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Biomedical subjects

A Crowe

Publications and source records attributed to A Crowe.

At least 37 records · Page 2Linked to original sources
PubMed1994

A mutation in the second largest subunit of TFIIIC increases a rate-limiting step in transcription by RNA polymerase III.

In previous studies, we have shown that the PCF1-1 mutation of Saccharomyces cerevisiae suppresses the negative effect of a tRNA gene A block promoter mutation in vivo and increases the transcription of a variety of RNA polymerase III genes in vitro. Here, we report that PCF1 encodes the second largest subunit of transcription factor IIIC (TFIIIC) and that the PCF1-1 mutation causes an amino acid substitution in a novel protein structural motif, a tetratricopeptide repeat, in this subunit. In agreement with the nature of the mutation, in vitro transcription studies with crude extracts indicate that PCF1-1 facilitates the rate-limiting step in transcription, namely, the recruitment of TFIIIB to the template. Additionally, biochemical fractionation of wild-type and mutant cell extracts shows that PCF1-1 increases the amount of the 70-kDa TFIIIB subunit detectable by Western (immunoblot) analysis in purified TFIIIB fractions and the transcription activity of a TFIIIB" fraction containing the 90-kDa subunit of this factor. We suggest that the effect of PCF1-1 on TFIIIB activity in vitro is a consequence of its increased rate of recruitment in vivo.

Amino Acid Sequence↗
PubMed1992

Iron and transferrin uptake by brain and cerebrospinal fluid in the rat.

Iron and transferrin uptake into the brain, CSF and choroid plexus, and albumin uptake into the CSF and choroid plexus, were determined after the intravenous injection of [59Fe-125I]transferrin and [131I]albumin into control rats aged 15, 21 and 63 days and 21-day iron-deficient rats. Iron uptake by the brain was unidirectional, greatly exceeded that of transferrin and was equivalent to 39 and 36% of the plasma iron pool per day in the 15-day control and 21-day iron-deficient rats. The rate of transferrin catabolism in the rats was only about 20% of the plasma pool per day. Iron and transferrin uptake into the brain and CSF decreased with increasing age and was greater in the iron-deficient than in the control 21-day rats. The quantity of 125I-transferrin recovered in the CSF could account for only a small proportion of the iron taken up by the brain. Albumin transfer to the CSF also decreased with age but was lower than that of transferrin and was not affected by iron deficiency. Similarly, the plasma: CSF concentration ratios of transferrin and albumin, as determined immunologically, decreased with age and were greater for transferrin than albumin. It is concluded that iron uptake by the brain is dependent on iron release from transferrin at the cerebral capillary endothelial cells with recycling of transferrin to the plasma and transfer of the iron into the brain interstitium. Only a small fraction of the transferrin bound by brain capillaries is transcytosed into the brain and CSF, this being one source of CSF transferrin while other sources are local synthesis and transfer from the plasma by the choroid plexuses.

Animals↗
PubMed1992

Immunocytochemistry of neurofibrillary tangles with antibodies to subregions of tau protein: identification of hidden and cleaved tau epitopes and a new phosphorylation site.

Antibodies to multiple epitopes spanning the length of the tau molecule were used to study Alzheimer neurofibrillary tangles (NFT) using immunocytochemical methods and several different methods of fixation and tissue processing, including staining of vibratome sections, hydrated autoclaving of paraffin sections and immunofluorescence of NFT isolated from fresh brain tissue. Smears and sections were pretreated with trypsin and/or phosphatase to further characterize antibody binding. In tissue fixed briefly in periodate-lysine-paraformaldehyde, tau immunoreactivity was detected in astrocytes, but only a few tau epitopes were detected in NFT with this fixation method. In contrast, all tau epitopes were detected in NFT in tissue fixed in formaldehyde for prolonged periods of time. In the hippocampus, the number of NFT detected in the dentate fascia was in proportion to the duration of dementia, as we previously noted. Dentate fascia NFT were intracellular (i-NFT) and were reactive with antibodies recognizing epitopes in both the carboxy- and amino-terminal regions of tau, but not the microtubule-binding domain of tau, suggesting that microtubule-binding domain epitopes are hidden in i-NFT. In contrast, NFT in the subiculum and layer II of the parahippocampal cortex were mostly extracellular (e-NFT), especially in severe cases of long duration. e-NFT were immunoreactive with antibodies to the microtubule-binding domain, but only weakly reactive with antibodies to carboxy- or amino-terminal epitopes, suggesting that e-NFT may contain fragments of tau. In both isolated NFT and NFT in sections, amino-terminal epitopes, including the Alz-50 epitope, were sensitive to trypsin proteolysis, which suggests that the lack of staining of e-NFT by antibodies to the amino-terminal regions of tau is due to proteolysis. Antibodies reactive with amino-terminal epitopes also stained fewer NFT following hydrated autoclaving, while those reacting with the carboxy half of tau stained more NFT after hydrated autoclaving. Thus, although carboxy-terminal regions are not detected in e-NFT, they are probably masked, rather than proteolytically cleaved, since they can be revealed by hydrated autoclaving. Finally, phosphatase treatment of isolated NFT revealed enhanced immunostaining not only with Tau-1, as in previous studies demonstrating abnormal phosphorylation of tau proteins in NFT, but also with an antibody to exon 2, which reveals yet another phosphorylation site in tau of NFT.

Aged↗
PubMed1992

Proprioceptive accuracy in idiopathic scoliosis.

Defects in proprioceptive postural control have been linked to the etiology of idiopathic scoliosis. In particular, a rearrangement of the internal representation of the body has been proposed in these cases. In this study, upper-extremity proprioceptive accuracy was compared among the following groups: 1) patients with idiopathic scoliosis (n = 25); 2) subjects with nonprogressive spinal asymmetry detected by screening in school (n = 23); 3) subjects undergoing behavioral training for nocturnal enuresis (n = 17); and 4) normal subjects (n = 134). A significant inaccuracy was found among the right-handed subjects of the scoliosis and spinal asymmetry groups as compared to the normal group. It is postulated that proprioceptive dysfunction, or borderline function, is a causative factor of spinal asymmetry, which is often observed in early adolescence and which in some cases may be progressive.

Adolescent↗
PubMed1992

Portal vein thrombosis in a complicated case of Crohn's disease.

Portal vein thrombosis is a rare complication of ulcerative colitis and is invariably fatal. This report describes a patient with severe Crohn's disease who underwent elective surgery complicated by an anastomotic disruption with faecal peritonitis. Following emergency laparotomy he developed left hypochondrial pain which was a manifestation of splenomegaly consequent upon portal vein thrombosis. Anticoagulation was successful in preventing further spread of the thrombosis as monitored by colour Doppler ultrasound. Severe active disease, surgery and sepsis have been recognized as predisposing factors for thromboembolic complications in inflammatory bowel disease and this patient was exposed to all three. It is conceivable that portal vein thromboses occur more commonly than suspected and ultrasound scanning could ascertain the prevalence if performed prospectively.

Adult↗
PubMed1992

Iron uptake in relation to transferrin degradation in brain and other tissues of rats.

The possibility that iron uptake by the brain involves transcytosis of the iron-transferrin complex across the brain capillaries, followed by degradation of the transferrin (Tf) within the brain, was investigated using diferric 125I-[59Fe]Tf and [59Fe]Tf coupled to 125I-tyramine cellobiose (TC). The radiolabeled catabolic products of proteins labeled with 125I-TC remain in the cells where degradation occurs. The TCTf complex behaved normally with respect to its ability to donate iron to rat reticulocytes in vitro or to the brain, liver, kidneys, and femurs in vivo. In the brain there was little difference in the uptake of 125I derived from Tf and TCTf, and the amounts were equivalent to only a small fraction of the 59Fe uptake. Hence, the rate of Tf catabolism in the brain was insufficient to account for the rate of accumulation of iron from plasma Tf. It was concluded that Tf recycles to the plasma after delivering its iron to the brain. The uptake of 125I from TCTf by the liver and kidneys accounted for 40-50% of the total rate of Tf catabolism. This indicated that they were important but not the only sites of degradation of this protein.

Aging↗
PubMed1991

Transferrin and iron uptake by the brain: effects of altered iron status.

Transferrin (Tf) and iron uptake by the brain were measured in rats using 59Fe-125I-Tf and 131I-albumin (to correct for the plasma content of 59Fe and 125I-Tf in the organs). The rats were aged from 15 to 63 days and were fed (a) a low-iron diet (iron-deficient) or, as control, the same diet supplemented with iron, or (b) a chow diet with added carbonyl iron (iron overload), the chow diet alone acting as its control. Iron deficiency was associated with a significant decrease and iron overload with a significant increase in brain nonheme iron concentration relative to the controls. In each dietary treatment group, the uptake of Tf and iron by the brain decreased as the rats aged from 15 to 63 days. Both Tf and iron uptake were significantly greater in the iron-deficient rats than in their controls and lower in the iron-loaded rats than in the corresponding controls. Overall, iron deficiency produced about a doubling and iron overload a halving of the uptake values compared with the controls. In contrast to that in the brain, iron uptake by the femurs did not decrease with age and there was relatively little difference between the different dietary groups. 125I-Tf uptake by the brains of the iron-deficient rats increased very rapidly after injection of the labelled proteins, within 15 min reaching a plateau level which was maintained for at least 6 h. The uptake of 59Fe, however, increased rapidly for 1 h and then more slowly, and in terms of percentage of injected dose reached much higher values than did 125I-Tf uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

The N terminal region of human tau is present in Alzheimer's disease protein A68 and is incorporated into paired helical filaments.

Antibody (Ab) E-1 was raised to the amino terminus (19 to 33 amino acid residues) of human tau. It recognized Alzheimer's disease proteins A68 (MW 60, 64, 68 kd), labeled paired helical filaments, and had no reactivity with tau from rat, mouse, and bovine brains. The results indicate that the N terminus of tau is incorporated in A68 proteins and paired helical filaments and that human tau proteins contain species-specific amino acid sequences.

Alzheimer Disease↗
PubMed1989

Simulation of quadrupedal locomotion using a rigid body model.

Locomotion of the horse is simulated using a mathematical model based on rigid body dynamics. A general method to generate the equations of motion for a two-dimensional rigid body model with an arbitrary number of hinge joints is presented and a numerical solution method, restricted to tree-structured models, is described. Joint movements originating from muscular forces or moments are simulated, but the method also allows that parts of the model follow strictly the pattern of kinematic data. Moment-generators with first-order linear feedback were used as a rotational muscle-equivalent. Ground-hoof interaction forces are approximated by a viscoelastic model and pseudo-Coulomb friction in vertical and horizontal directions respectively. Results of model simulations are compared to experimentally recorded data. Subsequently, adjustments are made to improve the agreement between simulation and experimental results.

Animals↗
PubMed1989

Effect of timing of transient diastolic changes in ventricular filling on LV performance in dogs.

The influence of acute volume changes during diastole on the contractile state of the left ventricle has been studied in the closed-chest dog. Volume changes were introduced by means of a servo-controlled pump system connected to the left ventricular cavity by an apical cannula. Pressure measurements were made in the left ventricle and aorta. Flow sensors in the mitral valve and around the ascending aorta monitored ventricular inflow and outflow patterns. The ventricular performance was evaluated in terms of the ratio between end-systolic pressure and end-systolic volume (P/Ves). By changing the time of occurrence of the volume interventions from the rapid filling phase of diastole to the atrial contraction phase, the relative contributions of rapid filling and atrial contraction to the mitral flow were changed. When the rapid filling was changed by the volume intervention, the effect on the contractile status of the heart, expressed as the P/Ves value, was small. In contrast, when the volume intervention took place during the atrial contraction phase, the effect on the P/Ves value was much larger. Comparison with muscle fiber experiments suggests that length-dependent calcium sensitivity of troponin and length-dependent conductivity of the sarcolemma are the underlying fundamental mechanisms. Therefore, we conclude that the influence of an intervention in ventricular filling on the inotropic state of the left ventricle is dependent on the timing of the intervention.

Animals↗
PubMed1989

Influence of age on proprioceptive accuracy in two dimensions.

Slow arm movements were made over a smooth horizontal table at shoulder height. With visual cues excluded, target position was indicated by the index finger of the nonmoving arm touching the underside of the table. 134 subjects (including 26 left-handed subjects) in the age range 8.0 to 24.6 yr. were examined to see if the results were age-related. Accuracy slightly but significantly increased with age. The younger subjects showed a greater accuracy with the dominant hand--a situation which tended to be reversed in the older subjects.

Adolescent↗
PubMed1988

Information transmission in non-visual fingertip matching along a horizontal track in the median plane.

Non-visually triggered arm movements over a horizontal table at shoulder height were analysed by an Information Theory approach according to a method suggested by Sakitt et al. (1983) and Sakitt (1980). The movement track was along the subject's median line and was indicated by a vertical metal ridge fixed to the table. The observer passively moved the subject's left index finger along the left side of the ridge to the target position. The blindfolded subject then had to move his right index finger along the right side of the ridge to match the left finger position. Direct contact between the two fingers was prevented by the ridge. We compared our results, which involve the transmission of information through the arm and shoulder joints of both arms, with those of Sakitt et al. which involved just one elbow joint. We supplemented our experimental results with simulations and show that the value for the transmitted information, obtained using the method of analysis suggested by Sakitt et al., is very dependent upon the number of trials, and number and spacing of the targets. Sakitt et al. suggest that the Information Theory approach permits easy comparison between different tasks and different observers. Our results suggest that comparisons should be made with caution.

Adult↗
PubMed1987

Biosynthesis of reovirus-specified polypeptides. Molecular cDNA cloning and nucleotide sequence of the reovirus serotype 1 Lang strain s2 mRNA which encodes the virion core polypeptide sigma 2.

Human reovirus serotype 1 Lang strain s2 mRNA, which encodes the virion inner capsid core polypeptide sigma 2, was cloned as a cDNA:mRNA heteroduplex in Escherichia coli using phage M13. A complete consensus nucleotide sequence was determined. The Lang strain s2 mRNA is 1331 nucleotides in length and possesses an open reading frame with a coding capacity of 335 amino acids, sufficient to account for a sigma 2 polypeptide of 37,682 daltons. Comparison of the serotype 1 Lang s2 sequence derived from cDNA clones of s2 mRNA with the serotype 3 Dearing S2 sequence derived from cDNA clones of the S2 dsRNA genome segment reveals 86 percent homology at the nucleotide level. The predicted sigma 2 polypeptides of the Lang and Dearing strains display 98 percent homology at the amino acid level. Of 147 silent nt differences in the translated region, 136 were in the third base position of codons.

Amino Acid Sequence↗
PubMed1987

Relaxation time constant of isolated rabbit left ventricle.

Experiments were performed on isolated rabbit left ventricles. Controlled ejections during otherwise isovolumic contractions were studied. The time constant of relaxation was defined as the slope of the linear approximation of the ln(P)-t relation over a 40-ms period starting 20 ms after the minimum of the first time derivative of left ventricular pressure (dP/dt) of the isovolumic contraction. Variations in time of ejection, its amplitude, and velocity are applied independently. No direct effect of the variations in time and velocity of the ejection on the time constant of relaxation was found. This is in conflict with the findings of Hori et al. (Circ. Res. 55: 31-38, 1984). The difference is due to the influence of the recovery of pressure directly after the end of ejection in their study. This effect is present especially when ejection was timed to take place late in the contraction phase. The effect of the variation of the amplitude of the ejection on the time constant was similar to the effect of the end-diastolic pressure on the end-diastolic volume. It is concluded that the time constant of relaxation depends linearly on the same processes that are responsible for the height of the end-diastolic pressure.

Animals↗
PubMed1987

Proprioceptive accuracy in two dimensions.

Slow arm movements were made over a smooth horizontal table at shoulder height. With visual cues excluded, target position was indicated by the index finger of the nonmoving arm touching the underside of the table. 11 students (mean age 21.9 yr.) and 24 children (mean age 10.3 yr.) were compared. Both groups showed an 'overlap effect': movements with the right hand went too far to the left, while movements with the left hand went too far to the right. The children as a group were significantly less accurate than the students and showed a significant asymmetry in that movements with the dominant hand were more accurate than those with the nondominant hand.

Adult↗