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Copyright of International Forestry Review is the property of Commonwealth Forestry Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To evaluate the relationships between perceived stigma and duration of untreated psychosis (DUP), demographic characteristics, and clinical and psychosocial functioning in persons with a first episode of psychosis (FEP). Method: A total of 399 participants with FEP presenting for treatment at 34 sites in 21 states throughout the United States were evaluated using standardized instruments to assess diagnosis, symptoms, psychosocial functioning, perceived stigma, wellbeing, and subjective recovery. Results: Perceived stigma was correlated with a range of demographic and clinical variables, including DUP, symptoms, psychosocial functioning, and subjective experience. After controlling for symptom severity, perceived stigma was related to longer DUP, schizoaffective disorder diagnosis, more severe depression, and lower wellbeing and recovery. The associations between stigma and depression, wellbeing, and recovery were stronger in individuals with long than short DUP, suggesting the effects of stigma on psychological functioning may be cumulative over the period of untreated psychosis. Conclusion: The findings suggest that independent of symptom severity, perceived stigma may contribute to delay in seeking treatment for FEP, and this delay may amplify the deleterious effects of stigma on psychological functioning. The results point to the importance of reducing DUP and validating interventions targeting the psychological effects of stigma in people with FEP. [ABSTRACT FROM AUTHOR]

Understanding how rising seawater pCO2 and temperatures impact coral aragonite accretion is essential for predicting the future of reef ecosystems. Here, we report 2 long-term (10-11 month) studies assessing the effects of temperature (25 and 28 °C) and both high and low seawater pCO2 (180-750 μatm) on the calcification, photosynthesis and respiration of individual massive Porites spp. genotypes. Calcification rates were highly variable between genotypes, but high seawater pCO2 reduced calcification significantly in 4 of 7 genotypes cultured at 25 °C but in only 1 of 4 genotypes cultured at 28 °C. Increasing seawater temperature enhanced calcification in almost all corals, but the magnitude of this effect was seawater pCO2 dependent. The 3 °C temperature increase enhanced calcification rate on average by 3% at 180 μatm, by 35% at 260 μatm and by > 300% at 750 μatm. The rate increase at high seawater pCO2 exceeds that observed in inorganic aragonites. Responses of gross/net photosynthesis and respiration to temperature and seawater pCO2 varied between genotypes, but rates of all these processes were reduced at the higher seawater temperature. Increases in seawater temperature, below the thermal stress threshold, may mitigate against ocean acidification in this coral genus, but this moderation is not mediated by an increase in net photosynthesis. The response of coral calcification to temperature cannot be explained by symbiont productivity or by thermodynamic and kinetic influences on aragonite formation. [ABSTRACT FROM AUTHOR]

To investigate the Mg2+ regulation in neuropile glial (NG) cells and pressure (P) neurones of the leech Hirudo medicinalis the intracellular free Mg2+ ([Mg2+]i) and Na+ ([Na+]i) concentrations, as well as the membrane potential ( Em), were measured using Mg2+- and Na+-selective microelectrodes. The mean steady-state values of [Mg2+]i were found to be 0.91 mM (mean Em=–63.6 mV) in NG cells and 0.20 mM (mean Em=–40.6 mV) in P neurones with a [Na+]i of 6.92 mM (mean Em=–61.6 mV) and 7.76 mM (mean Em=–38.5 mV), respectively. When the extracellular Mg2+ concentration ([Mg2+]o) was elevated, [Mg2+]i in P neurones increased within 5–20 min whereas in NG cells a [Mg2+]i increase occurred only after long-term exposure (6 h). After [Mg2+]o was reduced back to 1 mM, a reduction of the extracellular Na+ concentration ([Na+]o) decreased the inwardly directed Na+ gradient and reduced the rate of Mg2+ extrusion considerably in both NG cells and P neurones. In P neurones Mg2+ extrusion was reduced to 15.4% in Na+-free solutions and to 6.0% in the presence of 2 mM amiloride. Mg2+ extrusion from NG cells was reduced to 6.2% in Na+-free solutions. The results suggest that the major [Mg2+]i-regulating mechanism in both cell types is Na+/ Mg2+ antiport. In P neurones a second, Na+-independent Mg2+ extrusion system may exist. [ABSTRACT FROM AUTHOR]

Background/objectives: The body's immune response to infections and vaccination leads to the formation of memory B cells (MBCs), which protect against future infections. MBCs circulate in the blood, and the strength of the MBC response is measured with different tests. In this study, tests to measure the MBC response were compared., Methods: An MBC enzyme-linked immunospot assay (MBC-ELISpot), which counts the antibody-releasing cells (MASCs) that arise from memory B cells in vitro, and two versions of an MBC enzyme-linked immunosorbent assay (MBC-ELISA), which measures the concentration of antibodies released by the MASCs, were compared. The lower measurement limit of MBC-ELISpot and ELISA was determined, and it was investigated how the measurement results of individual samples and in a sample of test persons correlate., Results: Both methods had similar lower limits of detection, and the antibody concentration correlated strongly with the number of MASCs in individual samples. The antibody concentrations measured on a sample correlated with Pearson correlation coefficients of R = 0.83-0.87 with the number of MASCs, and the proportion of antigen-specific antibodies in total IgG correlated with R = 0.74-0.82 with the proportion of antigen-specific MASCs in all antibody-secreting cells., Conclusions: Since the measurement sensitivity of MBC-ELISA and MBC-ELISpot is similar and the measurement results correlate strongly in a random sample, the tests are interchangeable. The MBC-ELISA has an advantage over the ELISpot in that the antibody measurements can be divided up over time, repeated, and extended. This creates new possibilities for measuring the MBC response.

Ocean acidification typically reduces coral calcification rates and can fundamentally alter skeletal morphology. We use atomic force microscopy (AFM) and microindentation to determine how seawater pCO 2 affects skeletal structure and Vickers hardness in a Porites lutea coral. At 400 µatm, the skeletal fasciculi are composed of tightly packed bundles of acicular crystals composed of quadrilateral nanograins, approximately 80-300 nm in dimensions. We interpret high adhesion at the nanograin edges as an organic coating. At 750 µatm the crystals are less regular in width and orientation and composed of either smaller/more rounded nanograins than observed at 400 µatm or of larger areas with little variation in adhesion. Coral aragonite may form via ion-by-ion attachment to the existing skeleton or via conversion of amorphous calcium carbonate precursors. Changes in nanoparticle morphology could reflect variations in the sizes of nanoparticles produced by each crystallization pathway or in the contributions of each pathway to biomineralization. We observe no significant variation in Vickers hardness between skeletons cultured at different seawater pCO 2 . Either the nanograin size does not affect skeletal hardness or the effect is offset by other changes in the skeleton, e.g. increases in skeletal organic material as reported in previous studies., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Biomolecules play key roles in regulating the precipitation of CaCO 3 biominerals but their response to ocean acidification is poorly understood. We analysed the skeletal intracrystalline amino acids of massive, tropical Porites spp. corals cultured over different seawater pCO 2 . We find that concentrations of total amino acids, aspartic acid/asparagine (Asx), glutamic acid/glutamine and alanine are positively correlated with seawater pCO 2 and inversely correlated with seawater pH. Almost all variance in calcification rates between corals can be explained by changes in the skeletal total amino acid, Asx, serine and alanine concentrations combined with the calcification media pH (a likely indicator of the dissolved inorganic carbon available to support calcification). We show that aspartic acid inhibits aragonite precipitation from seawater in vitro, at the pH, saturation state and approximate aspartic acid concentrations inferred to occur at the coral calcification site. Reducing seawater saturation state and increasing [aspartic acid], as occurs in some corals at high pCO 2 , both serve to increase the degree of inhibition, indicating that biomolecules may contribute to reduced coral calcification rates under ocean acidification.

Deciding whether to disclose one's psychiatric disorder to a prospective employer is a complex decision for people with severe mental illness seeking to return to work, with potential advantages and disadvantages. The present study examined the rates, patterns, and correlates of disclosure in 51 participants (74.5% schizophrenia or schizoaffective disorder) receiving high fidelity Individual Placement Support (IPS) who obtained competitive work over a two-year study period. Most participants (64.7%) disclosed their psychiatric disorder in their first job, and there was a tendency for those with multiple jobs who did not disclose initially to shift to disclosure in subsequent jobs. Participants who disclosed for their first job had worse baseline cognitive scores on the Positive and Negative Syndrome Scale (PANSS), lower self-esteem, and poorer psychosocial functioning than those who did not disclose. However, participants who disclosed to their first employer were more likely to obtain jobs that matched their interests, and worked significantly longer than those who did not disclose (32.55 vs. 12.50 weeks, respectively). The findings suggest that individuals receiving supported employment who disclose their mental illness to prospective employers may have better work outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coral skeletal Sr/Ca is a palaeothermometer commonly used to produce high resolution seasonal sea surface temperature (SST) records and to investigate the amplitude and frequency of ENSO and interdecadal climate events. The proxy relationship is typically calibrated by matching seasonal SST and skeletal Sr/Ca maxima and minima in modern corals. Applying these calibrations to fossil corals assumes that the temperature sensitivity of skeletal Sr/Ca is conserved, despite substantial changes in seawater carbonate chemistry between the modern and glacial ocean. We present Sr/Ca analyses of 3 genotypes of massive Porites spp. corals (the genus most commonly used for palaeoclimate reconstruction), cultured under seawater pCO2 reflecting modern, future (year 2100) and last glacial maximum (LGM) conditions. Skeletal Sr/Ca is indistinguishable between duplicate colonies of the same genotype cultured under the same conditions, but varies significantly in response to seawater pCO2 in two genotypes of Porites lutea, whilst Porites murrayensis is unaffected. Within P. lutea, the response is not systematic: skeletal Sr/Ca increases significantly (by 2-4%) at high seawater pCO2 relative to modern in both genotypes, and also increases significantly (by 4%) at low seawater pCO2 in one genotype. This magnitude of variation equates to errors in reconstructed SST of up to -5 °C.

Prior research into the link between cognitive and psychosocial functioning in bipolar disorder has examined primarily asymptomatic patients, has measured these domains concurrently, and has failed to establish convergent validity in the assessment of psychosocial dysfunction. The present study examines the relation between cognitive and psychosocial functioning at the time of discharge from hospitalization for acute mood disturbance. We obtained measures of psychosocial functioning that were both close and distant to the time of neuropsychological testing; the former from the discharging psychiatrists, and the latter from reports of formally recognized disability status, determined by persons wholly unrelated to the present research. Sixty-three patients with bipolar I disorder, hospitalized for acute mood disturbance, completed a neuropsychological test battery 24 to 48 h prior to discharge. We compared patients with versus without formal disability status on the Global Assessment of Functioning (GAF) scale and on scores of neuropsychological tests. We also tested associations between GAF scores and cognitive test scores. Results supported the convergent validity in the measurement of psychosocial disability, underscored the robust connection between cognitive and psychosocial impairment, and highlighted the presence of this connection during an important clinical state - time of discharge from psychiatric hospitalization., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We propose a unifying hypothesis of schizophrenia to help reconcile findings from many different disciplines. This hypothesis proposes that schizophrenia often involves pre- or perinatal exposure to adverse factors that produce a latent immune vulnerability. When this vulnerability is manifested, beginning around puberty with changes in immune function and involution of the thymus, individuals become more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Our hypothesis suggests theoretical bridges between different lines of evidence on schizophrenia and offers explanations for many puzzling findings about schizophrenia. For example, the hypothesis helps account for why schizophrenia patients tend to have had increased exposure to neurotropic infections, but most individuals with such exposure do not develop schizophrenia, and why prenatal hardships increase risk for schizophrenia, but the onset of symptoms typically does not occur until after puberty. The hypothesis also explains another paradox: lower socioeconomic status and poor prenatal care increase risk for schizophrenia at the same geographic site, but international comparisons indicate that countries with higher per capita incomes and better prenatal care actually tend to have higher schizophrenia prevalences. As the hypothesis predicts, (1) prenatal adversity, which increases risk for schizophrenia, also impairs post-pubertal immune competence, (2) schizophrenia patients experience elevated morbidity from infectious and auto-immune diseases, (3) genetic and environmental risk factors for schizophrenia increase vulnerability to these diseases, (4) factors that exacerbate schizophrenic symptoms also tend to impair immune function, (5) many anti-psychotic medications combat infection, (6) effects of early infections may not appear until after puberty, when they can produce neurologic and psychiatric symptoms, and (7) immune dysfunctions, such as imbalances of pro- and anti-inflammatory cytokines, may contribute to the onset of psychotic symptoms and the progressive loss of brain tissue in schizophrenia. The disruptive effects of prenatal adversity on the development of the immune system may often combine with adverse effects on prenatal brain development to produce schizophrenia. This paper focuses on the adverse immune system effects, because effects on the brain have been extensively discussed in neurodevelopmental theories of schizophrenia. We propose new tests of scientific predictions. We also point out potential clinical implications of the hypothesis; for example, individuals with schizophrenia may often have underlying infections or immune dysfunctions, such as imbalances in inflammatory cytokines, that contribute to the illness. This possibility could be tested experimentally--e.g., by clinical trials in which patients' exposure to infection is reduced or immune function is normalized., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Antiviral antibody production during respiratory syncytial virus (RSV) infection in infants is poorly understood. To characterize local B lymphocyte responses, lung tissue and secretions from infants with RSV bronchiolitis were analyzed for innate B cell-stimulating factors and antiviral antibodies. In lung tissues of infants with fatal RSV bronchiolitis, CD20(+) lymphocytes and IgM-positive, IgG-positive, and IgA-positive plasma cells were prominent but CD4(+) T lymphocytes were not. Type I interferon-induced proteins and B cell tropic factors, including B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), were colocalized in infected epithelium. In nasopharyngeal secretions from infants who survived RSV infection, class-switched antiviral and antinucleosomal antibodies were detected at presentation and correlated with BAFF and APRIL levels. Expression of APRIL and antiviral antibodies of IgA and IgM but not IgG isotype predicted better oxygen saturation. We conclude that B lymphocyte-stimulating factors derived from infected epithelium are primary determinants of the mucosal antibody response in infant RSV bronchiolitis.

At the request of the United States Defense Advanced Research Projects Agency, we attempted to replicate the data of Professor Jacques Benveniste that digital signals recorded on a computer disc produce specific biological effects. The hypothesis was that a digitized thrombin inhibitor signal would inhibit the fibrinogen-thrombin coagulation pathway. Because of the controversies associated with previous research of Prof. Benveniste, we developed a system for the management of social controversy in science that incorporated an expert in social communication and conflict management. The social management approach was an adaptation of interactional communication theory, for management of areas that interfere with the conduct of good science. This process allowed us to successfully complete a coordinated effort by a multidisciplinary team, including Prof. Benveniste, a hematologist, engineer, skeptic, statistician, neuroscientist and conflict management expert. Our team found no replicable effects from digital signals.

Mg2+-extrusion from Mg2+-loaded neurons of the leech, Hirudo medicinalis, is mediated mainly by Na+/Mg2+ antiport. However, in a number of leech neurons, Mg2+ is extruded in the nominal absence of extracellular Na+, indicating the existence of an additional, Na+-independent Mg2+ transport mechanism. This mechanism was investigated using electrophysiological and microfluorimetrical techniques. The rate of Na+-independent Mg2+ extrusion from Mg2+-loaded leech neurons was found to be independent of extracellular Ca2+, K+, NO3-, HCO3-, SO4(2-), HPO4(2-), and of intra- and extracellular pH. Na+-independent Mg2+ extrusion was not inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), furosemide, ouabain, vanadate, iodoacetate, 4-amino-hippurate, or alpha-cyano-4-hydroxycinnamate and was not influenced by changes in the membrane potential in voltage-clamp experiments. Na+-independent Mg2+ extrusion was, however, inhibited by the application of 2 mM probenecid, a blocker of organic anion transporters, suggesting that Mg2+ might be co-transported with organic anions. Extracellularly, of all organic anions tested (malate, citrate, lactate, alpha-ketoglutarate, and 4-amino-hippurate) only high, but physiological, concentrations of malate (30 mM) had a significant inhibitory effect on Na+-independent Mg2+ extrusion. Intracellularly, iontophoretically injected malate, citrate, or fura-2, but not Cl-, alpha-ketoglutarate, glutamate, succinate, or urate, were stimulating Na+-independent Mg2+ extrusion from those neurons that initially did not extrude Mg2+ in Na+-free solutions. Our data indicate that Mg2+ is co-transported with organic anions, preferably with malate, the predominant extracellular anion in the leech. The proposed model implies that, under experimental conditions, malate drives Mg2+ extrusion, whereas under physiological conditions, malate is actively taken up, driven by Mg2+, so that malate can be metabolized.

Diabetes and hypertension both produce myocardial dysfunction that accelerates cardiovascular morbidity and mortality. Coexistence of the two often results in a more severe cardiomyopathy than either process alone. The purpose of this study was to characterize the contractile function of diabetic hypertensive cardiomyopathy at the single myocyte level. Adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were made diabetic with a single injection (55 mg/kg) of streptozotocin (STZ). Contractile properties of ventricular myocytes were evaluated, including peak shortening (PS), time-to-peak shortening (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (+/-dL/d t). The experimental animals exhibited enlarged heart size, elevated blood glucose and systolic blood pressure. PS was unchanged (SHR), enhanced (WKY-STZ) or depressed (SHR-STZ) compared to control (WKY). Myocytes from all experimental groups displayed prolonged TPS and TR90 compared to the WKY group, although only those from the hypertensive groups (SHR, SHR-STZ) were associated with reduced +/-dL/d t. Additionally, myocytes from the WKY-STZ but not the SHR or the SHR-STZ groups exhibited impaired responsiveness to increased extracellular Ca2+. Myocytes from the SHR-STZ group displayed a leftward shift of the stimulus frequency-peak shortening response curve compared to the WKY group. These results confirmed observations at the multicellular levels that combination of diabetes and hypertension results in a greater impairment of cardiac contractile function than is seen with either disease alone., (Copyright 2001 Academic Press.)

It has been suggested that the pathogenesis of respiratory syncytial virus (RSV) infection is related to the development of T helper (Th) type 2 cytokine responses. The presence of Th1 and Th2 cytokines and the chemokines macrophage inflammatory protein (MIP)-1alpha and monocyte chemotactic protein (MCP)-1 were assessed by ELISA in nasopharyngeal secretions of infants with RSV infection. Infants with mild bronchiolitis had increased Th1 cytokines and reduced Th2 cytokines, compared with infants with upper respiratory tract illness alone. Severe bronchiolitis was characterized by a more balanced Th1-Th2 response that did not differ from that of infants with upper respiratory tract illness alone. In contrast, MIP-1alpha was markedly increased in infants with severe bronchiolitis. MIP-1alpha and MCP-1 levels also were inversely related to oxygen saturation (P<.005). Thus, the severity of RSV bronchiolitis appears to be related more to chemokine release than to Th2 cytokine production.

We studied the effect of ovariectomy (OVX) on cardiac contraction in myocytes maintained under a 'diabetes-simulated high-glucose' environment. Female rats were ovariectomized or sham operated (SHAM) and kept for 6 weeks. Isolated myocytes were maintained in a diabetes-simulated high [glucose] medium (HG; 25.5 mM) for 24 h before mechanical properties were measured. Contractile indices analyzed included peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening and relengthening (+/- dL/dt), intracellular Ca2+ fura-2 fluorescence intensity and decay rate (tau). Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a longer TR(90), slower +/- dL/dt, lower fluorescence intensity and higher tau (slower decay rate) when compared to SHAM myocytes. In the SHAM group, HG exerted diabetes-like contractile dysfunctions, including depressed PS, prolonged TR90, reduced fluorescence intensity, higher tau and enhanced NOS activity when compared to myocytes maintained in low [glucose] medium (5.5 mM). Interestingly, the HG- induced mechanical alterations were significantly exaggerated (TPS, TR90 and tau), reversed (PS and NOS) or lost (+/- dL/dt and fluorescence intensity) in the OVX group. These data suggest that ovarian hormones play a role in the regulation of cardiac contractile function, and may have potentially protective effects against diabetes-associated cardiac dysfunction., (Copyright 2001 National Science Council, ROC and S. Karger AG, Basel)

Beavers store and consume tree parts in the bodies of water where they live. We examined whether such soaking renders food more palatable by leaching out undesirable compounds. In experiment 1, saplings of red maple, Acer rubrum (RM), were first soaked in a pond for periods of 2, 18, and 36 days, then offered to free-ranging beavers. Soaking for two days rendered RM slightly more acceptable to beavers. To further examine the time window around two days, RM sticks were soaked in distilled water in the laboratory for 1, 2, 4, and 6 days before presenting them to beavers (experiment 2). In experiment 3, twigs of three species were placed on land. Beavers placed RM in the water for 1 to 3 days before consuming the twigs. In experiment 4, sticks were provided in the water at Cranberry Lake Biological Station (CLBS). Most quaking aspen (QA) was consumed during the first night, and most witch hazel, Hamamelis virginiana (WH), during the third night. At Allegany State Park (ASP), no such difference was found. Twigs were provided in the water in experiment 5. At ASP, WH was taken after three days in the water, and at CLBS little WH was consumed, and only during the third night. A meta-analysis of all experiments shows that relatively more WH is consumed after two days than any other species. Experiment 6 traced the time beavers left their own harvested branches in the water. Unlike other tree species, WH remained in the water for two to four days before being consumed. Experiment 7 measured the phenolics leached into water from RM twigs and small pieces of bark soaked for 10 and 8 days, respectively. Shredded bark lost 50-60% of leachable phenolics into the water, and twigs 70-80%. We conclude that beavers can use water to leach undesirable compounds from their food. Although this effect was not robust, our study is the first of its kind.

Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and impaired ventricular function in a manner similar to postnatal chronic alcohol ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and dietary Mg2+ supplementation was shown to ameliorate ethanol- induced cardiovascular dysfunction such as hypertension. However, the role of gestational Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study was conducted to examine the influence of gestational dietary Mg2+ supplementation on prenatal ethanol exposure-induced cardiac contractile response at the ventricular myocyte level. Timed-pregnancy female rats were fed from gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on standard rat chow through adulthood, and ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix soft-edge system, and intracellular Ca2+ transients were measured as changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups displayed similar growth curves. Myocytes from the ethanol group exhibited reduced cell length, enhanced peak shortening (PS), and shortened time to 90% relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS). Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI, as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol group exhibited impaired responsiveness to increased extracellular Ca2+ or stimulating frequency, which were restored by gestational Mg2+ supplementation. These data suggest that although gestational Mg2+ supplementation may be beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics itself.

Immunologic mechanisms are thought to contribute to the pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in humans. RSV-infected BALB/c mice exhibit tachypnea and signs of outflow obstruction, similar to symptoms in humans. Interferon gamma (IFNgamma) has been found to be the predominant cytokine produced in humans and mice with RSV infection. We therefore undertook this study to evaluate the role of IFNgamma in the development of respiratory illness in RSV-infected mice. BALB/c mice were infected with RSV, and lung function was assessed by plethysmography. Bronchoalveolar lavage (BAL) fluids were analyzed for the concentration of interferon gamma (IFNgamma) and the presence of inflammatory cells, and lung tissue sections were examined for histopathologic changes. The role of IFNgamma was further addressed in studies of IFNgamma knock-out mice (IFNgamma(-/-)) and of mice depleted of IFNgamma by in vivo administration of a neutralizing antibody. After infection, mice developed respiratory symptoms that were strongly associated with the number of inflammatory cells in BAL, as well as with the concentrations of IFN-gamma. Both IFN-gamma(-/-) mice and mice treated with anti-IFNgamma developed more extensive inflammation of the airways than control mice. However mice lacking IFNgamma exhibited less severe signs of airway obstruction. Together these data suggest a protective role of IFNgamma in RSV infection in terms of limiting viral replication and inflammatory responses but also a pathogenic role in causing airway obstruction., (Copyright 2000 Wiley-Liss, Inc.)

Background: An imbalance of production of T-helper lymphocyte cytokines, favoring overproduction of IL-4, is believed to be important in the pathogenesis of allergic asthma. However, less is known about the cytokine response in virus-induced wheezing, which is a major cause of morbidity in asthma., Objective: We undertook this study to determine the magnitude of IFN-gamma, IL-4 and IL-10, and leukotriene (LT) responses in infants and children with virus-induced wheezing., Methods: We measured the concentrations of IFN-gamma, IL-4 and IL-10, and cysteinyl LTs in respiratory secretions of 82 infants and young children during acute episodes of virus-induced wheezing. Control subjects were 47 infants and children with uncomplicated upper respiratory infections and 18 normal healthy infants., Results: Ratios of IFN-gamma to IL-4 were higher (due to increased quantities of IFN-gamma) in subjects with wheezing than in those with upper respiratory infection alone (P =. 003). Quantities of LTs were also increased in wheezing subjects in comparison with those with upper respiratory infections (P =.009). There was a significant correlation between measured concentrations of IFN-gamma and LTs (correlation coefficient =.451, P =.007). Quantities of IL-4 were slightly suppressed in the wheezing groups., Conclusions: An imbalance favoring overproduction of IFN-gamma appears to be associated temporarily with virus-induced wheezing. A possible mechanism is the enhanced release of LTs from eosinophils or mast cells after sensitization by IFN-gamma.

Previously, we demonstrated an energy-dependent injury to cultured liver endothelial cells during cold incubation in University of Wisconsin (UW) solution. Here, the effects of Histidine-Tryptophan-Ketoglutarate (HTK) and Euro-Collins (EC) solutions on these cells were studied. In HTK solution, 83% +/- 4% of the cells had lost viability after 9 h of incubation at 4 degrees C. The addition of cyanide (1 mM) to simulate hypoxic conditions protected the cells to the extent that only 9% +/- 1% of the cells lost viability over the same period; the addition of glucose (10 mM) led to increased cell injury. ATP levels were highest in the incubations with the most rapid loss of viability. In Krebs-Henseleit buffer and EC solution, in contrast, cell injury increased upon addition of cyanide; the addition of glucose to Krebs-Henseleit buffer decreased injury. We conclude that the injury to cultured liver endothelial cells during cold incubation in HTK solution is energy-dependent, as it is in UW solution, whereas cells behave differently in EC solution and Krebs-Henseleit buffer.