AIDS. To the lighthouse. Interview by Janet Snell.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
C Spence
Publications and source records attributed to C Spence.
Audiovisual links in endogenous covert spatial attention.
In 7 experiments we investigated cross-modal links for endogenous covert spatial orienting in hearing and vision. Participants judged the elevation (up vs. down) of auditory or visual targets regardless of their laterality or modality. When participants were informed that targets were more likely on 1 side, elevation judgments were faster on that side, even if the modality of the target was uncertain. When participants expected a target on a particular side in just 1 modality, corresponding shifts of covert attention also took place in the other modality, as evidenced by faster elevation judgments on that side. However, it was possible to "split" auditory and visual attention when targets in the 2 modalities were expected on constant but opposite sides throughout a block, although covert orienting effects were larger when targets were expected on the same side in both modalities. These results show that although endogenous covert attention does not operate exclusively within a supramodal system, there are strong spatial links between auditory and visual attention.
Adolescent↗
Humanized antibody directed to the IL-2 receptor beta-chain prolongs primate cardiac allograft survival.
IL-2Rs are expressed by T cells activated in response to foreign histocompatibility Ags but not by normal cells. This difference in IL-2R expression is exploited by blockade of IL-2Rs to achieve immunosuppression. High affinity IL-2Rs involve three subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma. Murine Mik beta 1, a mAb that blocks IL-2 binding to IL-2R beta, was developed as an immunosuppressive agent. There was modest prolongation of cynomolgus cardiac allograft survival in animals treated with murine Mik beta 1 (mean survival 11.8 +/- 1.6 days compared with 8.2 +/- 0.4 days in untreated animals; p = 0.06). However, murine Mik beta 1 is ineffective in recruiting primate effector cells and is neutralized by monkey Abs directed toward the infused Ab. To circumvent these limitations, a humanized form of Mik beta 1, which is a largely human IgG1k Ab, except that murine hypervariable regions are retained, was developed. In vivo plasma survival of humanized Mik beta 1 was threefold longer than simultaneously administered murine Mik beta 1 (terminal t1/2, 104 +/- 10 h vs 37 +/- 2 h). Furthermore, humanized Mik beta 1 manifests Ab-dependent cellular cytotoxicity, an activity that is absent with the parental murine Mik beta 1. Graft survival was significantly prolonged by humanized Mik beta 1 treatment with survivals of 22, 22, 24, 27, 44, and > 300 days (p vs control < 0.01; p vs murine Mik beta 1 < 0.01). Survival was not prolonged further (p > 0.3) by the addition of humanized anti-Tac, which blocks interaction of IL-2 with IL-2R alpha subunits. There was no toxicity attributable to the use of Mik beta 1 Abs. Thus, humanized Mik beta 1 prolonged cardiac allograft survival in primates without toxicity and may be effective as an adjunct to standard immunosuppressive therapy.
Animals↗
The use of a confirmatory assay to increase the sensitivity and specificity of the Chlamydiazyme test.
The blocking assay was used to reexamine 15,662 patient specimens (2,565 male specimens, 13,097 female specimens) that were submitted for Chlamydia detection using the Chlamydiazyme EIA assay (Abbott Laboratories, North Chicago, IL). Specimens that gave optical density (OD) readings between 1.99 to cutoff and between cutoff to 3 times the negative control in the Chlamydiazyme EIA assay were analyzed further by the blocking assay during the phase 1 study. In the phase 2 study, another 1,120 specimens (473 male specimens and 647 female specimens) that had the above mentioned OD range in the Chlamydiazyme assay were tested with the blocking assay and the direct fluorescent antibody test using the cytospin method. Significant finding from phase 1 study demonstrated that 42.3% of the male specimens with optical density between cutoff to three times the negative control can be blocked by blocking assay (confirmed positive), whereas only 50% of the female specimens with OD range between cutoff to .5 were blocked by the blocking assay. In the phase 2 study, similar results were obtained with the blocking assay. The direct fluorescent antibody test showed excellent correlation with the blocking assay. These data showed that both blocking or direct fluorescent antibody tests can be used for confirmation purposes to increase the sensitivity and specificity of the assay. However, for specimens with OD values below the cutoff to 3 times the negative control, it was necessary to reassess the specimens by either of the methods. This was true especially with the male specimens.
Antibodies, Monoclonal↗
Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury.
Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Implementing computerized tracking at a community health center: challenges and solutions.
A computerized tracking system for both preventive care and chronic disease tracking was implemented at a community health center, using a PC based local area network interfaced with a mainframe scheduling and billing system. Initial database construction used downloads of historical billing data, but ongoing database maintenance is accomplished by using an optical mark-sense scanner to construct both billing and clinical tracking files from custom-designed encounter forms. In this way, expanded clinical data is collected with an actual reduction in manually keyed data, reducing the ongoing cost of the system.
Ambulatory Care Information Systems↗
Child abuse and mental health among adolescents in dependent care.
Do adolescents in dependent care who have been abused or neglected demonstrate more mental health problems than their nonabused peers? This study examined relationships of child abuse, depression, and self-esteem among 82 adolescents (mean age 14.5 years, 52% male, 82.9% white) living in a dependent care facility. Of these, 32 adolescents were victims of child abuse or neglect. Upon admission, 54 adolescents were identified as depressed on the Beck Depression Inventory. Initial scores on the depression and self-esteem instruments did not differ by age, race, or history of maltreatment, though trends among subtypes of abuse were identified. Females had significantly lower self-esteem and tended toward more depression. Repeat evaluation 6 months after admission revealed significant improvement in both depression and self-esteem scores for the entire sample. As a group, however, the maltreated adolescents did not demonstrate significant improvement in depression, and a history of neglect was associated with less improvement. Depression in this dependent care sample was common, however, we did not identify the maltreated adolescents as having significantly more problems with self-esteem or depression. For some adolescents, dependent care may be an appropriate and helpful alternative.
Adolescent↗
Reduced immunogenicity and improved pharmacokinetics of humanized anti-Tac in cynomolgus monkeys.
The anti-Tac mAb has been shown to bind to the p55 chain of the IL-2R, block IL-2 binding and inhibit T cell proliferation. A humanized form of anti-Tac (HAT) has been constructed that retains the binding properties of murine anti-Tac (MAT). These two mAb were evaluated in cynomolgus monkeys to compare relative immunogenicity and pharmacokinetic properties. Monkeys treated with HAT daily for 14 days exhibited anti-HAT antibody titers which were 5- to 10-fold lower than their MAT-treated counterparts and these antibodies developed later than in the MAT-treated monkeys. Two of four monkeys receiving a single injection of MAT developed anti-MAT antibodies, whereas none of four monkeys developed antibodies after a single treatment with HAT. In monkeys injected with either HAT or MAT daily for 14 days, the anti-antibody titers induced were inversely related to the amount of anti-Tac administered. Antibodies that developed against MAT were both anti-isotypic and anti-idiotypic, whereas those developed against HAT appeared to be predominantly anti-idiotypic. The pharmacokinetic properties, that is the half-life and area under the curve values, of HAT were also significantly different from those of MAT. The area under the curve values for HAT in naive monkeys were approximately twofold more than those for MAT, and the mean serum half-life of HAT was 214 h, approximately four- to fivefold more than MAT. These pharmacokinetic values were reduced in monkeys previously sensitized with HAT or MAT suggesting that the presence of anti-antibodies altered these parameters.
Animals↗
Localization in human interleukin 2 of the binding site to the alpha chain (p55) of the interleukin 2 receptor.
Human interleukin 2 (IL-2) analogs with defined amino acid substitutions were used to identify specific residues that interact with the 55-kDa subunit (p55) or alpha chain of the human IL-2 receptor. Analog proteins containing specific substitutions for Lys-35, Arg-38, Phe-42, or Lys-43 were inactive in competitive binding assays for p55. All of these analogs retained substantial competitive binding to the intermediate-affinity p70 subunit (beta chain) of the receptor complex. The analogs varied in ability to interact with the high-affinity p55/p70 receptor. Despite the lack of binding to p55, all analogs exhibited significant biological activity, as assayed on the murine CTLL cell line. The dissociation constants of Arg-38 and Phe-42 analogs for p70 were consistent with intermediate-affinity binding; the Kd values were not significantly affected by the presence of p55 in binding to the high-affinity IL-2 receptor complex. These results confirm the importance of the B alpha-helix in IL-2 as the locus for p55-receptor binding and support a revised model of IL-2-IL-2 receptor interaction.
Amino Acid Sequence↗
Automation of dideoxynucleotide DNA sequencing reactions using a robotic workstation.
We report here a system for automation of the dideoxynucleotide DNA sequencing method. The system consists of a Beckman Biomek 1000 robotic workstation which has been modified by the addition of a thin heater/cooler block directly on the instrument table. The heater/cooler block, which is regulated by a user-specified program integrated into the Biomek software, facilitates the use of both single- and double-stranded DNA sequencing procedures. Using this system, we are able to perform 24 sets of dideoxynucleotide DNA sequencing reactions in approximately 45 min. The reactions are performed in 96-well microtiter plates, using a prepared reagent pack which includes primer, enzyme, nucleotide mixes and radioactive label. Using standard gel electrophoresis technology, we are able to resolve over 500 nucleotides per sequencing reaction in about 5 h. Currently, we are able to perform three runs of 24 samples each, with subsequent gel analysis per 8-h period. Excluding autoradiography, this represents a daily data output of 36,000 base pairs.
DNA↗
Community response to the challenge of AIDS.
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Acquired Immunodeficiency Syndrome↗
When is serum albumin worth measuring?
This paper critically examines the usefulness of serum albumin measurement in the light of current laboratory practice and knowledge of the pathophysiology of albumin metabolism. The main conclusions and recommendations are as follows: (i) Albumin measurement forms a limited, but useful part of the investigation of liver disease; a normal serum albumin concentration makes the diagnosis of cirrhosis unlikely, while a low level in viral hepatitis suggests either severe hepatocellular damage or other complications. (ii) Albumin measurement is essential in selecting patients for, and in determining the amount and frequency of, albumin replacement. (iii) Serum albumin concentration provides a useful indication of prognosis in myeloma. (iv) In the long-term management of patients undergoing enteral or parenteral nutrition, serum albumin concentration is one of several parameters which, together, are useful in predicting the outcome of treatment. (v) The serum albumin concentration may provide a clue to the aetiology of unexplained oedema. (vi) Serum albumin measurement is useful in indicating the level of ionised calcium and of unbound unconjugated bilirubin.
Albumins↗
The faith assembly. A follow-up study of faith healing and mortality.
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Female↗
Perinatal and maternal mortality in a religious group avoiding obstetric care.
We investigated perinatal and maternal deaths occurring among women who were members of a religious group in Indiana; these women received no prenatal care and gave birth at home without trained attendants. Members of the religious group had a perinatal mortality rate three times higher and a maternal mortality rate about 100 times higher than the statewide rates. These findings suggest that, even in the United States, women who avoid obstetric care have a greatly increased risk of perinatal and maternal death.
Adult↗
The Faith Assembly: a study of perinatal and maternal mortality.
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Female↗
Meningism due to intravenous iron dextran.
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Adult↗
Reliability of goniometric measurements.
This study determined the intratester and intertester variability and reliability of goniometric measurements taken by four physical therapists on upper and lower extremity motions of normal male subjects. The same subjects were measured once weekly for four weeks by testers with varied experience in goniometry. Data were analyzed by analyses of variance with repeated measures. Intratester variation for all measurements was less than intertester variation. Further, intertester variation was less for the three upper extremity motions than for those of the lower extremity. These findings indicate the necessity for using the same tester when effects of treatment are evaluated. When the same tester measures the same movement, increases in joint motion of at least three to four degrees determine improvement for either the upper or lower extremity. When more than one tester, however, measures the same movement, increases in joint motion should exceed five degrees for the upper extremity and six degrees for the lower extremity to determine improvement.
Adult↗