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PubMed1986

Fibrinolytic therapy.

The state of the art of fibrinolytic therapy is constantly changing; perhaps no other area of medicine is developing as rapidly. This paper presents the status of fibrinolytic therapy from the authors' viewpoint. Many statements are controversial. It is possible to find divergent opinions expressed by experts on almost any aspect of fibrinolysis. Objective data are rapidly accumulating, but because new substances continue to be developed, the present and future statuses of fibrinolysis remain unclear. The current results of fibrinolytic therapy are excellent but will be dwarfed by the effects of new compounds and techniques in the near future. Continued developments in this field will have a major impact on improved health care delivery.

Arterial Occlusive Diseases↗

PubMed1998

The utility of futility: the construction of bioethical problems.

The aim of this article is to analyse the contemporary 'futility discourse' from a constructivist perspective. I will argue that bioethics discourse typically disregards the context from which controversies emerge and the processes that inform and constrain such discourse. Constructivists have argued that scientific knowledge is expressive of the dominant paradigm within which a scientific community is working. I will outline an analysis of 'medical futility' as a construction of biomedical and bioethical communities (and their respective paradigms). I will trace the emergence and utilization of futility in the literature. My analysis of the context (i.e. the historical circumstances, the particular actors involved) within which the futility discourse emerged suggests that medical futility was constructed, in part, as a means of enhancing physician domination of a context wherein medical authority was threatened. The actors in this debate express widely divergent frameworks of 'the good', arguing from distinctive representations of moral agency. At times, this controversy has been argued from incommensurate moral horizons wherein the discussants debate incomparable problems. This discussion is related to a study of the 'practice' of futility in the clinical context. Further studies on the construction of bioethical problems are a necessary condition for supporting the truth claims of bioethical arguments.

Adult↗

PubMed1996

Talin contains three actin-binding sites each of which is adjacent to a vinculin-binding site.

We have determined the sequence of chicken talin (2,541 amino acids, M(r) 271,881) which is very similar (89% identity) to that of the mouse protein. Alignments with the Caenorhabditis elegans and Dictyostelium discoideum talin sequences show that the N- and C-terminal regions of the protein are conserved whereas the central part of the molecule is more divergent. By expressing overlapping talin polypeptides as fusion proteins, we have identified at least three regions of the protein which can bind F-actin: residues 102-497, 951-1,327 and 2,269-2,541. The N-terminal binding site contains a region with homology to the ERM family of actin-binding proteins, and the C-terminal site is homologous to the yeast actin-binding protein Sla2p. Each of the actin-binding sites is close to, but distinct from a binding site for vinculin, a protein which also binds actin. The Pro1176 to Thr substitution found in talin from Wistar-Furth rats does not destroy the capacity of this region of the protein to bind actin or vinculin. Microinjection studies showed that a fusion protein containing the N-terminal actin-binding site localised weakly to stress fibres, whereas one containing the C-terminal site initially localised predominantly to focal adhesions. The former was readily solubilised, and the latter was resistant to Triton extraction. The N-terminal talin polypeptide eventually disrupted actin stress fibres whereas the C-terminal polypeptide was without effect. However, a larger C-terminal fusion protein also containing a vinculin-binding site did disrupt stress fibres and focal adhesions. The results suggest that, although both the N- and C-terminal regions of talin bind actin, the properties of these two regions of the protein are distinct.

Actins↗

PubMed2004

[The meaning of team work in the rehabilitation of people with congenital craniofacial malformation].

This study aimed to understand the meaning of teamwork of rehabilitation professionals in craniofacial anomalie. It was carried out a phenomenological analysis for contemplating the understanding and interpretation of the sense considering the subject. Twelve professionals from different areas were interviewed, guided to the subject: What does work in a team on the rehabilitation of craniofacial anomalies mean to you? These themes were brought up: training for the task, difficulty in working with a team, relationship with patient and family, work conditions and the professional insertion in the team. The analysis sought to reflect the phenomenon engendering convergences and divergences to express the differences and continuous learning.

Craniofacial Abnormalities↗

PubMed2005

Mass tag-assisted identification of naturally processed HLA class II-presented meningococcal peptides recognized by CD4+ T lymphocytes.

The meningococcal class I outer membrane protein porin A plays an important role in the development of T cell-dependent protective immunity against meningococcal serogroup B infection and is therefore a major component of candidate meningococcal vaccines. T cell epitopes from porin A are poorly characterized because of weak in vitro memory T cell responses against purified Ag and strain variation. We applied a novel strategy to identify relevant naturally processed and MHC class II-presented porin A epitopes, based on stable isotope labeling of Ag. Human immature HLA-DR1-positive dendritic cells were used for optimal uptake and MHC class II processing of (14)N- and (15)N-labeled isoforms of the neisserial porin A serosubtype P1.5-2,10 in bacterial outer membrane vesicles. HLA-DR1 bound peptides, obtained after 48 h of Ag processing, contained typical spectral doublets in mass spectrometry that could easily be assigned to four porin A regions, expressed at diverging densities ( approximately 30-4000 copies/per cell). Epitopes from two of these regions are recognized by HLA-DR1-restricted CD4(+) T cell lines and are conserved among different serosubtypes of meningococcal porin A. This mass tag-assisted approach provides a useful methodology for rapid identification of MHC class II presented bacterial CD4(+) T cell epitopes relevant for vaccine development.

Amino Acid Sequence↗

PubMed2000

Decisions at the end of life.

This paper presents a system for making decisions at the end of life. It emphasizes the role of patient autonomy and the importance of patient and family participation with the physician in decision-making. Definitions are presented for the terms: terminal illness, withholding and withdrawing life sustaining treatment, physician assisted suicide and euthanasia. Three cases are briefly described to illustrate the application of the decision-making system. A detailed discussion is then presented of the divergent views expressed by different authors about the moral differences or similarities between foregoing life sustaining treatment and physician assistance in dying. It is concluded that the view that these two actions are fundamentally different, as supported by the United States Supreme Court, in 1997, is the correct one. Physician assisted suicide (PAS) remains a controversial issue. Physicians and societies in individual countries must work out their own approaches to PAS. However, foregoing invasive or intensive life support in terminally ill patients consistent with their wishes is considered appropriate.

Aged↗

PubMed2002

Lymphoplasmacytic lymphoma with monoclonal gammopathy-related pseudo-Gaucher cell infiltration in bone marrow and spleen--diagnostic and therapeutic dilemmas.

Gaucher-like cells have occasionally been described in various haematological malignancies including Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma (MM) and chronic myelogenous leukaemia (CML). A special type of this phenomenon is crystal-storing histocytosis or the so-called pseudo-pseudo Gaucher cells (PPGC) in which crystalline protein storage in macrophages is induced by paraproteinemia. Here we describe a 54-year-old man with an initial suspicion of Gaucher disease and monoclonal IgA gammopathy in whom a correct diagnosis of lymphoplasmacytic lymphoma (LPL) with massive infiltration of bone marrow and spleen by PPGC was confirmed by immunological, ultrastructural and molecular characterisation. The activity of leukocyte beta-glucocerebrosidase was only slightly elevated (7.3 nmol/mg protein/1 h) which ruled out the diagnosis of classic Gaucher's disease. The patient received two courses of CHOP without improvement and anti-CD20 monoclonal antibody (rituximab) with only temporary stabilisation. Subsequently, he underwent splenectomy because of prolonged severe pancytopenia and a suspicion of hypersplenism. After splenectomy significant haematological improvement was observed. Following anti-CD20 therapy, changes in immunoprofile and morphology of tumour cells were evident. Before treatment the population of LPL was more divergent, with expression of LCA, CD20, CD38 and CD138. However, after the treatment, there were more mature plasma cells which no longer expressed CD20 antigen-this picture was more consistent with the diagnosis of plasma cell myeloma. Similarly, in the spleen there were no CD-20-positive cells evident. Finally, the patient received two courses of VAD vincristine, doxorubicin, dexamethasone) with further haematological improvement but complete response was not achieved.

Antibodies, Monoclonal↗

PubMed2006

Structural complexity of the environment affects the survival of alternative male reproductive tactics.

Alternative reproductive tactics in males are often associated with divergent phenotypes expressed as phenotypically plastic threshold traits. The evolution of threshold traits in these species has been modeled under the conditional evolutionarily stable strategy (ESS). Both strategic and genetic models predict that perturbations to the fitness trade-off between the male morphs will lead to a shift in the ESS switch point of the threshold. So far, demographic factors that influence the competitive ability of male morphs have been investigated and related to intraspecific population variation in male dimorphic thresholds. Here we reveal evidence for the theoretical prediction that abiotic features of the environment, in particular its structural complexity, are likely to influence the ESS threshold. In the male dimorphic mite Sancassania berlesei, we monitored the survival of aggressive fighter males and their benign scrambler counterparts in populations that differed in structural complexity. We found that, consistent with our prediction, the complex habitat favored fighter males, enabling them to kill a greater number of rival scramblers. We found no effect of habitat complexity on the survival of fighter males. These results demonstrate how abiotic as well as biotic aspects of the environment can be important in determining the frequencies of males adopting alternative tactics in different species or populations.

Aggression↗

PubMed1990

Neuroendocrine differentiation in poorly differentiated lung carcinomas: a light microscopic and immunohistologic study.

Frozen, unfixed tissue sections from 56 poorly differentiated, non-small cell primary lung tumors were examined by the immunoperoxidase technique with a panel of monoclonal antibodies to neuroendocrine (chromogranin A (CGA), synaptophysin (SYN), S-100) and intermediate filament (cytokeratin, vimentin, neurofilament) antigens. Although light microscopic features of neuroendocrine (NE) differentiation were not present, staining for CGA and/or SYN was identified in 5/17 (29%) large cell carcinomas (LCC) and 4/19 (21%) poorly differentiated adenocarcinomas (PDA). Diffuse, strong SYN staining was present in two LCC and one PDA. Heterogeneous intermediate filament expression (vimentin and/or neurofilament) was frequent (LCC, 10/17 (59%); PDA, 10/19 (53%)) and accompanied NE markers in 8/9 (89%) cases. Poorly differentiated squamous carcinomas were more homogeneous, with focal SYN in only 1/20 (5%) and focal presence of intermediate filaments other than cytokeratin in only 2/20 (10%). We conclude: (a) immunohistologic evidence of NE differentiation is present in a significant proportion of pulmonary large cell and poorly differentiated adenocarcinomas and rare in poorly differentiated squamous carcinomas; (b) NE differentiation is generally accompanied by heterogeneous intermediate filament expression; (c) divergent NE differentiation is not necessarily reflected by light microscopic features.

Adenocarcinoma↗

PubMedDate not supplied

[New aspects for the caries of deep cavities].

This article refers to the contemporary aspects about the carious lesions in the deepest parts of a cavity near the pulp. In these situations the problem that arises is to how deeply this carious dentine should be excavated without the risk of destroying the pulp. On this question there have been expressed two divergent opinions based also on two divergent theories. The one theory supports that during the carious process the microorganisms proceed the decalcification of the dentin, whereas the other theory supports the opposite view. According to the new aspects, in acute carious lesions the decalcification proceeds the bacteria, while in chronic caries the microorganisms, the discoloration and the bacterial invasion are closer to each other. This article also refers to the microflora of deep carious lesions and to the fate of bacteria that remain under the fillings. From this paper we come to the following conclusions: 1) In certain clearly defined conditions some carious dentine should be left at the base of a cavity in order to avoid the pulp exposure. But the periphery of the cavity must be unquestionably caries-free. 2) Few microbes always remain after the excavation of the carious cavities. 3) These microbes under well-fitting restorations do not proliferate and gradually die. 4) The defensive properties of the pulp play also a significant role, because pulp immunoglobulins are able to react upon invasive bacteria. 5) Finally, it must be emphasized that the clinical dentist must not underestimate the microbial role and action.

Dental Caries↗

PubMed1987

[Surveys of the treatment and socio-professional future of patients with spondylarthritis. Our impressions in 1986].

After a brief historical reminder, the authors emphasize the difficulties of such investigations; difficulties of realization, analysis and synthesis since the results depend on ethnic and socio-cultural origins, socio-professional factors, primary or secondary forms or the length of evolution of the disease. From their experience, the authors draw a certain number of figures which they compare to those from other authors, especially concerning factors which aggravate the functional prognosis of the disease, or condition its complications. As for the therapy, considering the divergent opinions expressed about the results obtained with modern treatments, and used for thirty years, the authors have initiated an opinion survey among the members of the FSR (French Society of Rheumatology). The analysis of personal cases, the synthesis of various publications, the results of their survey, lead them to conclude that the problem of the treatment of ankylosing spondylo-arthritis and its professional consequences, is currently still more medico-social than scientific. The picture of rheumatoid pelvispondylitis seems less severe today than before, but it is necessary to have a longer follow-up to evaluate it statistically.

Africa, Northern↗

PubMed1983

Assessment of the diet of patients with rheumatoid arthritis and osteoarthritis.

There have been many and divergent thoughts expressed both in the scientific and in the lay literature regarding diets for patients with arthritis (1-8). However, few experimental observations pertain to either the nutritional status of arthritis patients or the clinical value of putative nutritional therapies (1-8). Until such time as the notion that dietary manipulation can alleviate particular symptoms for selected patients is proved, it is prudent to advise patients to maintain sound nutritional practices in accordance with contemporary standards (4-8, 13-16). Our data indicate that many arthritis patients are at least marginally inadequate in selected nutrients, some of which (vitamin E and zinc) might relate to immunologic events important in perpetuating the disease. These observations provide a basis for nutritional counseling of arthritis patients.

Adolescent↗

PubMed1982

Prediction of modeled velopharyngeal orifice areas during steady flow conditions and during aerodynamic simulation of voiceless stop consonants.

Results of a small number of studies (Warren and DuBois, 1964; Lubker, 1969; Smith and Weinberg, 1980; Horii and Lang, 1981) have led to expression of divergent views concerning the accuracy of modeled velopharyngeal orifice area estimates obtained on the basis of hydrokinetic principles. In this work, the hydrokinetic equation (Warren and DuBois, 1964) was subjected to experimentation: (1) in which flow rates through a vocal tract model were not varied and (2) in which flow rates were varied to simulate pressure/flow events found during voiceless, stop consonant production. With consideration given to instrumental and procedural factors, results indicated that accurate estimates of modeled velopharyngeal orifice areas can be obtained during steady flow conditions and during alternating flow conditions when measurements are made at airflow peaks. Results were interpreted to provide strong support for clinical and research use of the hydrokinetic equation to predict velopharyngeal orifice areas during stop consonant production.

Forecasting↗

PubMedDate not supplied

The stromal Schwann cell during maturation of peripheral neuroblastomas. Immunohistochemical observations with antibodies to the neuronal class III beta-tubulin isotype (beta III) and S-100 protein.

This immunohistochemical study compares the localization of the neuronal class III beta-tubulin isotype (beta III; analogous to the beta' 1-/beta 2-tubulin isoform) to the Schwann cell-associated S-100 protein focusing on topographic relationships of Schwann-like cells to differentiating neuronal phenotypes during stromal development in human peripheral neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein-immunoreactive cells in close association with tumor blood vessels. In subsequent stages of maturation, i.e. maturing neuroblastoma (ganglioneuroblastoma and gangliocytoma), S-100 protein-positive cells are mostly confined to the connective tissue septa dividing tumor into lobules, and are not freely interspersed with beta III-immunoreactive neoplastic neurons. Significant ensheathment of individual axon-like processes by Schwann cells occurs only in mature ganglioneuromas. beta III is localized in a full spectrum of neoplastic neuronal phenotypes, ranging from poorly-differentiated apolar neuroblasts (often signaling ensuing neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schwann cells in peripheral neuroblastomas are stroma-derived cells and not an expression of divergent neoplastic differentiation.

Adolescent↗

PubMed1996

A new Drosophila Ca2+/calmodulin-dependent protein kinase (Caki) is localized in the central nervous system and implicated in walking speed.

Calcium/calmodulin-dependent protein kinases (CaM kinases) have been reported to be involved in neuroplasticity. We have cloned a new Drosophila CaM kinase gene named caki. We describe the molecular characterization of caki and a behavioral effect of its elimination. The caki gene is extremely large; comparison of the genomic and cDNA sequences reveals that the caki transcription unit is at least 150 kb. The catalytic domain of this new CaM kinase protein shares homology (41%) with type II CaM kinases, while the C-terminal part is divergent. Constitutively expressed Caki protein is enzymatically active since it causes a 3-fold increase in the level of the Rous sarcoma virus long terminal repeat (RSV LTR) promoter in a co-transfusion assay. In situ hybridization shows that during embryogenesis, larval and pupal life, transcription of caki is restricted almost exclusively to the central nervous system. In the adult head, immunohistochemistry reveals Caki protein in the lamina, the neuropil of the medulla, lobula, lobula plate and in the central brain. Mutant caki flies show reduced walking speed in 'Buridan's paradigm'.

Amino Acid Sequence↗

PubMed1996

The divergent homeobox gene PBX1 is expressed in the postnatal subventricular zone and interneurons of the olfactory bulb.

In the mammalian brain, an important phase of neurogenesis occurs postnatally in the subventricular zone (SVZ). This region consists of a heterogeneous population of cells, some mitotically active, others postmitotic. A subset of mitotically active SVZ precursor cells gives rise to a population of neurons that migrates over a long distance to their final destination, the olfactory bulb. Other SVZ precursor cells continue to proliferate or undergo cell death. The combination of genes that regulates proliferation and cell fate determination of SVZ precursor cells remains to be identified. We have used the rat homolog of the human homeobox gene PBX1 in Northern analysis and in situ hybridization studies to determine the temporal and regional localization of PBX1 expression during embryonic and postnatal rat brain development. PBX1 is expressed embryonically in the telencephalon. In addition, it is expressed at high levels postnatally in the SVZ, in the migratory pathway to the olfactory bulb, and in the layers of the olfactory bulb that are the targets of these migratory neurons. Combining in situ hybridization for PBX1 with immunostaining for markers of cell proliferation (PCNA), postmitotic neurons (class III beta-tubulin), and glia (GFAP), we show that SVZ proliferating cells and their neuronal progeny express rat PBX1 mRNA, whereas glial cells do not express detectable levels of PBX1. The expression of PBX1 in SVZ precursor cells and postmitotic neurons suggests a role for PBX1 in the generation of olfactory bulb interneurons and in mammalian neurogenesis.

Aging↗

PubMed1977

[Genetic aspects of keratoconus (author's transl)].

The diverging views expressed in the literature on the inheritance of keratoconus gave us cause to examine the genetic relationships in 304 cases of keratoconus from our own clinic material. In the 22 cases (19 families) where two or more family members were affected, the genetic relationships generally indicated a multifactorial mode of inheritance, although isolated dominant or recessive variants could not be excluded. The assumption of a multifactorial inheritance is further supported by the occurrence of keratoconus in connection with various syndromes, as well as the fact that keratoconus does not only express itself in sharply defined stages, but also occurs in all possible degrees, from almost normal to the extreme.

Chromosome Aberrations↗

PubMed1993

Identification of a novel sequence element in the common promoter region of human collagen type IV genes, involved in the regulation of divergent transcription.

The expression of the heterotrimeric collagen IV molecule alpha 1(IV)2 alpha 2(IV) is essential for the structural integrity and functional properties of all basement membranes. The two genes COL4A1 and COL4A2 that code for the subunits are found closely linked on chromosome 13 in a head-to-head arrangement and are transcribed in divergent directions. We have identified a novel trans-acting factor that binds in vitro to a unique homopyrimidine/homopurine stretch within the shared promoter region of the two collagen IV genes. Additional binding sites have been identified within the first introns of both genes and the consensus sequence CCCTYCCCC for efficient binding has been deduced; the factor was named therefore 'CTC-binding factor' or 'CTCBF'. Mutations in the binding site of CTC-binding factor within the promoter inhibited binding in vitro and resulted in reduced transcription from both genes. The effect of mutations on the transcription of COL4A2 is more pronounced than on the transcription of COL4A1. CTC-binding factor is a nuclear factor that binds dominantly in vitro to the collagen IV promoter and is involved in regulating the expression of both collagen IV genes.

Base Sequence↗