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At least 523 records · Page 29Linked to original sources

PubMed2006

Missense mutations of BRCA1 gene affect the binding with p53 both in vitro and in vivo.

Women with BRCA1 gene mutations have an increased risk for breast and ovarian cancer (BOC). Classification of missense variants as neutral or disease causing is still a challenge and has major implications for genetic counseling. BRCA1 is organized in an N-terminal ring-finger domain and two BRCT (breast cancer C-terminus) domains, involved in protein-protein interaction. The integrity of the C-terminal, BRCT repeat region is also critical for BRCA1 tumor suppressor function. Several molecular partners of BRCA1 have so far been identified; among them, the tumor suppressor protein p53 seems to play a major role. This study was aimed at evaluating the impact of two missense mutations, namely the W1837R and the S1841N, previously identified in BOC patients and located in the BRCT domain of the BRCA1 gene, on the binding capacity of this protein to p53. Co-immunoprecipitation assays of E. coli-expressed wild-type and mutated BRCTs challenged with a HeLa cell extract revealed, for the S1841N variant a significant reduction in the binding activity to p53, while the W1837R mutant showed an inverse effect. Furthermore, a clonogenic soft agar growth assay performed on HeLa cells stably transfected with either wild-type or mutant BRCA1 showed a marked decrease of the growth in wild-type BRCA1-overexpressing cells and in BRCA1S1841N-transfected cells, while no significant changes were detected in the BRCA1W1837R-transfected cells. These results demonstrate that: i) distinct single nucleotide changes in the BRCT domain of BRCA1 affect binding of this protein to the tumor suppressor p53, and ii) the two missense mutations here described are likely to play a role in breast tumorigenesis. We suggest that in vitro/in vivo experiments testing the effects of unclassified BRCA1 gene variants should therefore be taken in to consideration and that increased surveillance should be adopted in individuals bearing these two BRCA1 missense alterations.

Agar↗

PubMed1990

Viruses and cancer, with particular focus on human papillomaviruses in neoplastic lesions of the cervix uteri.

Oncogenic viruses serve as useful experimental tools and models of cellular transformation and cancer biology. Tumour virology has made enormous contributions towards the molecular elucidation of malignancy, especially in the concept of oncogenes and anti-oncogenes. Here we consider the criteria, mechanisms and co-factors of viral carcinogenesis. Some viruses associated with cancers in man and animals are reviewed, with special focus on the role of human papillomaviruses (HPV) in cervical cancer. Southern hybridization and polymerase chain reaction (PCR) data demonstrating the presence of genital HPV types 11, 16, 18 and 31 in cervical neoplastic lesions from Singapore patients are presented. Sensitivity standardisation and specificity of the Southern and PCR techniques are emphasised. Common themes in viral oncology are highlighted, such as epidemiological associations; viral type, host and tissue specificities; transforming genetic elements; viral integration; and interaction with co-factors.

Female↗

PubMed1990

Computer diagnosis of skin disease.

A transferable computer program for the differential diagnosis of diseases of the skin, CLINDERM, has been produced for use by physicians on standard IBM and compatible personal microcomputers. This program lists the differential diagnosis and definitive diagnosis of any presented disease of the skin, except single tumors. The physician operator indicates the distribution and detailed description of lesions, which the interactive system integrates with a comprehensive knowledge base. The computer diagnosis in 129 cases was compared with independent interpretation of the same information by an academic dermatologist. Results were synonymous in 66.7% of all diseases and similar in an additional 4.7%. A common differential diagnosis was obtained in 24%, for a 95.3% rate of synonymous, similar, or common differential diagnoses. Diagnosis was different in 3.9% and description was inadequate for diagnosis in 0.8%. The variation in diagnosis showed that some descriptive terms are prejudicial of certain diagnoses; that diagnostic terms are not all completely standardized; that some diagnoses are variants of another disease; and that drug-induced eruptions simulate many other diseases. A skin disease can usually be diagnosed by specific description. Most lesions that are not diagnostic from inspection are nodular. A computer can be programmed to list diagnoses according to morphologic description.

Dermatology↗

PubMedDate not supplied

[Study of bromthymol blue binding with plasma membranes].

It has been established that sorption of bromthymol blue by membranes is due to interaction with integral proteins. The value of the bond is ascribed both to the structural state and electrochemical property of membranes.

Animals↗

PubMed1988

Colocalization and coprecipitation of ankyrin and Na+,K+-ATPase in kidney epithelial cells.

Interactions between integral proteins of the plasma membrane and the cytoskeleton may be important for localizing certain membrane proteins in a nonrandom fashion at specialized domains of the cell surface. Here, we show that ankyrin, the key protein for the linkage of the erythrocyte anion exchanger (band 3) to the spectrin-based membrane cytoskeleton, is also present in kidney distal tubular cells where ankyrin is precisely colocalized with Na+,K+-ATPase. Both proteins are confined to the basolateral plasma membrane and are absent from the apical membrane, the junctional complex and the membrane surface that contacts the basal lamina. Purified Na+,K+-ATPase of sheep and pig kidney contains a binding site for erythrocyte ankyrin as demonstrated by immunoprecipitation experiments. A band 3-like binding site for ankyrin is likely, since binding of ankyrin to Na+,K+-ATPase could be inhibited in a competitive fashion by the isolated cytoplasmic domain of erythrocyte band 3.

Animals↗

PubMed1987

Pharmacy: a profession in transition or a transitory profession?

Areas in pharmacy that are in transition are described, and ways to prevent the perception of pharmacy as a transitory profession are detailed. Pharmacy has adapted itself over the past 75 years to changes in the health-care system and in societal demands of the profession. The evolution of pharmacy functions has included drug product preparation, establishment of standards, drug distribution, and clinical pharmacy. The profession is continuing to change in reaction to economic and social forces. Hospital pharmacy flourished when it shifted from a profit to a cost center because pharmacy practice researchers documented the contribution of clinical pharmacy to patient care and because hospital pharmacy administrators developed sound management procedures to maintain efficient inventories. Current controversies in pharmacy practice are discussed, including pharmacist prescribing, physician dispensing, and therapeutic substitution. These terms inadequately describe the concepts, especially when they are taken out of context of the total health-care process involving a physician-pharmacist team. Because of the success of this teamwork in acute-care institutions, ambulatory pharmaceutical services should involve cooperative activities of pharmacists in professional service administrative organizations (PSAOs) and physicians in independent practice associations. The cost-effectiveness of PSAOs is discussed. Marketing of drug products is changing as the physician-pharmacist interaction becomes integral to the drug therapy decision-making process. Drug distribution should not be viewed as less professional than clinical activities. Although the pharmacy profession is reorienting itself toward patient care and the rational use of drugs in society, it must maintain its authority over the drug distribution system.

Drug Prescriptions↗

PubMed1982

Transneuronal and peripheral mechanisms for the induction of motor neuron sprouting.

After injury to the nerve to one cutaneous pectoris muscle of the frog, the intact nerve to the contralateral muscle sprouts and forms additional synaptic connections with already innervated muscle fibers. It has been suggested (Rotshenker, S. (1979) J. Physiol. (Lond.) 292: 535-547; Rotshenker, S., and F. Reichert (1980) J. Comp. Neurol. 193: 413-422) that axotomy initiates a signal for sprouting in the injured neurons that is transferred transneuronally across the spinal cord to intact motor neurons. The present study was designed to test the hypothesis that axotomy initiates the signal for sprouting by interfering with some trophic signaling between the injured neurons and denervated muscle. Colchicine therefore was applied to the nerve to the left muscles to inhibit axonal transport on whose integrity trophic interactions depend. Consequently, supernumerary innervation developed in contralateral right intact muscles much the same as after axotom. Surprisingly, axons that were exposed to the drug also sprouted and formed synapses. Furthermore, the sprouting response of axons that were exposed to the drug also was produced in nerve fibers that were separated from their cell bodies. These results suggest two ways in which colchicine may produce sprouting and synapse formation and thereby suggest two mechanisms by which motor neurons may be induced to sprout: (a) transneuronally, by presenting growth stimuli to their cell bodies and central processes in the central nervous system and (b) by presenting growth stimuli to their peripheral extensions.

Animals↗

PubMed1984

Proteins closely related to spectrin and ankyrin are general components of cell membranes.

Membrane-associated analogues of erythrocyte spectrin and ankyrin have been detected in nonerythroid cells by crossreaction with antibodies. Brain spectrin and a spectrin-binding domain of brain ankyrin have been purified and demonstrated to have all known functional activities of their erythrocyte counterparts. The nonerythroid forms of spectrin and ankyrin may have functions such as providing support for the lipid bilayer, mediating some types of actin-membrane interactions, and integrating membrane-spanning proteins with cytoplasmic structural proteins.

Actins↗

PubMed1995

Localisation of glycoproteins and glycosaminoglycans during early eye development in the macaque.

The composition of the extracellular matrix (ECM) was examined in the developing lens and optic cup (stages 11-16) of the long-tailed monkey (Macaca fascicularis) using peroxidase immunocytochemistry. The glycoproteins, fibronectin, laminin, and collagen types I and IV, were consistently associated with basement membranes (BM) of ocular epithelia at all stages examined. Discontinuity of the optic cup BM was observed during the early stages of evagination (stages 11 and 12); the even distribution of all 4 components was reestablished by stage 13 when the optic vesicle is closely apposed to the thickened lens placode. While fibronectin was most predominant in the mesenchymal matrix, all 4 glycoproteins were observed to variable degrees in the periocular mesenchyme. Particularly strong glycoprotein reactivity was observed in the interspace between the invaginating lens vesicle and optic cup whereas no significant reactivity occurred within the lens, developing retina or future corneal epithelium. Two glycosaminoglycans, hyaluronic acid and chondroitin sulphate, had virtually identical widespread staining patterns in all ocular BM and throughout the periocular mesenchyme and adjacent epithelial tissues, including the lens and retina. The observed temporal and regional staining patterns suggest that these ECM components are morphogenetic factors in the macaque eye, facilitating the complex series of integrated tissue interactions, movements and shape changes during the earliest stages of lens and optic vesicle morphogenesis. The macaque offers a valuable model to study these interactions due to the prolonged period of ocular development which is morphologically identical to humans.

Animals↗

PubMed1995

Perturbation of red blood cell membrane rigidity by extracellular ligands.

It is known that binding of extracellular antibodies against the major sialoglycoprotein, glycophorin A, reduced the deformability of the red blood cell membrane. This has been taken to result from new or altered interactions between the glycophorin A and the membrane skeleton. We have shown by means of the micropipette aspiration technique that antibodies against the preponderant transmembrane protein, band 3, induce similar effects. A definite but much smaller reduction in elasticity of the membrane is engendered by univalent Fab fragments of the anti-band 3 antibodies. By examining cells genetically devoid of glycophorin A or containing a variant of this constituent, truncated at the inner membrane surface, we have shown that the anti-band 3 antibodies do not act through the band 3-associated glycophorin A. We examined the effect of anti-glycophorin A antibodies on homozygous Wr(a+b-) cells, in which an amino acid replacement in band 3 annihilates the Wright b (Wrb) epitope (comprising sequence elements of glycophorin A and band 3) and thus, by implication disrupts or perturbs the band 3-glycophorin A interaction; these cells show a much smaller response to an anti-glycophorin A antibody than do normal controls. We infer that in this case anti-glycophorin A antibodies exert their rigidifying effect through the associated band 3. Another anti-glycophorin A antibody, directed against an epitope remote from the membrane surface, however, increases the rigidity of both Wr(a+b-) and normal cells. This implies that not all antibodies act in the same manner in modifying the membrane mechanical properties. The effect exerted by anti-band 3 antibodies appears not to be transmitted through the band 3-ankyrin-spectrin pathway because the rigidifying effect of the intact antibody persists at alkaline pH, at which there is evidence that the ankyrin-band 3 link is largely dissociated. The large difference between the effects of saturating concentrations of the divalent and univalent anti-band 3 antibodies implies the existence of an overriding effect on rigidity, resulting from the bifunctionality of the intact antigen. Freeze-fracture electron microscopy shows that the anti-band 3 promotes the formation of small clusters of intra-membrane proteins. Extracellular ligands may in general act by promoting strong or transient interactions between integral membrane proteins, thereby impeding local distortion of the membrane skeletal network in response to shear.

Anion Exchange Protein 1, Erythrocyte↗

PubMedDate not supplied

Description and initial applications of the Staggers & Parks Nurse-Computer Interaction Framework.

The authors developed a nurse-computer interaction framework by integrating concepts from human-computer interaction, nursing informatics, and developmental psychology. In this framework, nurses and computers interact in a system of mutual influences, with information being the medium of exchange between them. Nurse behaviors and computer interface actions occur according to their respective characteristics. In turn, the nurse-computer dyad is embedded within a nursing context and moves along a nursing informatics developmental trajectory. A sample of findings from empirical studies is placed in the framework, and framework uses are described.

Computer Simulation↗

PubMed1993

Transfected m2 muscarinic acetylcholine receptors couple to G alpha i2 and G alpha i3 in Chinese hamster ovary cells. Activation and desensitization of the phospholipase C signaling pathway.

Muscarinic acetylcholine receptor subtypes (m1-m5) differentially regulate phosphoinositide-specific phospholipase (PLC) through the activation of distinct guanine nucleotide-binding (G) proteins which can be distinguished on the basis of their sensitivity to inhibition by pertussis toxin (PTX). In transfected Chinese hamster ovary cells, the m2 receptor subtype regulates the stimulation of PLC and inhibition of adenylyl cyclase (AC) through PTX-sensitive G proteins. In this study, we utilized the ability of cholera toxin (CTX) to ADP-ribosylate PTX-sensitive alpha subunits as part of the ternary complex formed by heterotrimeric G proteins and agonist-bound receptors to detect and characterize the interactions between transfected m2 receptors and endogenous G proteins in Chinese hamster ovary cells. In membranes derived from cells expressing the m2, but not the m3 receptor, the cholinergic agonist carbachol stimulated CTX modification of a 40-kDa species (G alpha 40). Importantly, similar carbachol dose dependence values and PTX dose sensitivities were observed for m2 receptor-mediated PLC signaling and G alpha 40-CTX modification. High resolution urea-SDS-polyacrylamide gel electrophoresis analysis revealed that G alpha i2 (40 kDa) and G alpha i3 (41 kDa) were components of the G alpha 40 identified by m2 receptor-dependent CTX modification. Furthermore, the sensitivities of G alpha i2 and G alpha i3 to PTX modification were determined to be the same as those for PTX inhibition of G alpha 40 labeling by CTX and m2 receptor-mediated PLC signaling. Similarly, agonist-induced desensitization of m2 receptor-G protein signaling required doses of agonist associated with stimulation of PLC. Desensitization involved receptor sequestration and down-regulation of G alpha i3; however, only the reduction of G alpha i3 required prior activation PLC signaling. Finally, desensitization of m2-G protein coupling could be partially mimicked by treatment with thapsigargin, an inducer of intracellular Ca2+ release, without altering the number of cell surface receptors or G protein levels. These results demonstrate that m2 receptors couple to both G alpha i2 and G alpha i3 in vivo and that this interaction is integral to both positive and negative regulatory pathways leading to activation of PLC and desensitization of receptor signaling.

Adenylate Cyclase Toxin↗

PubMedDate not supplied

[The effect of epiphysectomy and destruction of the lateral septal nucleus of the brain on the genital system in juvenile rats under different light regimens (the interaction of gonadostat++ and photoperiodic mechanisms in the regulation of ovarian functions)].

Results of experimental investigations of the effect of the epiphysectomy and brain lateral septal nucleus (LSN) destruction on the morphofunctional conditions of the genital system of juvenile female white rats kept under different illumination conditions are described. The analysis of consequences of epiphysectomy and LSN destruction as well as of these operative influences taken together shows that the morphofunctional condition of the female genital apparatus changes more intensively in rats kept under the constant illumination and less intensively in those kept under variation of light and darkness, which affected the estradiol production function of rats. A conclusion is made that the epiphysis influences the hypothalamo-hypophysis-ovary system (HHOS) in case of the intact LSN, and efficiency of the LSN effect on the HHOS depends on the presence of the epiphysis. Some possible mechanisms of interaction and integration of the gonadostat and photoperiodic mechanisms of the HHOS function regulation are discussed.

Animals↗

PubMed1997

[Current problems in health protection for servicemen].

The important directions in the field of preservation and strengthening of health of the servicemen are creation of an effective prophylaxis system in the troops on the basis of command and all services efforts integration, and interaction with other departments and the local authorities, and also perfection of medical maintenance organization of the Armed Forces and its preventive component. The analysis of health risk factors permits to distinguish the factors of water supply, municipal and household services, food. As priority such directions, as organizational perfection of management of water supply, municipal and household services of garrisons, practical work in interests of the particular person, perfection of system of preventive medical measures should be considered.

Communicable Disease Control↗

PubMedDate not supplied

Defining apoptosis: players and systems.

OBJECTIVE: To summarize the basic principles and concepts of apoptosis and some of the information to date regarding the nature of the regulation of apoptosis at the molecular level. METHODS: In the past few years, research in cell and molecular biology has led to a much better understanding of the underlying mechanisms that regulate apoptosis. RESULTS: Positive and negative regulatory elements that function in specific cell types to activate apoptosis have been identified. This activation involves signaling pathways that activate distinct proteolytic cascades that lead to the execution of cell death. CONCLUSION: Homeostasis involves a delicate balance between the processes of proliferation, differentiation, and death by apoptosis. The current challenge is to understand how specific stimuli regulate the execution of programmed cell death in basic reproductive cells and how these interactions are integrated into the overall physiology and pathophysiology of reproduction during life.

Animals↗

PubMed1997

Food systems for improved health: linking agricultural production and human nutrition.

OBJECTIVES: Link traditional agricultural production disciplines to the food sciences and the various disciplines concerned with human nutrition and health in order to find sustainable solutions to malnutrition. DESIGN: Develop a new integrated program area within a university by forging explicit linkages within a wide array of disciplines concerned with food systems and human health. SETTING: The College of Agriculture and Life Sciences, the College of Human Ecology, the Division of Nutrition, and the Cornell International Institute for Food, Agriculture, and Development at Cornell University, Ithaca, New York, USA. INTERVENTIONS: Use food-based, system approaches to meet human nutrition goals. Current focus is on the provision of micronutrients (especially iron, vitamin A and iodine) for people globally. RESULTS: A new program area 'Food Systems for Health' has been developed at Cornell University. The program fosters effective interdisciplinary research, teaching and extension activities directed towards sustainable improvements in human nutrition and health. CONCLUSIONS: The old paradigms of agriculture, human nutrition, and public health must be shifted from current linear approaches to integrated and interactive approaches if effective long-term, food-based solutions to micronutrient malnutrition are to be found.

Agriculture↗

PubMed1998

[Issues in mental health services for children and adolescents].

Existing system of psychiatric care for children and adolescents is in need of basic reorganization. The authors propose: 1) reestablishment of the speciality of children's and adolescent psychiatrist, a specialist in children's and adolescent narcology, a psychiatrist of early child's age and a pediatric medical psychologist; 2) carrying out the reform of child mental care equal in rights with general psychiatry; 3) preservation and widening of both specialized inpatient and outpatient clinics in general system of child's mental care; 4) legislative and public rehabilitation of children's psychiatry, which suffered considerably from antipsychiatric campaign; 5) professionally organized systematic elevation of psychohygienic, psychiatric and psychotherapeutic knowledges of allied medical and other specialists as well as of parents and of all population too; 6) integration and interaction of govermental services concerning mental health of children and adolescent; 7) organization of regional psychoprophylaxic interdisciplinary centers for children and adolescent.

Adolescent↗

PubMed1997

[Analysis of pure titanium implants-bone interface by TOF-SIMS].

In order to study the Titanium-bone interaction and integration mechanism, the titanium implant was implanted in the tibia of 9 Newzealand rabbits, and the Ti-bone interface performed for 1, 3, and 6 months were examined and analyzed by fluorescence microscope and advanced TOF-SIMS techniques. The results showed that Ti-bone tissue was integrated closely in a very reactive manner. Both physical and chemical integration occurred in the Ti-bone interface. The Ti-bone could diffuse into the bone tissue though the diffusion was very limited. It was up to 100 microns in depth during the early period. The diffusion density was high, and later in a smooth distribution. Furthermore, while Ti+ diffused into the bone tissue, other elements such as Ca+, OH-, O-, etc, could also diffuse into titanium in exchange. The growth pattern around the bone tissue was in two fashions, one was implantefugal and the other was implantopetal. In this study, based on the ionic distribution, osmosis and impurity elements distribution, the Ti-bone integration mechanism was discussed at molecular and atomic level.

Animals↗