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Biomedical subjects

J P Morris

Publications and source records attributed to J P Morris.

At least 19 recordsLinked to original sources

Home visiting intervention for vulnerable families with newborns: follow-up results of a randomized controlled trial.

OBJECTIVE: This study aimed to: (1) Assess the community utility of a screening tool to identify families with child abuse or neglect risk factors in the immediate postnatal period (2) Determine the social validity and effectiveness of a home visiting program using community child health nurses and offering social work services for identified families, and (3) Identify factors in the immediate postnatal period associated with the child's environment that predict poor adjustment to the parenting role. METHOD: A randomized controlled trial using a cohort of 181 families was undertaken to evaluate the impact of a home visiting program. Mothers were recruited in the immediate postnatal period and allocated either into the home visiting program or into a comparison group. The research design required self-identification into the study by providing positive responses to a range of risk factors. A repeated measures design was used to test parenting stress and maternal depression from the immediate postnatal period to 12-month follow-up and physical child abuse potential to 18-month follow-up. To test whether measures taken in the immediate postnatal period were predictive for poor adjustment to the parenting role, a linear regression model was used. RESULTS: The screening procedure was shown to have utility in the context of recruitment to a research trial and mothers were willing to accept the home visiting program examined by this study from the immediate postnatal period. From as early as 6 weeks the program demonstrated ability to impact positively on maternal, infant, family, and home environment variables (testing 90 randomly allocated intervention vs. 91 comparison families). At follow-up, parental adjustment variables were not significantly different between groups (testing the remaining 68 (75.5%) intervention vs. 70 (76.9%) comparison families) and home environment assessment scores had converged. Predictive analysis of factors measured in the immediate postnatal period revealed an absence of any predictive value to demographic characteristics, which secondary prevention efforts typically target. CONCLUSIONS: Follow-up evaluation did not demonstrate a positive impact on parenting stress, parenting competence, or quality of the home environment confirming the need to test early program success on longer term outcomes. Further, thestudy not only demonstrated that there was a relationship between maternal, family and environmental factors identified in the immediate postnatal period. and adjustment to the parenting role, but also challenged demographic targeting for child abuse and neglect risk. At the same time, the immediate postnatal period presented an exciting window of opportunity to access high-risk families who may otherwise have become marginalized from traditional services.

Adaptation, Psychological↗

EEG changes in 4-week-old lambs in response to castration, tail docking and mulesing.

OBJECTIVE: To interpret changes in EEG in relation to perceived pain of castration, mulesing and docking in lambs. DESIGN: Analysis of covariance (randomised block design) to determine the effects of treatment on eight bandwidths of the EEG frequency spectrum. PROCEDURE: Ninety-eight, 3- to 4-week-old lambs were subjected to one of seven treatments: castration, tail docking, mulesing, ear tagging, sham shearing, formalin injection (to induce lameness) and handling. EEG was recorded for 15 min before treatment, during treatment, and for 15 min after treatment. RESULTS: Consistently lower mean power values across all bandwidths of the EEG were found at the time of mulesing and docking than at handling and shearing (P < 0.01). Formalin injection resulted in lower power values than handling and shearing (P < 0.01). Castration had lower power values than handling and shearing. Similarly, for 15 min after treatment, mulesing and formalin injection had significantly lower power values than handling, shearing, ear tagging and castration (P < 0.05). CONCLUSION: The consistent effects associated with mulesing, docking and castration compared to handling, shearing and ear tagging suggest that mulesing at both the time of treatment and during 15 min after treatment results in a response that is similar to that of induced lameness. Docking and castration result in a response at the time of treatment that is similar to induced lameness and mulesing, but during 15 min after treatment is similar to the non-noxious control treatments. However, the depressing effects on the mean power values are the reverse of that anticipated from a previously developed pain model, highlighting the need for further research to develop this technology to evaluate pain associated with husbandry procedures.

Animal Husbandry↗

Behavioural and EEG changes in sheep in response to painful acute electrical stimuli.

OBJECTIVE: To measure acute pain in sheep, based on a human pain model, and examined changes in both electroencephalogram frequency spectrum and behavioural responses to increased electrical stimulation in sheep. DESIGN: Analysis of variance (treatment and animal effects) for stimulus intensity where each animal received each electric shock treatment given in the order 0, 5, 10 and 20 mA. PROCEDURE: Eight sheep with electrodes implanted over the surface of the brain were examined for escape-avoidance and electroencephalogram responses to four levels of electrical stimulation from 0-20 mA. RESULTS: With increasing stimulus intensity at the time of feeding, the sheep were more hesitant to return to the feeder or remain near the feeder following stimulation. There was little difference between the 0 and 5 mA stimuli for any of the behaviour variables (P > 0.05). However, there were marked increases in the time taken to re-approach the feeder after receiving an electric shock of 5 mA and of 20 mA (P < 0.05; mean values 3 and 119 s, respectively) and remaining near the feeder for 5 s (P < 0.001; mean values 10 and 167 s, respectively). Following the stimulus, there was an overall increase in the electroencephalogram power spectrum in the first four seconds, which then rapidly returned to normal. In particular, the 20 mA stimulus resulted in higher absolute power values than in the control (0 mA) treatment for delta 2 (P < 0.001), theta 1 (P < 0.05), theta 2 (P < 0.05), alpha 1 (P < 0.001), alpha 2 (P < 0.001) and beta 1 (P < 0.01), bandwidths. Similarly, for the 10 mA stimulus, the absolute power values were greater than the control treatment for delta 2 (P < 0.05), alpha 1 (P < 0.01), alpha 2 (P < 0.001) and beta 1 (P < 0.01) bandwidths. CONCLUSION: The experiment suggests that a human acute pain model is applicable to sheep and that these electroencephalogram changes may provide a good measure of acute pain in sheep

Analysis of Variance↗

Pain-related cerebral potentials in response to acute painful electrical stimulation in sheep.

OBJECTIVE: To examine associations between late event-related cerebral potential amplitudes and behavioural responses to noxious electrical stimulation as an indicator of acute pain in sheep. DESIGN: Analysis of variance for the effects of stimulus intensity on the behaviour and event-related cerebral potential variables. PROCEDURE: Ninety-six brief constant current electrical pulse trains were presented to the front left leg of eight sheep at four intensities (2.5 to 10 mA) in a randomised order. An event-related cerebral potential and a graded flinch response were recorded for each stimulus and the 24 event-related cerebral potentials at each intensity were averaged to produce a mean waveform. Various components of this waveform were analysed and changes in these measures and the sheep's flinch response, as stimulus intensity increased, were determined. RESULTS: Both the flinch response and some event-related cerebral potential components, that is, peak amplitudes 114 [N1], 187 [P1], 318 [P2] and 230 [Pm] ms after stimulus onset, were significantly affected as stimulus intensity increased. CONCLUSION: These corresponding behavioural and event-related cerebral potential changes indicate the usefulness of using changes in the event-related cerebral potential to measure acute pain in sheep.

Analysis of Variance↗

Dietary acid and alkali loading do not alter taurine uptake by renal proximal tubule brush border membrane vesicles in kittens.

Kittens adapted to a purified control diet containing 43.5% soy protein plus 0.15% taurine were randomly divided into three groups: control, acid-loaded or alkali-loaded. For dietary acid or alkali loadings, 2% NH4Cl or 0.87% NaHCO3 plus 0.87% KHCO3 were added to the control diet. Acid-loaded, control and alkali-loaded kittens had venous blood pH of 7.33 +/- 0.01, 7.37 +/- 0.02 and 7.39 +/- 0.02, and urine pH of 5.5 +/- 0.1, 7.2 +/- 0.1 and 8.1 +/- 0.1, respectively. After 6 wk of the dietary treatment, the plasma taurine concentrations of acid-loaded, control and alkali-loaded kittens were 74 +/- 4, 77 +/- 7 and 87 +/- 8 mumol/L (P greater than 0.05) respectively. Compared with the control group, dietary acid or alkali loading did not significantly change the taurine uptake by brush border membrane vesicles (BBMV) when BBMV were at the same in vitro pH (7.35). However, when the pH of the medium was changed to 8.0 for the alkali-loaded group or to 5.5 for the acid-loaded group, the initial taurine uptake was significantly elevated (55%) or decreased (31%) (P less than 0.05), respectively, compared with the values for the control group at pH 7.35. When BBMV prepared from the same group were tested at different pH levels (8.0 vs. 7.35 vs. 5.5), the initial uptake significantly increased (30%) at pH 8.0 and decreased (37%) at pH 5.5 compared with that observed at pH 7.35 (P less than 0.05), regardless of the acidity of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗

Control of human plasminogen activation.

The activation of Glu1-plasminogen (Glu-Pg) by streptokinase (SK), urokinase (UK) and tissue plasminogen activator (tPA) is under rigorous control by molecules such as epsilon-aminocaproic acid (EACA), fibrinogen (Fg), fibrin (Fn) and, as we have recently discovered, anions. This presentation will focus on the biochemical mechanisms that are involved in these processes. In the case of activation by SK, a species of activator complex, composed of Glu-Pg and SK, can be identified that is inhibited by anions, such as Cl-, and stimulated by Fg and Fn. This species rapidly decays to another activator complex, also consisting of Glu-Pg and SK, that is much less sensitive to control by these effector molecules. The most stable activator complex, containing equimolar SK and plasmin, is not affected to a great extent by anions, Fg or Fn. In the overall activation of Glu-Pg by SK, Cl- behaves as a mixed inhibitor, with a Ki of 6.4-9.2 mM, and Fg functions as a mixed activator, displaying a Ka of 110-240 nM. These results show that activation of Glu-Pg by SK in physiological samples would be considerably inhibited by Cl- in the absence of Fg. The activation of Glu-Pg by both high- and low-molecular weight UK is also inhibited by Cl-, but is stimulated by EACA. The inhibition by Cl- does not occur in the presence of concentrations of EACA that saturate its weak binding sites on Glu-Pg, and the stimulation by EACA is maximally exhibited in the presence of Cl-.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproic Acid↗

Rapid formation of an anion-sensitive active site in stoichiometric complexes of streptokinase and human [Glu1]plasminogen.

We have examined the time-dependent appearance of amidolytic activity in equimolar complexes of streptokinase (SK) and human [Glu1]plasminogen (HPg) under various conditions. When stoichiometric levels of the two proteins are incubated and assayed in hypotonic buffers at 4 degrees C, amidolytic activity toward the chromogenic substrate D-Val-Leu-Lys-p-nitroanilide (S-2251), within the resulting complex, appears with an observed first-order rate constant of 1.03 +/- 0.06/min. On the other hand, when the assay for amidolytic activity is conducted at a C1- concentration of 0.15 M, this same activity develops with an observed first-order rate constant of 0.13 +/- 0.01/min. Under all conditions of assay of importance to the mechanism proposed, the only molecular components present are SK and HPg. The rate of appearance of an enzyme species displaying amidolytic activity is dependent on the anion in its assay; a much slower rate constant is obtained with C1- than with AcO-. These observations are consistent with the formation, within the complex, of an early anion-sensitive active site (SK-HPg) that is converted to a form (SK-HPg') that is much less sensitive to the presence of anions. During the time period of this process, no conversion of plasminogen to plasmin occurs within the complex. Steadystate kinetic properties of SK-HPg and SK-HPg' have been measured toward the substrate S-2251. Consistent with the mechanism suggested above, the amidolytic activity of SK-HPg is inhibited by C1- to a much greater extent than is that of SK-HPg'.

Anions↗

Effects of human fibrinogen and its cleavage products on activation of human plasminogen by streptokinase.

The influence of human fibrinogen (Fg) and its terminal plasminolytic digestion products, fragment D and fragment E, on the kinetics of activation of human plasminogen (Pg) by catalytic levels of streptokinase (SK) has been investigated. Both Fg and fragment D enhanced the rates of activation of human Glu1-Pg, Lys77-Pg, and Val442-Pg. Fragment E was refractive in this regard. In the case of Glu1-Pg, the Km for activation by SK, 0.4 microM, was not affected by the presence of Fg or fragment D. The kcat for this same reaction, 0.12 s-1, was elevated to 0.3 s-1 at saturating levels of these effector molecules. On the other hand, the Km for activation of Lys77-Pg, 0.5 microM, was decreased to 0.09 microM, whereas the kcat, 0.33 s-1, was not altered in the presence of saturating concentrations of Fg or fragment D. In the case of Val442-Pg, the Km for this same activation, 2.0 microM, was lowered to 0.4 microM and 0.25 microM in the presence of Fg and fragment D, respectively. The kcat for this process, 1.0 s-1, was unchanged in the presence of these agents. The concentrations of Fg (KFg) and fragment D (KFD) that led to half-maximal stimulation of the activation rates were determined. For Fg with Glu1-Pg, Lys77-Pg, and Val442-Pg, the KFg values were 0.08 microM, 0.14 microM, and 0.17 microM, respectively. The KFD values for these same plasminogens were 0.25 microM, 2.0 microM, and 1.7 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme Activation↗

The role of the lysine binding sites of human plasminogen in the fibrinogen stimulated rate of active site formation in the streptokinase-plasminogen equimolar complex.

The effect of various concentrations of epsilon-amino caproic acid (EACA) on the rate of active site formation in the human plasminogen moiety of the streptokinase-plasminogen equimolar complex has been studied in the absence and presence of human fibrinogen fragment D1 (FD1). In the absence of FD1, the pseudo first order rate constant (kobs) for active site development in this complex ranges from 8.4-17.9 x 10(-3) sec-1 with Glu1-plasminogen (Glu1-Pg), Lys77-plasminogen (Lys77-Pg), and Val442-plasminogen (Val442-Pg), at levels of EACA from 0-25 mM. In the presence of 2 microM FD1, the kobs for active site formation in the SK . Glu1-Pg complex, of 60.1 x 10(-3) sec-1, was not altered significantly as the EACA level was increased to 25 mM. Similarly, in the SK . Lys77-Pg complex, the kobs for active site formation, of 62.1 x 10(-3) sec-1, was essentially unchanged as the EACA level was increased to 25 mM. Finally, the kobs for active site formation in the SK . Val442-Pg complex, of 113.6 x 10(-3) sec-1, was also unaffected at levels of EACA up to 5 mM, with a slight inhibition at 25 mM EACA. These results show that the stimulation of active site formation in the equimolar Sk . Pg complex by fibrinogen fragment D1 is mediated by sites separate from the lysine binding sites of plasminogen.

Aminocaproic Acid↗

The role of the lysine binding sites of human plasmin in the hydrolysis of human fibrinogen.

The importance of the lysine binding sites of human plasmin for its ability to digest human fibrinogen has been assessed by analyzing the nature and rate of the products formed in the presence of epsilon-aminocaproic acid. No major differences in this regard were found when comparing Lys77-plasmin and Val442-plasmin, in the absence of epsilon-aminocaproic acid, the latter plasmin being devoid of the lysine binding sites present on residues Glu1-Val441 (K 1-4). The presence of epsilon-aminocaproic acid, at concentrations ranging from 0.5-5.0 mM, results in progressively stronger inhibition of the digestion of fibrinogen and in appearance of fibrinogen degradation products Y, D and E, for both Lys77-plasmin, and Val442-plasmin, showing the importance of lysine binding regions in this property. However, since both plasmin forms were inhibited equally well at all levels of epsilon-aminocaproic acid, these studies show that lysine binding sites other than those present on region K 1-4 of Lys77-plasmin are of primary importance to fibrinogenolysis by plasmin.

Binding Sites↗

Purification, composition, and physical properties of a thermal hysteresis "antifreeze" protein from larvae of the beetle, Tenebrio molitor.

Proteins which produce a thermal hysteresis (difference between the freezing and melting points) in aqueous solution are well-known for their antifreeze activity in polar marine fishes. Much less is known about the biology and biochemistry of similar antifreeze proteins found in certain insects. A thermal hysteresis protein was purified from cold acclimated larvae of the beetle, Tenebrio molitor, by using ethanol fractionation, DEAE ion-exchange chromatography, gel filtration, and high-pressure liquid chromatography. The purified protein had a molecular mass of 17 000 daltons and its N terminus was lysine. The amino acid composition of the antifreeze protein contained more hydrophilic amino acids than the fish antifreezes. This is consistent with the compositions of previously purified insect thermal hysteresis proteins. However, the percentage of hydrophilic amino acids in this Tenebrio antifreeze protein was considerably less than that of other insect thermal hysteresis proteins. The freezing point depressing activity of the Tenebrio antifreeze was less than that of fish proteins and glycoproteins at low protein concentrations but was greater at high protein concentrations.

Amino Acids↗

Enhancement of the streptokinase-catalyzed activation of human plasminogen by human fibrinogen and its plasminolysis products.

The effects of human fibrinogen, and several plasmin-derived fragments of fibrinogen, on the streptokinase-induced activation of human plasminogen (Pg) have been investigated. Fibrinogen stimulates the rate of activation of human Glu1-Pg, Lys77-Pg, and Val442-Pg. The cofactor activity of fibrinogen appears to reside mainly in the D-domain region, since purified fragment D is active in this system. Fibrinogen fragment E was not active in this regard. The cofactor activity of fragment D was partially dependent on the presence of Ca2+. This effect of Ca2+ was likely due to its stabilizing influence on fragment D, as revealed by studied employing differential scanning calorimetry. Conversion of fragment D1 to fragments D2--5 did not alter the cofactor activity. Steady-state kinetic analysis of the activation of Val442-Pg by the streptokinase-Val442-plasmin complex demonstrated that the Km decreased approximately 2-fold, in the presence of fragment D1. Very little change in the steady-state kinetic parameters for Glu1-Pg and Lys77-Pg, when activated by the streptokinase-Lys77-plasmin complex, was noted in the presence of fragment D1. It was also found that both fibrinogen and fibrinogen fragment D1 increased the rate of formation of the active site in the streptokinase-plasminogen complex, of all forms of plasminogen, and that this effect was sufficient to explain the overall stimulation of the activation of plasminogen by fibrinogen and fibrinogen fragment D1.

Calcium↗

Effects of fasting on the control of fatty-acid synthesis in hepatoma 7777 and host liver. Role of long-chain fatty acyl-CoA,, the mitochondrial citrate transporter and pyruvate dehydrogenase activity.

The effects of fasting on the rate of fatty acid synthesis, the properties of the mitochondrial citrate transporter and on pyruvate dehydrogenase activity were investigated in "poorly-differentiated" tmorris hepatoma 7777 and in host liver preparations. The properties of the citrate transporter from hepatoma mitochondria were similar to those of host liver mitochondria, with the exception that the Km for the liver mitochondrial citrate transporter was 248 plus or minus 20 mu M while that in hepatoma mitochondria was less than 75 mu M. The acid-insoluble CoA content was 180 plus or minus 20 pmol/mg protein in the hepatoma and remained essentially unchanged in the fasted state, while the acid-insoluble CoA levels in livers from fed rats was 720 plus or minus 80 pmol/mg protein and were increased to 1050 plus or minus 50 pmol/mg protein during fasting. After a 36-h fast, the rate of lipogenesis and the percentage of pyruvate dehydrogenase present in the active form were each decreased by approximately 80% in host liver preparations. In contrast, the rate of lipogenesis by hepatoma slices did not decrease during fasting, and essentially all pyruvate dehydrogenase present was in the active form of hepatomas obtained from either fed or fasted animals. Implications concerning the identification of possible regulatory sites in the control of lipogenesis were discussed in relation to the above observations.

Acetyl Coenzyme A↗

Partial D 15 trisomy. A case and general review.

A profoundly retarded girl with cyanotic congenital heart disease, recurrent myoclonic seizures, an external strabismus and not very unusual facial features was found to have a 47, XX chromosome complement. The extra chromosome is a small G-size chromosome with small projections extending from the ends of the long arms and no satellites observed on the short arms. By Geimsa-trypsin banding techniques this aberrant chromosome appears to be a partially deleted D 15 chromosome. A comparison of the clinical features is made with those described in the nine other reported specifically identifies cases of 'partial trisomy 15'. For clinical and chromosome morphology reasons, this was felt not to be trisomy in the G group nor an extra Y. We speculate that the long arm projections are satellites derived from a ring-type intrachromosomal translocation.

Child↗