive response to an environmental stimulus was 43 seconds (left foci, 57 seconds; right foci, 29 seconds; not significantly) and for first correct verbal response was 219 seconds (left foci, 275 seconds; right foci, 167 seconds; not significant). Impaired comprehension with fluent but unintelligible speech, as well as anomia, occurred after seizures arising from either temporal lobe. All nine seizures followed by global or nonfluent aphasia originated on the left side. Paraphasic errors were significantly more common after left temporal CPSs. Prolonged disorientation for place and flat affect were significantly more common after right temporal CPS. Postictal automatisms were frequent and included rubbing of the face, fumbling and picking hand movements, and repetitive oral movements. CONCLUSIONS: Postictal paraphasias, disorientation for place, and flat affect most likely reflect the functions of the area from which seizures arise but not the areas involved by spread.

Adolescent↗
PubMed1994

Novel soluble, high-affinity gastrin-releasing peptide binding proteins in Swiss 3T3 fibroblasts.

Swiss 3T3 cells contained substantial amounts of soluble and specific [125I]GRP binders. Like the membrane-associated GRP receptor, they were of high affinity, saturable, bound to GRP(14-27) affinity gels, and exhibited specificity for GRP(14-27) binding. They differed in that acid or freezing destroyed specific binding, specific binding exhibited different time and temperature effects, no detergent was required for their solubilization, ammonium sulfate fractionation yielded different profiles, the M(rs) were lower, GRP(1-16) also blocked binding, and a polyclonal anti-GRP receptor antiserum did not bind on Western blots. The isolated, soluble GRP binding protein(s) rapidly degraded [125I]GRP. These soluble GRP binding proteins may play a role in the regulation of the mitogenic effects of GRP on these cells.

3T3 Cells↗
PubMed1994

The secondarily generalized tonic-clonic seizure: a videotape analysis.

We studied 120 generalized tonic-clonic seizures (GTCSs) in 47 patients with video-EEG telemetry. GTCSs were preceded by antecedent seizures, including 13 simple partial, 70 complex partial, 17 simple partial leading to complex partial, seven tonic, seven clonic, and one typical absence. We divided GTCSs into the following phases: onset of generalization, pretonic clonic, tonic, tremulousness, and clonic. The mean GTCS duration was 62 seconds. There was a non-significant trend toward longer duration on reduced antiepileptic drug doses. Marked heterogeneity in GTCS phenomenology was present; only 27% of seizures included all five phases. Individual phase duration and clinical expression, including tonic and clonic phases, was highly variable. The clinical phenomena suggest that multiple cortical and subcortical routes of spread may exist. When GTCSs last longer than 2 minutes, intravenous antiepileptic drug treatment should be initiated.

Adolescent↗
PubMed1994

Mechanisms associated with human alveolar macrophage stimulation by particulates.

Asbestos and silica are well-known fibrogenic dusts. However, there is no comprehensive understanding of the molecular and cellular events that lead to fibrosis as a consequence of asbestos or silica inhalation. Previous studies have shown that asbestos stimulates superoxide anion production in alveolar macrophages through the phospholipase C/protein kinase C pathway. In contrast, silica does not appear to activate this pathway nor stimulate superoxide anion production, but silica does stimulate cytokine release by some undetermined pathway. Therefore, using human alveolar macrophages isolated from normal healthy volunteers, we evaluated the potential involvement of intracellular calcium and tyrosine kinases as potential signal transduction pathways. In the absence of serum, crystalline silica, and to a lesser extent amorphous silica, caused a rapid and dose-dependent elevation of intracellular calcium coming from the extracellular space. However, in the presence of serum, which is required for silica-stimulated cytokine release, neither form of silica caused noticeable elevation of intracellular calcium. Silica, however, did increase the extent of tyrosine phosphorylation, most notably of proteins at approximately 46 and 50 kDa, suggesting activation of a tyrosine kinase pathway. Preincubation of alveolar macrophages for 24 hr with silica-primed human alveolar macrophages for enhanced interleukin-1 beta (IL-1 beta) release stimulated by endotoxin (LPS) that was dose dependent. The enhanced LPS-stimulated release of IL-1 beta correlated with enhanced mitogen-activated protein kinase activity. Taken together, these results indicate that a tyrosine kinase pathway is activated during silica stimulation of human alveolar macrophages.

Calcium↗
PubMed1994

Fluorescence in situ hybridization of interphase nuclei isolated from whole blood of transgenic mice.

Homozygosity in transgenic mice is typically confirmed by the time-consuming practice of breeding suspected homozygotes to non-transgenics and looking for 100% transmittance of the transgene to offspring. We have devised a simple reproducible method for isolating white blood cell nuclei from small quantities of mouse whole blood and have utilized fluorescence in situ hybridization to confirm the presence of one (hemizygous) or two (homozygous) copies of the transgene locus in interphase nuclei fixed to microscope slides. This method should have other applications where in situ hybridization of interphase nuclei is desirable.

Animals↗
PubMed1993

Quantitative assessment of human fetal renal blood flow.

OBJECTIVE: Our purpose was to longitudinally quantify human fetal renal blood flow. STUDY DESIGN: Twenty-two normal fetuses underwent a color-pulsed Doppler evaluation of the renal artery. The Doppler waveforms were digitized to assess the velocity-time integral. The size of the vessel was determined during systole with color high-resolution two-dimensional ultrasonography. Renal blood flow was estimated by multiplying the time-velocity integral (i.e., area under the curve) by the area of the renal artery. The combined cardiac output was calculated by adding right and left inflow Doppler-derived volumes. RESULTS: Renal artery size, peak flow velocity, time-velocity integral, and renal blood flow significantly increased with advancing gestational age. The resistivity indexes, such as the systolic/diastolic ratio or the Pourcelot index of the fetal renal artery, did not significantly change with advancing gestational age. The pulsatility index, however, was correlated with gestational age. The percentage of the combined cardiac output to the fetal kidney remained constant throughout gestation. CONCLUSIONS: Color pulsed Doppler can be used to visualize small and deep vascular structures in the human fetus. Renal blood flow increased with advancing gestational age. This increase seems to be related to the increase in the combined cardiac output.

Blood Flow Velocity↗