Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen

Estrogen is a negative regulator of lymphopoiesis and provides an experimental tool for probing relationships between lymphocyte precursors and stem cells. We found that expression of lymphocyte-associated genes and immunoglobulin (Ig) gene rearrangement occurred before CD45R acquisition. Lymphoid-restricted progenitors that were Lin(-)IL-7R alpha(+)c-kit(lo)TdT(+) (lineage marker(-), interleukin receptor 7 alpha(+), c-kit(lo) and terminal deoxynucleotidyl transferase(+)) were selectively depleted in estrogen-treated mice; within a less differentiated Lin-c-kit(hi) fraction, functional precursors of B and T, but not myeloid, cells were also selectively depleted. TdT and an Ig heavy chain transgene were detected within a hormone-regulated Lin(-)c-kit(hi)Sca-1(+)CD27(+)Flk-2(+)IL-7R alpha(-) subset of this multipotential progenitor population. Identification of these extremely early lymphoid precursors should facilitate investigation of the molecular mechanisms that control lineage-fate decisions in hematopoiesis.     

Hemispheric control of unilateral and bilateral responses to lateralized light stimuli after callosotomy and in callosal agenesis

Normally, simple digital or manual responses to a light stimulus in the right or left visual hemifields are performed faster with uncrossed hand-field combinations than with crossed hand-field combinations. Because of the organization of visual and motor pathways, the integration of uncrossed responses is assumed to occur within a single hemisphere, whereas a time-consuming inter-hemispheric transfer via the corpus callosum is considered to be necessary for the integration of crossed responses. However, callosal transfer may be dispensable for those crossed responses which can be controlled through ipsilaterally descending motor pathways by the hemisphere receiving the visual stimulus. We investigated crossed-uncrossed differences (CUDs) in speed of simple visuomotor responses to lateralized flashes in one subject with total section of the corpus callosum and two subjects with complete callosal agenesis. We recorded the reaction times as well as the premotor times, as indicated by the electromyographic latencies of the prime movers, of three types of responses: a distal response involving a thumb flexion, a proximal response chiefly involving a forearm flexion and an axial response involving a shoulder elevation. Further, the three types of responses to a single lateralised flash were performed both unilaterally and bilaterally. The three acallosal subjects showed CUDs greatly exceeding normal values on distal responses, either unilateral or bilateral, and on unilateral proximal responses. These abnormally long CUDs stood in sharp contrast to the insignificant CUDs exhibited by the same subjects on bilateral proximal responses and on unilateral and bilateral axial responses in agreement with correspondingly insignificant CUDs reported for normal subjects. These results confirm that a callosal contribution is important for the execution of fast distal and unilateral proximal responses to a visual stimulus directed to the hemisphere ipsilateral to the responding hand. By contrast, the other types of crossed responses appear to be efficiently coordinated across the midline without the aid of the corpus callosum. This is in keeping with the hypothesis that they are governed by a bilaterally distributed motor system which is preferentially activated for the execution of symmetrical bilateral movements, employing axial and proximal limb muscles.     

Serological survey of human immunodeficiency virus (HIV) in Ethiopia

The presence of anti-human immunodeficiency virus 1 antibodies was tested in 5,565 serum samples from Ethiopia of which 5,265 were collected from military recruits in the framework of a hepatitis B (HBV) seroepidemiological study performed on a national scale in 1985-1986; the remaining were 300 sera from a population of outpatients belonging to the Arsi region. Of the 5,565 sera, 121 (2.1%) were found to be repeatedly reactive by enzyme-linked immunosorbent assay (ELISA) test for HIV-1 antibodies, but these reactivities were confirmed by Western Blot (WB) assay in only four cases (0.07%) and by ENVACOR (confirmatory competitive ELISA) in three samples. Twenty-three sera were positive by WB to one or two bands related to core proteins but were all negative by ENVACOR. However, according to accepted criteria for positivity, these sera must be regarded as indeterminant reactors. A sample of 409 sera, both reactive and nonreactive by HIV-1 ELISA, were further tested for antibodies to HIV-2 by ELISA. Reactive sera were analysed by WB and by radioimmunoprecipitation assay (RIPA) using 35S-cysteine metabolically labelled SIVmac (HTLV-IV) infected cell lysates. Only 11 sera were found to be slightly reactive in ELISA, but this was not confirmed by WB or RIPA. Data indicate that HIV infection was not widespread in the general population of Ethiopia up to 1986.     

Development of an intracorporeal Thoratec ventricular assist device for univentricular or biventricular support

There is a need for a small, simple, and versatile intracorporeal ventricular assist device (IVAD) as an alternative to the large implantable electromechanical LVAD systems in current use. Because the basic design of the Thoratec paracorporeal VAD has been demonstrated in over 1,000 patients, weighing from 17 to 144 kg, and for durations up to 515 days including patient discharge (by using the portable driver), we are developing a new intracorporeal version of our VAD. This IVAD has a smooth contoured, polished titanium housing, and maintains the same blood flow path and Thoralon polyurethane blood pumping sac as the paracorporeal VAD. The IVAD is controlled with the Thoratec TLC-II Portable VAD Driver, which is a small briefcase sized, battery powered, pneumatic control unit. Intracorporeal LVADs and/or RVADs are implanted in a preperitoneal position, with a single small (9 mm OD) percutaneous pneumatic driveline for each VAD. The major advantages of the new IVAD design are size and simplicity. The IVAD weight (339 g) and implanted volume (252 ml) are substantially smaller than current implantable electromechanical LVAD systems. Only the small blood pump is implanted, leaving the more complex control unit external, where it can be serviced and replaced. The versatile design is intended for left and/or right heart support in large or small patients. The IVAD in combination with the TLC-II portable driver will be a viable and attractive alternative to large, implanted electromechanical systems.     

Development and evaluation of a capture ELISA for IgM antibody to the human cytomegalovirus major DNA binding protein.

A new capture ELISA (ELAb) for determination of the IgM antibody response to the human cytomegalovirus major DNA binding protein (p52) was developed by using a p52-specific monoclonal antibody. As a reference test, a capture ELISA using in parallel viral- and cell-control labeled antigens (ELA) was employed. General specificity, which was determined on 180 unselected IgM-negative sera from an adult population was 100%; stringent specificity, which was evaluated on 108 potentially interfering sera from patients with Epstein-Barr virus infectious mononucleosis, autoimmune diseases, rheumatoid factor or treated with radioimmunotherapy, was 96.3%; finally, clinical specificity, determined on 79 IgM-negative sera drawn prior to onset of primary HCMV infection, was 100%. Thus, the overall specificity was 98.9% (363/367 IgM negative tested sera). Sensitivity assayed on 277 IgM-positive sera was 100%. The study of the kinetics of the IgM antibody response in sequential blood samples from 9 immunocompetent and 9 heart transplanted patients showed that, while in the immunocompetent p52-specific IgM titer fell sharply 2-3 months after onset and was virtually undetectable 12 months after onset, in the immunocompromised the IgM response persisted for longer than a year. Recurrent HCMV infections were associated with a high titer IgM response in 6 (30%), and with a low IgM response in another 6 (30%) heart transplanted patients within a group of 20 patients sequentially examined. Finally, IgM antibodies were detected in all 4 infants with congenital infection and in 5 of 6 infants with neonatal infection. The results show that the HCMV p52-specific IgM antibody response parallels that obtained by ELA, thus representing a major component of it. ELAb is highly sensitive, specific and reproducible. It represents a major advance among capture ELISA techniques, allowing detection of IgM antibody reactive to a specific viral protein.     

Intracranial tuberculomas in a child: regression on the CT scan under conservative therapy

The case of a four-year-old boy is reported in whom the diagnosis of multiple cerebral and cerebellar focal tuberculous infections ("tuberculomas") was made. The diagnosis was based on a positive skin test, a history of contact, typical x-ray findings in the lung, CSF findings, and CT scan. The patient was treated during a three-year-period with antituberculous therapy. Sequential CT scans showed a relatively slow modification of the lesions, during a period of at least eighteen months, and thereafter their almost complete regression.     

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.     

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.