Employers who are developing strategies to reduce health-related productivity loss may benefit from aiming their interventions at the employees who need them most. We determined whether depression's ...negative productivity impact varied with the type of work employees performed. Subjects (246 with depression and 143 controls) answered the Work Limitations Questionnaire and additional work questions. Occupational requirements were measured objectively. In multiple regression analyses, productivity was most influenced by depression severity (P < 0.01 in 5/5 models). However, certain occupations also significantly increased employee vulnerability to productivity loss. Losse increased when employees had occupations requiring proficiency in decision-making and communication and/or frequent customer contact (P < 0.05 in 3/5 models). The Work Limitations Questionnaire can help employers to reduce productivity loss by identifying health and productivity improvement priorities.
Exposure to nitrogen dioxide (NO2) increases phosphatidylserine (PS) content in the plasma membranes of pulmonary artery endothelial cells (PAEC). We examined whether the increased PS content is ...associated with increased uptake of L-serine and/or biosynthesis of PS. Exposure to 5 ppm NO2 increased uptake and incorporation of exogenous L-14Cserine into whole cells, total cellular lipids, phospholipids, and phospholipid subclasses compared to control. Incorporation of L-14Cserine into the total lipid extracts from isolated plasma membranes, mitochondria, and microsomes from NO2-exposed cells was increased by 45, 32, and 31%, respectively (p < 0.05 for all membranes). Increased incorporation of L-14Cserine into the total phospholipids of plasma membranes, mitochondria, and microsomes of NO2-exposed cells was increased by 31, 48, and 33%, respectively (p < 0.05 for all membranes). Incorporation of L-14Cserine into the PS of plasma membranes and microsomes from NO2-exposed cells was increased by 63 and 89%, respectively (p < 0.05 for both membranes). The incorporation of radioactivity from L-14Cserine into the phosphatidylethanolamine and phosphatidylcholine contents of plasma membranes, mitochondria, and microsomes from NO2-exposed cells was also observed. Exposure of PAEC to NO2 resulted in a significant (p < 0.01) increase in the activity of PS synthase, the serine base-exchange enzyme located in the microsomes of these cells. When L-14Cserine-prelabeled microsomes were incubated with unlabeled mitochondria from control and NO2-exposed cells, transfer of PS-derived radioactivity from microsomes to mitochondrial phospholipids was observed. These results demonstrate that exposure to NO2 increases uptake and incorporation of exogenous serine as well as intracellular biosynthesis of PS, resulting in increases in the PS content of PAEC and their plasma membranes.
Although neonatal alloimmune thrombocytopenia (NAIT) due to maternal sensitization to human platelet antigens is well described, the role of maternal anti-human lymphocyte antigen (HLA) antibodies in ...NAIT is not yet firmly established.
A 31-week-old girl born prematurely to a G2POA1 mother was noted to have thrombocytopenia which lasted 18 days without any evidence of infection.
Platelet-associated IgG, anti-platelet antibody, and platelet PL(A1) antigen typing were determined using a commercial solid-phase red cell adherent test. Antibodies to platelet glycoproteins human platelet antigen (HPA) 1 to 5 were determined using a commercial ELISA. Anti-HLA antibodies were assayed using a standard lymphocytotoxicity test. Activities and IgG subclass of anti-HLA antibodies in plasma of the mother and other postpartum mothers were measured using purified HLA antigens in an enzyme linked immunoassay.
Both mother and infant were positive for HPA-1 (PL(A1)) antigens. The mother's HLA phenotype was A3, A31, B7, B27. The level of platelet-associated IgG was not increased on maternal platelets; however, increased platelet-associated IgG was detected on the infant's platelets. Antibodies to platelet glycoproteins HPA1 to 5 were not detectable in the maternal plasma. Maternal serum was positive for anti-HLA antibodies, which reacted to 23 of 27 panel cells. The presence of HLA antibodies was confirmed by enzyme-linked immunoassay. Of note, the maternal antibodies reacted positively to the infant's platelets and anti-IgG anti-HLA antibodies were detected in the serum sample from the infant collected at birth. When the activity and IgG subclass of the maternal anti-HLA antibodies were compared with those of other mothers known to have high anti-HLA antibody activity, no differences were noted.
This report documents a patient with neonatal thrombocytopenia induced by maternal IgG anti-HLA antibody. Neither activity nor IgG subclass could explain the occurrence of NAIT. The factors that contribute to NAIT induced by maternal anti-HLA antibodies remain to be identified.
Reduced protein expression of the cardiac ryanodine receptor type 2 (RyR2) is thought to affect the susceptibility to stress-induced ventricular tachyarrhythmia (VT) and cardiac alternans, but direct ...evidence for the role of RyR2 protein expression in VT and cardiac alternans is lacking. Here, we used a mouse model (
) that expresses a reduced level of the RyR2 protein to determine the impact of reduced RyR2 protein expression on the susceptibility to VT, cardiac alternans, cardiac hypertrophy, and sudden death. Electrocardiographic analysis revealed that after the injection of relatively high doses of caffeine and epinephrine (agents commonly used for stress test), wild-type (WT) mice displayed long-lasting VTs, whereas the
mutant mice exhibited no VTs at all, indicating that the
mutant mice are resistant to stress-induced VTs. Intact heart Ca
imaging and action potential (AP) recordings showed that the
mutant mice are more susceptible to fast-pacing induced Ca
alternans and AP duration alternans compared with WT mice. The
mutant mice also showed an increased heart-to-body-weight ratio and incidence of sudden death at young ages. Furthermore, the
mutant hearts displayed altered Ca
transients with increased time-to-peak and decay time (
), increased ventricular wall thickness and ventricular cell area compared with WT hearts. These results indicate that reduced RyR2 protein expression suppresses stress-induced VTs, but enhances the susceptibility to cardiac alternans, hypertrophy, and sudden death.
We present seismic and auditory frequency tuning curves of individual bullfrog, Rana catesbeiana, saccular and amphibian papilla axons that responded to both seismic and auditory stimuli. In this ...study we found: 1) most saccular axons respond well to auditory stimuli with moderate signal strength (50-70 dB SPL) as well as to seismic stimuli; 2) most amphibian papilla axons respond well to seismic stimuli as well as to auditory stimuli, and their seismic sensitivities are comparable to those of saccular axons (responding to sinusoidal stimuli with peak accelerations in the range 0.001 to 0.1 cm/S2); 3) the responses to both seismic and auditory stimuli from both saccule and amphibian papilla are tuned, i.e. the strength of the response varies with the frequency of the stimulus; and this tuning is clearly not the result of second order resonance; 4) in individual axons the tuning properties for seismic stimuli often are not the same as those for auditory stimuli, a fact that may provide clues about how the stimulus signal energy is transferred to the hair cells in each case.
Genetically engineered mice are used to study the role of single genes in cerebral ischemia, but inherent, strain-dependent differences in neuronal vulnerability may affect experimental end points. ...To examine this possibility, tissue injury resulting from focal ischemia and its relationship to cerebral hemodynamics were determined in 3 common mutant mouse strains.
Permanent middle cerebral artery ligation was performed in male C57BL/6J, Balb/C, and 129X1/SvJ mice. Mean arterial blood pressure, blood gases, basal and postischemic cortical blood flow ((14)Ciodoantipyrine autoradiography and laser-Doppler flowmetry), posterior communicating artery patency, and infarct size were determined.
Basal cortical blood flow did not differ among strains. Ten minutes after middle cerebral artery ligation, relative red cell flow in the ischemic cortex was 6% to 7% of preischemic flow in every strain. Despite similar hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than those in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains was not significantly different. The posterior communicating artery was either poorly developed or absent in >90% of the Balb/C and C57BL/6J but in <50% of the 129X1/SvJ mice.
The extent of ischemic injury differed markedly between the 3 strains. The presence and patency of posterior communicating arteries, although variable among strains, did not affect preischemic or postischemic cortical blood flow or bear any relationship to ischemic injury. Therefore, intrinsic factors, other than hemodynamic variability, may contribute to the differences in ischemic vulnerability among strains. These findings underscore the importance of selecting genetically matched wild-type controls.
The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A ...recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the primary isolates tested at concentrations that could be achieved by passive immunization, for example, to interrupt maternal-fetal transmission of virus. The broad specificity and efficacy of the antibody implies the conservation of a structural feature on gp120, which could be important in vaccine design.
Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24-/-) have indicated a role for Zmpste24 in the ...processing of CAAX-type prenylated proteins. Here, we report the pathologic consequences of Zmpste24 deficiency in mice. Zmpste24-/-mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures-akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in Zmpste24-/-mice. Zmpste24-/-mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated CAAX protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle weakness in Zmpste24-/-mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.
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