The CD40-CD154 system in anti-infective host defense

Research in the past few years has documented significant advances in our understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions. This system influences many T cell mediated inflammatory immune responses and effector functions, unmasking a previously unexpected role for CD40-CD154 in cell mediated immunity. Manipulation of CD154 in animal models of infection by the use of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this system in the initiation of the inflammatory response, in the activation of antigen-presenting cells and in resistance to infections.     

Neuropsychological functioning of girls with attention-deficit/hyperactivity disorder followed prospectively into adolescence: Evidence for continuing deficits?

The current study prospectively followed girls with attention-deficit/hyperactivity disorder (ADHD), along with a matched comparison sample, 5 years after childhood neuropsychological assessments. Follow-up neuropsychological measures emphasized attentional skills, executive functions, and language abilities. Paralleling childhood findings, the childhood-diagnosed ADHD group displayed moderate to large deficits in executive/attentional performance as well as in rapid naming relative to the comparison group at follow up (Mage 14.2 years). ADHD-inattentive versus ADHD-combined contrasts were nonsignificant and of negligible effect size, even when a refined, sluggish cognitive tempo subgroup of the inattentive type was examined. Although ADHD versus comparison group differences largely withstood statistical control of baseline demographics and comorbidities, control of childhood IQ reduced executive function differences to nonsignificance. Yet when the subset of girls meeting diagnostic criteria for ADHD in adolescence was compared with the remainder of the participants, neuropsychological deficits emerged even with full statistical control. Overall, childhood ADHD in girls portends neuropsychological and executive deficits that persist for at least 5 years. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The function of the reproductive system in x-ray-irradiated male rats after the transplantation of a culture of testicular cells from newborn piglets

The effect exerted by transplantation of the 5 day culture of testicles from newly born piglets on the hypogonadal state of mature X-ray irradiated (3 Gy) rats was studied. It has been found that a month after transplantation (two months after irradiation) the hypogonadal state disappeared for a while, which is confirmed by normalization of the weight of seminal vesicles, content of testosterone and biologically active lutropine, restoration of the reproductive function of rats. No significant changes in steroidogenesis activity have been found, which proves a substituent character of transplantation. The effect disappears three months later but certain restoration of the content of nucleic acids in the testicles is observed.     

Stochastic model for a wavelike exothermal reaction in condensed heterogeneous systems

The labile protons of two 32-base-pair, four-arm models of immobile Holliday junctions have been studied by two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy. Overlap of resonances in the imino-imino region of two-dimensional nuclear Overhauser enhancement (NOE) spectra necessitates the use of a multi-pathway approach for obtaining sequence-specific assignments wherein all possible NOE connectivities to the labile protons are utilized, including those from the 2H of adenine, 5CH3 of thymine, and 5H of cytosine. Resonance assignments are obtained for all slowly exchanging imino and cytosine amino protons. Base-pairing up to and including the junction point is found in all four arms of both Holliday junctions. Several cross-arm NOE connectivities are identified and can be used to infer the geometry of the helical stacking domains. The two Holliday junctions studied, which differ only by the exchange of two base pairs at the branch point, appear to have opposite arm stacking geometries. These assignments form an important part of the critical background for detailed NMR analysis of Holliday junction structure and dynamics.     

Supramedullary modulation of sympathetic vasomotor function

1. Supramedullary structures including the ventral medial prefrontal cortex (MPFC) and the midbrain cuneiform nucleus (CnF) project directly and indirectly to premotor sympatho-excitatory neurons of the rostral ventrolateral medulla (RVLM) that are critically involved in the generation of sympathetic vasomotor tone. 2. Electrophysiological studies have demonstrated that activation of depressor sites within the MPFC is associated with splanchnic sympathetic vasomotor inhibition and inhibition of the activity of RVLM sympathoexcitatory neurons. 3. Antidromic mapping and anatomical studies support the notion that a relay in the nucleus tractus solitarius is involved in the cardiovascular response to MPFC stimulation. 4. The midbrain CnF, which lies adjacent to the midbrain periaqueductal grey, is a sympathoexcitatory region of the midbrain reticular formation. Sympathoexcitatory responses evoked from the CnF are associated with short-latency excitation of RVLM neurons. 5. Cuneiform nucleus stimulation induces the expression of mRNA for the immediate early genes c-fos and NGFI-A in mid-brain, pontine and hypothalamic structures. 6. The MPFC and CnF are supramedullary structures with opposing modulatory influences on sympathetic vasomotor drive, whose roles in cardiovascular control mechanisms warrant further investigation.     

An epidemiologic, clinical, and therapeutic study of childhood Guillain-Barré syndrome in Kuwait: is it related to the oral polio vaccine?

We studied Guillain-Barré syndrome, affecting children 12 years old or less, throughout Kuwait, in the period between January 1, 1992, and March 31, 1997. Nineteen children had the diagnostic criteria of Guillain-Barré syndrome, with an overall annual incidence rate of 0.95/100,000 population at risk. Female patients outnumbered male patients with a sex ratio of 1.4:1. There was a clustering of cases in winter and spring and in the year 1996. The disease symptoms were relatively severe in our patients because only 16% (3 of 19) of them were able to walk at the height of their illness, whereas the rest were bed or chair bound or needed assisted ventilation. Two patients had the electrodiagnostic features of axonal neuropathy and both had residual deficits on follow-up, whereas the rest recovered fully. All the patients received intravenous immunoglobulin. The mean time to walk unaided was 23.5 days (range, 2-84 days) after intravenous immunoglobulin and excluding the two patients with axonal neuropathy, and full recovery was achieved in a mean time of 103 days (range, 30-300 days). Contrary to previous studies, we found no correlation between oral polio vaccine administration and Guillain-Barré syndrome in 2 successive years (1995 and 1996) during a nationwide campaign targeting children less than 5 years old.     

Sulfation of parabens and tyrosylpeptides by bacterial arylsulfate sulfotransferases

Arylsulfate sulfotransferase purified from Eubacterium A-44 has higher specific activity than the enzymes from Klebsiella K-36 and Haemophilus K-12. Propylparaben and butylparaben were good substrates among several parabens. The antibacterial activity of parabens was reduced by the sulfation of the phenolic hydroxy group. Tyrosine-containing peptides, kyotorphin, enkephalin and cholecystokinin non-sulfate, were effective as acceptor substrates by A-44, K-36 and K-12 sulfotransferases.     

Sexual dimorphism of circulating somatotropin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, and insulin: relationships to growth rate and carcass characteristics in growing lambs

The effects of sex and age on patterns of circulating somatotropin (ST) concentration and plasma IGF-I, IGF-II, insulin, and IGF binding protein-3 (IGFBP-3) were studied in ram, wether, and ewe lambs (n = 7 or 8) sampled at mean ages of 81 (I1) and 158 d (I2). Between 81 and 158 d of age, rams grew more rapidly than wethers (P < .01), and wethers grew more rapidly than ewes (P < .01). The sex differences in growth were reflected in empty body weight at slaughter: rams > wethers > ewes (P < .05). Mean plasma ST concentrations, ST pulse amplitude, and integrated plasma ST concentrations were greater (P < .05) in rams than in ewes at I1 and I2. Characteristics of the ST plasma profile in wethers were generally intermediate between those of rams and ewes. The interpulse interval was greater in ewes than in wethers at I2. The IGF-I and IGFBP-3 concentrations were greater in rams than in ewes at both sampling times. Plasma IGF-II was greater in ewes than in rams at I2. Mean plasma ST was approximately two thirds less at I2 than at I1 regardless of sex. Mean plasma ST and IGF-I at both ages were positively correlated with growth. Mean plasma ST at I2 was negatively correlated with fatness at slaughter. Sex and age significantly affected patterns of circulating ST and concentrations of IGF-I and IGFBP-3 in prepubertal growing lambs, under conditions for which growth rates and composition were also sexually dimorphic.     

p53 protein expression in extrahepatic bile duct cancer

p53 mutations, a tumor suppressor gene located on chromosome 17p, are the most common genetic alterations found in human cancers. Although the p53 expression or mutation has been investigated in a variety of cancers there have been very few studies in extrahepatic bile duct cancers. In this study, we investigated the immunohistochemical expression of p53 in formalin fixed paraffin embedded archival specimens of 36 extrahepatic bile duct cancers in which p53 expression was found in eighteen (50%) cases. There was no significant difference in age, gender, size of tumor, histologic grade, extent of tumor involvement, lymph node metastasis and tumor resectability according to p53 immunoreactivity. Comparison of survival duration according to p53 expression showed no significant difference. In conclusion, we reported 50 percent of p53 expression in extrahepatic bile duct cancers by immunohistochemical staining and we found no prognostic significance of p53 expression in dinicopathologic parameters.     

Selective monitoring of peptidase activities with synthetic polypeptide substrates and polyion-sensitive membrane electrode detection

A novel method to monitor specific peptidase activities in biological samples as complex as undiluted plasma/blood is described. The approach is based on the design of synthetic polypeptide substrates in which di- or triarginine sequences are linked to each other via one or more other amino acids recognized specifically by the peptidase to be determined. Detection of chymotrypsin and renin activities using synthetic substrates P4 (F-R-R-R-F-V-R-R-F-NH2) and P5 (R-R-R-L-L-R-R-L-L-R-R-R), respectively, serves to demonstrate the principles of this new assay system. A polyion-sensitive membrane electrode, prepared by doping polymer films with dinonylnaphthalene-sulfonate (DNNS), is shown to exhibit significant nonequilibrium electromotive force (EMF) responses toward these and other polycationic substrates at microgram/milliliter levels under physiological conditions. The same electrode, however, exhibits much smaller total EMF response toward the shorter fragments of the synthetic peptides generated by peptidase activity; hence, the addition of peptidase to a solution containing the synthetic substrate yields a change in electrode EMF response, the rate of which is proportional to the activity of peptidase present. Other synthetic polycationic peptides as well as natural polycationic peptides (e.g., protamine) that lack specific cleavage sites for chymotrypsin and renin, yet are detected by the DNNS-based membrane electrode, do not elicit any significant change in EMF response in the presence of the peptidases, confirming the feasibility and utility of the proposed bioanalytical method.