National Institutes of Health

About: National Institutes of Health is a government organization based out in Bethesda, Maryland, United States. It is known for research contribution in the topics: Population & Gene. The organization has 149298 authors who have published 297896 publications receiving 21337431 citations. The organization is also known as: NIH & U.S. National Institutes of Health.

Properties of the Novel Proinflammatory Supergene "Intercrine" Cytokine Family

Abstract: A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines are characterized by conserved single open reading frames, typical signal sequences in the 5' region, and AT rich sequences in the 3' untranslated regions. Those human cytokines known as interleukin 8, platelet factor 4, beta thromboglobulin, IP-10 and melanoma growth stimulating factor or GRO can be assigned to a subfamily based on their location on chromosome 4 and unique structural features, whereas the second subset consisting of LD78, ACT-2, I-309, RANTES, and macrophage chemotactic and activating factor (MCAF) are all closely linked on human chromosome 17. In this review we have summarized and discussed the available information concerning the regulation and structure of the genes, the structure and biochemical properties of the polypeptide products, their receptors, signal transduction, cell sources, and in vitro as well as in vivo activities of these cytokines.

5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression

Abstract: Carriers of the short allele of a functional 5¢ promoter polymorphism of the serotonin transporter gene have increased anxietyrelated temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdalacingulate feedback circuit critical for emotion regulation implicate a developmental, systems-level mechanism underlying normal emotional reactivity and genetic susceptibility for depression. Depression is among the four leading causes of disability and disease burden throughout the world and is associated with serious medical conditions and mortality across the lifespan 1,2 . The importance of serotonergic neurotransmission for the pathogenesis of depression is suggested clinically by the efficacy of serotonin re-uptake inhibitors (SSRIs), the first-line treatment of depression and most related anxiety disorders 1 and by induction of depression by tryptophan depletion in susceptible individuals 2 . Post-mortem and in vivo studies of the serotonin transporter (5-HTT) and receptors support a role for this neurotransmitter system in depression and anxiety disorders 1 . Further

Fibronectin at a glance.

Abstract: Fibronectin (FN) mediates a wide variety of cellular interactions with the extracellular matrix (ECM) and plays important roles in cell adhesion, migration, growth and differentiation ( [Mosher, 1989][1]; [Carsons, 1989][2]; [Hynes, 1990][3]; [Yamada and Clark, 1996][4]). FN is widely expressed by

Incidence of Early Loss of Pregnancy

Abstract: We studied the risk of early loss of pregnancy by collecting daily urine specimens from 221 healthy women who were attempting to conceive. Urinary concentrations of human chorionic gonadotropin (hCG) were measured for a total of 707 menstrual cycles with use of an immunoradiometric assay that is able to detect hCG levels as low as 0.01 ng per milliliter, with virtually 100 percent specificity for hCG in the presence of luteinizing hormone. Our criterion for early pregnancy--an hCG level above 0.025 ng per milliliter on three consecutive days--was determined after we compared the hCG levels in the study group with the levels in a comparable group of 28 women who had undergone sterilization by tubal ligation. We identified 198 pregnancies by an increase in the hCG level near the expected time of implantation. Of these, 22 percent ended before pregnancy was detected clinically. Most of these early pregnancy losses would not have been detectable by the less sensitive assays for hCG used in earlier studies. The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent. Most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.

Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

Abstract: To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.