High antibody levels to the mycobacterial fibronectin-binding antigen of 30-31 kD in tuberculosis and lepromatous leprosy.

Immunoblot assays showed that mycobacterial fibronectin-binding antigens are important targets of the humoral immune response in tuberculosis and leprosy. Using culture filtrate antigens of Mycobacterium tuberculosis, strong reactivity with the fibronectin-binding of 30-31 kD (Fn 30-31) was demonstrated in 55.9% of tuberculosis sera and in 56.5% of lepromatous leprosy sera. Sera from patients with tuberculoid leprosy and control sera gave very weak binding. Reactivity of tuberculosis and lepromatous leprosy sera with the fibronectin-binding antigen of 58-60 kD (Fn 58-60) was less conspicuous. The ability to react with fibronectin of the antigens of 58-60 and 30-31 kD was demonstrated by parallel labelling with a fibronectin-biotin conjugate. Fn 30-31 was purified to homogeneity by a two-step procedure and used for ELISA. Positive titres were found in 63% out of 65 tuberculosis sera and in 60.5% out of 43 lepromatous leprosy sera. Antibody titres in lepromatous leprosy sera were higher than in tuberculosis sera. Our observations indicate indirectly that M. leprae possess a highly immunogenic molecule homologous to M. tuberculosis Fn 30-31, which elicits a high antibody response in lepromatous leprosy but not in tuberculoid leprosy. In this investigation, direct evidence for the presence of this antigen in M. leprae was obtained by immunochemistry of lepromatous leprosy lesions with a monospecific antibody raised against M. tuberculosis Fn 30-31.     

Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model

Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood–brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00884-9) contains supplementary material, which is available to authorized users.     

Nonsecretory multiple myeloma. Immunohistologic and ultrastructural observations on two patients

Two well documented examples of nonsecretory multiple myeloma were studied by electron microscopic and immunohistologic methods. In one case, repeat studies revealed no intracytoplasmic immunoglobulins, and the cells displayed a "plasmacytoid" appearance with poor development of rough endoplasmic reticulum and Golgi regions. In the other case, most cells contained intracytoplasmic immmunoglobulins of a monoclonal type and the ultrastructural appearance was that of cells actively engaged in protein synthesis. These findings and others in the literature suggest that myelomas without an M component can be separated into nonproducers and true nonsecretors of immunoglobulins. In one case, immunofluorescence of bone marrow smears with double labels demonstrated three different plasma cell populations: those producing either monoclonal immunoglobulins M (IgM) or A (IgA) and those synthesizing simultaneously IgM and IgM. Dual immunoglobulin production, although known to occur in myelomas with paraproteinemia, has not been previously documented in the nonsecretory variety.     

Renal Transplantation in Second-Level Private Hospitals in the State of Mexico

Background

Kidney transplantation (KT) is the replacement therapy of choice in patients with end-stage renal disease (ESRD). Here we show a cohort of kidney transplant recipients from the period of May 1994 to May 2016 in 2 2nd-level private hospitals from the city of Toluca in the state of Mexico.

Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations

Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates cellular uptake and efflux of 3,3',5-triiodothyronine (T3). Mutations in MCT8 are associated with severe psychomotor retardation, high serum T3 and low 3,3',5'-triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two subjects with the F501del mutation have mild psychomotor retardation with slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in F501del fibroblasts and strongly decreased in fibroblasts from other MCT8 patients, while T3 efflux was always strongly reduced. Moreover, type 3 deiodinase activity was highly elevated in F501del fibroblasts, whereas it was reduced in fibroblasts from other MCT8 patients, probably reflecting parallel variation in cellular T3 content. Additionally, T3-responsive genes were markedly upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with other MCT8 mutations. In conclusion, mutations in MCT8 result in a decreased T3 uptake in skin fibroblasts. The much milder clinical phenotype of patients with the F501del mutation may be correlated with the relatively small decrease in T3 uptake combined with an even greater decrease in T3 efflux. If fibroblasts are representative of central neurons, abnormal brain development associated with MCT8 mutations may be the consequence of either decreased or increased intracellular T3 concentrations.     

Mycobacterium tuberculosis 38-kDa Lipoprotein is Apoptogenic for Human Monocyte-derived Macrophages

Mycobacterium tuberculosis is the main aetiologic agent of tuberculosis, a disease of great concern in less-developed regions. Apoptosis is a conspicuous event in macrophages infected in vitro with mycobacteria, a phenomenon also observed in vivo in granulomas of patients with tuberculosis. To determine its significance, it is important to define the mycobacterial moieties involved and how they cause apoptosis. Here we show that the 38-kDa lipoprotein induces macrophage caspase-dependent apoptosis involving TNF-α and FasL and, interestingly, with the upregulation of cell-death receptors TNFR1, TNFR2 and Fas. A role for the Toll-like receptor 2 was also demonstrated. In conclusion, the ability to induce apoptosis of host cells is another property of the 38-kDa lipoprotein, a molecule that has focused attention for being an immunodominant antigen that participates in phosphate transport.     

Stratospheric ozone intrusions during the passage of cold fronts over central Chile

This study analyzes tropospheric column ozone variability in the southern hemisphere as a function of ozone transport from the stratosphere to the troposphere and photochemical formation. Geographically, the study area was located in the mid-latitudes in South America (33° S), to the west of the Andes mountain range, in an area highly susceptible to stratospheric intrusions. Monthly ozonesonde measurements were recorded in Colina to ascertain seasonal vertical ozone distribution from the surface to the stratosphere between September 2010 and May 2012. Vertical distribution of the tropospheric ozone was measured in Talagante for fronts crossing from west to east in central Chile, during two periods in September 2014 and March 2015. These periods were significantly different in terms of the stratospheric ozone annual cycle and height of the tropopause. Our results showed rapid increases of approximately 50% in the tropospheric column ozone at time intervals shorter than 1 week. At the surface level, unusually enhanced ozone levels up to 10 parts per billion volume (ppbv) were observed during nighttime. Additionally, stratosphere-troposphere exchange (STE) preferentially occurred in spring and winter, with higher contribution during spring when the tropospheric column ozone attained its maximum concentration. These results provide valuable information regarding tropospheric ozone, a major local and global climate pollutant, to decision makers. In addition, they provide the research community with experimental data from the southern hemisphere, which helps bridge knowledge gaps in a region that has been rarely studied by national and international scientific communities.     

Characterization of the raphe nuclei of the reptile Ctenosaura pectinata.

The brain stem of the lizard Ctenosaura pectinata was studied in 10 microns thick sections following the Nissl and eosin-hematoxilin techniques. Furthermore, the distribution of serotonin-containing neuronal somata in this encephalic region was determined by means of an indirect immunofluorescence technique using a specific antibody to serotonin. Two of the cellular groups of the brain stem were identified as the superior and inferior raphe nuclei, which show serotonergic cells of variable size (between 17 and 30 microns). The results obtained in the present study together with information coming from other authors, suggest that serotonergic neuronal systems placed at brain stem level of vertebrates are phylogenetically ancient.     

Retinoic acid is a potent regulator of growth plate chondrogenesis

Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by 3H-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by 35SO4 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis.