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Biomedical subjects

A Baron

Publications and source records attributed to A Baron.

At least 109 records · Page 6Linked to original sources

Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2.

We have isolated a murine homeobox-containing gene, Hox-5.1, by virtue of its relatedness to the Hox-1.4 gene. In situ hybridization to metaphase spreads mapped Hox-5.1 to band D of mouse chromosome 2. Sequence comparisons indicate that Hox-5.1 is the murine homolog of the human C13 homeobox-containing gene. Hox-5.1 also bears significant similarity to the Xenopus Xhox-1A homeobox-containing gene and the Drosophila deformed homeotic gene at N-terminal and homeobox regions. Hox-5.1 transcripts were detected in mouse embryos, in adult mouse testis, kidney, heart, and intestine, and in mouse embryonal carcinoma cells treated with retinoic acid. In situ hybridization to sections from whole mouse embryos revealed Hox-5.1 expression in spinal cord and prevertebrae.

Amino Acid Sequence↗

Myosin filaments in cytoskeletons of Dictyostelium amoebae.

Cytoskeletons were prepared from vegetative amoebae of Dictyostelium discoideum by extraction with Triton X-100. The cytoskeletons were suspended in buffers known to induce the assembly or disassembly of myosin filaments. The samples were fixed, and thin sections were examined by transmission electron microscopy. In both types of buffers, myosin-containing cytoskeletons exhibited a ring of densely staining proteinaceous material within the cortical filament matrix; this ring was not observed in myosin-free cytoskeletons. When myosin-containing cytoskeletons were placed in buffers that induced myosin polymerization, the ring appeared as an array of rodlike filaments approximately 13 nm wide and up to 0.5 micron in length--dimensions appropriate for myosin thick filaments. If ATP was added to cytoskeletons containing such filaments, the cytoskeletons contracted and the ring of filaments disappeared. ATP-induced contraction of cytoskeletons was also visualized by indirect immunofluorescence by using monoclonal antibodies to Dictyostelium myosin. All data were consistent with the identification of the protein ring seen by electron microscopy as cortical myosin. Its location and organization were appropriate for the production of cortical contraction through a sliding filament mechanism.

Adenosine Triphosphate↗

Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex.

Hox-1.6, a mouse homeo-box-containing gene member of the Hox-1 complex, is described. The Hox-1.6 homeo-box shows more divergence than the other members of the complex with the Drosophila Antennapedia-like homeo-box class. This previously undescribed gene was studied with respect to its transcription pattern and was found to be expressed during mouse fetal development in an intestine-specific manner in adults, and in tumours or cell types exhibiting early endodermal-like differentiation. The study of embryonic partial Hox-1.6 cDNA clones revealed structural features common to other Drosophila and vertebrate homeo-box-containing genes, but also indicated that Hox-1.6 transcripts might display splicing patterns more complex than those known for other vertebrate homeo-genes. One of these cDNA clones contains a rather short open reading frame which would encode a protein of approximately 14.5 kd. The use of this clone as a probe for S1 nuclease mapping confirmed that different Hox-1.6 transcripts were present both in embryonic total RNA and in embryonal carcinoma cell cytoplasmic RNA. These various transcripts are probably generated by an alternative splicing mechanism and may thus encode a set of related proteins.

Amino Acid Sequence↗

Determinants of survival 10 to 14 years after coronary bypass: analysis of preoperative variables in 1,448 patients.

To determine which preoperative variables were most predictive of long-term survival after coronary bypass surgery, the status of 1,448 consecutive patients was determined 10 to 14 years after operation. All patients were operated on at least 10 years ago and follow-up at 10 years was 93.8% complete. The overall 14-year survival probabilities were: for one-vessel disease, 73.3%; for two-vessel disease, 45.9%; for three-vessel disease, 34.2%; and for left main coronary artery disease, 41.9%. Patients with good left ventricular function had an overall survival rate of 53.3%, and patients with poor ventricular function had a survival rate of 31.9%. Preoperative variables predictive of greater risk of total mortality were: digoxin usage, multivessel disease, poor quality of left ventricular function, age at operation, electrocardiographic evidence of myocardial infarction, previous stroke, diabetes, heart failure, diuretic usage, cigarette smoking, and residual ungrafted coronary artery disease. The major determinants of long-term survival were variables associated with preoperative left ventricular function. Diabetes was the only important metabolic risk factor identified. This study suggests that unfavorable preoperative conventional risk factors should not be considered a contraindication to operation in patients with adequate coronary anatomy and left ventricular function.

Coronary Artery Bypass↗

Age and practice effects in continuous recognition memory.

Older and younger women identified new and repeated items in extended lists of letter-number combinations (e.g., "A42G"). Repeated items occurred at intervals ranging from 0 to 32 items (0 to 160 s) and for different lists the items were either visual or auditory. The older women's performances declined at a more rapid rate as the retention interval was increased. When the older women practiced the auditory task, performances improved and gains transferred to the visual task. Gains by the younger women were equivalent, so that initial age differences were maintained. Signal detection analyses attributed age effects to differences in sensitivity rather than bias. For women of both ages, conservative bias was greater when the intervals were long and when the task was visual. The absence of age-bias effects was contrary to the hypothesis that older adults adopt more conservative decision strategies. The presence of sensitivity differences, even when the task was well practiced, suggests fundamental age differences in recognition memory.

Adult↗

A new homeo-box is present in overlapping cosmid clones which define the mouse Hox-1 locus.

A new murine homeo-box (Hox1-3) has been isolated and studied with respect to its structure and transcriptional pattern. This homeo-box is part of a gene which is specifically regulated during mouse prenatal development and expressed in a restricted number of teratocarcinoma tumours as well as in adult testis. Hox1-3 is shown to be a member of a cluster of at least four homeo-boxes lying within a 75-kb segment of DNA on mouse chromosome 6. The structure of the whole cluster, the Hox-1 locus is presented.

Animals↗

Age-related effects of practice and task complexity on card sorting.

Eight younger and 8 older women (17 to 25 and 62 to 75 years) practiced card sorting under timed conditions. Task complexity was varied by increasing the number of stimuli and by making sorting conditional on a second stimulus. The older women generally were slower, and age difference increased as a function of task complexity. Women of both ages responded at increasing rates over the five practice sessions. Gains were maintained during a follow-up test 10 days later and transferred to sorts with different stimuli. Practice did not reduce age differences (gains by the older women were matched by the younger ones), but there was some indication that the age-complexity relationship was attenuated.

Adult↗

Age-related effects of temporal contingencies on response speed and memory: an operant analysis.

Single-subject methods were used to study influences of extended training and temporal contingencies. Five younger (18 to 21 years) and five older (65 to 74 years) healthy men responded to a series of matching-to-sample discriminations with sample-choice intervals of 0, 5, 10, and 15 s. During baseline sessions, there was no time limit placed on the response to the choice stimuli. Subsequently, correct responses were reinforced only if they occurred within a specified limit. Men of both ages responded faster to the choice stimuli as increasingly stringent limits were imposed, and speeds exceeded those under the baseline condition when the men had been instructed to be accurate and prompt. When the limits subsequently were removed, response speeds decreased somewhat but still were above earlier baseline performances. Under both baseline and time limit conditions, responding was slower when the choice stimuli were delayed, indicating that the procedure tapped short-term memory processes as well as psychomotor speed. Responding also was slower when the stimulus pool involved eight rather than two stimuli. Although performances of the older men improved substantially during the course of training, the younger men improved to the same extent so that age differences were not appreciably reduced.

Adolescent↗

Reaction times of younger and older men: effects of compound samples and a prechoice signal on delayed matching-to-sample performances.

Five younger (18 to 23 yrs) and five older (65 to 73 yrs) men were exposed to a series of immediate and delayed (0 to 15 seconds) matching-to-sample problems. Presentation of the pairs of delayed comparison stimuli was either signaled or unsignaled, and the sample contained either 1, 2, or 3 elements, one of which appeared as the positive stimulus. During initial sessions, unlimited time was available to respond. Subsequently, correct responses were reinforced only if they occurred within a specified time limit. A general finding was slower responding with increased delay and with increased number of sample elements. These effects were reduced when the comparison stimuli were signaled and when time limits were in effect. Errors increased as a function of the manipulations of sample complexity and time limits, but did not change systematically when the delay between sample and comparison stimuli was varied. Although the younger men generally responded more quickly than the older ones, men of both ages showed increased speeds when limits were placed on response time, and these changes were maintained when the temporal contingencies were removed.

Adolescent↗

Social housing of rats: life-span effects on reaction time, exploration, weight, and longevity.

Sprague-Dawley rats were housed throughout their lives either in group cages or singly in standard laboratory cages. Locomotor activity was observed at selected ages and, in addition, operant conditioning procedures were used with an extensively trained subset of the animals to study reaction time and fixed ratio responding. The major effect of prolonged isolation was to induce timidity and inactivity during open field and emergence tests. Responding by isolates was depressed relative to socially-housed animals at 13 and 19 months of age although the higher levels of the social animals progressively declined during tests at 19 and 25 months. By comparison, neither housing condition nor age (7 to 25 months) systematically influenced the well-practiced operant responses (response rates, postreinforcement pauses, reaction times, foreperiod responses). A serendipitous finding was that isolated animals tended to die at earlier ages, an outcome that may be related to the fact that isolates also tended to weigh more throughout the experiment.

Age Factors↗

Striated flagellar roots: isolation and partial characterization of a calcium-modulated contractile organelle.

We report the isolation of striated flagellar roots from the Prasinophycean green alga Tetraselmis striata using sedimentation in gradients of sucrose and flotation on gradients of colloidal silica. PAGE in the presence of 0.1% SDS demonstrates that striated flagellar roots are composed of a number of polypeptides, the most predominant one being a protein of 20,000 Mr. The 20,000 Mr protein band represents approximately 63% of the Coomassie Brilliant Blue staining of gels of isolated flagellar roots. Two-dimensional gel electrophoresis (isoelectric focusing and SDS PAGE) resolves the major 20,000 Mr flagellar root protein into two components of nearly identical Mr, but of differing isoelectric points (i.e., pl's of 4.9 and 4.8), which we have designated 20,000-Mr-alpha and 20,000-Mr-beta, respectively. Densitometric scans of two-dimensional gels of cell extracts indicate that the 20,000-Mr-alpha and -beta polypeptides vary, in their stoichiometry, between 2:1 and 1:1. This variability appears to be related to the state of contraction or extension of the striated flagellar roots at the time of cell lysis. Incubation of cells with 32PO4 followed by analysis of cell extracts by two-dimensional gel electrophoresis and autoradiography reveals that the more acidic 20,000-Mr-beta component is phosphorylated and the 20,000-Mr-alpha component contains no detectable label. These results suggest that the 20,000-Mr-alpha component is converted to the more acidic 20,000-Mr-beta form by phosphorylation. Both the 20,000-Mr-alpha and -beta flagellar root components exhibit a calcium-induced reduction in relative electrophoretic mobilities in two-dimensional alkaline urea gels. Antiserum raised in rabbits against the 20,000-Mr protein binds to both the 20,000-Mr-alpha and 20,000-Mr-beta forms of the flagellar root protein when analyzed by electrophoretic immunoblot techniques. Indirect immunofluorescence on vegetative or interphase cells demonstrate that the antibodies bind to two cyclindrical organelles located in the anterior region of the cell. Immunocytochemical investigations at ultrastructural resolution using this antiserum and a colloidal gold-conjugated antirabbit-IgG reveals immunospecific labeling of striated flagellar roots and their extensions. We conclude that striated flagellar roots are simple ion-sensitive contractile organelles composed predominantly of a 20,000 Mr calcium-binding phosphoprotein, and that this protein is largely responsible for the motile behavior of these organelles.

Calcium↗

Age-related preferences for paced and unpaced tasks in chained schedules of reinforcement.

Younger and older men were studied on chained operant schedules. A response in the initial link produced a terminal link where a sequence of 10 key presses was reinforced with money. In different conditions, the time available for each key press was varied from .5 sec to an unlimited amount, and the speed with which the men produced the terminal links containing the paced and unpaced sequences was taken as an index of preference for the terminal link conditions. When the men had difficulty adjusting to pacing, initial link speed was directly related to reinforcement rate in the terminal link: the greater the reinforcement, the faster the speed. This effect was stronger among the older men, who had more difficulty adjusting to pacing. With continued exposure to pacing, however, men of both ages adjusted more readily and the speed-reinforcement relationship decreased. These results suggest that the role of monetary reinforcement in determining task preferences is moderated by other factors such as task difficulty.

Adolescent↗

Insulin receptors in isolated human adipocytes. Characterization by photoaffinity labeling and evidence for internalization and cellular processing.

We photolabeled and characterized insulin receptors in isolated adipocytes from normal human subjects and then studied the cellular fate of the labeled insulin-receptor complexes at physiologic temperatures. The biologically active photosensitive insulin derivative, B2(2-nitro-4-azidophenylacetyl)des-PheB1-insulin (NAPA-DP-insulin) was used to photoaffinity label the insulin receptors, and the specifically labeled cellular proteins were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. At saturating concentrations, the binding of 125I-NAPA-DP-insulin to the isolated adipocytes at 16 degrees C was rapid (half-maximal in approximately 1 min and maximal in approximately 10 min) and approximately 25% of the specifically bound ligand was covalently linked to the cells by a 3-min exposure to long-wave (366 nm) ultraviolet light. Analysis of the photolabeled cellular proteins by PAGE in the absence of disulfide reductants revealed the specific labeling of a major protein band of Mr 330,000 and two less intense bands of Mr 295,000 and 260,000. Upon reduction of disulfide bonds with dithiothreitol, all three unreduced forms of the insulin receptor were converted into a major labeled Mr-125,000 band and a less intensely labeled Mr-90,000 band. The labeling of the Mr-125,000 receptor subunit was saturable and native porcine insulin effectively inhibited (half-maximal inhibition at 12 ng/ml) the photolabeling of this binding subunit by NAPA-DP insulin. When intact adipocytes photolabeled at 16 degrees C (a temperature that inhibits endocytosis) were immediately trypsinized, all of the labeled receptor bands were converted into small molecular weight tryptic fragments, indicating that at 16 degrees C all of the labeled insulin-receptor complexes remained on the cell surface. However, when the photolabeled cells were further incubated at 37 degrees C and then trypsinized, a proportion of the labeled receptors became trypsin insensitive, indicating that this fraction has been translocated to the cell interior and thus was inaccessible to the trypsin in the incubation medium. The intracellular translocation of the labeled receptors was observed within 2 min, became half-maximal by 10 min, and maximal by approximately 30 min of incubation at 37 degrees C. Cellular processing of the internalized insulin-receptor complexes also occurred, since incubation at 37 degrees C (but not 16 degrees C) resulted in the generation of a Mr-115,000 component from the labeled receptors. Inclusion of chloroquine, a drug with lysosomotropic properties, in the incubation media caused a time-dependent increase (maximal increase of 50% above control by 2 h at 37 degrees C) in the intracellular pool of labeled receptors. In contrast to these findings in human adipocytes, no appreciable internalization of insulin-receptor complexes and no chloroquine effect was observed in cultures human IM-9 lymphocytes during a 1-h incubation at 37 degrees C. We concluded that in isolated human adipocytes: (a) the subunit structure of insulin receptors is the same as that reported for several other tissues, (b) insulin-receptor complexes are rapidly internalized and processed at physiologic temperatures, and (c) the cellular processing of insulin-receptor complexes occurs at one or more chloroquine-sensitive intracellular site(s).

Adipose Tissue↗