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Signaling “cross-talk” between TGF-β1 and ECM signals in chondrocytic cells
No full textThe objective of this investigation was to clarify how the integrin pathway modulates downstream effectors of the TGF-β1 pathway in chondrocytic cell signaling. The levels of Smad2 and Smad3 phosphorylation upon TGF-β1 or α2β1 integrin (Type II collagen) stimulation were analyzed by Western blotting techniques. Cellular response was determined by quantitation of procollagen gene expression.
Stimulation of cells with TGF-β1 and Type II collagen led to rapid phosphorylation of Smad2 and 3 with phosphorylation peaking between 15 min and 1 h. Combined stimulation led to a synergistic increase in the phosphorylation of Smad2 and Smad3. Type II collagen gene expression paralleled Smad phosphorylation.
Type II collagen modulates the TGF signaling cascade involving Smad2 and Smad3 leading to an increase in Type II collagen transcription. Therefore, we conclude that TGF-β1 and integrin stimuli interact prior to Smad2 and 3 phosphorylation in the cytoplasm of chondrocytic cells and regulates the expression of ECM components in chondrocytes
A Genomic Point Mutation in the Extracellular Domain of the Thyrotropin Receptor in Patients with Graves’ Ophthalmopathy
No full textOrbital and pretibial fibroblasts are targets of autoimmune attack in Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD). The fibroblast autoantigen involved in these peripheral manifestations of Graves' disease and the reason for the association of GO and PTD with hyperthyroidism are unknown. RNA encoding the full-length extracellular domain of the TSH receptor has been demonstrated in orbital and dermal fibroblasts from patients with GO and normal subjects, suggesting a possible antigenic link between fibroblasts and thyrocytes. RNA was isolated from cultured orbital, pretibial, and abdominal fibroblasts obtained from patients with severe GO (n = 22) and normal subjects (n = 5). RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction, using primers spanning overlapping regions of the entire extracellular domain of the TSH receptor. Nucleotide sequence analysis showed an A for C substitution in the first position of codon 52 in 2 of the patients, both of whom had GO, PTD, and acropachy. Genomic DNA isolated from the 2 affected patients, and not from an additional 12 normal subjects, revealed the codon 52 mutation by direct sequencing and AciI restriction enzyme digestions. In conclusion, we have demonstrated the presence of a genomic point mutation, leading to a threonine for proline amino acid shift in the predicted peptide, in the extracellular domain of the TSH receptor in two patients with severe GO, PTD, acropachy, and high thyroid-stimulating immunoglobulin levels. RNA encoding this mutant product was demonstrated in the fibroblasts of these patients. We suggest that the TSH receptor may be an important fibroblast autoantigen in GO and PTD, and that this mutant form of the receptor may have unique immunogenic properties
[29] Polymerase chain reaction amplification of specific alleles: A general method of detection of mutations, polymorphisms, and haplotypes
No full textPolymerase Chain Reaction Amplification of Specific Alleles: A General Method of Detection of Mutations, Polymorphisms, and Haplotypes
No full textInhibition of MMP-1 expression by antisense RNA decreases invasiveness of human chondrosarcoma
No full textExpression of the sodium iodide symporter in human kidney
No full textExpression of the sodium iodide symporter in human kidney.BackgroundThe human sodium iodide symporter (hNIS) is a transmembrane protein that mediates the active transport of iodide in the thyroid gland. Following cloning of NIS, NIS expression has been detected in a broad range of nonthyroidal tissues, suggesting that iodide transport in these tissues is conferred by the expression of functional NIS protein.MethodsThe aim of this study was to examine functional hNIS expression in kidney by reverse transcription-polymerase chain reaction (RT-PCR), ribonuclease protection assay (RPA), immunohistochemistry, and Western blot analysis accompanied by iodide accumulation studies in kidney cells.ResultsUsing a pair of full-length hNIS-specific oligonucleotide primers, RT-PCR followed by Southern hybridization revealed hNIS mRNA expression in normal human kidney tissue. The PCR products were subjected to automated sequencing and revealed full identity with the published human thyroid-derived NIS cDNA sequence. Furthermore, positive protected bands indicating the presence of hNIS mRNA were apparent in RPA gel lanes corresponding to human kidney cells as well as Chinese hamster ovary (CHO) cells stably transfected with hNIS cDNA and Graves' thyroid tissue. Immunohistochemical analysis of normal human kidney tissue using a mouse monoclonal hNIS-specific antibody showed marked hNIS-specific immunoreactivity confined to tubular cells, while no hNIS-specific immunoreactivity was detected in the glomeruli. NIS protein expression in human kidney cells was further confirmed by Western blot analysis. In addition, accumulation of 125I was detected in human kidney cells in vitro and was shown to be sodium dependent and sensitive to perchlorate.ConclusionsFunctional hNIS expression was demonstrated in the renal tubular system, suggesting that renal iodide transport may be, at least in part, an active process driven by NIS
Juvenile homicide : a criminological study on the possible causes of juvenile homicidal delinquency in Jamaica
No full textJamaica, the so-called land of wood and water, normally is the embodiment of a dream holiday destination with white sandy beaches, tropical palm trees, dazzling sunshine and the typical Caribbean flair. Generally, murder and manslaughter are not associated with Jamaica. However, international comparisons of crime rates reveal that Jamaica has persistently had one of the highest homicide rates in the world. Jamaica has been described as the murder capital of the world in 2006 by the BBC news after more than 1’600 people were killed in the year 2005; a tally of at least five people murdered a day. The majority of the homicides are caused by young men. Despite the dimension and severity of the homicidal problem in Jamaica, it is astonishing that literature on this phenomenon in Jamaica is very sparse and the literature that is available either doesn’t conform to the current homicide situation in Jamaica anymore or is inconsistent with other studies. The aim of the present research study was thus to close this gap and to help the process of comprehending the problem of fatal juvenile delinquency by engaging empirical research in serious efforts to describe and explain the epidemic. According to the author, understanding juvenile homicidal delinquents and their actions and thus ascertaining a plausible explanation for their high homicide rate can only be achieved by going back to those whose acts are to be explained: The juvenile homicidal delinquents themselves. The findings of the present study are therefore based upon the data gathered by means of 20 face-to-face, semi-standardised interviews with young men who have committed at least one homicide during the last five years prior to the interview and were aged between 12 and 25 years at the time of the respective homicide(s). The author acts on the assumption that homicides by juveniles can be understood as a reaction that emerges situationally and is based on a complex bundle of causes which leads to an increased susceptibility to homicides. The aim of the present study was to generate a plausible and scientifically substantiated hypothesis to explain the high proportion of male juveniles responsible for the homicide rate in Jamaica. Three groupings were examined: The individual personality characteristics of the homicide delinquents, the social context influencing the individual’s thoughts and actions and the triggering factors in the homicide context.
The study comes to the conclusion that the homicides of the respondents of the present study – additionally to the basic prerequisites of the occurrence of homicides in general such as a life in deprivation and the failure of the institutions of socialisation to sufficiently socialise their members – can be explained in high gear by the widely dispread culture of violence. Within this culture, violence constitutes a part of every-day behaviour and killing is perceived as a legitimate form of dispute resolution to which one has adapted because it utterly works. This is an instrumental understanding of violent behaviour. This apparent culture of violence of the underclass society with the deeply embedded willingness to apply violence to solve even seemingly minor disputes is intensified by a high gun prevalence and easy firearm accessibility as well as the wide distribution of and attachment to gangs. Firearms as well as delinquent gangs are two powerful factors that accord power, a feeling of strength and superiority to the individual. Status, power and respect rank high within the impecunious underclass society in Jamaica. Violence is perceived as a necessary instrument to sustain the own identity, status and respect. Thus, the fight for respect in the street culture of Jamaica’s urban inner-city youth depicts an act in self-defence for the parties involved. And such an act in self-defence legitimises to kill
