Showing papers by "University of Miami published in 1987"

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: a double-blind placebo-controlled trial.

Abstract: We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

A comparison of the equilibrium constants for the dissociation of carbonic acid in seawater media

Abstract: The published experimental data of Hansson and of Mehrbach et al. have been critically compared after adjustment to a common pH scale based upon total hydrogen ion concentration. No significant systematic differences are found within the overall experimental error of the data. The results have been pooled to yield reliable equations that can be used to estimate pK1∗and pK2∗ for seawater media a salinities from 0 to 40 and at temperatures from 2 to 35°C.

Small Differences in Intraischemic Brain Temperature Critically Determine the Extent of Ischemic Neuronal Injury

Abstract: We have tested whether small intraischemic variations in brain temperature influence the outcome of transient ischemia. To measure brain temperature, a thermocouple probe was placed stereotaxically into the left dorsolateral striatum of rats prior to 20 min of four-vessel occlusion. Rectal temperature was maintained at 36-37 degrees C by a heating lamp, and striatal temperature prior to ischemia was 36 degrees C in all animals. Six animal subgroups were investigated, including rats whose intraischemic striatal brain temperature was not regulated, or was maintained at 33, 34, 36, or 39 degrees C. Postischemic brain temperature was regulated at 36 degrees C, except for one group in which brain temperature was lowered from 36 degrees C to 33 degrees C during the first hour of recirculation. Energy metabolites were measured at the end of the ischemic insult, and histopathological evaluation was carried out at 3 days after ischemia. Intraischemic variations in brain temperature had no significant influence on energy metabolite levels measured at the conclusion of ischemia: Severe depletion of brain ATP, phosphocreatine, glucose, and glycogen and elevation of lactate were observed to a similar degree in all experimental groups. The histopathological consequences of ischemia, however, were markedly influenced by variations in intraischemic brain temperature. In the hippocampus, CA1 neurons were consistently damaged at 36 degrees C, but not at 34 degrees C. Within the dorsolateral striatum, ischemic cell change was present in 100% of the hemispheres at 36 degrees C, but in only 50% at 34 degrees C. Ischemic neurons within the central zone of striatum were not observed in any rats at 34 degrees C, but in all rats at 36 degrees C. In rats whose striatal temperature was not controlled, brain temperature fell from 36 to 30-31 degrees C during the ischemic insult. In this group, no ischemic cell change was seen within striatal areas and was only inconsistently documented within the CA1 hippocampal region. These results demonstrate that (a) rectal temperature unreliably reflects brain temperature during ischemia; (b) despite severe depletion of brain energy metabolites during ischemia at all temperatures, small increments of intraischemic brain temperature markedly accentuate histopathological changes following 3-day survival; and (c) brain temperature must be controlled above 33 degrees C in order to ensure a consistent histopathological outcome. Lowering of the brain temperature by only a few degrees during ischemia confers a marked protective effect.

Dispositional optimism and physical well-being: the influence of generalized outcome expectancies on health

Abstract: This article explores the implications that dispositional optimism holds for physical well-being. Research is reviewed that links optimism to a number of different positive health-relevant outcomes, ranging from the development of physical symptoms to recovery from coronary artery bypass surgery. Additional findings are described which suggest that these beneficial effects are partly due to differences between optimists and pessimists in the strategies that they use to cope with stress. A number of other potential mediators are also discussed, including some that are physiologic in nature. The article closes with a discussion of the relationships between our own theoretical account of the effects of optimism and several other conceptual approaches.

Functional identity of proliferating cell nuclear antigen and a DNA polymerase-δ auxiliary protein

Abstract: The mechanism of replication of the simian virus 40 (SV40) genome closely resembles that of cellular chromosomes, thereby providing an excellent model system for examining the enzymatic requirements for DNA replication. Only one viral gene product, the large tumour antigen (large-T antigen), is required for viral replication, so the majority of replication enzymes must be cellular. Indeed, a number of enzymatic activities associated with replication and the S phase of the cell cycle are induced upon SV40 infection. Cell-free extracts derived from human cells, when supplemented with immunopurified SV40 large-T antigen support efficient replication of plasmids that contain the SV40 origin of DNA replication. Using this system, a cellular protein of relative molecular mass 36,000 (Mr = 36K) that is required for the elongation stage of SV40 DNA replication in vitro has been purified and identified as a known cell-cycle regulated protein, alternatively called the proliferating cell nuclear antigen (PCNA) or cyclin. It was noticed that, in its physical characteristics, PCNA closely resembles a protein that regulates the activity of calf thymus DNA polymerase-delta. Here we show that PCNA and the polymerase-delta auxiliary protein have similar electrophoretic behaviour and are both recognized by anti-PCNA human autoantibodies. More importantly, both proteins are functionally equivalent; they stimulate SV40 DNA replication in vitro and increase the processivity of calf thymus DNA polymerase-delta. These results implicate a novel animal cell DNA polymerase, DNA polymerase-delta, in the elongation stage of replicative DNA synthesis in vitro.

Bipolar affective disorders linked to DNA markers on chromosome 11.

Abstract: An analysis of the segregation of restriction fragment length polymorphisms in an Old Order Amish pedigree has made it possible to localize a dominant gene conferring a strong predisposition to manic depressive disease to the tip of the short arm of chromosome 11.

Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases.

Abstract: Progressive multifocal leukoencephalopathy, a common complication of infections with human immunodeficiency virus (HIV), occurs in as many as 3.8% of patients with the acquired immunodeficiency syndrome (AIDS). We report 16 cases and review 12 previously reported cases of progressive multifocal leukoencephalopathy associated with HIV infection. This illness was the presenting manifestation of HIV infection in 8 cases. Limb weakness, gait abnormalities, visual loss, aand altered mental status were the commonest initial complaints. Computed tomography of the brain frequently showed hypodense, nonenhancing white matter lesions. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions. Cerebrospinal fluid analysis and electroencephalography were nondiagnostic. Impaired cell-mediated immunity was typically noted, even in the absence of other immunodeficiency-associated illnesses. Death occurred within 10 days to 18 months of the onset of symptoms in 22 patients. However, 4 patients remain alive at 3 to 23 months; of these 4, 2 have had significant improvement without treatment. Various therapies were unsuccessful.

Radiographic assessment of progression in osteoarthritis

Abstract: We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12-60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0-3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight-bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.

Optimism, pessimism, and postpartum depression

Abstract: This study examined the role of dispositional optimism versus pessimism as a moderator of the tendency to become depressed after a specific stressful life change: the birth of a child. The optimism-pessimism dimension was operationally defined as generalized expectancies for favorable versus unfavorable life outcomes. Both optimism and depressive mood were assessed several weeks before childbirth. Depressive mood was measured again three weeks postpartum. Even after statistically controlling for initial dysphoria, optimism was inversely correlated with subsequent dysphoria. The effect of optimism was most pronounced among women who initially were not depressed, suggesting that optimism confers resistance to the development of depressive symptoms. Discussion centers on the relation between optimism and attributional style, and on the self-regulatory functions of optimism.

Effect of membrane potential changes on the calcium transient in single rat cardiac muscle cells

Abstract: The mechanism that links membrane potential changes to the release of calcium from internal stores to cause contraction of cardiac cells is unclear. By using the calcium indicator fura-2 under voltage-clamp conditions, changes in intracellular calcium could be monitored in single rat ventricular cells while controlling membrane potential. The voltage dependence of the depolarization-induced increase in intracellular calcium was not the same as that of the calcium current (Isi), which suggests that only a small fraction of Isi is required to trigger calcium release from the sarcoplasmic reticulum. In addition, sarcoplasmic reticulum calcium release may be partly regulated by membrane potential, since repolarization could terminate the rise in intracellular calcium. Thus, changes in the action potential will have immediate effects on the time course of the calcium transient beyond those associated with its effects on Isi.

Evaluation of heterosexual partners, children, and household contacts of adults with AIDS

Abstract: Forty-five adults with the acquired immunodeficiency syndrome (AIDS) and their 45 spouses, 109 children, and 29 household contacts were studied for evidence of heterosexual, perinatal, and household spread of human T-cell lymphotropic virus type III (HTLV-III) infection. Of the 45 spouses enrolled, 26 (58%) had antibody to HTLV-III, including 12 (71%) of 17 male spouses and 14 (50%) of 28 female spouses. Of the 12 seropositive male spouses, nine were seropositive at enrollment and three had seroconversion. Of the 14 seropositive female spouses, four were seropositive at enrollment and ten seroconverted. Lack of barrier contraceptive use and oral sex were associated with seroconversion. Of the 109 children enrolled, 15 had AIDS or an AIDS-related illness, two had evidence of passive transfer of maternal antibodies, and two had HTLV-III infection acquired outside the household. None of the 90 seronegative children seroconverted. Of 29 household contacts studied, none developed antibody to HTLV-III. ( JAMA 1987;257:640-644)

Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group.

Abstract: Between March 1973 and June 1979, patients with advanced operable squamous cell carcinoma of the supraglottic larynx or hypopharynx were randomly allocated to receive either preoperative radiation therapy (5,000 rad) or postoperative radiation therapy (6.000 rad). Patients with oral cavity or oropharynx lesions were randomly assigned either preoperative radiation, postoperative radiation, or definitive radiatio therapy (6,500–7,000 rad), with surgery reserved for slavage if residual disease was present 6 weeks after completion of irradiation. Three hundred twenty patients were evaluable with a median follow-up of 60 months. Based on results in 277 patients across all four region combined, locoregional control was significantly better for patients assigned to receive psotoperative radiation therapy (65%) compared with those assigned to receive preoperative radiation therapy (48%, P=0.04). This was due to higher rate of both persistent and recurrent local and regional disease in the preoperative group. Survival also showed a trend to be better in the postoperative group (38%) compared with the preoperative group (38%) compared with the preoperative group (33%, P = 0.10). Rates of severe surgical and radiation therapy complications were similar overall. Forty-three patients were evalauble for each of the three treatment regimens assigned to patients with oral cavity or oropharynx lesions. Due to the small number of patients available for this portion of the trial, the observed differences for overall survival (4-year percentage 33% overall; 30% preoperative, 36% postoperative, 33% definitive radiation therapy) and for locoregional control (45% overall; 43% preoperative, 52% postoperative, 38% definitive radiation therapy) were not statistically significant. The use of definitive radiation therapy with surgical rescue as an ethically justified alternative treatment for these tumors remains a question for further research.

The Western Equatorial Pacific Ocean Circulation Study

Abstract: A recent set of oceanographic measurements in the western equatorial Pacific has revealed the existence of previously undescribed major ocean currents and upper-ocean mixed-layer structure. The measurements also confirm a 20-year-old hypothesis on the water-mass origins of the Equatorial Undercurrent in the Pacific Ocean.

Oxidation of H2S in seawater as a function of temperature, pH, and ionic strength.

Abstract: The formation of H/sub 2/S occurs in a number of areas in natural waters.The production in pore waters and anoxic basins is due to biological processes while the production in hydrothermal systems is due to geochemical processes. At the interface between anoxic and oxic waters, large changes occur in the state of metals and nonmetals (1,2). This is due to the changes in the redox conditions, solubility conditions, and bacterial activity. Although one can question the importance of abiotic thermodynamic and kinetic processes at this interface, it is useful to use simple inorganic models to approximate the real system. Recently, researchers (3) have examined the thermodynamics and kinetics of the H/sub 2/S system in natural waters. From this review, it became apparent that large discrepancies existed in the rates of oxidation of H/sub 2/S in natural waters from various studies. Studies on the effect of various parameters such as temperature, salinity, and pH for seawater were nonexistent. In this paper data is presented on the oxidation of H/sub 2/S in water, seawater, and NaCl solutions as a function of temperature (5-65 /sup 0/C), pH (1-12), and ionic strength (I = 0-6 M). These results will hopefully fill some of themore » gaps and yield equations valid for most natural waters. 21 references, 8 figures, 4 tables.« less

Organizational Commitment: Analysis of Antecedents

Abstract: A model of the antecedents (personal-demographic, organizational relationship, and person-organization fit) of organizational commitment was empirically analyzed. The study used a sample of employees (N = 406) from a wide variety of organizations to test the hypotheses. The results of the multiple regression analysis supported the hypothesized relationships and the proposed model on the antecedents to organizational commitment. In particular, this study uncovered heretofore unknown implications that attributional processes such as locus of control have on organizational commitment as well as supporting previous research on the impact of demographics and leader behavior. Overall, the antecedent model, tested empirically, has important practical implications for predicting employees' organizational commitment.

Ergodic properties of linear dynamical systems

Abstract: The Multiplicative Ergodic theorem, which gives information about the dynamical structure of a cocycle $\Phi $, or a linear skew product flow $\pi $, over a suitable base space ${\bf M}$, asserts that for every invariant probability measure $\mu $ on ${\bf M}$ there is a measurable decomposition of the vector bundle over ${\bf M}$ into invariant measurable subbundles, and that every solution with initial conditions in any of these subbundles has strong Lyapunov exponents. These exponents depend on the measure $\mu $, and when $\mu $ is ergodic, they are constant (almost everywhere) on ${\bf M}$ and form a finite set mess $\Sigma (\mu )$. The dynamical spectrum dyn $\Sigma $ consists of those values $\lambda \in {\bf R}$ for which the shifted flow $\pi _\lambda $ fails to have an exponential dichotomy over ${\bf M}$. The Spectral theorem for linear skew product flows states that when ${\bf M}$ is compact and dynamically connected then dyn $\Sigma $ is the finite union of k disjoint compact intervals and th...

Energy Partitioning in Fish: The Activityrelated Cost of Osmoregulation in a Euryhaline Cichlid

Abstract: SUMMARY We have investigated how the maintenance, net cost of swimming and total (maintenance + net cost of swimming) metabolic rates of red, hybrid tilapia {Oreochromis mossambicus $ XO. hornorum cf) responded to different acclimation salinities, and if these responses correlated with changes in ion-osmoregulation (= osmoregulation) costs. Three groups of fish were acclimated to either fresh water (FW, 0%o), isosmotic sea water (ISW, 12%o) or full strength sea water (SW, 35 %o) and oxygen consumption was measured while they swam at 10, 20, 30 and 40cms" 1 . Maintenance oxygen consumption (estimated by extrapolation), for an average fish (63g), increased among groups in the following order: FW

Geochemical formation of organosulphur compounds (thiols) by addition of H 2 S to sedimentary organic matter

Abstract: Organosulphur compounds constitute a significant fraction of organic matter in both recent and ancient iron-poor marine sediments as well as in petroleum generated in such sediments1,2. Most studies on organosulphur compounds in marine sediments have focused on hydrophobic compounds, for example, thiophenes3–6, sulphur-containing hopanoids7 and volatile compounds. Recently, hydrophilic, organic thiols were found in significant concentrations in anoxic marine sediments8,9. Several studies10–13 have shown that H2S formed from bacterial sulphate reduction can become incorporated into organic matter during early diagenesis, however, the exact chemical mechanisms by which this sulphur reacts with sedimentary organic matter are not well understood. Here we describe the widespread occurrence of 3-mercaptopropionic acid in coastal marine sediments (Biscayne Bay, Florida) and present evidence for its formation by an abiotic reaction between hydrogen sulphide and acrylic acid, which is a cleavage product of the common algal osmolyte β-dimethylsulphoniopropionate14,15. The reaction probably occurs by nucleophilic addition of bisulphide (HS−) ion to the activated double bond in the α,β-unsaturated car bony 1 system of acrylic acid. Reactions between hydrogen sulphide and activated unsaturated bonds in organic molecules are probably responsible for the formation of other thiols in sediments and could represent a major pathway for the incorporation of sulphur into sedimentary organic matter during early diagenesis.

Photochemically induced cerebral infarction. I. Early microvascular alterations.

Abstract: Alterations in the blood-brain barrier to proteins, and regional water and electrolyte content were documented in a rat model of photochemically induced small-vessel thrombosis leading to infarction. Horseradish peroxidase (HRP) or Evans blue was given immediately following a 2-min photochemical sensitization period. At 5 min following irradiation, multifocal sites of peroxidase extravasation were noted within the irradiated area. Ultrastructural examination revealed endothelial cells filled with HRP which in some cases extended into the basal lamina and extracellular spaces. At 15 min, protein leakage was more pronounced within the irradiated zone and reaction product was also apparent within the subarachnoid and perivascular spaces of brain regions remote from the site of irradiation. Widespread staining on the surface of the irradiated hemisphere was apparent in rats perfused 8 h following Evans blue infusion. Water content increased significantly by 15 min within the irradiated zone but not in brain regions remote from this site. Although vasogenic edema is an early event in this stroke model, increases in water content are restricted to the irreversibly damaged site. In contrast, protein tracer escaping from microvessels coursing within the irradiated zone was widely distributed. These findings implicate endothelial barrier dysfunction in the genesis of tissue injury in this model. Morphological evidence for the capability of macromolecules to escape from a site of evolving infarction and to migrate to distances remote from the area of primary microvascular damage is also discussed.

Electric stimulation of protein and DNA synthesis in human fibroblasts.

Abstract: Human fibroblast cell cultures were employed as a model system to rapidly examine several potentially important variables involved in the use of high-voltage, pulsed galvanic stimulation (HVPGS) to increase the healing rate of soft tissue injuries. Fibroblasts were grown on Millipore filters and exposed to HVPGS of various voltages and pulse rates for 20 min in a rectangular, plastic chamber filled with growth medium. Filters with attached cells were placed either in the center of the chamber or close to the positive or negative electrode. Protein synthesis and DNA synthesis were monitored after stimulation using the radioactively labeled precursors, [3H]proline and [3H]thymidine, respectively. The major results obtained in this study are as follows: 1) the rates of both protein and DNA synthesis can be significantly increased by specific combinations of HVPGS voltage and pulse rate; 2) maximum stimulation of protein and DNA synthesis was obtained at 50 and 75 V, respectively, with a pulse rate of 100 pulses/s and the cells located near the negative electrode; and 3) exposure to HVPGS intensities greater than 250 V (at all pulse rates and locations within the chamber) is inhibitory for both protein and DNA synthesis. In view of the results obtained in preliminary clinical studies on the use of HVPGS for the treatment of dermal ulcers, it appears that similar voltages, pulse rates, and relative electrode location may be required for maximum acceleration of human skin wound healing.