Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells

RFB-1 is a monoclonal antibody previously shown to react with granulocyte-monocyte progenitors (CFU-GM) and immature lymphoid cells in human bone marrow. RFB-HLA-DR is a monoclonal antibody that reacts with HLA-DR (la-like) antigens. The present study shows that the bone marrow subset reactive with both RFB-1 and RFB-HLA-DR contains all the cells that give rise to mixed hematopoietic colonies (derived from CFU- GEMM; a pluripotent human progenitor cell) as well as to megakaryocytic (megakaryocyte-CFU-derived) and erythropoietic (derived from erythroid burst-forming units, BFU-E) colonies, as shown by fluorescence- activated cell sorting and complement-mediated cytotoxicity. These results indicate that CFU-GEMM, BFU-E, and megakaryocyte-CFU express RFB-1 and la-like antigens. RFB-1 antigen is also expressed on erythroid colony-forming units (CFU-E). RFB-1 and RFB-HLA-DR are useful reagents in the study of hematopoietic stem cells.     

Exercise-induced left ventricular dysfunction in young men with asymptomatic diabetes mellitus (diabetic cardiomyopathy)

Radionuclide ventriculographic studies were performed at rest and during exercise on 30 consecutive men, aged 21 to 35 years with diabetes mellitus without evidence of coronary artery or any other cardiovascular disease, and in 20 normal age-matched subjects. Sixteen (53%) were treated with insulin and 14 (47%) were treated with either diet (6 patients) or oral antidiabetic therapy (8 patients). All patients from both groups had normal left ventricular (LV) ejection fraction (EF) at rest. In 5 of the 30 diabetic patients (17%), LVEF decreased after exercise, in 8 (27%) it remained unchanged and in 17 it increased normally. Mean LVEF at rest and after exercise in this group was 66 +/- 7% and 72 +/- 7% (+/- standard deviation), respectively. In all normal subjects, LVEF increased after exercise. Mean LVEF at rest and after exercise in the normal group was 66 +/- 7% and 76 +/- 9%, respectively. No patient had evidence of regional dysfunction at rest or after exercise. LV function was not related to serum glucose levels during the test, modality of treatment, insulin dependency or duration of the disease. Three of 4 patients with diabetic microvascular complications showed LV dysfunction. In 4 of 5 patients in whom LVEF decreased after exercise, thallium studies showed normal perfusion. Thus, diabetes mellitus may cause exercise-induced global LV dysfunction in young men with no evidence of cardiovascular disease. This phenomenon apparently does not seem to follow the known course of diabetic microvascular complications.     

Alpha-2 adrenoceptors on nerves and muscles of rat uterus

To test the hypothesis that functional postsynaptic alpha-2 adrenoceptors exist in rat myometrium, we examined whether specific binding sites for [3H]rauwolscine were present on microsomal membranes from myometrium of nonpregnant, day 16 pregnant and delivering rats and whether an alpha-2 adrenoceptor agonist has functional effects. The myometrium of rats at term undergoes a physiological denervation, confirmed in this study by ultrastructural examination of uterine samples and by [3H]saxitoxin binding studies. Binding sites for rauwolscine of similar Kd (11-15 nM) were present in all groups of myometrium and were localized on plasma membranes. There was no significant change in the density of rauwolscine binding sites in membranes from day 16 animals compared to nonpregnant ones, but a significant fall (38%) from these values at term. Strips of uterine circular or longitudinal muscle from nonpregnant, day-16 or day-22 pregnant rats failed to respond to the selective alpha-2 agonist, BHT-920, in the presence of propranolol; i.e., BHT-920 neither caused contraction nor inhibited contractions induced by oxytocin. BHT-920 did not affect the inhibitory effects of isoproterenol which were antagonized by propranolol. However, it antagonized contractions to norepinephrine in the presence of propranolol with a pKB value of 5.6 to 5.7. These contractions were phentolamine-sensitive. BHT-920 displaced rauwolscine from binding to all groups of myometria (IC50 = 2 to 3 x 10(-6) M) and displaced prazosin (Kd = 0.65 nM) from binding to myometria of nonpregnant rats (IC50 value congruent to 2 x 10(-4) M). Phentolamine also displaced rauwolscine from binding (IC50 = 2 x 10(-8) M). 5-Hydroxytryptamine displaced rauwolscine from binding only at higher concentrations (IC50 greater than 10(-5) M). We conclude that binding sites for alpha-2 adrenoceptor antagonists in myometrial microsomes were located primarily on smooth muscle plasma membrane. A smooth muscle alpha-2 adrenoceptor agonist appeared to occupy a site on muscle with the same affinity as it displayed toward rauwolscine binding site and competitively inhibited effects of an alpha-1 agonist. Our data suggest that alpha-2 adrenoceptor binding sites may exist on smooth muscle without coupling to contractile function, but their occupancy competitively prevents occupancy of alpha-1 agonist receptor activation sites.     

The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury

Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI by means of microarray analysis. Adolescent rats were subjected to TBI and treated with either placebo or a neural cell adhesion molecule (NCAM)-derived fibroblast growth factor receptor (FGFR) agonist, FGL peptide, which has been demonstrated to have neuroprotective effects. mRNA levels were measured at various time-points postlesion (6 h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL-treatment in non-injured animals rendered genes regulating signaling, transport and cytoskeleton maintenance significantly increased. Thus, the hypothesis of a putative neuroprotective role of FGL was supported by our findings.     

Treatment of children with neurogenic bladder dysfunctions using dynamic nero-electrostimulation(DENS) and M-Cholinolytic therapy

【Objective】 To investigate effects of combined usage of dynamic neuro-electric stimulation(DNES) and M-cholynolytic therapy(oxybutynin) upon manifestations of neurogenic bladder dysfunctions(NBD) in children.【Method】 Urodynamics examination included registration of extemporaneous urinary excretion,urofluometry,and retrograde cytometry in horizontal and vertical position by example of urodynamic system(UDS) ACS 180 Plus(MENFIS BioMed.,USA).In accordance to severity of clinician manifestations,three groups of patients have been defined(27-highest one,49-middle and 51 low levels).Dynamic neuro-electrostimulation(DNES) procedures were conducted using the"DiaDNES-PKM"device(Russian Federation).The children were exposed to juxtaspinal stimulation on S1-S3 level-altogether 10 sessions have been performed.Oxybutynin(driptan) was used in dosage of 2.5 mg per diem.【Result】It was established that combined usage of DNES and oxybutynin in the group with highest severity caused the reduction of manifestations by 3.1 times while separately given DNES and basic therapy were followed by 34.1% and 28.0% reduction correspondently.Meanwhile,DNES and oxybutynin reduced severity in patients with pronounced disturbances by 7.5 times.Combined usage of oxybutynin and DNES in severely manifested NBD increased the effective volume of bladder by 2.3 times.Also significant reduction of both intrabladder pressure(by 48.0%) and compliance of the bladder(by 4.8 times) were detected under condition of combined usage of DNES and oxybutynin.All mentioned indices were modified to less extent in case of separate usage of DNES or oxybutynin when compared with the one registered after the combined their usage(P <0.05).【Conclusion】Combined usage of DENS and oxybutinin(driptan) is effective in most severe cases in children suffered from neurogenic overactive bladder.