Influences of approaching tropical cyclones on water vapor and aerosols in the atmospheric boundary layer of Guangdong-Hong Kong-Macau Greater Bay Area of China.

The outer circulation of tropical cyclones (TCs) on the western North Pacific has been reported to substantially influence the atmospheric environment over the Guangdong-Hong Kong-Macau Greater Bay Area (GBA) of China, whereas dynamic evolution and redistribution of water vapor and aerosol in the atmospheric boundary layer (ABL) responding to moving TCs have yet to be understood. This study aims to answer three key research questions related to the influences of the approaching TCs: (1) how do water vapor and aerosol particles over the GBA change during the TC approaching stage? (2) how does the ABL in terms of vertical wind structure respond to the approaching TCs? and (3) how does turbulence influence the vertical profile of aerosol during the approaching stage? Based on an intensive analysis of three-year reanalysis and Doppler LiDAR data, this study identified a dry-polluted time over the GBA when a TC was located at ~1000 km away on South China Sea. Before that, horizontal wind has consistently come from the northeast, creating a favorable condition for weak transboundary air pollution to the GBA. During the dry-polluted time, the highest surface PM2.5 concentration was resulted from the enhanced downdraft and early-stage wind shear, i.e., stronger wind started occurring at upper-level ABL, while the further turbulent mixing induced by wind shear enhancement and updrafts recovery pumped surface pollution upward to the upper level when TCs became closer. Our findings are expected to improve both weather and PM2.5 forecasts under the impacts of approaching TCs.

The role of tropospheric ozone in flagging COVID-19 pandemic transmission.

COVID-19 pandemic outbreak, caused by the SARS-CoV-2 virus, affected millions of people worldwide causing hundreds of thousands of related fatalities. It is crucial to understand why the virus transmission seems to spread more easily in some regions than others. The residuals, with respect to the modeled COVID-19 per-day hospitalized patients in intensive care unit, are correlated to the meteorological and air-pollutant variables in four major metropolitan areas in Italy during a strict lockdown implemented by the Italian government, making the analysis independent from socio-economic factors. The results show that COVID-19 pandemic-related infections are slowed down by higher tropospheric ozone concentrations and eased by the atmospheric particulate. We quantitatively assessed that higher levels of tropospheric ozone, already proven effective against viruses and microbial contaminants, play a role in flagging COVID-19 pandemic transmission. Because the tropospheric ozone production is depending, among others, by air-quality and sunlight, this can explain why the virus is spreading in different ways.

The involvement of IgH enhancer HS1.2 in the pathogenesis of Crohn's disease: how the immune system can influence a multifactorial disease.

OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections. We conducted a selective PCR, which amplified the hs1.2-A region. The nested second PCR to amplify the polymorphic core of the enhancer was performed. RESULTS: No differences between cases and controls were observed with respect to sex distribution (43.8% females among controls and 49.5% among cases), age, tTG IgA, RF, serum or secretory IgA, IgG1, IgG2 and IgG3. No correlation was found between both seric and secretory immunoglobulins levels, with except of statistically significant differences between cases and controls with respect to IgA and IgG ASCA positivity (p<0.001), serum IgG4 (p<0.001) and IgD (p=0.001). CONCLUSIONS: We have demonstrated that in Crohn's disease, the HS1,2 immunoglobulins enhancer is not implicated in the disease pathogenesis. Moreover, we have found that IgG4 levels are lower in Crohn's disease patients than in controls; these data may be related to an impairment of number and function of Tregs, further linked to the presence of tissue inflammation. Crohn's disease is a complex multifactorial disease. The pathogenesis of Crohn's disease is incompletely understood although it is clear that the disease involves multiple interacting agents.

Strategies to overcome obstacles to successful immunotherapy of melanoma.

The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.

Abnormal synthesis of IgA in coeliac disease and related disorders.

The pathogenesis of coeliac disease (CD) is complex. One controversial aspect is the role of IgA anti-endomysial (EMA) antibodies. Despite being the most reliable marker for CD diagnosis, its role in the pathogenesis (if any) remains obscure. The paradox is reinforced by the observation that CD is more common in IgA-deficient individuals. In this review, we discuss recent data suggesting that IgA autoantibodies may be related to aspecific dysregulation of IgA. In addition, new insights have elucidated new genes involved in IgA production and linked to CD. Allelic frequency of HS1,2 enhancer which regulates Ig synthesis is altered in CD and other IgA mediated disorders. We suggest that in CD, a T-cell mediated disease, the role of IgA anti-EMA autoantibodies remains elusive and could well be merely an epiphenomenon not directly related to pathogenic mechanisms, but rather to a state of heightened immunological responsiveness in genetically predisposed individuals.

Active thymopoiesis in idiopathic chronic pancreatitis.

BACKGROUND/AIMS: Cellular immunity has a pivotal role in the pathogenesis of chronic pancreatitis (CP), resulting in pancreas infiltration by T-cells. Studies on systemic immunity are few and contradictory. One study reported a decrease of naive CD45RA+ cells. The presence of naive T cells, detected as recent thymic emigrants (RTEs), is evaluated with a new molecular technique by using real-time PCR to detect the T-cell receptor excision circles (TREC). To elucidate the role of naive T-cells in the pathogenesis of CP, we investigated the percentage of sj-TREC in CP patients. PATIENTS: Thirty CP patients were studied and compared to 30 sex- and age-matched healthy volunteers. METHODS: Genomic DNA was isolated from peripheral blood mononuclear cells (PBMC) of each patient. RTEs were evaluated by measuring sj-TREC by real-time PCR. RESULTS: The mean percentage of sj-TREC+ cells present in CP was not significantly different from that of control group (0.02319% vs 0.02338%, respectively). CONCLUSION: Our data show that naive TREC+ cells are normally represented in CP. The presence of active thymopoiesis may be the underlying mechanism resulting in continuous production of T-cells, responsible of maintaining the inflammatory process.

Effect of automatic milking systems on milk yield in a hot environment.

A comparative study was performed to evaluate differences in milk yield between an automatic milking system (AMS) and a conventional herringbone milking parlor system. Two herds of Italian-Friesian cows were reared in the same barn, located in the Po Valley in northern Italy. Twenty-five primiparous cows and 10 multiparous cows were milked with an AMS, while at the same time 29 primiparous and 9 multiparous were milked twice daily in a milking parlor on the other side of the barn. A selection gate allowed cows to access the AMS only if the interval from last milking was >5 h. Multiparous cows in the AMS yielded more milk than multiparous cows in the milking parlor (34.2 +/- 0.7 vs. 29.4 +/- 0.6 kg/d). There was no difference in milk yield between primiparous cows in the AMS and in the milking parlor (28.9 +/- 0.4 vs. 28.8 +/- 0.3 kg/d). Milking frequency in the AMS was significantly higher in primiparous (2.8 +/- 0.03) than in multiparous cows (2.5 +/- 0.04). The hot season negatively affected milk yield; the milk yield reduction was higher for cows milked with the AMS (-4.5 +/- 0.6 kg/d) than in the milking parlor (-3.0 +/- 0.8 kg/d). In the AMS, milking frequency decreased during the hot season in primiparous cows (-0.3 +/- 0.1). We concluded that a positive AMS effect on milk yield is possible, but that steps must be taken to alleviate the discomfort involved with attracting cows to the AMS.

Evaluation of three different commercial procedures for quantifying human immunodeficiency virus type-1 RNA levels.

A branched DNA method for the quantification of human immunodeficiency virus type 1 (HIV-1) RNA levels (Quantiplex HIV RNA 2.0) was compared with a reverse transcriptase-coupled polymerase chain reaction method (Amplicor HIV-1 Monitor) and a nucleic acid sequence-based assay (Nuclisens HIV-1 QT) in plasma samples from a group of HIV-1 seropositive patients. We found a high correlation between Nuclisens and Quantiplex (r = 0.89; p < 0.001) and between Amplicor and Quantiplex (r = 0.94; p < 0.001), a shift of RNA viral load to higher Nuclisens and Amplicor values compared with the Quantiplex results and a significant positive correlation (rS = 0.60; p < 0.001) between the p24 antigen level and the RNA viral load determined with the Quantiplex assay. We also found higher sensitivities of the Nuclisens and the Amplicor procedures compared with the Quantiplex assay. The total sensivity of the Quantiplex assay in our study was 70% whereas that of the p24 antigen was only 29%.

Effect of antibody to HIV-1 Tat protein on viral replication in vitro and progression of HIV-1 disease in vivo.

In HIV-1-infected cell cultures, a relatively low concentration (5 micrograms/ml) of monoclonal antibody (mAb) against HIV-1-transactivating Tat protein was an efficient inhibitor of HIV-1 replication both in HIV-1(IIIB)-infected Jurkat cell and peripheral blood mononuclear cell (PBMC) cultures and significantly reduced the expression of a Tat-responsive CAT-reporter construct in HIV-1(IIIB)-infected Jurkat cells. Anti-Tat mAb also caused a significant reduction and a consistent delay in HIV-1 replication when added to PBMCs from HIV-1-infected patients cocultivated with phytohemagglutinin (PHA)-stimulated normal PBMCs. These data indicate that an autocrine-paracrine loop sustained by extracellular Tat protein, which is actively released by HIV-1-infected cells, may affect HIV-1 replication in cell cultures in vitro. An inverse relationship between natural anti-Tat antibody levels and p24 antigenemia was demonstrated by retrospective analysis of serial serum samples obtained from 10 HIV-1-seropositive hemophiliac patients followed over a 7-9-year period. This datum points to a possible influence of anti-Tat antibody on the progression of HIV-1 disease in vivo. These findings have strong implications for Tat protein as a possible target for specific immunotherapy in HIV-1-infected patients.

In situ polymerase chain reaction technique revealed by flow cytometry as a tool for gene detection.

We report a methodology for detecting specific DNA sequences directly inside cells, combining in situ PCR and flow cytometry. This technique is based on in situ PCR performed in the presence of digoxigenin-labeled dUTP to obtain a digoxigenin-labeled amplicon, which is then revealed by an anti-digoxigenin polyclonal antibody directly conjugated to fluorescein. Fluorescence intensity is next evaluated by flow cytometry. Our experimental models were represented by the lymphoblastoid cell lines 8E5LAV, carrying an integrated HIV-1 DNA proviral copy per cell, and A.301, infected in vitro with HIV-1 (strain IIIB). The technique is described in detail with particular attention to the optimization of critical fixation and permeabilization steps. This method allows not only the detection but also an accurate quantification of the number of positive cells in a background of negative cells. Moreover, it has the potentiality to develop into a multiparametric method for the simultaneous study of specific DNA or RNA sequences and surface or intracellular markers.

"Non-dipper" hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study.

Patients with a blunted or absent nocturnal blood pressure (BP) drop may be subject to increased risk for target organ damage. In this 3-year longitudinal case-control study we tested the hypothesis that an association exists between a reduced or absent night-time fall in BP and a future decline of kidney function in renal hypertensive patients. The case subjects were 48 hypertensives with renal insufficiency, divided into two groups according to the presence (dippers: n 20) or absence (non-dippers: n 28) of a nocturnal diastolic BP decline greater than 10% of daytime values, detected by ambulatory BP monitoring. At the baseline evaluation the two groups did not differ with respect to age, sex, body weight, office systolic and diastolic BP, mean daytime ambulatory BP, creatinine clearance, 24 h proteinuria. In the ambulatory BP profiles over a 3-year follow-up the nocturnal reductions of systolic and diastolic BP in the dippers were 14% and 15%, respectively, vs 7% and 5% in the non-dippers (p = 0.002/0.003). The non-dippers had a faster rate of creatinine clearance decline than the dippers (0.37 +/- 0.26 vs 0.27 +/- 0.09 ml/min/month; p = 0.002). Urinary protein excretion increase was higher in the non-dipper group than in the dipper group (993 +/- 438 vs 691 +/- 222 mg/24 h; p = 0.009). This longitudinal study suggests that the non-dipping pattern of ambulatory BP can be associated with a faster progression of renal insufficiency in renal hypertensives and that a proper nocturnal BP control is an additional aim of antihypertensive therapy.

CD4 engagement by HIV-1 in TF-1 hematopoietic progenitor cells increases protein kinase C activity and reduces intracellular Ca2+ levels.

Starting from our previous observations that the HIV-1-mediated engagement of CD4 induced apoptotic death of TF-1 hematopoietic progenitor cells, in this study we evaluated PKC activity and intracellular Ca2+ levels in TF-1 cells treated with viable and heat-inactivated HIV-1 (strain IIIB) or anti-CD4 Leu3a monoclonal antibody (mAb). Both viable and heat-inactivated HIV-1 or anti-CD4 mAb, but not anti-human cytomegalovirus (HCMV) 66kD protein or anti-CD8 mAb induced a rapid (5-10 min) increase in PKC activity under both serum-containing and serum-free conditions. The same treatment also induced both a transient and a long-lasting (48 hours) decrease (p < 0.05) in intracellular Ca2+ levels in serum-containing cultures. We propose that the observed changes in PKC activity and intracellular Ca2+ levels might be involved in the HIV-1 mediated apoptosis of hematopoietic progenitor cells.

Circadian blood pressure changes in patients with chronic renal insufficiency: a prospective study.

Circadian blood pressure (BP) rhythm was prospectively studied by ambulatory 24-h monitoring in normotensive (n = 27) and hypertensive (n = 41) patients with stable progression of chronic renal insufficiency, and in matched control groups (healthy subjects: n = 28 and patients with essential hypertension: n = 47) without renal disease. The follow-up period lasted 24 months. The renal patients showed a disturbance in the 24-h profile of BP, with significantly blunted nocturnal pressure reduction as compared with the respective control groups (p < 0.01 and p < 0.001, respectively). In addition to the rearrangement of circadian rhythm, the normotensive and hypertensive renal patients displayed a wider distribution of systolic and diastolic BP values and a greater nocturnal variability. Among the normotensive and hypertensive patients with chronic renal insufficiency, a significant correlation was found between the decline in creatinine clearance over the 24-month period and the average nighttime diastolic BP (r = 0.526; p < 0.01 and r = 0.613; p = 0.001, respectively) and nocturnal diastolic fall (r = 0.612; p < 0.001 and r = 0.496; p < 0.01, respectively). These data offer support for the view that renal normotensive patients are exposed to a relative hypertension at nighttime and that renal hypertensive subjects can be underestimated in their hypertensive status if the measurement of BP is confined to daytime. In both groups, nocturnal BP overload can accelerate the progression rate of renal insufficiency.

Absence of HTLV-I/II infection in blood donors with positive and inconclusive HTLV-I/II serology.

The pathogenetic potential and the true extent of human T leukemia/lymphotropic virus type I (HTLV-I) and type II (HTLV-II) infection are unknown. To find out more about HTLV-I/II seroepidemiology and the risks of iatrogenic transmission, we performed a serological study, screening 4086 healthy blood donors. A surprisingly high percentage of serum reactivity to HTLV-I/II antigens was observed by commercial ELISA (2.08%) and immunoblotting (IB) (0.85%) analysis, although none of the samples satisfied the (IB) criteria for positivity based on detection of gag protein p24 and at least one env gene product, either gp46 or gp61/68. To clarify these inconclusive results, we performed polymerase chain reaction (PCR) analysis for HTLV-I and HTLV-II provirus detection in peripheral blood lymphocytes, obtained from individuals with an apparent pattern of seropositivity. The data obtained by PCR failed to reveal evidence of HTLV-I/II provirus integration in peripheral blood cells, ruling out the possibility of a viral infection in these cases, and pinpointing the limitations of both serological methods used. Our observations suggest that serological assays alone are not a reliable tool for blood donor screening of HTLV-I/II infection and raise the important question of interpreting inconclusive results.

The spectrum of cardiovascular abnormalities in autosomal dominant polycystic kidney disease: a 10-year follow-up in a five-generation kindred.

Clinical, electrocardiographic and echocardiographic data were collected in a group of 228 patients with autosomal dominant polycystic kidney disease (PKD) and in another group of 146 unaffected members (NPKD) both comprised in a five-generation kindred followed for 10 years, in order to determine the profile and prevalence of cardiovascular derangement of the genetic disease. A family of 181 members was used as a control. The prevalence of left ventricular hypertrophy in the three groups was 24, 14 and 6% respectively (p less than 0.01); after 10 years it increased up to 35, 26 and 13% respectively (p less than 0.05). The evidence of mitral-valve prolapse was more frequent in PKD and in NPKD group (25 and 20% respectively) than in control subjects (2%) (p less than 0.0001). Mitral incompetence was found in 30, 18 and 8% of those groups respectively (p less than 0.002). The large difference in mitral involvement did not change over time. Tricuspid valve prolapse was detected in 5, 4 and 1% of the three groups, respectively (p less than 0.05). A small increase in frequency was found after 10 years only in polycystic kidney disease patients. Regurgitant aortic lesions were present in higher prevalence in PKD (19%) and NPKD (17%) members than in controls (5%) (p less than 0.001). After 10 years they were 23, 20 and 8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxprenolol on the sympathetic drive during working stress.

Epinephrine and norepinephrine urinary excretion was evaluated in 35 healthy confectioner workers on piece-wage (PW) and in 35 metal workers on the assembly-line (AL) before and after oral administration of oral oxprenolol (and identical placebo on double blind conditions) in order to evaluate the effect of beta-blockade on the adrenosympathetic overactivity due to psychological working stress. When the workers performed their job without any drug and when they were on placebo conditions, urinary levels of epinephrine and norepinephrine rose significantly; whereas when they were given oxprenolol the values of two catecholamines were normal. It could be argued that this study might lead to beta-blocking drugs introduced in circumstances of high scores of psychological stress due to some modern types of work.