Early Increase Research Articles

CERAMIC VARIABILITY, SUBSISTENCE ECONOMIES, AND SETTLEMENT PATTERNS IN THE JORNADA MOGOLLON

This paper examines the contrast in subsistence and settlement adaptations in early pithouse villages between the highland and lowland regions of southern New Mexico and trans-Pecos Texas, notably more substantial pithouses and an earlier increase in agricultural dependence in the highlands than the lowlands, from the point of view of ceramic variability. Since subsistence and settlement patterns influence ceramic manufacture, we test for differences between highland and lowland utilitarian wares (brown wares) that parallel the region’s subsistencesettlement contrast. Evaluating ceramic mineralogy, we demonstrate that our highland sample brown wares were locally made and therefore distinct from adjacent lowland brown wares. We then compare the ceramic technology from the two elevation zones, hypothesizing that technological characteristics of highland pottery should foreshadow changes in lowland ceramics by several hundred years since agricultural dependence increased this much earlier in the highlands. We do not find significant technological differences between contemporary highland and lowland brown wares and suggest that assumptions linking ceramic technology and agricultural dependence may need to be refined.

Homicide due to mental disorder in England and Wales over 50 years

It has been stated that rates of homicide due to mental disorder are constant over time. To examine whether there were changes in the rates of homicide due to mental disorder over time, and whether changes in these rates were associated with changes in the rates of other homicides in England and Wales. Examination of four sets of official homicide statistics from England and Wales from 1946 to 2004. The rate of total homicide and the rate of homicide due to mental disorder rose steadily until the mid-1970s. From then there was a reversal in the rate of homicides attributed to mental disorder, which declined to historically low levels, while other homicides continued to rise. The reasons for the rise and fall in homicides attributed to mental disorder are not clear. The earlier increase in such homicides may have been due to the same sociological factors that caused the increase in other homicides over that time. The subsequent decline may have been due to improvements in psychiatric treatments and service organisation. Another possibility is that there has been an informal change to the legal tests for the finding of homicide due to mental disorder.

Serum Immunoglobulin free light chains as markers of disease burden and response to treatment in patients with Waldenstrom’s macroglobulinemia

8617 Background: Waldenstrom’s macroglobulinemia (WM) is a B-cell malignancy characterized by the presence of a serum monoclonal IgM protein, which is used to monitor both disease burden and response to treatment. Serum free light chains (sFLC) have recently emerged as a reliable tool to assess disease activity in patients with plasma cell disorders. Methods: To determine the role of sFLC in WM, we retrospectively-assessed the baseline levels of sFLC in 145 untreated, asymptomatic, patients using the Freelite sFLC assay (The Binding Site Ltd. UK). We also correlated sFLC with response to treatment, and performed serial measurements on symptomatic patients who received treatment on a clinical trial with BDR [Bortezomib, Dexamethasone, Rituximab]. Results: Of the 145 WM patients evaluated, 114 (78.6%) had an IgM-k and 31 (21.4%) had an IgM-λ paraprotein. Of the 114 patients with IgM-k, 88 (77%) had an elevated free k-LC and 103 (90%) had an abnormal κ/λ ratio. In the remaining 31 patients with IgM-λ, 23 (74%) had an elevated free λ-LC while 18 (58%) had an abnormal κ/λ ratio. Baseline sFLC levels were lower in asymptomatic patients [mean k-LC 129.42 mg/L (n=34) and mean λ- LC 49.97 mg/L (n=6)] compared to those with symptomatic disease [mean k-LC 261.45 mg/L (n=62) and mean λ-LC 301.73 mg/L (n=19), but did not reach statistical significance. Serial measurements of FLCs and comparison to the changes in the corresponding IgM values demonstrated a significant decrease in 2/6 responders tested 10 and 46 days post-treatment (10 days: 55% vs. 18%, 46 days: 81% vs. 39%). Similarly, an earlier increase in sFLCs was observed in the 2/4 non-responder patients after the 2nd-course of therapy, with a 44% and 128% increase in k and l-FLC vs. a 16% and 17% decrease in IgM, respectively. Conclusion: These results demonstrate that sFLC are significantly-elevated in patients with WM. Higher levels were observed in symptomatic versus asymptomatic patients. Preliminary evidence also suggests that sFLC maybe a more-sensitive and a better marker of response to treatment and disease progression than the current standard of serum IgM. No significant financial relationships to disclose.

Roux-en-Y Gastric Bypass is Associated with Early Increased Risk Factors for Development of Calcium Oxalate Nephrolithiasis

Patients treated for obesity with jejunoileal bypass (JIB) experienced a marked increased risk of hyperoxaluria, nephrolithiasis, and oxalate nephropathy developing. Jejunoileal bypass has been abandoned and replaced with other options, including Roux-en-Y gastric bypass (RYGB). Changes in urinary lithogenic risk factors after RYGB are currently unknown. Our purpose was to determine whether RYGB is associated with elevated risk of developing calcium oxalate stone formation through increased urinary oxalate excretion and relative supersaturation of calcium oxalate. A prospective longitudinal cohort study of 24 morbidly obese adults (9 men and 15 women) recruited from a university-based bariatric surgery clinic scheduled to undergo RYGB between December 2005 and April 2007. Patients provided 24-hour urine collections for analysis 7 days before and 90 days after operation. Primary outcomes were changes in 24-hour urinary oxalate excretion and relative supersaturation of calcium oxalate from baseline to 3 months post-RYGB. Compared with their baseline, patients undergoing RYGB had increased urinary oxalate excretion (31 +/- 10 mg/d versus 41 +/- 18 mg/d; p = 0.026) and relative supersaturation of calcium oxalate (1.73 +/- 0.81 versus 3.47 +/- 2.59; p = 0.030) 3 months post-RYGB in six patients (25%). De novo hyperoxaluria developed. There were no preoperative patient characteristics predictive of development of de novo hyperoxaluria or the magnitude of change of daily oxalate excretion. This prospective study indicates that RYGB is associated with an earlier increase in urinary oxalate excretion and relative supersaturation of calcium oxalate than previously reported. Additional studies are needed to determine longterm post-RYGB changes in urinary oxalate excretion and identify patients that might be at risk for hyperoxaluria developing.

CMV increases tubular apoptosis through the TNF-α–TNF-R1 pathway in a rat model of chronic renal allograft rejection

IntroductionDestruction of transplanted kidneys through chronic allograft nephropathy [CAN], also known as chronic rejection, is the greatest obstacle in successful kidney transplantation. Causes behind CAN are many, from pre-transplant causes to infections. Viral infections, especially CMV, are a risk factor for chronic rejection. We have previously developed a rat kidney transplant model, in which CMV enhances the development of chronic rejection under triple drug treatment. In this model we have now further studied the routes of apoptosis in virus induced early CAN vs. the routes of apoptosis in a later developing non-infectious CAN. Materials and methodsRenal transplantations were performed in a strain combination of DA/BN under immunosuppression. One group of animals was infected with RCMV and the other was left uninfected. The grafts were harvested on days 3–40 after transplantation. Apoptotic cells were visualised by in situ terminal transferase mediated dUTP nick end labelling [TUNEL] from paraffin embedded, formalin fixed kidney grafts. Cytokines were labelled imunohistochemically from frozen sections, among them tumour necrosis factor alpha [TNF-α] and its receptor-protein 1 [TNF-R1] as well as CD 95 [FAS], caspase 3 and CD14. The results were semi-quantitatively scored from 0 to 3+ over various tissues structures separately. ResultsIn the CMV infected grafts, we could demonstrate a more intense TUNEL reaction in tubular epithelium [2.0±1.0 vs. 0.8±0.5 at day 14, P<0.05] as well as an earlier increase in the expression TNF-α in the vascular endothelium [2.0+1.0 vs. 0.0+0.0 at days 3–5, P<0.05] than in the non-infected group. There was also an earlier increase in the tubular TNF-R1 expression [2.2+0.8 vs. 1.0+0.0 at days 5–7, P<0.05]. There was no difference in the expression of CD14, caspase 3 or FAS between the groups. ConclusionsCMV enhanced development of CAN was associated with tubular apoptosis and concomitant increase of TNF-α-TNF-R1, rather than the FAS–FAS-ligand activation.

Physiological effects of ultrasound mist on fibroblasts

Chronic wounds present an increasing challenge in healthcare and consume a substantial portion of healthcare cost. Although new treatments have been developed, treatment success has not been improved greatly. Ultrasound has long been employed in medicine. Its unique ability to deliver energy makes it an ideal candidate as a wound care modality. We proposed that ultrasound would differentially affect intracellular signaling pathways and, with the ability to assess this effect using a noncontact form of ultrasound, were provided with a means to test this proposal. The cellular morphology, mitogenic activities, expression of keratinocyte growth factor (KGF) and transforming growth factor beta-1 (TGF-beta1), and activation of extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways of dermal fibroblasts were studied after ultrasound treatment. Untreated and scrape-wounded fibroblasts were utilized as controls. There was no difference in morphology observed, except for vacuolization in ultrasound-treated fibroblasts. Mitogenic activities were similar between ultrasound-treated and scrape-wounded fibroblasts. Ultrasound-treated fibroblasts exhibited a much earlier increase in KGF expression, ERK activation, and JNK activation. The ERK/JNK ratio was increased markedly in ultrasound-treated fibroblasts. We conclude that ultrasound induces cellular responses that may be beneficial to wound healing.

Dielectric permittivity simulations of layered composites with rough interfacial surfaces

Finite difference quasi-electrostatic simulations are used to predict the interfacial dielectric permittivity of a rough-surfaced contact zone between two distinct materials in a layered composite. Fractional Brownian surfaces, which have fractal geometry, are used to represent the rough interfaces in a model space. The interfacial simulations are combined with a macroscopic analytic model for planar dielectric layers, which allows the calculation of composite permittivity for a layered composite with an arbitrary ratio of surface roughness-to-layer thickness and arbitrary volumetric filling fractions of the constituents. Examples are given for a ceramic-polymer system, and the effects of alternate ratios of constituent dielectric permittivities and changes in surface fractal character are also explored. Compared to the behavior of composites with perfectly flat interfaces, the rough-surfaced composite exhibits a significantly earlier increase in permittivity as a function of the volumetric filling fraction of the higher permittivity material. The behavior with extremely rough surfaces tends towards the predictions of the effective medium approximation

Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales

To estimate long-term trends in cannabis use and projections of schizophrenia assuming a causal relation between cannabis use and schizophrenia. Trends in cannabis use were estimated from a national survey, 2003; and incidence of schizophrenia was derived from surveys in three English cities, 1997-99. A difference equation cohort model was fitted against estimates of schizophrenia incidence, trends in cannabis exposure and assumptions on association between cannabis and schizophrenia. The model projects trends in schizophrenia incidence, prevalence and attributable fraction of cannabis induced schizophrenia. Between 1970 and 2002 cannabis exposure increased: incidence by fourfold; period prevalence by 10-fold; and use among under 18-year-olds by 18-fold. In 1997-99 incidence and prevalence of schizophrenia were 17 per 100 000 and 0.63% among men and 7.3 per 100 000 and 0.23% among women, respectively. If cannabis use causes schizophrenia, earlier increases in cannabis use would lead to increases in overall schizophrenia incidence and prevalence of 29% and 12% among men between 1990 and 2010. By 2010 model projections which assume an association between schizophrenia and light and heavy users suggest that approximately one-quarter of new schizophrenia cases could be due to cannabis, whereas if the association is twofold and confined to heavy cannabis users, then approximately 10% of schizophrenia cases may be due to cannabis. If cannabis use causes schizophrenia, and assuming other causes are unchanged, then relatively substantial increases in both prevalence and incidence of schizophrenia should be apparent by 2010. More accurate data on cannabis consumption and future monitoring of schizophrenia are critical.

Mice Lacking bi-1 Gene Show Accelerated Liver Regeneration

The liver has enormous regenerative capacity such that, after partial hepatectomy, hepatocytes rapidly replicate to restore liver mass, thus providing a context for studying in vivo mechanisms of cell growth regulation. Bax inhibitor-1 (BI-1) is an evolutionarily conserved endoplasmic reticulum (ER) protein that suppresses cell death. Interestingly, the BI-1 protein has been shown to regulate Ca(2+) handling by the ER similar to antiapoptotic Bcl-2 family proteins. Effects on cell cycle entry by Bcl-2 family proteins have been described, prompting us to explore whether bi-1-deficient mice display alterations in the in vivo regulation of cell cycle entry using a model of liver regeneration. Accordingly, we compared bi-1(+/+) and bi-1(-/-) mice subjected to partial hepatectomy with respect to the kinetics of liver regeneration and molecular events associated with hepatocyte proliferation. We found that bi-1 deficiency accelerates liver regeneration after partial hepatectomy. Regenerating hepatocytes in bi-1(-/-) mice enter cell cycle faster, as documented by more rapid incorporation of deoxynucleotides, associated with earlier increases in cyclin D1, cyclin D3, cyclin-dependent kinase (Cdk) 2, and Cdk4 protein levels, more rapid hyperphosphorylation of retinoblastoma protein, and faster degradation of p27(Kip1). Dephosphorylation and nuclear translocation of nuclear factor of activated T cells 1 (NFAT1), a substrate of the Ca(2+)-sensitive phosphatase calcineurin, were also accelerated following partial hepatectomy in BI-1-deficient hepatocytes. These findings therefore reveal additional similarities between BI-1 and Bcl-2 family proteins, showing a role for BI-1 in regulating cell proliferation in vivo, in addition to its previously described actions as a regulator of cell survival.

Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication

This study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD). In 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication. In the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120-180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004). After fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

Global Patterns and Determinants of Sex Differences in Smoking

The worldwide spread of tobacco use in recent decades raises questions about the relative prevalence of smoking among men and women. Does the degree of gender equality in nations promote equality in cigarette use? Does rising use of cigarettes by women stem from the stage of cigarette diffusion and earlier increases among men? Or have changes in economic factors and smoking policy affected the sexes differently? This study uses aggregate data for 106 nations, measures of smoking prevalence circa 2000, and lagged measures of gender equality, cigarette diffusion, and tobacco access to address these questions and evaluate the underlying theories. With the logged ratio of female to male prevalence as the dependent variable, regression results reveal that gender equality has inconsistent effects on women's smoking relative to men, cigarette diffusion has more consistent and moderately strong effects, and economic factors have weak effects. Global patterns of adoption of cigarettes by women appear most closely associated with the early adoption by men and then movement through a regular pattern of cigarette diffusion.

Control of molt in birds: Association with prolactin and gonadal regression in starlings

Despite the importance of molt to birds, very little is known about its environmental or physiological control. In starlings Sturnus vulgaris, and other species, under both natural conditions and experimental regimes, gonadal regression coincides with peak prolactin secretion. The prebasic molt starts at the same time. The aim of this series of experiments was to keep starlings on photo-schedules that would challenge the normally close relationship between gonadal regression and molt, to determine how closely the start of molt is associated with gonadal regression and/or associated changes in prolactin concentrations. In one series of experiments, photosensitive starlings were moved from a short photoperiod, 8 h light per day (8L), to 13 or 18L, and from 13 to 18L or 13 to 8L during testicular maturation. Later, photorefractory birds under 13L that had finished molting were moved to 18L. In another series of experiments, photorefractory starlings were moved from 18 to 8L for 7 weeks, 4 weeks, 2 weeks, 1 week, 3 days, 1 day, or 0 days, before being returned to 18L. There was no consistent relationship between photoperiod, or the increase in photoperiod, and the timing of the start of molt. Nor was there a consistent relationship with gonadal regression and the start of molt–molt could be triggered in the absence of a gonadal cycle. However, there was always an association between the start of molt and prolactin. In all cases where molt was induced, there had been an earlier increase in prolactin. However, the timing of molt was related to the time of peak prolactin, not the magnitude of that peak. This relationship between peak prolactin and the start of molt could explain the normally close relationship between the end of breeding activity and the start of molt.

Patterns of proopiomelanotropin and proopiocortin gene expression and of immunohistochemistry for gonadotropin-releasing hormones (lGnRH-I and III) during the life cycle of a nonparasitic lamprey: Relationship to this adult life history type

There are two adult life history types among lamprey species, nonparasitic and parasitic, with the former commencing the final interval of sexual maturation immediately after metamorphosis. There are no extensive studies that directly compare hormone profiles during the life cycles of nonparasitic and parastic lamprey species, yet such data may explain differences in development, reproductive maturation, and feeding status. The present study uses immunohistochemistry to show the life cycle profiles for gonadotropin-releasing hormones (GnRH-I and -III) in the brain of the nonparasitic species, the American brook lamprey, Lampetra appendix, for comparison with the extensive, published, immunohistochemical data on these hormones in the parasitic species, the sea lamprey, Petromyzon marinus. The complete cDNAs for the two lamprey prohormones, proopiocortin (POC), and proopiomelanotropin (POM), were cloned for L. appendix and both nucleotide and deduced amino acid sequences were compared with those previously published for P. marinus. The POC and POM cDNAs for both species were used in expression studies, with Northern blotting, throughout their life cycles. Although GnRH-I and -III immunohistochemistry revealed a similar distribution of immunoreactive cells and fibers in the two species during the life cycles, a qualitative evaluation of staining intensity in L. appendix, implied early activity in the brains of metamorphosis of this species, particularly in GnRH-I. GnRH-III seems to be important in larval life and early metamorphosis in both species. A novel feature of this immunohistochemical study is the monthly observations of the distribution and relative intensity of the two GnRHs during the critical period of final sexual maturation that lead to spawning and then the spent animal. L. appendix POC and POM nucleotide sequences had 92.9 and 94.6% identity, respectively, with P. marinus POC and POM and there was an earlier increase in their expression during metamorphosis and postmetamorphic life. Since there was some correlation between the timing of metamorphic development, gonad maturation, and brain irGnRH intensity with POC and POM expression in L. appendix, it was concluded that these prohormones yield posttranslational products that likely play a substantial role in development and maturation events that lead to the nonparasitic adult life history of this species.

Mechanisms of Increased Reactive Oxygen Species (ROS) Generation Induced by Organic Arsenic Derivative S-Dimethylarsino-Glutathione (SGLU; ZIO-101).

ZIO-101 is organic arsenic with similar anti-leukemia activity to arsenic trioxide (ATO) but much less toxicity. Consequently, ZIO-101 can be given at substantially higher doses than ATO and may be active in more diverse cancers than ATO. The precise anti-cancer mechanism of ZIO-101 is unknown: ZIO-101 increases intracellular production of reactive oxygen species (ROS) in dose dependent manner, resulting in apoptosis of leukemic cells. Modifying intracellular ROS levels alters the ability of ZIO-101 to induce apoptosis. We focused on the 2 most important intracellular ROS generators, mitochondria and NADPH oxidase. Cells were treated with ZIO-101 and NADPH oxidase expression levels, membrane translocation and interactions of subunits were studied. Effects of modified NADPH oxidase levels on ZIO-101-induced ROS production were studied (diphenyleneiodonium [DPI], a specific inhibitor of NADPH oxidase, and SiRNA technique were used to inhibit enzyme function, while bryostatin-1, a specific activator of NADPH oxidase, was used to increase enzyme function). Mitochondrial DNA-depleted HL60 Rho-0 cells were also used to evaluate mitochondrial input to ROS-generation. Our data show that ZIO-101 activates NADPH oxidase. A low concentration of ZIO-101 (1uM) requires 14 h to significantly increase intracellular ROS levels and kill leukemic cell. This effect is strongly inhibited by DPI-pretreatment and is also seen in P47-SiRNA transfected HL60 cells. On the other hand, this A higher dose of ZIO-101 (4uM) increases ROS levels more rapidly (2–6 h). This early increase is not inhibited by DPI-pretreatment or SiRNA transfection. A 14 h but not 2–6 h increase in ROS is detectable in Rho-0 HL60 cells. These data indicate dose-dependent mechanisms of ZIO-101 induction of ROS:1uM ZIO-101 induces NADPH oxidase activity which results in ROS production detectable at 14 h; there is no mitochondrial component;4uM ZIO-101 disrupts mitochondrial function resulting in an earlier increase in ROS levels and subsequent apoptosis. effect is significantly enhanced in cells that have increased enzyme function. ROS-production in Rho-0 HL60 cells is unaffected by these interventions.

Early changes in prostaglandins precede bone formation in a rabbit model of heterotopic ossification

We have tested the hypothesis that the formation of heterotopic ossification (HO) in a rabbit model is correlated with a local increase in specific prostaglandins that may modulate mechanisms of ossification. Rabbits were sacrificed at 1 to 21 days following the daily forcible flexion of immobilized knees. The extraction and analysis of prostaglandins (PG) E2, F2alpha, D2, 6-keto-F1alpha, and thromboxane B2 in vastus intermedius muscles of manipulated legs revealed increases compared to control hindlimbs for all five prostaglandins, albeit of differing magnitude. The earliest increase was observed for PGF2alpha after 24 h (to 2.6-fold of control) with peak levels observed at day ten (185-fold of control). PGE2 was increased above control from 2 to 21 days following manipulation, with a peak level of 33-fold of control after 10 days. In a separate arm of the study, the role of PGE2 was investigated through the use of pharmacological antagonist of the PGE2 receptors and one of its second messengers, cAMP. Rabbits were preadministered the PGE2/PGD receptor antagonist AH 6809 or the cAMP antagonist Rp-cAMP prior to undergoing the regimen of limb immobilization and passive exercise. Both AH 6809 and Rp-cAMP were found to prevent the later development of radiographically documented heterotopic ossification in 15 out of 16 animals, thus identifying prostaglandins as being required for the development of ectopic bone. In this latter group, all but one pharmacologically treated animal showed an absence of HO at 3, 4, 5, or 6 weeks. These findings suggest an obligate cascade of prostaglandins for HO that offers the potential for novel prophylactic therapies, including those that target receptors for specific prostaglandins.

Alveolar type II cells inhibit fibroblast proliferation: role of IL-1α

Alveolar type II (ATII) cells inhibit fibroblast proliferation in coculture by releasing or secreting a factor(s) that stimulates fibroblast production of prostaglandin E2 (PGE2). In the present study, we sought to determine the factors released from ATII cells that stimulate PGE2 production in fibroblasts. Exogenous addition of rat IL-1alpha to cultured lung fibroblasts induced PGE2 secretion in a dose-response manner. When fibroblasts were cocultured with rat ATII cells, IL-1alpha protein was detectable in ATII cells and in the coculture medium between days 8 and 12 of culture, correlating with the highest levels of PGE2. Furthermore, under coculture conditions, IL-1alpha gene expression increased in ATII cells (but not fibroblasts) compared with either cell cultured alone. In both mixed species (human fibroblasts-rat ATII cells) and same species cocultures (rat fibroblasts and ATII cells), PGE2 secretion was inhibited by the presence of IL-1 receptor antagonist (IL-1Ra) or selective neutralizing antibody directed against rat IL-1alpha (but not IL-1beta). Conditioned media from cocultures inhibited fibroblast proliferation, and this effect was abrogated by the addition of IL-1Ra. Addition of keratinocyte growth factor (KGF) resulted in an earlier increase in PGE2 secretion and fibroblast inhibition (day 8 of coculture). This effect was inhibited by indomethacin but was not altered by IL-1Ra. We conclude that in this coculture system, IL-1alpha secretion by ATII cells is one factor that stimulates PGE2 production by lung fibroblasts, thereby inhibiting fibroblast proliferation. In addition, these studies demonstrate that KGF enhances ATII cell PGE2 production through an IL-1alpha-independent pathway.

Physiological responses of ‘Murcott’ mandarins and ‘Star Ruby’ grapefruit to anaerobic stress conditions and their relation to fruit taste, quality and emission of off-flavor volatiles

During their postharvest handling citrus fruit may be exposed to various anaerobic stresses, which may occur, for example: during quarantine treatments, because of inadequate ventilation in containers and storage rooms, following application of waxes that restrict gas exchange through the peel and after packing the fruit in plastic liners. It is known that mandarins tend to develop off-flavors much more rapidly than other citrus varieties, for reasons that are not yet understood. In this study, we evaluated the physiological responses of ‘Murcott’ mandarins and ‘Star Ruby’ grapefruit to anaerobic stresses by exposing them to N 2 atmospheres for 6, 12, 24, 48 or 72 h at 20 °C. It was found that mandarins held in N 2 showed earlier and higher increases in respiration rate than grapefruit, with consequently earlier increases in CO 2 levels in their internal atmospheres. Furthermore, mandarins held in N 2 exhibited higher and earlier increases than grapefruit, in the accumulation of the off-flavor volatiles, ethanol and acetaldehyde in the juice. Unlike grapefruit, mandarins responded to the anaerobic treatment by increasing the production of the stress hormone ethylene. Finally, sensory evaluations indicated that the taste of mandarins markedly deteriorated following exposure to anaerobic conditions and was rated as unacceptable after 48 h in N 2, whereas the taste of grapefruit deteriorated only slightly and was rated acceptable even after 72 h of exposure to N 2. Overall, the data presented herein demonstrate that ‘Murcott’ mandarins are much more sensitive to exposure to anaerobic stresses than ‘Star Ruby’ grapefruit, and that this high sensitivity may be partly responsible for the much more rapid decline in their marketability and eating quality after harvest.

Properties and protective value of the secondary versus primary T helper type 1 response to airborne Mycobacterium tuberculosis infection in mice

Mice immunized against Mycobacterium tuberculosis (Mtb) infection by curing them of a primary lung infection were compared with naive mice in terms of the ability to generate a Th1 cell immune response and to control growth of an airborne Mtb challenge infection. Immunized mice generated and expressed Th1 cell immunity several days sooner than naive mice, as demonstrated by an earlier increase in the synthesis in the lungs of mRNA for Th1 cytokines and for inducible nitric oxide synthase, an indicator of macrophage activation. This Th1 cytokine/mRNA synthesis was accompanied by an earlier accumulation of Mtb-specific Th1 cells in the lungs and the presence of CD4 T cells in lesions. An earlier generation of immunity was associated with an earlier inhibition of Mtb growth when infection was at a 1-log lower level. However, inhibition of Mtb growth in immunized, as well as in naive, mice was not followed by resolution of the infection, but by stabilization of the infection at a stationary level. The results indicate that there is no reason to believe that the secondary response to an Mtb infection is quantitatively or qualitatively superior to the primary response.

Effects of Age and Fitness on Tolerance to Lower Body Negative Pressure

The purpose of this investigation was to determine the effects of age and fitness on tolerance to maximal lower body negative pressure (LBNP). Ten older fit (OF) [73.9 +/- 2 years; 39.0 +/- 2 ml.kg(-1).min(-1) (age and estimated VO(2)peak, respectively)], 10 older unfit (OU) (70.9 +/- 1 years; 27.1 +/- 2 ml.kg(-1).min(-1)), 10 young fit (YF) (22.6 +/- 0.5 years; 57.1 +/- 2 ml.kg(-1).min(-1)), and 10 young unfit (YU) (23.1 +/- 1 years; 41.1 +/- 2 ml.kg(-1).min(-1)) participants underwent graded LBNP of -10 mmHg every 4 minutes to either presyncope or -100 mmHg. Compared to the other groups, YF had an earlier increase in heart rate (-40 mmHg vs the last stage; YF vs OF, OU, and YU, respectively) and decline in stroke volume (-20 mmHg vs -40 mmHg; YF vs OF, OU, and YU, respectively). OU had a higher resting mean arterial pressure; this difference was maintained until the last stage. OF had an earlier decline in total peripheral conductance than the other groups (-20 mmHg vs -40 mmHg). Tolerance to maximal LBNP did not differ among the groups. Despite differences in the responses to submaximal LBNP, neither age nor cardiovascular fitness affect tolerance to maximal LBNP.

Molecular events associated with accelerated proliferative response in rat livers when partial hepatectomy is preceded by a sham operation

When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation. In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C). The early factors NF-kappaB and Stat3 were activated after S6 h + PH and S6 h + S. C-jun expression was increased 0.5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c-myc expression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c-Ha-ras mRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone. The first divergent response between the two combined models involved c-myc expression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c-Ha-ras and nuclear cyclin E.