Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines that mediate leukocyte chemotaxis. The potent and specific activation of monocytes by MCP-1 may mediate the monocytic infiltration of tissues in atherosclerosis and other inflammatory diseases. We have isolated cDNAs that encode two MCP-1-specific receptors with alternatively spliced carboxyl tails. Expression of the receptors in Xenopus oocytes conferred robust mobilization of intracellular calcium in response to nanomolar concentrations of MCP-1 but not to related chemokines. The MCP-1 receptors are most closely related to the receptor for the chemokines macrophage inflammatory protein 1 alpha and RANTES (regulated on activation, normal T expressed and secreted). The identification of the MCP-1 receptor and cloning of two distinct isoforms provide powerful tools for understanding the specificity and signaling mechanisms of this important chemokine.     

Estimation of hand preshaping during human grasping

A new method for evaluating hand preshaping during reaching-to-grasp movement is proposed. The method makes use of all five fingers in estimation of prehension. The investigation was performed on six healthy subjects grasping three different objects at various positions and orientations. The objects were presented to the subjects by means of a robot, which also induced perturbations in both object position and orientation. Positions of markers attached to the finger-tips and dorsum of the hand were recorded by means of a 3D optical tracking system. In the data analysis, the adjacent fingertips were interconnected, thus obtaining a planar pentagon whose various characteristics were investigated and discussed. New parameters for the evaluation of finger preshaping, such as pentagon surface area, angle between the pentagon and hand normal vectors, and the angle between the pentagon and object normal vectors were introduced. The proposed pentagon approach is expected to be useful in future work when examining grasping abilities of subjects with neuromuscular disorders.     

A quantitative gait assessment method based on energy exchange analysis during walking: a normal gait study

In this paper a gait efficiency assessment method, Gait Energy Efficiency Index (GEEI), which can be used in evaluation of the progress of the rehabilitation process in disabled persons, is proposed and described. The method is based on calculation of cross correlation between normalized time courses of kinetic and potential energy of the body's centre of mass (COM). We hypothesized that GEEI in energetically optimal normal walking should be high and invariable of gait speed. The method was tested on twelve healthy subjects walking at three different speeds and contrasted to five established gait energy consumption assessment methods. The results showed that GEEI in normal walking is close to 1 regardless of walking speed.     

Clinical suppression of experimental allergic encephalomyelitis by muramyl dipeptide “adjuvant”

Experimental allergic encephalomyelitis (EAE) is a model for several human diseases including multiple sclerosis and post-vaccinal encephalopathies. EAE is generally thought to be an autoimmune response to the antigen myelin basic protein (MBP). Oddly, MBP can also suppress EAE, and many observations suggest that an independent immune response to so-called "adjuvant" material is also necessary to EAE induction. Thus, EAE may be a result of a pair of interactive immune responses, one against MBP, and one against adjuvant. If so, the adjuvant should, like MBP, suppress EAE. We present data from experiments on strain 13 guinea pigs demonstrating EAE suppression by muramyl dipeptide, an active component of complete Freund's adjuvant. These results are striking because classically adjuvants are defined as immunopotentiators, not immunosuppressants. Our results, therefore, suggest that a revaluation of the role of adjuvants in inducing autoimmune diseases may be necessary.     

Infection by CagA-Positive Helicobacter pylori Strains and Bone Fragility: A Prospective Cohort Study

Helicobacter pylori (HP) infection is a common and persistent disorder acting as a major cofactor for the development of upper gastrointestinal diseases and several extraintestinal disorders including osteoporosis. However, no prospective study assessed the effects of HP on bone health and fracture risk. We performed a HP screening in a population-based cohort of 1149 adults followed prospectively for up to 11 years. The presence of HP infection was assessed by serologic testing for serum antibodies to HP and the cytotoxin associated gene-A (CagA). The prevalence of HP infection did not differ among individuals with normal bone mineral density (BMD), osteoporosis, and osteopenia. However, HP infection by CagA-positive strains was significantly increased in osteoporotic (30%) and osteopenic (26%) patients respect to subjects with normal BMD (21%). Moreover, anti-CagA antibody levels were significantly and negatively associated with lumbar and femoral BMD. Consistent with these associations, patients affected by CagA-positive strains had a more than fivefold increased risk to sustain a clinical vertebral fracture (HR 5.27; 95% CI, 2.23–12.63; p < .0001) and a double risk to sustain a nonvertebral incident fracture (HR 2.09; 95% CI, 1.27–2.46; p < .005). Reduced estrogen and ghrelin levels, together with an impaired bone turnover balance after the meal were also observed in carriers of CagA-positive HP infection. HP infection by strains expressing CagA may be considered a risk factor for osteoporosis and fractures. Further studies are required to clarify in more detail the underlying pathogenetic mechanisms of this association. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Chronic immobilization-induced stress increases plasma testosterone and delays testicular maturation in pubertal rats

We investigated whether chronic stress, applied from prepuberty to early puberty, interferes with the spermatogenic and androgenic testicular functions. Male pubertal rats (40 days old) were immobilized 6 h per day for 15 days. Plasma concentrations of corticosterone, prolactin and testosterone were significantly augmented following immobilization, whereas plasma luteinizing hormone decreased and follicle-stimulating hormone was not altered. Acute immobilization (5 min) increased prolactin and testosterone levels in control rats but caused a significantly higher increase in these hormones when superimposed on chronic stress. A lower extent of testicular maturation was observed in pubertal rats immobilized from prepuberty.     

Postural activity of constrained subject in response to disturbance in sagittal plane

This study examines the postural activity of partially constrained subjects for three different initial standing postures in response to disturbances in the sagittal plane. When the ankle strategy suffices for disturbance rejection in response to anterior disturbances, a mostly linear relationship between the ankle torque and ankle angle was observed, resulting in a constant stiffness at the ankles. However, when the ankle torque saturation was reached, a combined ankle-trunk postural strategy was utilized mainly in response to posterior perturbations due to the properties of the base-of-support. This caused a nonlinear scaling of ankle responses, thereby increasing variability of ankle stiffness. Distinctions in the ankle responses were also observed for different initial standing postures. The anterior initial stance generally increases the overall postural stability and renders the utilization of ankle strategy feasible, even for the rejection of posterior disturbances. Therefore, a linear torque-angle relationship at the ankles was observed for the anterior initial stance, regardless of the perturbation parameters.     

Modulation of gap junction mediated intercellular communication in TM3 Leydig cells

Long-term modulation of intercellular communication via gap junctions was investigated in TM3 Leydig cells, under low and high confluence states, and upon treatment of the cells for different times with activators of protein kinase A (PKA) and protein kinase C (PKC). Cells in low confluence were readily coupled, as determined by transfer of the dye Lucifer Yellow; on reaching confluence, the cells uncoupled. Western blots and RT-PCR revealed that connexin 43 (Cx43) was abundantly expressed in TM3 Leydig cells and its expression was decreased after the cells achieved confluence. Stimulation of PKA or PKC induced a decrease in cell-cell communication. Staurosporin, an inhibitor of protein kinases, increased coupling and was able to prevent and reverse the uncoupling actions of dibutyryl cAMP and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Under modulation by confluence, Cx43 was localized to the appositional membranes when cells were coupled and was mainly in the cytoplasm when they were uncoupled. In addition, cAMP and TPA reduced the surface membrane labeling for Cx43, whereas staurosporin increased it. These data show a strong correlation between functional coupling and the membrane distribution of Cx43, implying that this connexin has an important role in intercellular communication between TM3 cells. Furthermore, increased testosterone secretion in response to luteinizing hormone was accompanied by a decrease in intercellular communication, suggesting that gap junction mediated coupling may be a modulator of hormone secretion in TM3 cells.