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PubMed2002

The role of dendritic cells in the pharynx.

The tonsils are organized as lymphoepithelial structures that play an important role in protecting both the upper respiratory and alimentary tract regions against incoming antigens. This function requires dendritic cells, professional antigen-presenting cells that act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material. This article gives a brief review on dendritic cells with regard to their origin, life cycle and functions in the pharyngeal mucosa. The regulation of immune responses in tonsils by dendritic cells is discussed. Their importance in some disease states is also mentioned.

Cell Cycle↗
PubMed1992

Analyses of exobiological and potential resource materials in the Martian soil.

Potential Martian soil components relevant to exobiology include water, organic matter, evaporites, clays, and oxides. These materials are also resources for human expeditions to Mars. When found in particular combinations, some of these materials constitute diagnostic paleobiomarker suites, allowing insight to be gained into the probability of life originating on Mars. Critically important to exobiology is the method of data analysis and data interpretation. To that end we are investigating methods of analysis of potential biomarker and paleobiomarker compounds and resource materials in soils and rocks pertinent to Martian geology. Differential thermal analysis coupled with gas chromatography is shown to be a highly useful analytical technique for detecting this wide and complex variety of materials.

Chromatography, Gas↗
PubMed2000

Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life. A systematic review.

To review the evidence for efficacy of complementary and alternative medicine (CAM) modalities in treating pain, dyspnea, and nausea and vomiting in patients near the end of life, original articles were evaluated following a search through MEDLINE, CancerLIT, AIDSLINE, PsycLIT, CINAHL, and Social Work Abstracts databases. Search terms included alternative medicine, palliative care, pain, dyspnea, and nausea. Two independent reviewers extracted data, including study design, subjects, sample size, age, response rate, CAM modality, and outcomes. The efficacy of a CAM modality was evaluated in 21 studies of symptomatic adult patients with incurable conditions. Of these, only 12 were directly accessed via literature searching. Eleven were randomized controlled trials, two were non-randomized controlled trials, and eight were case series. Acupuncture, transcutaneous electrical nerve stimulation, supportive group therapy, self-hypnosis, and massage therapy may provide pain relief in cancer pain or in dying patients. Relaxation/imagery can improve oral mucositis pain. Patients with severe chronic obstructive pulmonary disease may benefit from the use of acupuncture, acupressure, and muscle relaxation with breathing retraining to relieve dyspnea. Because of publication bias, trials on CAM modalities may not be found on routine literature searches. Despite the paucity of controlled trials, there are data to support the use of some CAM modalities in terminally ill patients. This review generated evidence-based recommendations and identified areas for future research.

Complementary Therapies↗
PubMed2003

The construction of emergent order, or, how to resist the temptation of hylozoism.

Hylozoism, the doctrine that nature is imbued by life even in the apparently inert and lifeless, has as one of its "appealing" features the ability to duck the perplexing issue of how life originated. By so doing, hylozoism has generated even more conundrums such as why rocks, if indeed they are actually animated, don't appear alive. Hylozoism is not so much a resolution as a way of avoiding the possibility of the emergence of the radically novel. But, hylozoism is not just a relic of the past since modern strains of its specific explanatory strategy can be detected in three examples from the study of complex systems, namely, May's and Feigenbaum's explanation of complexity and universality in "one-humped" maps, Maturana's and Varela's idea of autopoeisis, and Goertzel's notion of self-generating systems. These three explanatory strategies are analyzed as to their hylozoist cast with the result that the first is found to be appropriate to the mathematical nature of the inquiry while the second two are found wanting in the same way that hylozoism in general proves unsatisfactory as an explanation. To remedy the problems associated with a hylozoist strategy, a constructional view of the emergence of new wholes is proposed including intimations as to how this constructional process might proceed.

Journal Article↗
PubMed2000

Unmet needs in the treatment of asthmatic children and adolescents: 1.

The paediatric asthma guidelines have been successful in providing a uniform approach to the management of asthma for the medical profession as a whole. Unfortunately, the guidelines were generated without input from patients themselves and consequently do not consider issues that are important to patients such as a preference for oral treatment. Asthma is a heterogeneous group of conditions and the guidelines do not sufficiently define subgroups of patients and their particular needs. As a result, there has been a tendency to assume that all wheezing in infancy is asthma and this had led to gross overtreatment in certain patients. In contrast, severe asthma often remains underdiagnosed and undertreated. The most recent revision of the guidelines has classified asthma in terms of the patterns of disease; infrequent episodic, frequent episodic and chronic persistent. The treatment required for each of these groups is clearly defined and there is no need for stepwise therapy. Other changes to the guidelines will occur and are needed. None of the treatments available can modify the natural history of asthma; they control the symptoms not the disease process. Evidence from bronchial biopsies suggests that both inflammation and remodelling occur early, even before the first symptoms appear. We need to look for the factors in early life that predict which children will go on to develop asthma and intervene at that stage. Anti-histamines and leukotriene receptor antagonists may be interesting as interventions in that respect. Two important unresolved issues are to understand what drives remodelling and inflammation, and to look at early life origins of asthma. These approaches may provide effective therapeutic targets and, ultimately, a means of prevention.

Adolescent↗
PubMed2001

Dendritic cells and their role in skin-induced immune responses.

This artide gives a brief review on dendritic cells (DC) with regard to their origin, life cyde and functions. The regulation of immune responses by DC functioning as antigen-presenting cells is discussed. Special attention is given to epidermal DC, e.g. Langerhans cells. The perspectives of DC-based therapy are also mentioned.

Cell Cycle↗
PubMed2002

The prevalence of asthma and wheezing illnesses amongst 10-year-old schoolchildren.

Asthma and wheezing illnesses carry a significant burden of disease during childhood. Prevalence studies have the capacity to provide invaluable insights into the nature of these common conditions. As part of the Isle of Wight Whole Population Birth Cohort Study (n=1456) we have examined wheezing and asthma development amongst 10-year-old children. At this age 1373 children completed ISAAC written questionnaires whilst 1043 children performed further testing including skin-prick testing, serum inhalant IgE antibody screening, spirometry and bronchial challenge. At 10-years, prevalence of current wheeze was 18.9%, current asthma (symptomatic bronchial hyper-responsiveness--BHR) 14.4% and currently diagnosed asthma (current wheeze and asthma ever--CDA) 13.0%. Both wheezing and asthma at 10 years were associated with average symptom onset at 3 years of age indicating an early life origin for such conditions. Current wheeze (P=0.011) and CDA (P=0.008) showed significant male predominance. Considerable disease morbidity was identified for these states that tended to be greatest amongst children defined asthmatic rather than simply current wheezers. Wheezing and asthma were significantly associated with both atopy (P<0.001) and allergic co-morbidity Children with these states, particularly current asthma, also demonstrated impaired lung function (FEV1, P<0.001 and FEV1/FVC, P=0.010) and increased BHR (inverse slope, P<0.001). In conclusion, Asthma and wheezing showed substantial prevalence at 10 years of age. Strong associations to male gender, atopy, impaired lung function and BHR were seen for both wheeze and asthma. In regard to prevalence and morbidity characteristics, a questionnaire-based definition of currently diagnosed asthma gave similar results to the use of symptomatic BHR in defining current asthma.

Age of Onset↗
PubMed2003

Male germ line stem cells: from cell biology to cell therapy.

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

Animals↗
PubMed2002

Seaweeds in cold seas: evolution and carbon acquisition.

Much evidence suggests that life originated in hydrothermal habitats, and for much of the time since the origin of cyanobacteria (at least 2.5 Ga ago) and of eukaryotic algae (at least 2.1 Ga ago) the average sea surface and land surface temperatures were higher than they are today. However, there have been at least four significant glacial episodes prior to the Pleistocene glaciations. Two of these (approx. 2.1 and 0.7 Ga ago) may have involved a 'Snowball Earth' with a very great impact on the algae (sensu lato) of the time (cyanobacteria, Chlorophyta and Rhodophyta) and especially those that were adapted to warm habitats. By contrast, it is possible that heterokont, dinophyte and haptophyte phototrophs only evolved after the Carboniferous-Permian ice age (approx. 250 Ma ago) and so did not encounter low (</=5 degrees C) sea surface temperatures until the Antarctic cooled some 15 Ma ago. Despite this, many of the dominant macroalgae in cooler seas today are (heterokont) brown algae, and many laminarians cannot reproduce at temperatures above 18-25 degrees C. By contrast to plants in the aerial environment, photosynthetic structures in water are at essentially the same temperature as the fluid medium. The impact of low temperatures on photosynthesis by marine macrophytes is predicted to favour diffusive CO(2) entry rather than a CO(2)-concentrating mechanism. Some evidence favours this suggestion, but more data are needed.

Antarctic Regions↗
PubMed2004

Antioxidant capacity of cultured mammalian cells estimated by ESR method.

In the present study, the antioxidant capacity against hydrogen peroxide (H2O2), one of the stress-inducing agents, was investigated in two distinct cell lines: L-41 (human epithelial-like cells) and HLF (human diploid lung fibroblasts), which differ in tissue origin, life span in culture, proliferate activity, and special enzyme system activity. The cell antioxidant capacity against H2O2 was estimated by the electron spin resonance (ESR) spin-trapping technique in the Fenton reaction system via Fe+2 ion action with H2O2 resulting in hydroxyl radical generation. The effects of catalase inhibitors, such as sodium azide and 3-amino-1,2,4-triazole, on the antioxidant capacity of cells were tested. Based on our observation, it can be concluded that the defensive capacity of cells against H2O2 depends on the ratio between catalase/GPx/SOD and H2O2, especially at high-stress situations, and the intracellular balance of these enzymes are more important than the influence of the single component.

Antioxidants↗
PubMed2006

Association between birth weight and blood pressure is robust, amplifies with age, and may be underestimated.

Data on the early life origins of adult hypertension have been widely reported: however, recent research shows that the strength of association between small size at birth and higher blood pressure weakens as study size increases. In this article, we retest the association between birth weight and systolic blood pressure in a large cohort, examine whether age interacts with birth weight to predict blood pressure, and explore reasons why birth weight-blood pressure associations tend to weaken with increasing study size. Measurements from 25874 employees of a large United Kingdom company (mean [SD] age: 38.0 [7.9] years), undertaking voluntary occupational health screening, were available. Using linear regression analysis, we observed that systolic blood pressure changed -0.8 (95% CI: -1.1 to -0.5) mmHg per 1-kg increase in birth weight (P<0.001) adjusted for age and sex and -1.1 (95% CI: -1.3 to -0.8) mmHg/kg (P<0.001) after further adjustment for body size. This inverse association amplified with age (age/birth weight interaction term P<0.001). In participants reporting birth weight from hospital records (n=744), systolic blood pressure changed -1.4 (95% CI: -3.1 to 0.2) mmHg/kg compared with -0.8 (95% CI: -1.0 to -0.5) mmHg/kg in all of the other participants. Finally, the data show evidence of "fixed-category blood pressure allocation," where participants are allocated certain blood pressure values, such as 120/80 mmHg, independent of actual blood pressure. Although the association between birth weight and systolic blood pressure was weaker than observed in smaller studies, recalled birth weight and fixed blood pressure measurement error may generate a trend toward weaker associations in larger studies.

Adult↗
PubMed2005

ADAM33 expression in asthmatic airways and human embryonic lungs.

RATIONALE: Polymorphic variation in ADAM33 (A Disintegrin And Metalloprotease) is strongly associated with asthma and bronchial hyperresponsiveness in different populations. OBJECTIVE AND METHODS: To study the role of ADAM33 in asthma, we investigated its expression in normal, asthmatic, and embryonic airways using reverse transcriptase-quantitative polymerase chain reaction and immunochemistry. RESULTS: Several ADAM33 mRNA splice variants were detected in bronchial biopsies and embryonic lung; however, the beta-isoform and variants encoding the metalloprotease domain were rare transcripts. Western blotting of bronchial biopsies confirmed the presence of multiple isoforms of ADAM33, which had molecular weights of 22, 37, 55, and 65 kD. Immunohistochemistry and laser confocal microscopy of adult bronchial biopsies showed that alpha-smooth muscle actin and ADAM33 immunoreactivity were mostly colocalized to smooth muscle and isolated cells in the submucosa. There was no significant difference in ADAM33 mRNA amplicons or protein in subjects with asthma compared with control subjects. In developing lung, ADAM33 was found around bronchial tubes; however, immunoreactivity was more widely distributed than alpha-smooth muscle actin within undifferentiated mesenchyme; on Western blots, an additional 25-kD ADAM33 variant was detected. CONCLUSIONS: Several ADAM33 protein isoforms occur in adult bronchial smooth muscle and in human embryonic bronchi and surrounding mesenchyme, strongly suggesting its importance in smooth muscle development and/or function, which could explain its genetic association with bronchial hyperresponsiveness. The occurrence of ADAM33 in embryonic mesenchymal cells suggests that it may be involved in airway wall "modeling" that contributes to the early life origins of asthma.

ADAM Proteins↗
PubMedDate not supplied

The association of low birthweight and chronic renal failure among Medicaid young adults with diabetes and/or hypertension.

OBJECTIVE: The purpose of this study was to assess the effect of low birthweight on chronic renal failure among young Medicaid patients with diabetes and/or hypertension. METHODS: The study included Caucasian and African American young adults, aged 18-50, who enrolled in the Medicaid program from 1993 to 1996 in South Carolina and were diagnosed with diabetes and/or hypertension. The odds of chronic renal failure by low birthweight (< 2,500 grams) was estimated using logistic regression. RESULTS: Of the 7,505 Medicaid patients with diabetes and/or hypertension, 179 (2.4%) were diagnosed with chronic renal failure. These patients were younger (mean age of 33.9 vs. 37.6, p = 0.0024) and had a higher proportion of low birthweight (15.1% vs. 11.4%, p = 0.07) compared with the 7,326 patients without renal failure. The odds ratio of chronic renal failure for low birthweight was significantly higher compared with normal birthweight (2,500-3,999 grams) (adjusted odds ratio [OR] 1.56, 95% confidence interval [95% CI] 1.0, 2.4). The association between low birthweight and chronic renal failure was stronger among the 888 patients with both diabetes and hypertension (OR 2.6, 95% Cl 1.3, 5.7) than the 1,812 diabetes or the 4,805 hypertension patients. CONCLUSIONS: The odds of chronic renal failure by low birthweight was highest in patients with both diabetes and hypertension, suggesting that the mechanism(s) involved in the disease progression to chronic renal failure may have a fetal early life origin.

Adolescent↗
PubMed2001

Molecular identification and characterization of a and b forms of the glucocorticoid receptor.

The human glucocorticoid receptor (hGRalpha) is a ligand-activated transcription factor that mediates the physiological effects of corticosteroid hormones and is essential for life. Originally cloned in 1986, the transcriptionally active hGRalpha was reported to be a single protein species of 777 amino acids (molecular mass = 94 kDa). Biochemical data, obtained using various mammalian tissues and cell lines, however, have consistently revealed an additional, slightly smaller, second hGR protein (molecular mass = 91 kDa) that is not recognized by antibodies specific for the transcriptionally inactive and dominant negative, non-hormone-binding hGRbeta isoform. We report here that when a single GR cDNA is transfected in COS-1 cells, or transcribed and translated in vitro, two forms of the receptor are observed, similar to those seen in cells that contain endogenous GR. These data suggest that two forms of the hGRalpha are produced by alternative translation of the same gene and are henceforth termed GR-A and GR-B. To test this hypothesis, we have investigated the role of an internal ATG codon corresponding to methionine 27 (M27) as a potential alternative translation initiation site for the GR. Mutagenesis of this ATG codon to ACG in human, rat, and mouse GR cDNA results in generation of a single 94-kDa protein species, GR-A. Moreover, mutagenesis of the initial ATG codon to ACG (Met 1 to Thr) also resulted in production of single, shorter protein species (91 kDa), GR-B. Mutagenesis of the Kozak translation initiation sequence strongly indicates that a leaky ribosomal scanning mechanism is responsible for generating the GR-A and -B isoforms. Western blot analysis using peptide-specific antibodies show both the A and B receptor forms are present in human cell lines. Both receptors exhibit similar subcellular localization and nuclear translocation after ligand activation. Functional analyses of hGR-A and hGR-B under various glucocorticoid-responsive promoters reveal the shorter hGR-B to be nearly twice as effective as the longer hGR-A species in gene transactivation, but not in transrepression.

Alternative Splicing↗
PubMed2004

[The tortuose path of human evolution].

The human genome sequencing and also the chimpanzee's, among others alive beings in every kingdom, and the similarities between genomes, due to an unique life origin, has developed two movements in the Biological Sciences to the XXI Century. In the first place to find a genetic explanation to understand the genomic affinity, very narrow in many cases, in front of the reality, with abyssal differences in behavior, which undervalue the significance of the genomic resemblance between the alive beings. The second movement is directed to ethological studies of the animal behavior and conduct, as a real fact. Special interest has the comparative studies since the two points of view, the genome and proteome in one side and ethology in front, both related to the Homo sapiens sapiens and his relatives, the great anthropomorphic apes, and consequently beside the names of Craig Venter, Collins and collaborators, artificers of the human genome sequencing, appear, unde revaluation, those of Leakey, Goodall, Fossey and Galdikas, specialists in anthropology and ethology of chimpanzees, gorillas and orangutans. These ideas are complementary in order to a better understanding of the origin, human evolution and behavior, shedding light on human cognitive abilities.

Animals↗
PubMed2004

[An important mission for microbiologists in the new century-cultivation of the unculturable microorganisms].

The present review summarizes the recent advances in cultivating the so-called recalcitrant microorganisms in various natural environments. Firstly, the use of new electron donors and acceptors reveals a list of unique and previously unrecognized physiotypes (Table 1), and the growth supporting reactions include oxidation of phosphite, arsenite, soil humic substances, benzene, Fe (II) and aryl-halides. The novel pure cultures obtained include: Desulfatogenum phosphitoxidans, lithochemotrophic arsenite oxidizing bacteria, Dechloromonas agitata, Dechalosoma suillum, and various Proteobacteria capable of decomposing soil humic substances anaerobically. Secondly, the adaption of nutrient-poor media (down to 1/100 of the traditional concentration), including sea water, soil extract and extension of natural habitats (insect hind-gut, submarine hot vent) are extremely rewarding. For example, cultivation of the ubiquitous SAR11 marine bacterioplankton clade reveals a phylum, small in cell size and genome, but dominating in ocean surface, thus constituting a huge biomass on earth. In addition, the nanosized hyperthermophilic Archaeon from a submarine hot vent, represents an unknown phylum, and because of its symbiotic living with Ignicocous cells, it is named Nanoarchaeum equitans. Its genome size is only 500kb, the smallest for prokaryote. Considering its hyperthermic living environment and small genome, N. equitans may possibly still a primitive form of microbial life and affords an advantageous culture for the study of life origin and evolution on earth. Thirdly, several novel isolation techniques have been developed such as gel microdrop encapsulation and diffusion chamber, both with the advantages of high-throughout operation and simulating to certain extent of the natural environment, thus allowing growth synergy based on cross-feeding to occur. Finally, it should be noted that the cultivation of unculturable microorganisms mentioned in this review does not require expensive and sophisticated equipments and most of the techniques can be adapted in our laboratory at home.

Bacteria↗
PubMed2006

Monte Carlo simulation of early molecular evolution in the RNA World.

The origin of life remains a highly speculative field, mainly due to the shortage of our knowledge on prebiotic chemistry and basic understanding on the essence of life. In this context, computer simulation is expected to play an important role. For instance, the scenario concerning the genesis of the widely accepted RNA World remains blurry, though we have gathered some circumstantial evidence and fragmented knowledge on several supposed stages, including formation of polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases (RNA molecules catalyzing their own replication), and evolution of RNA replicases. It is highly valuable to simulate the stages as a continuous process to evaluate the plausibility of the supposition and study the rules involved. Here we construct a computer simulation on the process using Monte Carlo method. It demonstrates that primordial RNA replicases may appear and spread in a nucleotide pool provided they could recognize their own sequence and their complements as catalytic targets, and then may evolve to more efficient RNA replicases. Apart from its indication on the genesis of the RNA World, the vivid simulation of emergence of the "first replicative molecules" and their subsequent evolution is impressive and may help to get insight into "how could self-replication and Darwinian evolution, two key features of life, emerge in a non-life background?" thus improve our understanding of "what is life" when studying origins of life.

Biological Evolution↗
PubMed2005

[Quality of life in medicine--origins, main concepts and directions of change].

Assessment of the quality of life depends not only health, but also on many other factors, which together make up the everyday life of the individual, including: independence, relationship to the environment, personal beliefs, attitudes and religion. The illness process, irrespective of its stage or magnitude, influences the life of the patient, very often leading to a break down in organisation and limiting his/her ability to fulfill his/her roles and social functions. In consequence, a lowering of living standards results. For many years, health was measured in very narrow terms and in a negative sense. Deviations from normal health were measured, with no attempt to find indicators of good health. The aim of this paper is to present the origins and main concepts underlying the notion of quality of life, which developed first within the social sciences, and since the 1970s has been recognised within medicine. The approach demonstrates a different perspective for understanding a sick person, not merely from the biological point of view, but also taking into account aspects of psychological social and spiritual functioning. Introduction of the concept of quality of life is determined by the fact that the aim of therapeutic interventions ought to be not only reducing the symptoms of an illness, but also providing an improvement in the sick person's functioning, thus leading to an improvement in his/her quality of life.

Clinical Medicine↗