Bentonite toxicosis in a cat from cat litter?
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Animals↗
Biomedical subjects
S McDonough
Publications and source records attributed to S McDonough.
Embryonic expression of tenascin-X suggests a role in limb, muscle, and heart development.
Tenascin-X (TN-X) is the newest member of the tenascin family of extracellular matrix proteins and it is highly expressed in muscular tissues during development. To gain insight into the possible functions of TN-X during development, we evaluated its expression in the rat embryo. Using an 800 bp cDNA encoding the fibrinogen-like domain of TN-X, we show that TN-X expression begins in migrating cells of the epicardium in the E12 heart. The epicardium provides progenitors of fibrous and vascular tissue to the developing heart. After the epicardium is complete, TN-X is expressed in the sub-epicardial space in association with developing blood vessels, and later by non-myocytes dispersed through the myocardial wall. A similar pattern of TN-X expression, first in connective tissue surrounding muscle, and then by a subset of cells within muscle, was seen in para-axial, body wall, craniofacial, and appendicular muscle. This pattern suggests a role in connective tissue cell migration and late muscle morphogenesis. TN-X is also highly expressed in the interdigital space at E15 and surrounding developing tendons, suggesting an additional role in cell fate determination. Although the pattern of TN-X expression is distinct from that of tenascin C, they are frequently expressed in close proximity. Indirect genetic evidence in humans suggests an essential function for TN-X, and the pattern of TN-X expression in heart, skeletal muscle, and limb is consistent with this hypothesis.
Amino Acid Sequence↗
Novel pore-lining residues in CFTR that govern permeation and open-channel block.
The cystic fibrosis transmembrane conductance regulator (CFTR) is both a member of the ATP-binding cassette superfamily and a Cl(-)-selective ion channel. We investigated the permeation pathway of human CFTR with measurements on conduction and open-channel blockade by diphenylamine-2-carboxylic acid (DPC). We used site-directed mutagenesis and oocyte expression to locate residues in transmembrane domain (TM) 6 and TM 12 that contact DPC and control rectification and single-channel conductances. Thus, TM 12 and the previously investigated TM 6 line the CFTR pore. In each TM, residues in contact with DPC are separated by two turns of an alpha helix. The contributions of TM 6 and TM 12 to DPC block and Cl- permeation, however, are not equivalent. The resulting structural model for the conduction pathway may guide future studies of permeation in other Cl- channels and ATP-binding cassette transporters.
Amino Acid Sequence↗
Human eosinophil cytotoxicity-enhancing factor. Eosinophil-stimulating and dithiol reductase activities of biosynthetic (recombinant) species with COOH-terminal deletions.
U937 cells produce eosinophil cytotoxicity-enhancing factor (ECEF) polypeptides of 14 and 10 kDa that have identical NH2-terminal amino acid sequences. The 10-kDa form has greater eosinophil-stimulating activity (half-maximal at > 20-fold lower concentration). We considered the hypothesis that there is a precursor-product relationship between the 14- and 10-kDa species. Recombinant 14-kDa 104-amino acid ECEF (rECEF-104) had a slight stimulatory effect on eosinophil cytotoxic function at concentrations of 160 nM and above. In contrast, two species, rECEF-80 and rECEF-84, representing cleavage products of approximately 10 kDa had substantial statistically significant cytotoxicity-enhancing activity at concentrations as low as 10 pM. This evidence demonstrates the potential to generate the high-activity ECEF species by proteolytic cleavage of the 104-amino acid species. Another feature of this cytokine is the sequence from amino acids 31 to 34, which constitutes the conserved and active site of the enzyme thioredoxin. When tested for dithiol reductase enzymatic activity, rECEF-104 was active in a dose- and time-dependent manner, whereas the truncated forms of the molecule had no dithiol reductase activity. Thus the eosinophil-stimulating functions of the molecule do not correlate with its enzymatic activity. The evidence shows that the enzymatic activity is not essential for the initial interaction of ECEF with the eosinophil, and it suggests that the ECEF molecule functions by means of two discrete mechanisms.
Base Sequence↗
Voltage-dependent block of the cystic fibrosis transmembrane conductance regulator Cl- channel by two closely related arylaminobenzoates.
The gene defective in cystic fibrosis encodes a Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is blocked by diphenylamine-2-carboxylate (DPC) when applied extracellularly at millimolar concentrations. We studied the block of CFTR expressed in Xenopus oocytes by DPC or by a closely related molecule, flufenamic acid (FFA). Block of whole-cell CFTR currents by bath-applied DPC or by FFA, both at 200 microM, requires several minutes to reach full effect. Blockade is voltage dependent, suggesting open-channel block: currents at positive potentials are not affected but currents at negative potentials are reduced. The binding site for both drugs senses approximately 40% of the electric field across the membrane, measured from the inside. In single-channel recordings from excised patches without blockers, the conductance was 8.0 +/- 0.4 pS in symmetric 150 mM Cl-. A subconductance state, measuring approximately 60% of the main conductance, was often observed. Bursts to the full open state lasting up to tens of seconds were uninterrupted at depolarizing membrane voltages. At hyperpolarizing voltages, bursts were interrupted by brief closures. Either DPC or FFA (50 microM) applied to the cytoplasmic or extracellular face of the channel led to an increase in flicker at Vm = -100 mV and not at Vm = +100 mV, in agreement with whole-cell experiments. DPC induced a higher frequency of flickers from the cytoplasmic side than the extracellular side. FFA produced longer closures than DPC; the FFA closed time was roughly equal (approximately 1.2 ms) at -100 mV with application from either side. In cell-attached patch recordings with DPC or FFA applied to the bath, there was flickery block at Vm = -100 mV, confirming that the drugs permeate through the membrane to reach the binding site. The data are consistent with the presence of a single binding site for both drugs, reached from either end of the channel. Open-channel block by DPC or FFA may offer tools for use with site-directed mutagenesis to describe the permeation pathway.
Animals↗
Clinical approaches to families in early intervention.
Clinical approaches to families with infants in early intervention programs require more sophisticated and individualized plans that have been traditionally available. Clinicians in early intervention programs, including those trained in child-oriented disciplines, will increasingly be expected to develop comprehensive family focused interventions. Empirical findings support the legislative mandate of PL99-457 in requiring that families have an active role in specifying the intervention services they require. In addition, the broader concept of risk that now includes multi-problem families also complicates the job of the early interventionist. As parents must learn to adapt to their infant's unique characteristics, early interventionists must adapt to the unique characteristics of each family with whom they are involved. To aid in this process, we apply the concept of a working alliance to the aspect of the parent-professional relationship that early interventionists must develop and maintain in providing empathic and individualized care to families in early intervention. Sensitivity to the families' unique characteristics, responsitivity to their concerns, positive connotation of parents' and infants' behavior, a nonjudgmental attitude, and a willingness to monitor one's feelings and responses elicited by the family are clinical principles essential for developing and maintaining the working alliance.
Child Guidance Clinics↗
The SM strain of feline sarcoma virus. Biologic and antigenic characterization of virus.
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Animals↗
Feline leukemia virus: occurrence of viral antigen in the tissues of cats with lymphosarcoma and other diseases.
Felinie leutkemia viruts antigen is demonstrable by immunodiffusion with rabbit precipitating antiserum to purified felinie leukemia virus. The felinie leukemia virus antigen was found in the tissues of 25 of 33 cats with lymphosarcoma and of 5 of 13 cats with infectious peritonitis. Its presence was correlated with the occurrence of felinie leukemia virus demonstrable by electron microscopy. The one clinically normal cat giving a positive test for feline leukemia virus antigen belonged to a household in which two cats had developed lymphosarcoma. With the exception of a dog with lymphosarcoma induced by feline leukemia virus, the antigent was absent from lymphosarcoma and nonlymphomatous tumors of other species (man, dog, cow, goat, or pig).
Animals↗
AIDS awareness in North Dakota--a knowledge and attitude study of the general population.
The AIDS program of the North Dakota Department of Health and Consolidated Laboratories has provided a broad range of information concerning AIDS (acquired immunodeficiency syndrome) and HIV (human immunodeficiency virus) to State residents over the past few years. The ultimate intent of these intervention efforts was to decrease viral transmission. To assess residents' knowledge and attitudes regarding AIDS, a statewide, random telephone study was conducted by AIDS Program personnel in the fall of 1987, 1988, and 1989, with technical assistance from the Bureau of Governmental Affairs, University of North Dakota. Study results indicated a majority of the respondents considered themselves to have at least "some" knowledge about AIDS. Participants' comprehension of viral transmission routes and prevention methods increased over the 3 years, yet misconceptions still exist. Identified areas of misconception were accentuated in subsequent State educational programs. When the results were compared with national studies, knowledge levels in North Dakota were generally similar to but frequently superior to the nationwide levels.
Acquired Immunodeficiency Syndrome↗