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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 127 records · Page 7Linked to original sources
PubMed1997

KDEL receptor expression is not coordinatedly up-regulated with ER stress-induced reticuloplasmin expression in HeLa cells.

Perturbation of the normal functioning of the endoplasmic reticulum (ER) increases the expression of lumenal proteins, such as grp78, and calreticulin. These proteins are retained within the compartment by a salvage mechanism involving the recognition of a C-terminal tetra-peptide sequence by the KDEL receptor. We have investigated whether disrupting normal ER function concomitantly increases the expression of the mRNAs encoding the two mammalian isoforms of the receptor, erd2.1 and erd2.2. Inhibition of N-linked glycosylation of proteins by tunicamycin had no effect upon the levels of the single mRNA species recognized by the erd2.1 probe, or the multiple transcripts detected with the erd2.2 cDNA probe. ER Ca2+ store depletion by thapsigargin did not increase erd2.1 mRNA, but actually caused a decrease in erd2.2 mRNA. Both thapsigargin, and tunicamycin, increased calreticulin secretion from the cells, although this might be due to more than simply saturation of KDEL receptor binding.

Calcium-Binding Proteins↗
PubMed1997

Comparison of patients with syncope of unknown cause having negative or positive tilt-table tests.

Many patients without an identified cause of syncope have negative tilt tests. We hypothesized that many of these might be falsely negative tilt tests. If so, then patients with negative and positive tilt tests should have similar pretest clinical characteristics, post-test probabilities of remaining free of syncope, and similar risk factors for syncope recurrence after the tilt-table test. Demographic characteristics and historic features were compared between 153 syncope patients with a positive tilt test, and 74 syncope patients with a negative tilt test and no obvious cause of syncope. Patients with negative and positive tests had similar numbers of syncopal spells, durations of symptoms, frequency of spells, and peak heart rate during tilt test, but patients with negative tests were older (48 +/- 19 vs 39 +/- 20 years). The actuarial probabilities of remaining free of syncope were very similar, with 2-year risks of syncope of 41% and 37% in patients with negative and positive tests, respectively. The regression coefficients of risk factors predicting syncope recurrence were similar for both populations, and the confidence intervals of all regression coefficients decreased when the populations were combined. The outcome of tilt testing did not predict the clinical outcome of patients. Patients with syncope and either negative or positive tilt tests share many pretest and post-test clinical characteristics, suggesting that they may be part of the same population.

Aged↗
PubMed1997

Purification and characterization of sn-1-stearoyl-2-arachidonoylglycerol kinase from pig testes.

1-Stearoyl-2-arachidonoylglycerol (SAG) kinase was identified in the particulate fraction of pig testes. This activity was enriched by hydroxyapatite and blue dye chromatography. The enzyme was selective for polyunsaturated diradylglycerol species and activity was not modulated by other diradylglycerol species or sphingomyelin metabolites. Further purification resulted in the isolation of 55 and 50 kDa proteins that corresponded with SAG kinase activity. These results support the view that the phosphorylation of polyunsaturated diradylglycerol is regulated by structural determinants in the molecule.

Animals↗
PubMed1997

Role of platelet-activating factor in hepatocellular Ca2+ alterations during hemorrhagic shock.

A role of the potent proinflammatory Ca2+ agonist platelet-activating factor (PAF) on hepatocellular Ca2+ homeostasis and oxidant injury was investigated, since Ca2+ dysregulation has been demonstrated as a pivotal pathomechanism causing hepatic dysfunction during hemorrhagic or septic shock. In anesthetized male Sprague-Dawley rats, blood was withdrawn to a mean arterial blood pressure of 40 mm Hg for 60 min. Rats were resuscitated with 60% of shed blood and threefold the shed blood volume of lactated Ringers' (shock group). After 60 min of resuscitation, hepatocytes were isolated by portal collagenase perfusion. Hepatocellular Ca2+ uptake (Caup2+), initial rate of Ca2+ influx (Cain2+), and membrane Ca2+ flux (Caflux2+) were determined using 45Ca2+ incubation techniques. Hepatocyte oxidant injury was fluorometrically determined by thiobarbituric acid reactive substances. Caup2+ (3.37 +/- 0.15 vs. 2. 53 +/- 0.08 nmole Ca2+/mg protein), Cain2+ (0.42 +/- 0.1 vs. 0.27 +/- 0.02 nmole Ca2+/mg protein/min), and Caflux2+ (31.3 +/- 4.3 vs. 16.9 +/- 2.4 pmole Ca2+/mg/min) significantly increased in the untreated shock group compared to untreated sham-operated rats (P < 0.05). The specific PAF receptor antagonist BN52021 given 5 min before (5 mg/kg b.w.) and continuously during resuscitation (5 mg/kg/hr) significantly reduced Caup2+ in the shock group (2.73 +/- 0.2; P < 0.01) and prevented hepatocyte lipid peroxidation (shock: 91.9 +/- 1; shockBN52021: 66.7 +/- 2 nmole/mg wet weight; P < 0.01). These data suggest that platelet-activating factor plays a pivotal role in promoting hepatocyte Ca2+ overload during hemorrhagic shock by releasing Ca2+ agonistic mediators and inducing oxidative membrane alterations both of which are capable of enhancing cellular Ca2+ influx.

Animals↗
PubMed1997

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain.

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug.

Animals↗
PubMed1997

Extent of Barrett's metaplasia: a prospective study of the serial change in area of Barrett's measured by quantitative endoscopic imaging.

BACKGROUND: An accurate determination of the extent of Barrett's metaplasia is critical to the study of its natural history and response to therapy. Our hypothesis is that area calculations offer advantages over length estimates of Barrett's. METHODS: Changes in both measures and estimates of progression or regression between two endoscopies in 17 patients were compared. Area was calculated using a computer image analysis technique. RESULTS: Although there was no significant difference in length correlation versus area correlation between endoscopies (r = 0.90 vs 0.99), the mean change in absolute length (1.4 +/- 0.2 cm) was greater than the change in area (4.5 +/- 1.4 cm2, equivalent to a length of 0.67 +/- 0.2 cm, p = 0.001). The percent change in absolute length (26.9%) was greater than the change in area (16%, p = 0.001). Discordance of estimates of progression or regression between area and length was found in nine patients. The image technique detected no change in the area of squamous islands. CONCLUSIONS: Imaging analysis can precisely measure the extent of Barrett's including squamous islands. Area showed little change, whereas measures of length were more varied. Computer based image analysis provides a more precise estimate of interval change of Barrett's.

Adolescent↗
PubMed1997

Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the progression of chronic myelogenous leukemia from diagnosis to blastic phase.

Chronic myelogenous leukemia (CML) has a progressive course but little is known about the biologic characteristics of disease progression. This study was designed to assess the changes in cell proliferative characteristics, apoptosis, the expression of the bcl-2 and c-myc genes between the time of initial diagnosis and entrance into the blastic phase of the disease. We observed that the rate of cell proliferation decreased and the cell death rate did not significantly change as the disease accelerated. The level of bcl-2 expression was significantly higher in accelerated/blastic phase cells than in the chronic phase cells in the population as a whole, however, the bcl-2 expression level did not change in blast cell subpopulation. c-myc Expression was significantly higher in the blast cell subpopulation of accelerated/blastic phase than in that of earlier phases of the disease. In conclusion, the characteristics of CML cells, namely proliferation rate, c-myc and bcl-2 change during the course of the disease. It is possible that the change in c-myc expression plays a causative role in evolution of the blastic phase from the chronic phase.

Adult↗
PubMed1997

Altered hepatocellular Ca2+ regulation during hemorrhagic shock and resuscitation.

The present study evaluated the effect of the benzothiazepine Ca2+ channel blocker diltiazem (DZ) on altered hepatocellular Ca2+ regulation and oxidant injury during hemorrhagic shock/resuscitation. In anesthetized, male Sprague-Dawley rats, hemorrhagic shock was induced by rapid blood withdrawal and maintaining the mean arterial blood pressure at 40 mm Hg over 60 minutes. Rats were then resuscitated with 60% of shed blood and threefold the shed blood volume of Ringer's lactate. At the end of ischemia, and 60 or 300 minutes after resuscitation, hepatocytes were isolated by liver collagenase perfusion. Hepatocellular Ca2+ exchange (Ca2+ex), rate of cellular Ca2+ influx (Ca2+in), and Ca2+ membrane flux (Ca2+flux) were determined using 45Ca incubation techniques. Hepatocyte oxidant injury was evaluated by fluorometrically measuring thiobarbituric acid reactive substances and oxidized/reduced glutathione. Both hemorrhage and hemorrhage/resuscitation increased hepatocellular Ca2+in, Ca2+ex, and Ca2+flux. In contrast to control and sham-operated rats, in vitro stimulation by the Ca2+ agonist epinephrine (100 nmol/L) of hepatocytes from either hemorrhaged or resuscitated rats did not further increase Ca2+in. Administration of DZ (.8 mg/kg) with resuscitation significantly decreased cellular Ca2+ex and Ca2+flux, but did not restore impaired epinephrine-induced Ca2+in. DZ prevented hepatocyte lipid peroxidation and glutathione oxidation. These findings suggest hepatocellular Ca2+ overload and impaired Ca2+ signaling during hemorrhage/resuscitation. Increased Ca2+ uptake could be because of a receptor-gated Ca2+ influx and/or oxygen-free radical induced membrane Ca2+ leaks.

Animals↗
PubMed1997

Superoxide radical scavenging prevents cellular calcium dysregulation during intraabdominal sepsis.

The role of superoxide in sepsis-altered hepatocyte Ca2+i regulation was studied by examining the effect of treatment of septic rats with superoxide dismutase-polyethylene glycol (SOD-PEG) on hepatocyte Ca2+ influx and efflux, and cytosolic [Ca2+]. Rats were implanted with sterile or bacteria-laden (Escherichia coli and Bacteroides fragilis) fecal pellets into the abdominal cavity. Eight hours after the implantation, rats were treated with SOD-PEG or its vehicle PEG. Septic and sterile implanted rats were killed 24 h postimplantation, and their livers were removed to isolate viable hepatocytes. Isolated hepatocytes were incubated with traces of 45Ca to assess Ca2+ influx and efflux. The 45Ca exchange assessments also allowed calculation of the intracellular exchangeable Ca2+ contents. [Ca2+]i was quantified by the use of fluorescent dye indo-1 and microfluorometric techniques. There were no differences in the Ca2+ influx, Ca2+ efflux, intracellular exchangeable Ca2+, or [Ca2+]i between the treated or untreated sterile and unoperated controls. However, compared with the nonseptic groups, the septic rats with or without administration of the vehicle (PEG) showed marked increases in Ca2+ influx, intracellular exchangeable Ca2+ and [Ca2+]i but not Ca2+ efflux. When challenged with vasopressin, the hepatocytes from septic rats, administered with PEG alone, did not elevate their [Ca2+]i as was characteristic of the hepatocytes from the nonseptic rats. The treatment of septic rats with SOD-PEG was effective in restoring Ca2+ influx, cellular exchangeable Ca2+, [Ca2+]i, and the [Ca2+]i response to vasopressin to levels found in the control and sterile groups. These findings support the concept that the generation of the superoxide free radical leads to Ca2+i-related derangements and related cell/organ dysfunction in sepsis.

Abdomen↗
PubMed1997

Fostering reader response and developing comprehension strategies in deaf and hard of hearing children.

In response to the increasing use of children's trade books in school reading programs, this article reviews the use of real text, drawing on the application and interaction of two distinct perspectives: reader response theory and comprehension instruction. The authors propose the need to combine knowledge of instruction with the new focus on the role of the reader within response theory and within comprehension research. This article suggests how comprehension instruction and response to literature activities can intersect in the classroom for students who are deaf or hard of hearing. Explicit models and instructional strategies are discussed in the framework of this bimodal approach to reading. A sample list of high quality children's books, including several trade books that feature deaf or hard of hearing characters and issues, is provided as a resource for teachers.

Child↗
PubMed1997

Anal sphincter structure and function in homosexual males engaging in anoreceptive intercourse.

OBJECTIVES: To evaluate the structure and function of the internal (IAS) and external (EAS) anal sphincters in anoreceptive homosexual men and to determine whether anoreceptive intercourse (ARI) is associated with a higher risk of incontinence in this population. METHODS: We studied 14 anoreceptive homosexual males and 10 age-matched non-anoreceptive heterosexual males in a controlled, prospective cohort study. Subjects underwent evaluation of resting and maximum squeeze anal canal pressures (maximum squeeze pressure obtained over resting pressure) by station pull-through technique, using a manometric perfusion catheter followed by endoanal ultrasonography to evaluate the structure of the IAS and EAS. Manometry also was performed in age-matched male controls. All subjects completed a questionnaire that assessed sexual practices and bowel habits, including fecal incontinence. RESULTS: Resting pressures were significantly lower in subjects engaging in ARI (70.7 +/- 3.2 mm Hg vs. 91.4 +/- 5.2 mm Hg; mean +/- SEM, p < 0.003), whereas there was no significant difference in the mean maximum squeeze pressures, compared with controls (177.1 +/- 14.1 mm Hg vs. 151.8 +/- 19.6 mm Hg; mean +/- SEM, p = 0.32). No disruptions of the IAS or EAS were identified in either the anoreceptive or control group. Anoreceptive men tended to have thinner anal sphincters than controls, but the difference was not statistically significant. Furthermore, there were no complaints of fecal incontinence by the study subjects. CONCLUSIONS: Passive ARI is associated with decreased resting anal canal pressures, but total pressures are normal. There were no IAS or EAS defects, as well as no fecal incontinence, in our subjects. Better relaxation of the ARI subjects during anal canal manometry may explain the lower resting pressures.

Adolescent↗
PubMed1996

Circulating human mononuclear cells exhibit augmented lysis of pig endothelium after activation with interleukin 2.

In immunohistochemical studies investigating the cellular infiltrates in pig xenografts undergoing delayed rejection by newborn and adult primate recipients, we observed extensive infiltration with primate macrophages and natural killer (NK) cells. To extend these studies in vitro, we investigated the functional properties of human NK cell precursors with respect to their potential interactions with pig aortic endothelial cells (PAEC). Using a short-term 51Cr release assay, human peripheral blood mononuclear cells (PBMC) demonstrated spontaneous and interleukin (IL) 2 augmented lytic activity against PAEC which increased with increasing effector to target cell ratio. Treatment of human PBMC with anti-CD2 significantly reduced this NK lytic activity by IL-2-activated PBMC. Finally, we investigated the effects of PAEC treatment with certain macrophage-derived human cytokines on adhesion of IL-2-activated human PBMC. Treatment of PAEC with IL-1 and tumor necrosis factor-alpha, in a dose-dependent manner, increased adherence of IL-2-activated human PBMC. These results demonstrate that humans contain circulating NK cells capable of lysing PAEC after activation with IL-2, that the mechanism involves interactions between CD2 and its ligand on porcine endothelium, and that these interactions may be influenced by macrophage-derived cytokines produced at the site of xenograft rejection.

Animals↗
PubMed1996

Isoproterenol tilt-table testing in patients with syncope and structural heart disease.

We studied 55 patients with syncope and structural heart disease using both tilt-table testing and electrophysiologic studies. Although sustained ventricular tachycardia was found in 21 of 55 patients (38%), and neuromediated syncope in 18 of 51 patients (35%), only 16% of patients with ventricular tachycardia had a positive tilt-table test.

Adrenergic beta-Agonists↗
PubMed1996

Effect of beta blockers on the time to first syncope recurrence in patients after a positive isoproterenol tilt table test.

Isoproterenol-headup tilt table testing provides a diagnosis of neuromediated syncope in many patients who faint. The involvement of beta-adrenoceptor stimulation in the provocation of syncope suggests that beta blockers might chronically prevent syncope. To assess this, a cohort of 153 syncope patients (age 39 +/- 20 years) underwent baseline assessment of demographic variables, symptomatic burden, and hemodynamic and clinical responses to tilt testing. Fifty-two patients then received beta blockers, and 101 did not receive drug therapy. The primary outcome was the time to the first recurrent syncopal spell. Actuarial survival analysis was used. Syncope recurred in 17 of 52 patients who received beta blockers and in 28 of 101 patients who were untreated. The actuarial probability of remaining free of syncope was similar in both groups. For example, the probability of remaining free of syncope 12 months following the tilt test was 0.72 in both populations. Thus, treatment with beta blockers may not have a significant effect in preventing syncope recurrence following a positive tilt test.

Adolescent↗
PubMed1996

Formation of chimeric DNA primer extension products by template switching onto an annealed downstream oligonucleotide.

Oligodeoxynucleotide sequences are described that anneal to a template downstream of a priming site. During polymerase-catalyzed extension of the primer, the extending primer shifts from the original template to a segment of the annealed oligonucleotide that acts as an alternative template. The resulting chimeric extended primer has one segment that is complementary to the template and a second segment that is complementary to the oligonucleotide. The influence of the sequence elements of the oligonucleotide and the reaction conditions on template switching have been explored. The sequence requirements for template switching are compared to those for transposon excision.

Base Sequence↗
PubMed1996

Risk factors for syncope recurrence after a positive tilt-table test in patients with syncope.

BACKGROUND: Recent work with head-up tilt-table testing has suggested that many patients with syncope may have recurrent neurally mediated episodes of bradycardia, hypotension, or both. The purpose of this study was to determine how to identify patients at high risk of a recurrence of neuromediated syncope after a positive isoproterenol/tilt-table test. METHODS AND RESULTS: A cohort of 101 drug-free patients in a university hospital outpatient clinic with syncope and a positive isoproterenol/tilt-table test underwent baseline assessment of demographic variables, symptomatic burden, and hemodynamic and clinical responses to tilt testing. The primary outcome measure was the time to the first recurrent syncopal spell. The actuarial probabilities of remaining syncope free after 1 and 2 years were 72% and 60%, respectively. Multivariate proportional hazards analysis demonstrated that the most powerful predictor of a recurrence of syncope was the logarithm of the number of preceding syncopal spells (P<.001). Other predictive variables included the duration of syncopal symptoms, tilt test symptomatic outcome, and trough heart rate. The probability of a recurrence of syncope also varied with the logarithm of the frequency of preceding spells (P=.008). The median frequency of pretest spells was 0.3/month; after the tilt test, the median frequency dropped approximately 90% to 0.03 per month. CONCLUSIONS: The risk of a recurrence of syncope after a positive tilt-table test can be predicted with simple pretest and intratest variables.

Adult↗