B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity

Senescent cells accumulate in the adipose tissue (AT) of individuals with obesity and secrete multiple factors that constitute the senescence-associated secretory phenotype (SASP). This paper aimed at the identification of B cells with a SASP phenotype in the AT, as compared to the peripheral blood, of individuals with obesity. Our results show increased expression of SASP markers in AT versus blood B cells, a phenotype associated with a hyper-metabolic profile necessary to support the increased immune activation of AT-derived B cells as compared to blood-derived B cells. This hyper-metabolic profile is needed for the secretion of the pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) that fuel local and systemic inflammation.     

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Frequency of molecular alterations in heterozygous beta-thalassemia in southern Spain and their relation to the hematologic phenotype

INTRODUCTION: Heterozygous beta-thalassemia manifests hematologically with microcytosis, reduced red blood cell hemoglobin concentration and high hemoglobin A2 levels. Almost all molecular alterations are due to point mutations. We attempt to determinate the frequency of that mutations in the Oriental Andalusia Area, and its relationship with the hematological phenotype. PATIENTS AND METHODS: We have studied 45 heterozygous patients. DNA samples were amplified by PCR, using the printers CD7 and HI1. A 16 Kb fragment corresponding to beta globin gene was obtained and analyzed by Dot Blot assay and hybridized with allelic specific oligonucleotide (ASO) probes to detect the 6 more frequent mutations found in the South of Spain. RESULTS: Codon 39 nonsense mutation (31.1%) was the most frequent finding followed by IVS-1 NT 110 (26.7%). The relationship between hematological parameters and molecular mutations concluded that IVS-I NT 6 mutation developed a minimal anemia. DISCUSSION: From the practical point of view, this study indicates that we were able to detect more than 90% of heterozygous beta-tal. with 5 out of 6 ASO probes used in this work. Thus, our data also provides a further implication in prenatal diagnosis.     

Neurochemical characterization of the alterations in the noradrenergic afferents to the cerebellum of adult rats exposed to X-irradiation at birth

A single dose of x-irradiation was applied on the cephalic end of newborn rats, and the alterations in the noradrenergic afferents to the cerebellum were studied 180 days later. A net increase in the noradrenaline content of cerebellum was found (122% of nonirradiated controls). The response of noradrenaline content to reserpine injection (0.9 mg/kg, i.p.) was similar in exposed and control rats. Likewise, the 3H release induced by Ro 4-1284 from cerebellar cortex slices labeled with [3H]noradrenaline was unmodified by x-rays, although a mild increase in the spontaneous efflux of 3H was found. The retention of 3H by the slices was reduced in exposed animals (58% of controls). Both the in vitro activity of tyrosine hydroxylase and the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) were not significantly different between x-treated rats and controls. In contrast, monoamine oxidase activity was markedly reduced in x-irradiated cerebellum (38% of controls). The x-ray-induced decrease in cerebellar weight (-60%) resulted in marked increases in noradrenaline concentration (223%), tyrosine hydroxylase activity per milligram of protein (206%), and 3H retention (50%). The accumulation of L-DOPA per gram of tissue was also increased at every time considered. These data indicate that x-irradiation at birth produces a cerebellar loss not completely shared by the noradrenergic afferents, and a permanent imbalance between the noradrenergic afferent input and its target cells might eventually result.(ABSTRACT TRUNCATED AT 250 WORDS)     

The ultrasound appearances of neonatal renal vein thrombosis

Renal vein thrombosis (RVT) is the most frequently occurring vascular condition in the new-born kidney. The predisposing factors include dehydration, sepsis, birth asphyxia, maternal diabetes, polycythaemia and the presence of an indwelling umbilical venous catheter. (RVT) may present clinically with a flank mass, haematuria, hypertension or renal failure. Many imaging modalities have been employed, but ultrasound is the technique most commonly used in the evaluation of neonates with suspected RVT. Thrombosis commences in the small renal veins and subsequently propagates via larger interlobar veins to the main renal vein and inferior vena cava (IVC). The ultrasound appearances depend upon the stage at which the examination is performed and extent of the thrombus. Initially, the interlobular and interlobar thrombus appears as highly echogenic streaks. These streaks commence in a peripheral, focal segment of the involved kidney and only persist for a few days. In the first week the affected kidney swells and becomes echogenic with prominent echopoor medullary pyramids. Later, the swelling increases and the kidney becomes heterogenous with loss of corticomedullary differentiation. Grey scale ultrasound readily demonstrates thrombus within the renal vein and IVC. Adrenal haemorrhage is a recognized association and may be identified ultrasonically. Colour Doppler scanning provides additional information. In the early stages of RVT, colour Doppler may demonstrate absent intrarenal and renal venous flow. Ultimately, the kidney may recover, show focal scarring or become atrophic. Thus, ultrasound provides an accessible and reliable tool in the assessment of suspected neonatal RVT.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.