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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 199 records · Page 11Linked to original sources
PubMed1993

Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for Elf-1 and the pets factor.

Infection with human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell lymphoma/leukemia. This disease occurs in only a small minority of people infected with HTLV-I and manifests itself many years after infection. Therefore, it appears that a fine balance exists between HTLV-I and the host T-cell factors with which it interacts. HTLV-I encodes a transactivating protein, Tax, which activates viral transcription via cellular mechanisms which are incompletely understood. As viral gene expression is negligible during latency, it is doubtful that Tax controls the initial transition to the replicative state. Tax-independent cellular factors which control HTLV-I transcription, and presumably latency, have received little study. Recently, the product of the chicken proto-oncogene ets-1 has been shown to bind to the HTLV-I enhancer and modestly activate transcription in certain cell types (S. C. Gitlin, R. Bosselut, A. Gégonne, J. Ghysdael, and J. N. Brady, J. Virol. 65:5513-5523, 1991). However, the functional significance of the ets-binding site in the intact enhancer has not previously been shown. We now demonstrate that site-specific mutation of the purine-rich ets-binding site significantly diminishes inducible enhancer function, but not Tax response, in the human Jurkat T-cell line. Similarly, mutation of the peri-ets (pets) site, not previously noted in the HTLV-I enhancer, markedly inhibits inducible enhancer function but not Tax response. Further, we show that the predominant protein binding the purine-rich HTLV-I enhancer element in human T cells is not ets-1 but Elf-1, a member of the ets family which is very similar to the Drosophila morphogen E74. Regulation of HTLV-I through Elf-1/pets enhancer motifs resembles that seen with human immunodeficiency virus type 2 (D. M. Markovitz, M. Smith, J. Hilfinger, M. C. Hannibal, B. Petryniak, and G. J. Nabel, J. Virol. 66:5479-5484, 1992; J. M. Leiden, C.-W. Wang, B. Petryniak, M. Smith, D. M. Markovitz, G. J. Nabel, and C. B. Thompson, J. Virol. 66:5890-5897, 1992), another human pathogenic retrovirus with a relatively long incubation period.

Animals↗
PubMed1993

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

The present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamics and renin release in the canine nonfiltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (p < 0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 +/- 1.3 to 67.4 +/- 1.2 mm Hg. However, with a higher rate of endothelin-1 infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5 +/- 1.3 and 51.5 +/- 1.8 mm Hg (p < 0.01), whereas renal blood flow was reduced from 154.5 +/- 15 to 83.0 +/- 9.5 and 53.5 +/- 9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9 +/- 5.6 to 26.6 +/- 4.9 units/min per gram kidney weight (p < 0.01), and it fell further to 16.1 +/- 4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Obesity-induced hypertension. Renal function and systemic hemodynamics.

This study examined the control of renal hemodynamics and tubular function, as well as systemic hemodynamics, during obesity-induced hypertension in chronically instrumented conscious dogs. Mean arterial pressure, cardiac output, and heart rate were monitored 24 hours a day using computerized methods, water and electrolyte balances were measured daily, and renal hemodynamics were measured each week during the control period and 5 weeks of a high-fat diet. After 7 to 10 days of control measurements, 0.5 to 0.9 kg of cooked beef fat was added to the regular diet, and sodium intake was maintained constant at 76 mmol/d throughout the study. After 5 weeks of the high-fat diet, body weight increased from 24.0 +/- 1.0 to 35.9 +/- 4.9 kg, mean arterial pressure increased from 83 +/- 5 to 100 +/- 4 mm Hg, cardiac output increased from 2.86 +/- 0.27 to 4.45 +/- 0.55 L/min, and heart rate rose from 68 +/- 5 to 107 +/- 9 beats per minute. Associated with the hypertension was an increase in cumulative sodium balance to 507 +/- 107 mmol after 35 days and a rise in sodium iothalamate space, an index of extracellular fluid volume, to 131 +/- 4% of control. Sodium retention was due to increased tubular reabsorption, because glomerular filtration rate and effective renal plasma flow increased throughout the 5 weeks of the high-fat diet, averaging 135 +/- 4% and 149 +/- 19% of control, respectively, during the fifth week of the high-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.

The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.

Animals↗
PubMed1993

Reasons for drinking alcohol: their relationship to psychosocial variables and alcohol consumption.

The present investigation was designed to gain a better understanding of the psychosocial factors that predict reasons for drinking alcohol and how these drinking motives differentially relate to alcohol consumption. Four distinct reasons for drinking alcohol scales were established through factor analysis: drink to cope, drink to be sociable, drink to enhance social confidence, and drink for enjoyment. Multiple regression analyses showed that 1) each reason for drinking was predicted by a somewhat different set of demographic and psychosocial variables, and 2) the reasons for drinking, in turn, differentially predicted multiple indicators of quantity and frequency of alcohol consumption. Theoretical implications of the study results and suggestions for future research are discussed.

Adaptation, Psychological↗
PubMed1993

Quantum leap into continuous quality improvement.

Prior to a JCAHO accreditation visit, Southeast Georgia Regional Medical Center implemented a program for improved prevention and treatment of nosocomial pressure ulcers. Forms were developed for monitoring skin integrity and therapy beds were tried from a vendor, which also provided a computerized assessment tool. Results included 15 percent pressure ulcer prevention in addition to enhanced collaborative nursing practice.

Cross Infection↗
PubMed1992

Inhibition of c-jun causes reversible proliferative arrest and withdrawal from the cell cycle.

We studied the effect of c-jun depletion in Friend murine erythroleukemia (F-MEL) cells stably transfected with a plasmid that allowed for the glucocorticoid-mediated conditional expression of c-jun antisense sequences. The c-jun cDNA used for the construction of the vector was modified so as to prevent the nonspecific targeting of junB and junD transcripts. High level and rapid induction of c-jun antisense transcripts was achieved with as little as 10(-8) mol/L dexamethasone (DEX) and resulted in a 80% to 90% reduction in c-jun protein levels. The continuous exposure of the transfected cells to DEX inhibited growth by greater than 85% over a 5-day period, whereas DEX had no effect on the growth rate of control F-MEL cells. This proliferative block was associated with a reversible accumulation of cells with a 2n DNA content. When these cells were recultured in the absence of DEX, c-jun protein rapidly reappeared and the immediate early response genes egr-1, junB, and c-myc were transiently expressed. Thus, inhibition of c-jun protein causes logarithmically growing cells to leave the cell cycle and to enter a state closely resembling, if not identical to, G0. These results underscore the importance of c-jun in maintaining cellular proliferation and provide additional evidence for the participation of proto-oncogenes in cell cycle control.

Animals↗
PubMed1992

Apnea and periodic breathing in healthy full-term infants, 12-18 months of age.

Many children older than 12 months of age are now on home monitors. Home pneumograms performed on normal infants have established standards, and have been used to evaluate infants during their first year. However, no standards have been described for infants older than 12 months. We, therefore, recorded the standard pneumogram on 88 full-term healthy infants who were 12-18 months of age. We analyzed the recordings for average respiratory and heart rates, apnea (greater than or equal to 6 seconds) density, longest apnea, periodic breathing, and bradycardia for 12 hours. We compared the values in males vs. females and in infants 12-14.9 months vs. 15.0-18.0 months of age. Since there was no difference in any parameter measured in any group, we combined the values to determine the normal values for this population.

Female↗
PubMed1992

Stress, computer-based work monitoring and measurement systems: a conceptual overview.

The design and implementation of computer-based work monitoring systems can result in changes in the organization, job and task. Electronic performance monitoring (EPM) systems are one type of change based on principles of work simplification and work rationalization. In this new work arrangement, control and coordination functions are allocated to the computer. The supervisor becomes a monitor of information and primarily provides negative performance feedback to the employee. The employee is constrained in his/her ability to use either job resources or social resources to meet the greater demands resulting from the system controlling the pace of work. It is proposed that these work arrangements provoke stress responses in employees that can result in short-term illness and potentially long-term changes in health status. Information enriched work environments are proposed as an alternative. These new work arrangements could improve job resources and social resources to manage job demands and reduce the potentially damaging stress responses. To provide a frame of reference we focus on the impact of EPM systems on the organizational and job elements involved in provoking individual stress responses. The impact of EPM systems on individual health is described using a psychosocial stress framework. Ergonomics interventions discussed include: participation in the design process; allocation of control and coordination functions between the computer and the employee; development of feedback systems; and work measurement and the development of performance appraisal systems.

Journal Article↗
PubMed1992

Employee stress and health complaints in jobs with and without electronic performance monitoring.

Current applications of electronic performance monitoring based on job design theories that consider worker performance rather than stress issues are likely to generate unsatisfying and stressful jobs (Smith et al, 1986). This study examines critical job design elements that could influence worker stress responses in an electronic monitoring context. A questionnaire survey of employees in telecommunications companies representative of each region in the United States examined job stress in directory assistance, service representative and clerical jobs with specific emphasis on the influence of electronic monitoring of job performance, satisfaction and employee health. Useable surveys were received from 745 employees representing seven operating companies and AT & T; a response rate of about 25%. The results of this survey indicated that employees who had their performance electronically monitored perceived their working conditions as more stressful, and reported higher levels of job boredom, psychological tension, anxiety, depression, anger, health complaints and fatigue. It is postulated that these effects may be related to changes in job design due to electronic performance monitoring.

Journal Article↗
PubMed1992

Effects of lithotripter-generated high energy shock waves of mammalian cells in vitro.

The effects of high energy shock waves on an established human prostatic carcinoma cell line (PC-3) were investigated. HESW were administered to PC-3 cell suspensions using an electrohydraulic lithotripter (Dornier HM3). Experimental variables included the number of shocks to which the cells were exposed, spark generator potential, and the position of the cell sample in the acoustic field. Two types of cellular damage were observed: immediate cell destruction (lysis) as measured by electronic particle counting and the loss of reproductive capacity (viability) among the remaining cells as determined by colony formation assay. Over the range of the experimental variables studied, cell lysis was dependent to a greater extent on the number of shocks administered than the generator potential. Viability was affected less but was also dependent on both the generator potential and shock number. Cell lysis was strongly dependent on the position of the sample in the acoustic field with the extent of damage increasing as the sample was moved along the central axis of the shock wave from the f2 focus towards the electrodes. Possible mechanisms of damage and the relationship of the in vitro effects to the damage observed in normal tissues of patients undergoing extracorporeal lithotripsy for kidney stone disease are discussed.

Cell Division↗
PubMed1992

Treatment of endocarditis due to Pseudomonas aeruginosa with imipenem.

Therapy for endocarditis due to Pseudomonas aeruginosa is complicated by the emergence of resistance during therapy, lack of universally available synergistic antimicrobial agents, and unacceptably high morbidity and mortality rates. The authors report a case of aortic valve endocarditis due to P. aeruginosa in which resistance to piperacillin developed during combined therapy with tobramycin. Bacteriologic cure was obtained with a combination of imipenem/cilastatin and tobramycin. The authors review six other cases of P. aeruginosa endovascular infections treated with imipenem.

Adult↗
PubMed1992

Mitochondrial DNA length variation and heteroplasmy in populations of white sturgeon (Acipenser transmontanus).

Southern blot analysis was used to quantify the extent of mtDNA D-loop length variation in two populations of white sturgeon, Acipenser transmontanus. Over 42% of individuals were heteroplasmic for up to six different mtDNA length variants attributable to varying copy numbers of an 82-bp repeat sequence. Chi-square analyses revealed that the frequencies of length genotypes and the incidence of heteroplasmy were significantly different between Fraser and Columbia River sturgeon populations but not between restriction site haplotypes. Heteroplasmic fish have, on average, higher copy number than homoplasmic fish. Forty-five of 101 homoplasmic individuals carry only a single copy of the repeat, while none of the 73 heteroplasmic fish has the single repeat as the predominant variant. On the basis of differences in frequency distributions of copy number within and between fish, we suggest that (1) heteroplasmy is maintained by high recurrent mutation of multiple copy genomes, favoring increased copy number and (2) the mutation pressure toward higher copy number heteroplasmy is partially offset by selection to reduced genome size and segregation to the homoplasmic condition.

Animals↗
PubMed1992

Selective impairment of neuroendocrine and hemodynamic responses to a mu-opioid peptide in aged rats.

The objective of this study was to determine if there are age-related alterations in hemodynamic and/or neuroendocrine responses to the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly(ol)5] enkephalin (DAMGO), or corticotropin releasing hormone (CRH) administered centrally. To this end, DAMGO (1-3 nmoles) or CRH (1 nmole) was injected intracerebroventricularly (icv) to freely moving young (6-8 month) and aged (24-26 month) Fischer 344 male rats. Blood pressure, heart rate (HR), and plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropin (ACTH), and prolactin (PRL) were measured over time. Under basal conditions, NE levels were higher and blood pressures were lower in aged rats, whereas there were no significant differences in EPI, ACTH, or PRL levels. The stimulatory effect of DAMGO on blood pressure, HR, and plasma EPI and ACTH was attenuated, but the PRL response was enhanced in aged cohorts. In contrast, there were no age-related differences in the NE responses to DAMGO or CRH nor in CRH-induced increases in EPI or ACTH. The sympathoadrenal and hemodynamic effects of DAMGO were blocked by naloxone in both age groups. These results indicate that alterations in mu-opioid function with age are specific for the opioid system and do not reflect a generalized decline in central regulation of neuroendocrine and cardiovascular function.

Adrenocorticotropic Hormone↗
PubMed1992

A dual-isotope method for studying protein kinetics in pleural effusions in humans.

A method is described for studying protein kinetics in pleural effusions in humans. In 15 patients with pleural effusions from a variety of causes, protein inflow was monitored by measuring the rate of appearance in the effusion of the plasma protein transferrin, radiolabelled in vivo by intravenous injection of 113InmCl3. Protein outflow was measured from the rate of appearance in the blood of intrapleurally administered 125I-albumin. Compartmental analysis has been used to determine rate constants k(in) and kout for the movement of labelled proteins into and out of the effusion, respectively. The mean value of k(in) for 15 patients was 9.4 x 10(-4) h-1 (range 2.2-21.4). The mean value of kout in the same patients was 28 x 10(-4) h-1 (range 6-68). Using appropriate assumptions where necessary, the absolute transfer rates of albumin and transferrin were also estimated. For albumin, the mean rate of outflow was 66 mg h-1 (range 27-158), compared to mean estimated inflow of 133 mg h-1 (range 36-381). Protein inflow was highest in a case of metastatic ovarian carcinoma with pleural and peritoneal seedlings, indicating high vascular permeability. Protein outflow was very low in a case of mesothelioma, suggesting severely impaired lymphatic drainage. The technique may prove to be a useful tool for studying mechanisms resulting in the formation of malignant and nonmalignant pleural effusions, and may also be useful for studying the effects of putative therapeutic intervention.

Aged↗
PubMed1992

Enhancing esthetic knowledge: a teaching strategy.

This article describes a teaching strategy that has been used with graduate students to enhance their esthetic knowing through representing, interpreting, and envisioning the lived experience of a caring presence in nursing practice. As students engaged in reflecting, writing, and discussion, the explicit and tacit meanings associated with a caring presence unfolded in esthetic knowing in nursing.

Creativity↗
PubMed1992

Activation of the human immunodeficiency virus type 1 enhancer is not dependent on NFAT-1.

The function of a putative NFAT-1 site in the human immunodeficiency virus type 1 enhancer has been analyzed. Activation by the T-cell antigen receptor is minimal in Jurkat cells and is mediated by the kappa B sites. The putative NFAT-1 region is not required for the response to anti-CD3 or to mitogens in T-cell, B-cell, or monocyte/macrophage leukemia lines, nor is it a cis-acting negative regulatory element.

Antigens, Differentiation, T-Lymphocyte↗