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At least 973 records · Page 54Linked to original sources
PubMed1999

Psoriasin (S100A7): a putative urinary marker for the follow-up of patients with bladder squamous cell carcinomas.

To search for bladder squamous cell carcinoma markers that are released to the urine a blind and systematic analysis of the protein profiles of fresh tumors, their secreted proteins, as well as the patient's urine was carried out using state-of-the-art proteomic technology. We review the data concerning the putative marker psoriasin (S100A7), which, alone or in combination with other biomarkers, may be valuable for the noninvasive follow-up of patients bearing these tumors.

Biomarkers, Tumor↗
PubMed2000

Afferent connections of the dorsal premammillary nucleus.

The dorsal premammillary nucleus (PMd) is thought to play a critical role for the expression of fear responses to environmental threats. We have reported previously that during an encounter with a predator the PMd presents an impressive increase in Fos levels and cell body-specific chemical lesions therein virtually eliminate the expression of escape and freezing responses. In the present study, we carried out a systematic analysis of PMd afferent connections combining anterograde and retrograde tracing methods in the rat. We show that the nucleus receives inputs from several widely distributed areas in the forebrain and, to a much lesser extent, from the brainstem as well. From this information, it seems that the major telencephalic source of input to the PMd is the interfascicular nucleus of the bed nuclei of the stria terminalis. In addition, substantial telencephalic inputs to the nucleus seem to arise from the infralimbic and prelimbic areas, and the lateral septal nucleus. In the diencephalon, massive inputs to the PMd arise from the anterior hypothalamic nucleus, specific parts of the perifornical region, the retinoceptive region of the lateral hypothalamic area, and the anterior and dorsomedial parts of the ventromedial hypothalamic nucleus. In contrast, the ventral tegmental nucleus seems to be the only brainstem site that provides substantial inputs to the PMd. Overall, the present analysis helps to delineate prosencephalic circuits seemingly critical for the organization of innate fear responses to environmental threats, where the PMd presents a major associative role. Furthermore, by means of massive inputs from the ventral tegmental nucleus, the PMd is in a position to integrate information from a neural system involved in spatial working memory, which may be of particular relevance for an effect of attentional mechanisms on the selection of appropriate escape strategies.

Afferent Pathways↗
PubMed2000

Yeast two-hybrid systems and protein interaction mapping projects for yeast and worm.

The availability of complete genome sequences necessitates the development of standardized functional assays to analyse the tens of thousands of predicted gene products in high-throughput experimental settings. Such approaches are collectively referred to as 'functional genomics'. One approach to investigate the properties of a proteome of interest is by systematic analysis of protein-protein interactions. So far, the yeast two-hybrid system is the most commonly used method for large-scale, high-throughput identification of potential protein-protein interactions. Here, we discuss several technical features of variants of the two-hybrid systems in light of data recently obtained from different protein interaction mapping projects for the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans.

Animals↗
PubMed1993

Scientific basis for cancer prevention. Intermediate cancer markers.

Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control.

Anticarcinogenic Agents↗
PubMed2000

Randomized population trials and screening for lung cancer: breaking the cure barrier.

BACKGROUND: At the current time, there is nearly universal agreement that screening for the early detection of lung carcinoma is not justified. This is based on the fact that, to the author's knowledge, no randomized population trial (RPT) to date has demonstrated a significant reduction in lung carcinoma mortality as a result of any screening intervention. METHODS: To date, four RPTs, which have included a total of 37,724 male cigarette smokers, have been conducted. Studies at Memorial Sloan-Kettering Cancer Center and Johns Hopkins demonstrate no incremental effect by the addition of sputum cytology to annual chest X-ray (CXR) screening alone. However, CXR screening in all participants likely was responsible for stage and long term survival rates that were two-to three-fold higher than predicted based on contemporary statistics. Studies at the Mayo Clinic and in Czechoslovakia demonstrated significantly superior stage distribution and survival, but slightly inferior mortality in experimental populations that underwent periodic CXR screening. Such contradictory findings were made possible by a higher cumulative incidence rate of lung carcinoma in experimental populations. The constellation of improved survival, higher rate of incidence, and similar mortality led to the hypothesis that CXR screening leads to the overdiagnosis of lung carcinoma. RESULTS: Abundant evidence based on epidemiologic, pathologic, and clinical considerations conclusively demonstrate that CXR screening does not lead to the significant overdiagnosis of lung carcinoma. Moreover, overdiagnosis is the only way to reconcile the results of existing RPTs with the conclusion that CXR screening is ineffective. The alternative conclusion is that significant stage, resectability, and long term survival advantages reflected the ability of CXR screening to improve cure rates. Population heterogeneity accounts for the failure of mortality to reflect screening efficacy accurately in these trials. There is direct evidence that population heterogeneity was responsible for the trend toward increased lung carcinoma mortality in the Czech study. Moreover, review of all RPTs demonstrates a consistent pattern in which population heterogeneity confounds the ability of mortality to represent an accurate measure of screening effectiveness. CONCLUSIONS: Systematic analysis of RPTs supports two major conclusions: 1) an improvement in the cure rate rather than a reduction is cause specific mortality is the proper measure of screening effectiveness in the RPT setting and 2) CXR screening is associated with a two- to three-fold improvement in lung carcinoma cure rates. A paradigm shift is mandatory for the proper evaluation of conventional and newer screening modalities. Indeed, hundreds of thousands of lives would be saved annually on a global basis if CXR screening were offered to individuals at high risk for lung carcinoma.

Bias↗
PubMed2001

Nuclear translocation of antizyme and expression of ornithine decarboxylase and antizyme are developmentally regulated.

The polyamines are important regulators of cell growth and differentiation. Cells acquire polyamines by energy-dependent transport and by synthesis where the highly regulated ornithine decarboxylase (ODC) catalyzes the first and rate-controlling step. Inactivation of ODC is mainly exerted by antizyme (AZ), a 20--25 kDa polyamine-induced protein that binds to ODC, inactivates it, and targets it for degradation by the 26S proteasome without ubiquitination. In the present study, we have performed a systematic analysis of the expression of ODC and AZ, at the mRNA and protein levels, during mouse development. The expression patterns for ODC and AZ were found to be developmentally regulated, suggesting important functions for the polyamines in early embryogenesis, axonogenesis, epithelial-mesenchymal interaction, and in apoptosis. In addition, AZ protein was found to translocate to the nucleus in a developmentally regulated manner. The nuclear localization is consistent with the fact that the amino acid sequence of AZ exhibits features that characterize nuclear proteins. Interestingly, we found that cultivation of mandibular components of the first branchial arch in the presence of a selective proteasome inhibitor caused ODC accumulation in the nucleus of a subset of cells, suggesting that the observed nuclear translocation of AZ is linked to proteasome-mediated ODC degradation in the nucleus. The presence of AZ in the nucleus may suggest that nuclear ODC activity is under tight control, and that polyamine production can be rapidly interrupted when those developmental events, which depend on access to nuclear polyamines, have been completed.

Adipose Tissue, Brown↗
PubMed2001

Prediction of the subcellular location of prokaryotic proteins based on a new representation of the amino acid composition.

A new representation of protein sequence is devoted in this paper, in which each protein can be represented by a 20-dimensional (20D) vector of unit length. Inspired by the principle of superposition of state in quantum mechanics, the squares of the 20 components of the vector correspond to the amino acid composition. Using the new representation of the primary sequence and Bayes Discriminant Algorithm, the subcellular location of prokaryotic proteins was predicted. The overall predictive accuracy in the jackknife test can be 3% higher than the result of using amino acid composition directly for the database of sequence identity is less than 90%, but 5% higher when sequence identity is less than 80%. The higher predictive accuracy indicates that the current measure of extracting the information from the primary sequence is efficient. Since the subcellular location restricting a protein's possible function, the present method should also be a useful measure for the systematic analysis of genome data. The program used in this paper is available on request.

Algorithms↗
PubMed2001

Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human.

Southern blot analyses of immunoglobulin light chain gene rearrangements in human leukemias and myelomas indicated that lambda loci in kappa-producing cells are largely unrearranged while kappa loci in lambda producers are often rearranged and inactivated by rearrangements of the kappa-deleting element (KDE). For a systematic analysis of the regulation of light chain rearrangements during early B cell development in normal human B cells also considering functionality of the rearrangements, we used FACS-sorted single naive kappa- and lambda-expressing B cells from peripheral blood of healthy humans. V(kappa)J(kappa) and V(lambda)J(lambda) joints and rearrangements involving the KDE were amplified simultaneously from single cells and sequenced. Whereas only 2 - 3 % of kappa-expressing cells carry V(lambda)J(lambda) joints, nearly all lambda-expressing cells have rearranged kappa loci and indeed carry V(kappa)J(kappa) joints. The V(kappa)J(kappa) joints in lambda-expressing cells exhibit preferential J(kappa)4 and J(kappa)5 over J(kappa)1 and J(kappa)2 usage compared to kappa-expressing cells. Thirty percent of the V(kappa)J(kappa) joints in lambda producers are rearranged in-frame. These data indicate extensive sequential V(kappa)-J(kappa) rearrangements and inactivation of functional V(kappa)J(kappa) joints in lambda-expressing cells, presumably before V(lambda)J(lambda) joining.

B-Lymphocytes↗
PubMed1999

Molecular basis of the charge selectivity of nicotinic acetylcholine receptor and related ligand-gated ion channels.

Nicotinic acetylcholine receptors are homo- or heteropentameric proteins belonging to the superfamily of receptor channels including the glycine and GABA-A receptors. Affinity labelling and mutagenesis experiments indicated that the M2 transmembrane segment of each subunit lines the ion channel and is coiled into an alpha-helix. Comparison of the M2 sequence of the cation-selective alpha 7 nicotinic receptor to that of the anion-selective alpha 1 glycine receptor identified amino acids involved in charge selectivity. Mutations of the alpha 7 homo-oligomeric receptor within (or near) M2, namely E237A, V251T and a proline insertion P236' were shown to convert the ionic selectivity of alpha 7 from cationic to anionic. Systematic analysis of each of these three mutations supports the notion that the conversion of ionic selectivity results from a local structural reorganization of the 234-238 loop. The 234-238 coiled loop, previously shown to lie near the narrowest portion of the channel, is thus proposed to contribute directly to the charge selectivity filter. A possible functional analogy with the voltage-gated ion channels and related receptors is discussed.

Amino Acid Sequence↗
PubMed2005

Factors contributing to construction injury at Denver International Airport.

BACKGROUND: Detailed information about factors contributing to construction injury is important to support design of safety programs directed at particular risks. METHODS: We linked over 4,000 injury reports, including text describing injury events, with an administrative workers' compensation (WC) database, and, using Haddon's matrix as a framework, classified factors contributing to injury during construction of Denver International Airport (DIA). RESULTS: Patterns of contributing factors varied according to injury mechanism and type of work: environmental factors contributed more than any other factor to slip/trip injuries, and building materials contributed to more than 40% of injuries to workers in carpentry, concrete construction, glass installation, and roofing. Rates at which factors contributed to injury also varied among types of work: environmental factors contributed at relatively high rates to injuries in glass installation, metal/steel installation and iron/steel erection >or= 2 stories, and victim factors contributed at high rates to conduit construction and metal/steel installation injuries. WC payment rates for different factors varied widely, ranging from $0.53/$100 payroll to $3.08/$100. DISCUSSION: This approach allows systematic analysis of classes of injuries, contributing factors, types of work, and other variables to assist in setting prevention priorities.

Accidents, Occupational↗
PubMed2003

Natural history of rhizomelic chondrodysplasia punctata.

Rhizomelic chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder with many associated medical complications. Prior to this study, natural history information about RCP was limited and based on experiences with small populations of affected individuals. We delineate the natural history of RCP through systematic analysis of 35 previously unreported individuals (as well as review of 62 literature cases with respect to survival and cause of death). Survival, growth, and developmental expectations and medical needs are summarized based upon experience with this population. Survival is greater among this population than previously reported, with 90% surviving up to 1 year and 50% surviving up to 6 years. Cause of death is most often respiratory problem. All infants with RCP have joint contractures, bilateral cataracts, and severe growth and psychomotor delays. Recommendations for health supervision of children with RCP and for parental counseling are presented.

Adolescent↗
PubMed1977

Functional implications of primate enamel thickness.

Recent evolutionary interpretations of Hominoidea have postulated functional relationships between tooth form, diet and masticatory biomechanics. A major consideration is the durability of the tooth under certain dietary conditions. Teeth with low cusps and thicker enamel are able to withstand heavy mastication of abrasive food bolus for a longer period. When comparisons are made between species of higher primates the variables of tooth size, cusp morphology, and enamel thickness appear to be related but until now no systematic analysis has been made to determine the functional relevance of several dental dimensions. This study provides data gained from comparisons of dentition of nine species of primates. Histological sections were made of the post canine teeth and 21 dimensions were compared. The relevant dimensions identified serve to withstand dental wear. The distribution of thicker enamel corresponded to the observed wear planes. Humans had thicker enamel than pongids while the macaque had the thinnest. These preliminary results tend to support theories which explain low, thick, enameled cusps in hominids.

Animals↗
PubMed1989

Trauma, degenerative disease, and other pathologies among the Gombe chimpanzees.

The well-known and extremely well-documented chimpanzees from Gombe National Park were analyzed for presence of skeletal pathologies. Of the 15 animals available for study, 11 were old and complete enough to permit systematic analysis. Of these, 10 showed some evidence of skeletal pathological involvement. The most common type of lesion seen resulted from trauma. Those chimps with the most fractures (Old Female, 3; Flo, 4; Hugo, 8) are consistently the oldest individuals in the sample. In addition to accidental falls, the most common cause of trauma was from interpersonal violence, resulting in bite wounds (see in two individuals) and fractures (see in three individuals). Conversely to trauma, degenerative disease was exceedingly rare in this population, found in no large intervertebral joints (N = 344) and only two major synovial joints (N = 186). In fact, the complete lack of osteophytosis, even in older individuals, stands in stark contrast to the situation seen in modern humans, perhaps in our species reflecting a biomechanical cost of bipedality.

Age Factors↗
PubMed2002

Structure of the conus arteriosus of the sturgeon (Acipenser naccarii) heart. I: the conus valves and the subendocardium.

Sturgeons are bony fish that retain structural traits typical of the more primitive Chondrostei. From an evolutionary viewpoint, sturgeons are considered relic fish. However, they show remarkable ecological plasticity and are well adapted to contemporary environmental conditions. Although development of the cardiovascular system is critical for all organs and systems, and is affected by evolutionary changes, the structure of the sturgeon heart has been mostly overlooked. This is also true for the conus arteriosus, which, as in Chondrostei, is endowed with several rows of valves and a layer of contractile myocardium. This work reports on the structure of the valves, the endocardium, and the subendocardium of the conus arteriosus of the sturgeon (Acipenser naccarii) heart. It is part of a broader study that aims to cover the entire structure of the sturgeon heart. The conus arteriosus of 15 A. naccarii hearts, ranging in age from juveniles to sexually-differentiated adults, has been studied by conventional light, transmission (TEM), and scanning electron microscopy (SEM). In addition, maceration of the soft tissues with NaOH, and actin localization by fluorescent phalloidin has been used. The conus is a tubular chamber that arises from the right ventricular side and presents two constrictions at the conus-ventricle and conus-aorta junctions. The conus is endowed with three rows of valves: one distal and two proximal. The segment of the conus located between the distal and the two proximal rows is devoid of valvular structures. The distal row has four leaflets, while the two proximal rows show the greatest variation in leaflet number, size, and shape. All leaflets have collagenous chordae tendineae arising from the free border and from the parietal side of the leaflets. The endocardium is a flat endothelium which shows a thick, irregular basement membrane. The leaflet body is formed by a loose connective tissue which blends with the subendocardium. The subendocardium is a connective tissue consisting of myofibroblasts, collagen, and elastin. It is divided into two distinct areas: one proximal, which shows little elastin and poorly organized collagen; and one distal, which is rich in elastin, with cells and extracellular fibers organized into layers that are oriented in alternative circumferential and longitudinal directions. The present report is the first systematic analysis of the structure of the sturgeon conus. Descriptions of the conus valves should recognize the existence of three valve rows only. The variability in valve morphology, and the loose structure of the leaflet tissue make it unlikely that the valves play an effective role in preventing blood backflow. In this regard, the ventricle-conus constriction may act as a sphincter. The subendocardium is an elastic coat capable of actively sustaining the tissue deformation that accompanies the heart contractile cycle. Further comparative studies are needed to provide deeper insight into the structural changes that accompany phyletic diversification.

Animals↗
PubMed2002

Models of intracellular transport and evolution of the Golgi complex.

We have performed a systematic analysis of models explaining the mechanisms of the intracellular biosecretory transport. The models assessed include not only those based on one mechanism (the dissociation model (and its individual case, the vesicular model), the progression model (and its individual cases, the cisterna maturation/progression and the carrier maturation models), and the lateral diffusion model (and its individual case, the bolus model), but also combined models of transport (the percolating-vesicles model and the synthetic model), including several transport mechanisms. Most of these models are not able to explain recent data on the evolution of genes involved in intracellular transport and Golgi evolution. The carrier maturation model proposing that fusion of the large cargo domain with the distal (closer to the plasmalemma) compartment precedes fission of the domain from the proximal compartment exhibits the best performance in correlation with the available information on evolution of the biosecretory pathway.

Biological Evolution↗
PubMed2005

Side-chain control of folding of the homologous alpha-, beta-, and gamma-peptides into "mixed" helices (beta-helices).

A systematic analysis of the substituent influence on the formation of the unique secondary structure type of "mixed" helices in the homologous alpha-, beta-, and gamma-peptides was performed on the basis of ab initio molecular orbital theory. Contrary to the common periodic peptide helices, mixed helices have an alternating periodicity and their hydrogen-bonding pattern is similar to those of beta-sheets. They belong, therefore, to the family of beta-helices. It is shown that folding of peptide sequences into mixed helices is energetically preferred over folding into their periodic counterparts in numerous cases. The influence of entropy and solvents on the formation of the various competitive mixed and periodic helix types is discussed. Among the oligomers of the various homologous amino acids, beta-peptides show the highest tendency to form beta-helices. The rules of substituent influence derived from the analysis of a wide variety of backbone substitution patterns might be helpful for a rational design of mixed helix structures, which could be important for mimicking membrane channels.

Hydrogen Bonding↗
PubMed2007

Computational study of the absorption spectra of green fluorescent protein mutants.

In this work, we present a theoretical study of the relationship between molecular structure and the red-shift in absorption spectra of S65G and S65T green fluorescent protein (GFP) mutants. To identify the effects of the protein environment, we combined results from molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics calculations to obtain structural properties, and applied time-dependent density functional theory to calculate the excitation energies. By using results from the MD simulations, we were able to provide a systematic analysis of the structural details that may effect the red-shift in the absorption spectra when taking into account temperature effects. Furthermore, a detailed study of hydrogen bonding during the MD simulations demonstrated differences between S65G and S65T, for example, regarding hydrogen bonding with Glu222. An analysis of the absorption spectra for different forms of the chromophore emphasized the dominance of the anionic forms in solution for the S65G and S65T GFP mutants.

Computer Simulation↗
PubMed2002

Transduction rate constant as more reliable index quantifying efficiency of retroviral gene delivery.

Although the efficiency of retrovirus-mediated gene delivery can be enhanced by several physicochemical approaches reported (e.g., addition of polycations and spinoculation), systematic analysis of retroviral transduction combined with experimental data remains to be challenged. With the aid of a reasonable mathematical description of an experimental system, we can therefore predict and optimize the retroviral gene delivery on a quantitative basis of understanding. In this study, we formulated a mathematical model involved with diffusion, decay and uptake of retroviral vectors onto the target cells resided on a solid culture surface. The model was solved analytically by the Laplace transform method. The analytical solutions were then fitted with experimental data to compute two unknown parameters: concentration of infectious retrovirus and transduction rate constant. Our results showed that the concentration of infectious retrovirus determined by the titration method was approximately hundred-fold lower than the one calculated by fitting experimental data with the mathematical solutions. More importantly, effects of polycation (i.e., Polybrene) on ex vivo retroviral transduction were illustrated in a quantitative way by estimating the transduction rate constant, which represents a more reliable parameter to determine the degree of transduction of a retroviral vector to a given target cell.

3T3 Cells↗