IS profits: the sky is the limit?
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Commerce↗
Biomedical subjects
R Johnson
Publications and source records attributed to R Johnson.
Adding pharmacists to the healthcare team enhances outcomes. Interview by Mary-Ellen Deily.
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Health Maintenance Organizations↗
F-16 Class A mishaps in the U.S. Air Force, 1975-93.
All USAF F-16 fighter Class A (major) aircraft mishaps from 1975-93 were analyzed, using records from the U.S. Air Force Safety Agency (AFSA). There were 190 Class A mishaps involving 204 F-16's and 217 aircrew during this 19-yr period. The overall Class A rate was 5.09 per 100,000 flight hours, more than double the overall USAF rate. The mishaps are categorized by year, month, time of day and model of aircraft in relation to mishap causes as determined and reported by AFSA. Formation position, phase of flight and primary cause of the mishap indicate that maneuvering, cruise and low-level phases account for the majority of the mishaps (71%), with air-to-air engagements associated with a higher proportion of pilot error (71%) than was air-to-ground (49%). Engine failure was the number one cause of mishaps (35%), and collision with the ground the next most frequent (24%). Pilot error was determined as causative in 55% of all the mishaps. Pilot error was often associated with other non-pilot related causes. Channelized attention, loss of situational awareness, and spatial disorientation accounted for approximately 30% of the total pilot error causes found. Pilot demographics, flight hour/sortie profiles, and aircrew injuries are also listed. Fatalities occurred in 27% of the mishaps, with 97% of those involving pilot errors.
Accidents, Aviation↗
Pre-operative health screening for total knee replacement.
One hundred patients on the waiting list for total knee replacement at the Wirral Hospitals underwent a domiciliary pre-operative assessment with the rheumatology clinical nurse specialist. As a result of this assessment the operations of 31 of the 100 patients were postponed and seven were cancelled because of a variety of medical and surgical problems. All patients, when eventually admitted, underwent their surgery on the appointed date with no further postponements.
Aged↗
The rate and characteristics of suicide attempters in the native Hawaiian adolescent population.
Native Hawaiian high school students, N = 1779, were surveyed for symptoms of psychopathology and suicide attempts in the previous 6 months. Seventy-seven (4.3%) of the students reported making a suicide attempt. There were no significant differences in prevalence rates for males and females. Depression, anxiety, aggression, substance abuse symptoms, and low family support, but not peer support, were significantly correlated with suicide attempts. On logistic regression, depression, substance abuse, and family support independently predicted attempts. The lack of gender difference may indicate a cultural characteristic of the Hawaiian population that differentiates it from mainstream American populations but likens it to the Native American population.
Adolescent↗
Psychiatric symptoms of Hawaiian adolescents.
The purpose of this study was to examine the interrelationship of depressive symptoms with symptoms of anxiety, aggression, and substance abuse in Native Hawaiian adolescents. A total of 1,819 Native Hawaiian students were recruited from three high schools as part of the initial phase of an ongoing, 4-year, longitudinal, cross-sequential study. Psychiatric symptoms were measured with the Center for Epidemiological Studies-Depression Scale (CES-D), Spielberger's State Anxiety Inventory (SAI), Braver Aggression Dimension Scale (BADS), and Substance Abuse Subtle Screening Inventory-Abbreviated (SASSI-A). Scales were standardized for this minority population. Depressive symptoms were strongly associated with symptoms of anxiety and aggression but only weakly associated with self-reported substance abuse. Girls had substantially higher scores than boys on all scales. Ninth graders reported more aggressive symptoms than did 12th graders. The educational level of the adolescent's main caregiver was not associated with symptoms reported in any of the scales. Native Hawaiian adolescents report similar symptoms and symptom clusters as do adolescents on the mainland U.S. However, Native Hawaiian adolescent girls report a greater number of symptoms in all categories when compared to boys. This distinguishes them from most mainland adolescent populations.
Adolescent↗
Antidepressant and cognition-enhancing effects of DHEA in major depression.
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Affect↗
Interactions of tubulin with guanine nucleotides that have paclitaxel-like effects on tubulin assembly: 2',3'-dideoxyguanosine 5'-[alpha,beta-methylene]triphosphate, guanosine 5'-[alpha,beta-methylene]triphosphate, and 2',3'-dideoxyguanosine 5'-triphosphate.
Despite reduced affinity for the exchangeable nucleotide binding site of tubulin relative to GTP, 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) and guanosine 5'-[alpha, beta-methylene]triphosphate [pp(CH2)pG] are highly active in promoting tubulin assembly. Like the antimitotic drug paclitaxel, which interacts with the same part of the beta-tubulin molecule as exchangeable-site GTP, both analogs enhance nucleation reactions and promote formation hyperstable polymers. These observations led us to synthesize the doubly modified analog 2',3'-dideoxyguanosine 5'-[alpha, beta-methylene]triphosphate [pp(CH2)pddG]. We compared the effects of pp(CH2)pddG to those of ddGTP, pp(CH2)pG, and the three-cognate diphosphates in their interactions with tubulin. We found that pp(CH2)pddG was as active as ddGTP and pp(CH2)pG in supporting formation of polymer of increased stability, but that its affinity for the exchangeable site was lower than that of both singly modified analogs [relative affinities for the exchangeable site for pp(CH2)pddG:ddGTP:pp(CH2)-pG:GTP were 1:2.8:10:273]. There were significant differences in interactions of each of the three analogs with tubulin, and the behavior of pp(CH2)pddG was intermediate between that of ddGTP and that of pp(CH2)pG. Most importantly, under the reaction conditions studied, with heat-treated microtubule-associated proteins (MAPs) ddGTP-induced polymer consisted of short microtubules, while polymer formed with both pp(CH2)pddG and pp(CH2)pG consisted of short sheets. On the other hand, assembly without MAPs had a fivefold lower critical concentration for tubulin with ddGTP and pp(CH2)pddG (0.5 mg/ml) than with pp(CH2)pG (2.5 mg/ml). De novo assembly, which occurs readily with 2',3'-dideoxyguanosine 5'-diphosphate, was not observed with either alpha, beta-methylenediphosphate GDP analog.
Antineoplastic Agents↗
Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis.
OBJECTIVE: To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease. DESIGN: A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression. SETTING: Community- and university-based cardiac catheterization laboratories. SUBJECTS: A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION: Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized). OUTCOME: Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary angiography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S). RESULTS: Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS: These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.
Adult↗
Domestic violence against women. Incidence and prevalence in an emergency department population.
OBJECTIVE: To determine the incidence, 1-year prevalence, and cumulative prevalence of domestic violence (DV) among female emergency department (ED) patients. DESIGN: Descriptive written survey. SETTING: Two teaching EDs, two hospital walk-in clinics, and one private hospital ED in Denver, Colo. PARTICIPANTS: Of 833 women presenting during 30 randomly selected 4-hour time blocks, 648 (78%) agreed to participate. Most respondents were young (median age, 34 years) and unemployed (62%); half (49%) had annual household incomes less than $10,000. MAIN OUTCOME MEASURES: Domestic violence was defined as an assault, threat, or intimidation by a male partner. Acute DV (incidence) and past DV exposure (1-year prevalence and cumulative prevalence) were determined. RESULTS: The incidence of acute DV among the 418 women with a current male partner was 11.7% (95% confidence interval [CI], 8.7% to 15.2%). Only 11 (23%) of these 47 women subjected to acute DV presented for care because of trauma, and only six (13%) either told staff about DV or were asked about DV by ED professionals. Among 230 women without current partners, 13 (5.6%) reported an episode of DV within the previous 30 days. For the entire sample, the cumulative lifetime prevalence of DV exposure was 54.2% (95% CI, 50.2% to 58.1%). Women exposed to acute or prior DV were more likely than unexposed women to have made suicide attempts (26% vs 8%; P < .001) and to report excessive ethanol use (24% vs 13%; P = .001). CONCLUSIONS: The incidence of acute DV is not as common among women visiting an ED as previously reported, although the cumulative prevalence of DV is strikingly high. Women who have experienced DV are seldom identified by ED professionals.
Adult↗
Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.
ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T-cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes.
Amino Acid Sequence↗
A transition in transcriptional activation by the glucocorticoid and retinoic acid receptors at the tumor stage of dermal fibrosarcoma development.
In transgenic mice harboring the bovine papillomavirus genome, fibrosarcomas arise along an experimentally accessible pathway in which normal dermal fibroblasts progress through two pre-neoplastic stages, mild and aggressive fibromatosis, followed by a final transition to the tumor stage. We found that the glucocorticoid receptor (GR) displays only modest transcriptional regulatory activity in cells derived from the three non-tumor stages, whereas it is highly active in fibrosarcoma cells. Upon inoculation into mice, the aggressive fibromatosis cells progress to tumor cells that have high GR activity; thus, the increased transcriptional regulatory activity of GR correlates with the cellular transition to the tumor stage. The intracellular levels of GR, as well as its hormone-dependent nuclear translocation and specific DNA binding activities, are unaltered throughout the progression. Strikingly, the low GR activity observed in the pre-neoplastic stages cannot be overcome by exogenous GR introduced by co-transfection. Moreover, comparisons of primary embryo fibroblasts and their transformed derivatives revealed a similar pattern--modest GR activity, unresponsive to overexpressed GR protein, in the normal cells was strongly increased in the transformed cells. Likewise, the retinoic acid receptor (RAR) displayed similar differential activity in the fibrosarcoma pathway. Thus, the oncogenic transformation of fibroblasts, and likely other cell types, is accompanied by a striking increase in the activities of transcriptional regulators such as GR and RAR. We suggest that normal primary cells have a heretofore unrecognized capability to limit the magnitude of induction of gene expression.
Animals↗
Antibody to hepatitis C virus second envelope (HCV-E2) glycoprotein: a new marker of HCV infection closely associated with viremia.
The second envelope protein (E2) of the hepatitis C virus (HCV) was cloned and expressed in Chinese hamster ovary (CHO) cells. This E2 glycoprotein was purified using ion exchange and lectin chromatography and used to construct an enzyme immunoassay for HCV E2 antibodies. The assay was shown to have good specificity, and detection of E2 antibodies was positively correlated (97.3%) to the presence of HCV RNA in serum and plasma. A high concordance between HCV 2.0 and E2 EIA reactivities was also observed. E2 antibody was the first serological marker to appear in 3/5 HCV seroconversion panels. This work demonstrated that 42.4% of core and 15.4% of NS3 indeterminate specimens also contained antibodies to E2, suggesting that HCV infection had occurred in these individuals. The E2 antibody assay was used to evaluate HCV 2.0 EIA-positive, HCV 3.0 EIA-negative plasma donors with indeterminate reactivity on RIBA HCV 2.0 or MATRIX HCV 1.0. Several HCV 3.0-negative specimens were shown to contain E2 antibodies in addition to an original indeterminate serological marker, primarily core. It is concluded that anti-E2 is a useful marker for determining HCV infection, and that the presence of antibodies to two nonoverlapping viral gene products suggests true HCV exposure. New HCV 3.0 blood screening tests should detect HCV 2.0-positive donors who present with an indeterminate pattern by RIBA or MATRIX and who also carry E2 antibodies.
Animals↗
Fabrication and characterization of dipalmitoylphosphatidylcholine-attracting elastomeric material for joint replacements.
Wear debris associated with the polyethylene components of total joint replacements has been shown to induce bone resorption which contributes to implant loosening. In an effort to promote lubrication and reduce wear in artificial hip joints, the use of the cushion bearing concept has been proposed previously; however, an elastomeric material tested as a cushion bearing has been shown to have poor tribological properties during initiation of motion from rest. The goal of this project was to fabricate and characterize an elastomer that has the ability to attract to its surface naturally occurring boundary lubricants from an aqueous solution. The test elastomer and appropriate controls were characterized using fluorescence, electron spin resonance and X-ray photoelectron spectroscopy. The test elastomer was found to have an enhanced ability to attract dipalmitoylphosphatidylcholine, a known physiological boundary lubricant. A cushion bearing that also encourages boundary lubrication represents a potential improvement over currently existing orthopaedic implant-bearing materials.
1,2-Dipalmitoylphosphatidylcholine↗
Proliferating cell nuclear antigen expression in sheep infected with bovine leukemia virus.
Proliferating cell nuclear antigen (PCNA) or cyclin (C), a major nuclear protein, has been shown to be associated with human leukemia and malignancies. PCNA protein was quantitated in this study, in lymphocytes from bovine leukemia virus (BLV) infected and non-infected sheep, using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and silver staining. The PCNA mean levels in lymphocytes of BLV-infected sheep (27 months post-infection) was significantly (P < 0.001) higher than in the lymphocytes of the non-infected sheep. The mean of PCNA levels in lymphocytes of sheep, 21 days after BLV infection, showed a two-fold increase compared with the non-infected sheep. Phytohemagglutinin (PHA) (3 days) treatment of lymphocytes from the non-infected and from the BLV-infected sheep resulted in a significant (P < 0.01) increase in the mean of PCNA levels only in the non-infected sheep. The mean lymphocyte counts of the BLV-infected sheep were not significantly different from the mean counts of the non-infected sheep at the time of lymphocyte protein analysis. Thus, these findings showed, similar to human leukemia and malignancies, that high levels of PCNA were found in lymphocytes from BLV-infected sheep compared with those from the non-infected sheep, and this was independent of high cell count. Our results also suggest that PCNA protein may play a role in the process of lymphoid transformation as a result of BLV infection of sheep.
Amino Acid Sequence↗
Short-contact anthralin treatment augments therapeutic efficacy of cyclosporine in psoriasis: a clinical and pathologic study.
BACKGROUND: Psoriasis is characterized by immune activation and increased epidermal proliferation. Cyclosporine acts by reducing T lymphocyte numbers and lymphokine production. Anthralin inhibits keratinocyte proliferation. OBJECTIVE: We investigated whether topical anthralin would augment clearing of psoriasis produced by systemic cyclosporine. METHODS: Twelve patients with psoriasis were treated with cyclosporine (5 mg/kg per day). Patients applied anthralin only to plaques on half of their body. They were treated until a remission or maximum benefit was achieved. Disease activity was assessed by a severity index and quantitative histopathologic markers. RESULTS: Of the 12 patients, the skin of five cleared within 10 weeks irrespective of anthralin use. The other seven (slow responders) continued treatment for a mean of 18 weeks. Slow responders had a significantly lower severity index, a thinner epidermis, fewer CD8+ cells, and fewer proliferating keratinocytes on the anthralin-treated side than on the non-anthralin-treated side. CONCLUSION: The combination of cyclosporine and topical anthralin is effective in patients who are slow to respond to cyclosporine alone.
Administration, Cutaneous↗
Increased expression and activity of ornithine decarboxylase in chicks genetically selected for rapid growth rate.
Polyamines are essential requirements for cell proliferation and their role in stimulation of RNA, DNA, and protein synthesis is clearly established. Ornithine decarboxylase is a key enzyme in the biosynthesis of the polyamines and its activity is regulated in response to factors that stimulate cell proliferation. Steady-state ODC mRNA levels and enzyme activity were measured in muscle of chicks genetically selected for increased growth rate or for egg production. In muscle, muscle satellite cells and myotubes, two ODC mRNA transcripts are present of molecular size 2.05 and 1.75 kb. Northern blotting analysis suggest that these transcripts are produced as a result of using different polyadenylation sites. Between day 1 and day 6 after hatching, a period of rapid muscle growth in these animals, a peak in muscle ODC mRNA levels is followed by a peak in enzyme activity in both lines. Significantly higher ODC mRNA levels and enzyme activity are associated with selection for rapid growth in the broiler line. The results are consistent with other data showing that ODC is a major factor in cell growth and provide further evidence that it is a candidate 'trait-gene' for growth.
Animals↗
Alignment of total knee arthroplasty: the relationship to radiolucency around the tibial component.
Between January 1982 and July 1985, 122 cemented 'Accord' total knee replacements were performed. Out of this number, 21 were lost to follow-up because of death (in 16), revision (2) due to infection, and failure to attend (3). The post-operative alignment of 101 prostheses were compared to the incidence of radiolucencies around the tibial component at 5 years follow-up. The mechanical axis was used as a reference. The mean alignment was 0.99 degrees valgus with a standard deviation of 2.48 degrees. Some 72% of knees were within 3 degrees and 94% within 5 degrees of true alignment. Using two methods of assessing radiolucencies there was a non-significant relationship between the alignment and radiolucencies. The alignment tolerance with this prosthesis is, therefore, at least 5 degrees.
Adult↗