Biomedical subjects

D L Jones

Publications and source records attributed to D L Jones.

At least 55 records · Page 3Linked to original sources

PubMed1998

Systemic gabapentin and S(+)-3-isobutyl-gamma-aminobutyric acid block secondary hyperalgesia.

Gabapentin (GBP) and S(+)-3-isobutyl-gamma-aminobutyric acid (IBG) are anticonvulsant agents which are effective against many clinical and experimental neuropathic pain states. We examined the efficacy of these agents in a new rat model of secondary mechanical hyperalgesia generated by a mild thermal injury. Under brief halothane anesthesia, an injury was induced by applying one heel to a hot surface (52.5 degreesC) for 45 s. GBP, IBG or saline was injected i.p. just prior to the injury. Mean mechanical withdrawal threshold (MWT) was determined using von Frey hairs before and at 30 min intervals for 3 h following the injury. MWT outside the injury area decreased post-injury (secondary hyperalgesia, allodynia), but primary (site of injury) mechanical hyperalgesia was not observed. Secondary hyperalgesia exhibited a tendency toward recovery over time. Time to onset of the anti-allodynic effect of GBP was 30-60 min. The minimum effective GBP dose was 100 mg/kg; 300 mg/kg GBP totally inhibited the drop in MWT, but was accompanied by pronounced sedation. Anti-allodynic effects of IBG were apparent at the first post-injury measure of MWT (30 min). Thirty milligrams per kilogram was the minimum effective dose; 100 mg/kg IBG totally blocked the allodynia with minimal side effects. Our findings demonstrate a dose-dependent blockade of the mechanical sensitivity caused by a mild thermal injury by both GBP and IBG. Results indicate that IBG is more effective than GBP in this model at doses which do not cause sedation. These observations support the suggested use of these or related gamma-amino acid analogues as an effective treatment for post-operative pain.

Acetates↗

PubMed1998

Effect of aluminum on cytoplasmic Ca2+ homeostasis in root hairs of Arabidopsis thaliana (L.).

Aluminum inhibition of root growth is a major world agricultural problem where the cause of toxicity has been linked to changes in cellular calcium homeostasis. Therefore, the effect of aluminum ions (Al) on changes in cytoplasmic free calcium concentration ([Ca2+]c) was followed in root hairs of wild-type, Al-sensitive and Al-resistant mutants of Arabidopsis thaliana (L.) Heynh. Generally, Al exposure resulted in prolonged elevations in tip-localized [Ca2+]c in both wild-type and Al-sensitive root hairs. However, these Al-induced increases in [Ca2+]c were not tightly correlated with growth inhibition, occurring up to 15 min after Al had induced growth to stop. Also, in 32% of root hairs examined growth stopped without a detectable change in [Ca2+]c. In contrast, Al-resistant mutants showed little growth inhibition in response to AlCl3 exposure and in no case was a change in [Ca2+]c observed. Of the other externally applied stresses tested (oxidative and mechanical stress), both were found to inhibit root hair growth, but only oxidative stress (H2O2, 10 microM) caused a prolonged rise in [Ca2+]c similar to that induced by Al. Again this increase occurred after growth had been inhibited. The lack of a tight correlation between Al exposure, growth inhibition and altered [Ca2+]c dynamics suggests that although exposure of root hairs to toxic levels of Al causes an alteration in cellular Ca2+ homeostasis, this may not be a required event for Al toxicity. The elevation in [Ca2+]c induced by Al also strongly suggests that the phytotoxic action of Al in root hairs is not through blockage of Ca2(+)-permeable channels required for Ca2+ influx into the cytoplasm.

Aluminum↗

PubMed1998

Role of octreotide on release of intact 1-84 parathyroid hormone from human parathyroid cells.

BACKGROUND: Octreotide has been shown to lower urinary calcium in primary hyperparathyroidism although the mechanism remains unclear. This study examined the effect of octreotide on parathyroid hormone (PTH) secretion from human parathyroid cells in culture and as isolated cells. Additionally in situ hybridization was performed for somatostatin receptor messenger RNA (mRNA) and immunocytochemistry for somatostatin in eight parathyroid adenomas. METHODS: Tissue from three hyperplastic glands and three adenomas was studied as dispersed cell suspensions. Incubation was in buffers containing high (2.0 mmol/l) and low (0.5 mmol/l) calcium concentrations, with or without octreotide 200 ng/ml. Cells were also seeded into tissue culture wells for 24 h to allow receptors to regenerate. Supernatant was removed at regular intervals and PTH levels were estimated using a two-site chemiluminescent assay. RESULTS: Mean(s.e.m.) PTH secretion at 90 min in hyperplastic cells was 445(75) pmol/l in low calcium and 160(42) pmol/l in high calcium (P< 0.02), and in adenoma cells was 170(21) pmol/l in low calcium and 137(27) pmol/l in high calcium (P=0.37). There was no significant difference in secretion of PTH from cells incubated with octreotide either in culture or as dispersed cells. In situ hybridization failed to demonstrate any mRNA for the somatostatin receptors and no somatostatin was detected in any cells with immunocytochemistry. CONCLUSION: Somatostatin has no direct action on PTH production and release from human parathyroid cells and is unlikely to be of any therapeutic value in the treatment of hyperparathyroidism.

Adenoma↗

PubMed1998

A comparison of physicians' and patients' attitudes toward pharmaceutical industry gifts.

OBJECTIVE: To compare physicians' and their patients' attitudes toward pharmaceutical gifts. DESIGN: Survey of physicians and their patients. SETTING: Two tertiary-care medical centers, one military and one civilian. PARTICIPANTS: Two hundred sixty-eight of 392 consecutively surveyed physicians, 100 of 103 randomly selected patients at the military center, and 96 patients in a convenience sample at the civilian center completed the survey. MEASUREMENTS: Participants rated 10 pharmaceutical gifts on whether they were appropriate for physicians to accept and whether they were likely to influence prescribing. Patients found gifts less appropriate and more influential than did their physicians. About half of the patients were aware of such gifts; of those unaware, 24% responded that this knowledge altered their perception of the medical profession. Asked whether they thought their own physician accepted gifts, 27% said yes, 20% no, and 53% were unsure. For patients, feeling that gifts were inappropriate was best predicted by a belief that gifts might influence prescribing, while for physicians, the best predictor was knowledge of guidelines. CONCLUSIONS: Patients feel pharmaceutical gifts are more influential and less appropriate than do their physicians. Physicians may want to consider this in deciding whether to accept particular gifts. Broader dissemination of guidelines may be one means of changing physician behavior. At the same time, future guidelines should further consider the potentially different viewpoints of patients and physicians.

Attitude of Health Personnel↗

PubMed1998

The high-risk sexual practices of crack-smoking sex workers recruited from the streets of three American cities. The Multicenter Crack Cocaine and HIV Infection Study Team.

BACKGROUND AND OBJECTIVES: Small ethnographic and clinic-based studies indicate that crack-smoking sex workers are at high risk for human immunodeficiency virus (HIV) and sexually transmitted diseases (STD). STUDY GOALS: To examine the prevalence of risky sexual behaviors and HIV and STD in a large sample of street-recruited crack-smoking sex workers. STUDY DESIGN: From 1991 to 1992, 419 crack-smoking sex workers were recruited from urban neighborhoods, interviewed, and serologically tested. RESULTS: Many female and male sex workers reported sex with injectors (30% to 41%) or HIV-infected persons (8% to 19%), past STD (73% to 93%), and inconsistent condom use (> 50% for all types of sex). Sex workers who worked in crack houses or vacant lots, were paid with crack, or injected drugs had the riskiest sex practices. Most sex workers initiated sex work before they first smoked crack. More than 25% were infected with HIV (27.9%), syphilis (37.5%), or herpes simplex virus type 2 (66.8%). CONCLUSIONS: Interventions to prevent HIV/STD transmission among crack-smoking sex workers are urgently needed.

Adult↗

PubMed1998

Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction.

Presently, the only therapy for ventricular fibrillation is delivery of high-voltage shocks. Despite "successful defibrillation," patients may have poor cardiac contractility, the mechanisms of which are unknown. Intracellular Ca2+ handling by the sarcoplasmic reticulum (SR) plays a major role in contractility. We tested the hypothesis that defibrillation shocks interfere with Ca2+ transport function of cardiac SR. Rats anesthetized with pentobarbital sodium had bilateral electrodes implanted subcutaneously for transthoracic shocks. A series of 10 shocks, 10 s apart, at 0-250 V was delivered from a trapezoidal defibrilator. The hearts were rapidly removed, SR-enriched membrane vesicles were isolated, and ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATP hydrolysis were determined. There was a marked, shock-related decline in Ca2+ uptake, whereas adenosinetriphosphatase activity remained unaltered. The polypeptide compositions were similar in control and shocked SR. In Langendorff hearts, shocks also decreased contractility and slowed relaxation. These data indicate that shocks with current densities similar to defibrillation depress Ca(2+)-pumping function of cardiac SR because of uncoupling of ATP hydrolysis and Ca2+ transport. Shock-induced impairment of Ca2+ pump function may underlie postshock myocardial dysfunction.

Animals↗

PubMed1998

Differential diagnosis of the hip vs. lumbar spine: five case reports.

With recent health care policy changes and the implementation of direct access in many states, physical therapists must be able to identify pathology that is beyond their scope of practice. The five case reports presented in this series required the differential diagnosis of hip vs. lumbar spine pathology. All of the cases required a referral from the physical therapist to either the patient's physician or a specialist because of abnormal screening test results. Each referral resulted in a new diagnosis of pathology that was beyond the scope of physical therapy. Cyriax's concepts of capsular and noncapsular patterns of joint restriction and the "Sign of the Buttock" proved useful in differentiating between hip and lumbar spine pathology in each patient. Our clinical experience indicates that utilizing the presence/absence of a capsular pattern and a "Sign of the Buttock" to screen out hip pathology in patients may be effective; however, further research is needed to support these claims.

Adult↗

PubMed1997

The human papillomavirus-16 E6 oncoprotein decreases the vigilance of mitotic checkpoints.

The E6 and E7 proteins of the high risk human papillomaviruses (HPVs) are consistently expressed in HPV-positive cervical carcinomas. We investigated the ability of HPV-16 E6 and E7 to disrupt mitotic checkpoints in normal diploid human cells. Acute expression of HPV-16 E6, but not HPV-16 E7, decreased the fidelity of multiple checkpoints controlling entry into and exit from mitosis. After irradiation, nearly 50% of cells containing HPV-16 E6 readily entered mitosis as opposed to less than 10% of control cells. Consistent with this, asynchronous populations of cells expressing HPV-16 E6 had increased cdc2-associated histone H1 kinase activity relative to control populations. In addition, HPV-16 E6 increased sensitivity to chemically-induced S-phase premature mitosis and decreased mitotic spindle assembly checkpoint function relative to control populations. HPV-16 E6 mutants with a reduced ability to target p53 for degradation were unable to abrogate mitotic checkpoints, suggesting a possible mechanism by which HPV-16 E6 disrupts mitotic checkpoints. Expression of a mutant p53 gene yielded an intermediate phenotype relative to HPV-16 E6, generating moderate increases in sensitivity to chemically-induced S-phase PCC and mitotic spindle disruption and a heightened propensity to enter mitosis after irradiation.

CDC2 Protein Kinase↗

PubMed1997

Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis.

Cells that express the human papillomavirus (HPV) type 16 E7 oncoprotein are predisposed to undergo apoptosis. Transgenic mice that have E7 expression targeted to either the retinal photoreceptor cells or the lens cells exhibit signs of apoptosis in cells attempting to undergo differentiation. We established a cell culture system to study this process and have determined the domains of E7 that are required for predisposing cells to undergo apoptosis in response to growth arrest signals. Regions within the core pRB binding site of E7 were necessary but not sufficient for inducing apoptosis. Residues within the adenovirus conserved region 1 homology domain and the consensus casein kinase II phosphorylation site are also important for this effect on cell viability. Our data also demonstrate that the ability of E7 to induce destabilization of pRB and stabilization of p53 coincides with E7-mediated transformation and apoptosis.

Animals↗

PubMed1997

The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2.

The high risk human papillomaviruses (HPVs) are associated etiologically with the majority of human cervical carcinomas. These HPVs encode two viral oncoproteins, E6 and E7, which are expressed consistently in cervical cancers. The function of these viral oncoproteins during a productive infection is to ensure viral replication in cells that have normally withdrawn from the cell division cycle and are committed to terminal differentiation. Expression of the E7 oncoprotein has been shown to lead to the abrogation of various negative growth regulatory signals, including a p53-mediated G1 growth arrest, TGFbeta-mediated growth inhibition, and quiescence of suprabasal keratinocytes. Here we describe a novel mechanism by which E7 can uncouple cellular proliferation and differentiation. In contrast to normal, differentiating keratinocytes, HPV-16 E7-expressing keratinocytes show delayed cellular differentiation and elevated cdk2 kinase activity despite high levels of p21(Cip1) and association of p21(Cip1) with cdk2. We show that the HPV E7 protein can interact with p21(Cip1) and abrogate p21(Cip1)-mediated inhibition of cyclin A and E-associated kinase activities. Based on these findings, we propose that this capacity of the HPV E7 oncoprotein to overcome p21(Cip1)-mediated inhibition of cdk2 activity during keratinocyte differentiation contributes to the ability of E7 to allow for cellular DNA synthesis in differentiated keratinocytes.

Animals↗

PubMed1997

Eliminating unnecessary lactate dehydrogenase testing. A utilization review study and national survey.

BACKGROUND: Consensus recommendations call for the elimination of lactate dehydrogenase (LDH) tests from routine rule out myocardial infarction (ROMI) protocols. METHODS: We conducted a utilization review project in which we evaluated the institutional impact of removing LDH and LDH isoenzyme tests from our hospital diagnostic panel. We then conducted a scripted telephone survey of 100 US hospitals to assess the generalizability of this project. RESULTS: All our cardiology staff members supported this intervention. Lactate dehydrogenase isoenzyme test results did not add clinically useful data for any of 200 consecutive patients discharged with a diagnosis of acute myocardial infarction, and selective use of LDH isoenzyme testing in cases where it was clinically believed to be indicated cut costs 99% during the year after our intervention. Furthermore, our telephone survey demonstrated that 66% of US hospitals polled continue to test for LDH isoenzymes in every patient with possible myocardial infarction. CONCLUSIONS: Our results corroborate prior recommendations for the removal of LDH testing from the routine ROMI protocol. Such an intervention may be accomplished easily, with excellent staff acceptance and considerable savings. Most US hospitals continue to include LDH testing in their ROMI panels despite national guidelines recommending otherwise.

Clinical Enzyme Tests↗

PubMed1997

Aluminum interaction with plasma membrane lipids and enzyme metal binding sites and its potential role in Al cytotoxicity.

The trivalent cation aluminum can cause chronic cytotoxicity in plants, animals and microorganisms. It has been suggested that Al interaction with cell membranes and enzyme metal binding sites may be involved in Al cytotoxicity. In this study, the binding of Al to microsomes and liposomes was found to be lipid dependent with the signal transduction element phosphatidylinositol-4,5-bisphosphate having the highest affinity for Al with an Al:lipid stoichiometry of 1:1. Al binding was only reduced in the presence of high concentrations of Ca2+ (> 1 mM). Both citrate and, to a lesser extent, malate were capable of preventing Al lipid binding, which is consistent with the involvement of these organic acids in a recently described Al detoxification mechanism in plants. The effects of AICl3, Al-citrate and ZnSO4 on metal-dependent enzyme activities (enolase, pyruvate kinase, H+-ATPase, myosin, Calpain, proteinase K, phospholipase A2 and arginase) was assayed in vitro. While Zn2+ was capable of inhibiting all the enzymes except the H+-ATPase, AlCl3 and Al-citrate had minimal effects except for with phospholipase A2 where an interaction with AlCl3 occurred. However, this could be negated by the addition of citrate. The results indicate that, contrary to current hypotheses, the toxic mode of Al is not through an interaction with enzymatic catalytic metal binding sites but may be through the interaction with specific membrane lipids.

Aluminum↗

PubMed1997

The carboxyl-terminal zinc-binding domain of the human papillomavirus E7 protein can be functionally replaced by the homologous sequences of the E6 protein.

The carboxyl-terminus is necessary for the functional and structural integrity of the human papillomavirus (HPV) E7 oncoprotein. Since many mutations in this domain of E7 result in the formation of unstable proteins, we have evaluated the importance of this region by replacing it with structurally related domains derived from HPV E6 proteins. Biological analysis of these mutant chimeric E7/E6 proteins showed that they retained E7-specific biological activities including cooperation with the ras oncogene to transform primary baby rat kidney cells and transcriptional activation of an E2F responsive reporter plasmid. One of the chimeric proteins was impaired in its ability to physically disrupt pRB/E2F complexes in vitro suggesting that there are defined molecular determinants in the carboxyl-terminus of E7 for this activity. In contrast, none of these proteins exhibited E6-like properties including binding to p53 and/or degradation of associated proteins.

Amino Acid Sequence↗

PubMed1997

Improving cardiopulmonary resuscitation skills retention: effect of two checklists designed to prompt correct performance.

Previous research has shown that regardless of an individual's experience, life support skills such as cardiopulmonary resuscitation (CPR) are poorly performed as soon as 1 month following training. The purpose of this study was to compare the effects of two checklists designed to prompt correct CPR performance. We compared the performance of 169 undergraduate students, at the time of course assessment, with retention testing that occurred 2 months following the course assessment. Students were randomly assigned to a control group, a short version of a CPR checklist and a longer more detailed version. Two groups of variables were created: procedural and compression-ventilation variables. In addition, an overall-performance variable was created, summarizing performance on the procedural variables. Binary variables were assessed with chi 2-tests of independence. One-way ANOVAs, using 'group' as the between-subjects factor, were used to assess each continuous variable. Comparisons between groups yielded significant differences of P < 0.05. The long checklist generally led to superior performance on the procedural variables. The results support the hypothesis that remembering the steps of CPR is too complex for some. Though preliminary, the findings of this study indicate that the detailed checklist was an effective strategy to improve the post-course performance of CPR.

Cardiopulmonary Resuscitation↗

PubMed1997

Diagnosis of trochanteric bursitis versus femoral neck stress fracture.

This case report describes a 46-year-old male runner who reported the sudden onset of right hip pain. A diagnosis of trochanteric bursitis was established by a physiatrist, and the patient underwent two courses of physical therapy for moist heat, ultrasound, and exercise. Because minimal improvement was seen in the patient's pain level and gait limitations following physical therapy, a consultation was requested of a fellow staff member in the same physical therapy department, who is both a chiropractor and a physical therapist. The consultant felt that the absence of tenderness to deep palpation of the greater trochanter, the presence of a noncapsular pattern of restriction of the right hip, and the patient's nonresponsiveness to physical therapy warranted further investigation. A differential diagnosis of avascular necrosis, fracture, or a loose body was made by the consultant. Magnetic resonance imaging (MRI) testing ordered by the consultant indicated a nondisplaced, complete stress fracture of the femoral neck. The results of the consultation and the MRI testing were communicated to the referring physiatrist. The patient was referred to an orthopedic surgeon, who performed an open reduction and internal fixation of the right hip. The patient was ambulatory without an assistive device or weight-bearing restrictions 5 weeks after surgery.

Bursitis↗

PubMed1997

Analysis of abnormal signals within the QRS complex of the high-resolution electrocardiogram.

This paper presents a new, quantitative approach to measuring abnormal intra-QRS signals, using the high-resolution electrocardiogram (HRECG). These signals are conventionally known as QRS "notches and slurs." They are measured qualitatively and form the basis for the ECG identification of myocardial infarction. The HRECG is used for detection of ventricular late potentials (LP), which are linked with the presence of a reentry substrate for ventricular tachycardia (VT) after a myocardial infarction. LP's are defined as signals from areas of delayed conduction which outlast the normal QRS period. Our objective is to quantify very low-level abnormal signals that may not outlast the normal QRS period. In this work, abnormal intra-QRS potentials (AIQP) were characterized by removing the predictable, smooth part of the QRS from the original waveform. This was represented as the impulse response of an ARX parametric model, with model order selected empirically from a training data set. AIQP were estimated using the residual of the modeling procedure. Critical AIQP parameters to separate VT and non-VT subjects were obtained using discriminant functions. Results suggest that AIQP indexes are a new predictive index of the HRECG for VT. The concept of abnormal intra-QRS potentials permits the characterization of pathophysiological signals contained wholly within the normal QRS period, but related to arrhythmogenesis. The new method may have other applications, such as detection of myocardial ischemia and improved ECG identification of the site of myocardial infarction, particularly in the absence of Q waves.

Electrocardiography↗

PubMed1997

Comparison of single-biphasic versus sequential-biphasic shocks on defibrillation threshold in pigs.

Current generation implantable cardioverter defibrillators use monophasic, biphasic, or sequential pulse shocks, most of which truncate after a given time, dumping the remaining charge on the capacitor through an internal resistor. We hypothesized that having an additional current pathway, and delivering the majority of the remaining charge on a single capacitor to the two pathways using additional shock phases, would improve defibrillation efficacy. This hypothesis was tested by comparing DFTs using a simulated single capacitor, single-biphasic shock (two 5-ms pulses separated by 0.2 ms), delivered to coupled pairs of electrodes, to those using a sequential-biphasic shock (four 5-ms pulses separated by 0.2 ms) delivered to separate opposing electrodes, delivered from the same electrodes for both waveforms. In eight open-chest anesthetized pigs, four mesh electrodes (Medtronic TX-7, 6.5 cm2), were sutured on the epicardium of the anterior and posterior surfaces of each ventricle. Shocks were delivered from a 200-microF capacitor bank. Triplicate DFTs were obtained using each waveform in a randomized crossover design. Initial leading edge voltage (mean +/- SEM: 420 +/- 33 V vs 497 +/- 34 V; P < 0.05), initial peak current (4.8 +/- 0.4 A vs 13 +/- 1.1 A; P < 0.001), and delivered energy (16.9 +/- 2.6 J vs 30.4 +/- 5.3 J; P < 0.05) at the DFT were all significantly lower using sequential-biphasic shocks than those using single-biphasic shocks, respectively. We conclude that for direct heart defibrillation, it is worthwhile to combine sequential capability to biphasic shocks and deliver the remaining charge on the capacitor to the two different pathways.

Animals↗

PubMed1997

Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the human papillomavirus type 16 E7 oncoprotein.

Cells expressing human papillomavirus type 16 (HPV-16) E7, similar to those which express HPV-16 E6, are resistant to a p53-mediated G1 growth arrest. We examined the p53-mediated DNA damage response pathway in E7-expressing cells to determine the mechanism by which E7-containing cells continue to cycle. In response to DNA damage, no dramatic difference was detected in G1- or S-phase cyclin or cyclin-dependent kinase (Cdk) levels when E7-expressing cells were compared to the parental cell line, RKO. Furthermore, Cdk2 kinase activity was inhibited in both RKO cells and E7-expressing cells, while Cdk2 remained active in E6-expressing cells. However, the steady-state levels of pRB and p107 protein were substantially lower in E7-expressing cells than in the parental RKO cells or E6-expressing cells. There was no reduction in pRB mRNA levels, but the half-life of pRB in E7-expressing cells was markedly shorter. Infection of primary human foreskin keratinocytes with recombinant retroviruses expressing HPV-16 E7 resulted in a decrease in pRB protein levels, indicating this phenomenon is a consequence of E7 expression, not of immortalization or transformation. These data strongly suggest E7 interferes with the stability of pRB and p107 protein. We propose that the removal of these components of the p53-mediated G1 growth arrest pathway in E7-expressing cells contributes to the ability of E7 to overcome a p53-mediated G1 growth arrest.

Amino Acid Chloromethyl Ketones↗