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K Pratt

Publications and source records attributed to K Pratt.

At least 19 recordsLinked to original sources
PubMed2005

Aspects of design, structure, performance and operation of reed beds--eight years' experience in northeastern New South Wales, Australia.

Reed beds (horizontal subsurface flow constructed wetlands) have been employed as secondary treatment devices in on-site and decentralised wastewater management systems in the northeast of the Australian state of New South Wales (NSW) for over a decade. This paper summarises some of the practical and research findings that have come to light in that time. Experience with various aspects of reed bed structure is discussed. A study of the evaporative performance of four small beds planted with Phragmites australis yielded an annual crop factor of 2.6. A total of 28 studies on reed beds treating a variety of commonly encountered wastewater streams yielded the following mean pollutant removal efficiencies: total suspended solids (TSS) 83%, biochemical oxygen demand (BOD) 81%, total nitrogen (TN) 57%, total phosphorus (TP) 35% and faecal coliforms (FC) 1.9 logs. The reed bed is becoming the preferred on-site technology for removing TN and BOD and polishing TSS from primary settled domestic wastewater. Sizing beds for a residence time of approximately five days has become standard practice. A study of six reed beds found six different species of earthworm present, mainly Perionyx excavatus (Indian Blue). A mesocosm experiment subsequently showed that the worms were translocating clogging material from the substrate interstices to the surface of the bed thereby indicating a possible method for prolonging reed bed life.

Animals↗
PubMed2000

Regulation of somatic growth by the p160 coactivator p/CIP.

A family of p160 coactivators was initially identified based on ligand-dependent interactions with nuclear receptors and thought to function, in part, by recruiting CREB-binding protein/p300 to several classes of transcription factors. One of the p160 factors, p/CIP/AIB1, often amplified and overexpressed in breast cancer, also exhibits particularly strong interaction with CREB-binding protein/p300. In this manuscript, we report that p/CIP, which exhibits regulated transfer from cytoplasm to nucleus, is required for normal somatic growth from embryonic day 13.5 through maturity. Our data suggest that a short stature phenotype of p/CIP gene-deleted mice reflect both altered regulation of insulin-like growth factor-1 (IGF-1) gene expression in specific tissues and a cell-autonomous defect of response to IGF-1, including ineffective transcriptional activities by several classes of regulated transcription factors under specific conditions. The actions of p/CIP are therefore required for full expression of a subset of genes critical for regulating physiological patterns of somatic growth in mammals.

Animals↗
PubMed2000

Up-regulation of beta-chemokines and down-modulation of CCR5 co-receptors inhibit simian immunodeficiency virus transmission in non-human primates.

A non-cognate mechanism of protection against human immunodeficiency virus-1 (HIV-1) infection involves up-regulation of beta-chemokines, which bind and may down-modulate the CCR5 co-receptors, thereby preventing transmission of M-tropic HIV-1. The objective of this investigation was to evaluate this mechanism in vivo in non-human primates. Rhesus macaques were immunized by a modified targeted lymph nodes (TLN) route with recombinant simian immunodeficiency virus (SIV) glycoprotein 120 (gp120) and p27 in alum, and adsorbed recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) with either interleukin (IL)-2 or IL-4. Immunization induced significant increases in the concentrations of CD8 cell-derived suppressor factor (CD8-SF), regulated on activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and down-modulation of the proportion of cells expressing CCR5 (r = 0.737, P<0.05). The macaques were then challenged with SIVmac 220 by the rectal mucosal route. The plasma SIVmac RNA showed a significant inverse correlation with the CD8-SF or the concentration of the three beta-chemokines (r = 0.831 and 0.824, P<0.01), but a positive correlation between the proportion of CCR5+ cells and SIVmac RNA (r = 0.613, P = 0.05). These results demonstrate for the first time in vivo that immunization up-regulates beta-chemokines, which may down-modulate CCR5 co-receptors, and both functions are significantly correlated with the viral load. Hence, the non-cognate beta-chemokine-CCR5 mechanism should be considered as complementary to specific immunity in vaccination against HIV.

Animals↗
PubMed1998

High affinity glutamate transport in rat cortical neurons in culture.

We assayed glutamate transport activity in cultures of rat cortical neurons containing < 0.2% astrocytes. Using [3H]L-glutamate as the tracer, sodium-dependent high affinity glutamate transport was demonstrated [K(m) = 17.2 +/- 2.4 microM; Vmax = 3.3 +/- 0.32 nmol/mg of protein/min (n = 5)]. Dihydrokainate (1 mM) inhibited uptake of radioactivity by 88 +/- 3% and had a Ki value of 65 +/- 7 microM. L-alpha-Aminoadipate (1 mM) inhibited uptake by only 25 +/- 4%. L-trans-2,4-Pyrrolidine dicarboxylate, L-serine-O-sulfate, and kainate potently inhibited transport activity with Ki values of 5.1 +/- 0.3, 56 +/- 6, and 103 +/- 9 microM, respectively (n = 3). Voltage-clamp studies of GLT1-expressing oocytes showed that, as in cortical neurons, glutamate transport was not inhibited by L-alpha-aminoadipate. Dihydrokainate was a potent inhibitor (Ki = 8 +/- 1 microM), and L-serine-O-sulfate produced a GLT1-mediated current with a K(m) value of 312 +/- 33 microM. Immunoblot analysis showed that neuronal cultures express excitatory amino acid carrier 1 (EAAC1), shown previously to be relatively insensitive to dihydrokainate, plus a trace amount of GLT1, but no GLAST. These studies establish that a major component of the glutamate transport activity of cortical neurons is dihydrokainate sensitive and distinct from the previously recognized neuronal transporter excitatory amino acid carrier 1.

2-Aminoadipic Acid↗
PubMed1995

Plasma and cerebrospinal fluid concentrations of 4-aminopyridine following intravenous injection and metered intrathecal delivery in canines.

Potassium channel blockade by 4-aminopyridine (4-AP) has been shown to initiate modest levels of functional recovery in spinal-injured dogs and people following intravenous administration; however, the relevant central nervous system (CNS) concentration mediating these effects is not known. We have determined the concentrations of 4-aminopyridine in plasma and cerebrospinal fluid following intravenous administration (0.5 mg/kg) in large (> 22 kg) dogs, using liquid column chromatography. Plasma levels are initially high (> 1 microgram/mL) and fall rapidly to levels less than 100 ng/mL by about 2 h postinjection. A characteristic secondary peak in plasma 4-AP is observed at about 1 h postinjection. Corresponding concentrations of 4-AP in CSF were relatively stable for nearly 2 h, never exceeding (as a mean) 50 ng/mL within the first 2 h postinjection. We suggest behavioral recovery in clinical cases of spinal cord injury in both dogs and humans is mediated by such low (< 50 ng/mL) concentrations of 4-AP bathing the lesion. Since the adverse side effects that accompany IV administration of the drug limit its potential clinical usefulness, we have evaluated the feasibility of an alternate route of administration, continuous metered delivery of 4-AP into the spinal cord's subarachnoid space. This is accomplished by using a surgically implantable pump and delivery catheter. The pump itself can be interrogated, and is fully programmable, by noninvasive telemetry. Intrathecal delivery rates of between 1 and 60 micrograms of 4-AP per hour never produced detectable levels of the drug in plasma or cervically sampled CSF in dogs independent of the amount or duration of infusion (hours to days). The levels of 4-AP in lumbar samples of CSF near the lumbar delivery site suggest a very steep gradient of the drug, with local concentrations easily reaching 1 microgram/mL or higher (10- to 20-fold higher than can be safely produced by IV administration). The most frequent adverse reaction to intrathecal 4-AP delivery was a mild hindlimb tremor, fully reversible following reduction in the rate of drug delivery or termination of delivery. This route of drug administration relative to clinical spinal cord injury is discussed.

4-Aminopyridine↗
PubMed1994

Teachers' perceptions of maladaptive behaviour in Lebanese refugee children.

Research on the psychological status of children who are refugees from war has led to varying results. Children from war conditions or who have been subject to evacuation have been shown to have relatively low levels of disturbed behaviour, have internalising symptoms of anxiety or depression, display behaviour with aggressive features, and suffer slight psychological disturbance, depending on their caretakers' response to the stressful experience. Based on the contrasting evidence and observations within an inner Melbourne Muslim school, this study aimed to determine whether more behaviour problems existed in Muslim children from Lebanese families. Compared with other war refugee Muslim immigrant children, Lebanese children were not found to be more aggressive, but were more anxious. Lebanese males displayed more inattentive behaviour at school than non-Lebanese males. Sex differences were found in adaptive functioning within Lebanese and non-Lebanese groups. Differences in school performance and adaptive functioning were found between Lebanese and normative samples when males and females were analysed separately. These results are discussed in the context of teacher expectations and perceptions of culturally acceptable behaviour.

Adaptation, Psychological↗
PubMed1994

The "88% saturation test": a simple lung function test for young children.

OBJECTIVE: The 88% saturation test (88%-SAT) was developed as an alternative to standard spirometry for those young children unable to perform standard forced expiratory maneuvers. In adults, this test revealed rapid desaturation in those persons with a history of asthma when compared with healthy control subjects. Similar findings in children were tested. SETTING: Tertiary care hospital. PATIENTS: Thirty-three former premature infants (28.3 +/- 2.3 weeks gestation), aged 5 to 7 years, who were participating in a follow-up study, were enrolled in this study. DESIGN: The study compared the 88%-SAT with standard spirometry and respiratory health characteristics ascertained through a parental questionnaire. The 88%-SAT consists of continuous measurement of hemoglobin saturation by pulse oximetry (SaO2) while the subject breathes a nonhumidified 12% oxygen and nitrogen mixture for 10 minutes or until SaO2 decreases to 88%, whichever occurs first. Abnormal 88%-SAT was defined as a decrease of SaO2 to 88% within the 10-minute period, and abnormal spirometry was defined using standardized values. RESULTS: Of the 20 children who successfully completed both spirometry and the 88%-SAT, 10 had normal spirometry results and did not desaturate to 88%, and 5 had abnormal spirometry and 88%-SAT results. Four children did not desaturate during the 88%-SAT, but had abnormal spirometry results, and one child had abnormal 88%-SAT results, but normal spirometry. Ten additional children completed the 88%-SAT, but not standard spirometry. Three children were unable to complete either test. Of those 30 children tested, 7 (23%) had a history of reactive airways disease, and all 7 had abnormal 88%-SAT results. The 88%-SAT had greater sensitivity (100% vs 75%) and specificity (87% vs 63%) than spirometry in identifying children with known reactive airways disease. The mean McCarthy general cognitive index (GCI) of the group performing both spirometry and the 88%-SAT (n = 20) achieved a mean (+/- SD) GCI of 96.2 +/- 16.7, and the group (n = 30) that completed the 88%-SAT had a mean (+/- SD) GCI of 75.2 +/- 26.3 (chi 2 P < .012). The 10 children able to perform only the 88%-SAT had a mean GCI (+/- SD) of 72.8 +/- 26.9, and the 3 children unable to perform either test had a mean GCI (+/- SD) of 63 +/- 11. CONCLUSIONS: Our data suggest that the 88%-SAT may be more effective than spirometry for identifying reactive airways disease in young, uncooperative, or developmentally delayed children. The dry air of the hypoxic inspired gas may function as an airway challenge, leading to decreased oxygenation in patients with reactive airways.

Child↗
PubMed1993

A nuclear protein with enhanced binding to methylated Sp1 sites in the AIDS virus promoter.

We report here the discovery of HMBP, a protein in nuclei of human T-helper lymphocytes and other human cell types, which binds with enhanced affinity to a promoter element in the HIV-1 long terminal repeat when that element is methylated at CpGs, the target site of the human DNA methyltransferase. This promoter element contains three (degenerate) binding sites for Sp1, a general activator of transcription. Gel shift assays and footprinting experiments indicate that HMBP binding overlaps two of these methylated Sp1 sites. Although HMBP binds these methylated Sp1 sites, it does not bind consensus Sp1 sites. Competition studies, differences in binding site specificities, binding conditions, and, in some cases, chromatographic separation further distinguish HMBP from Sp1 and from each of four previously identified methylated-DNA binding proteins. HMBP binds hemimethylated DNA in a strand dependent manner. These binding characteristics suggest that HMBP may recognize newly replicated DNA and thereby play a role in differentiation. If HMBP is able to compete with Sp1 for binding at methylated, non-consensus Sp1 sites in vivo and repress transcription, it may play a role in AIDS latency.

Animals↗
PubMed1993

Synthesis, in vitro binding profile, and autoradiographic analysis of [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine, a highly potent and selective nonpeptide substance P receptor antagonist radioligand.

The synthesis of a highly potent and selective NK1 receptor antagonist radioligand, [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine (6a) is described. The in vitro binding pharmacology and autoradiographic distribution of 6a in guinea pig brain following peripheral administration are also reported.

Amino Acid Sequence↗
PubMed1993

Beryllium competitively inhibits brain myo-inositol monophosphatase, but unlike lithium does not enhance agonist-induced inositol phosphate accumulation.

Despite limiting side-effects, lithium is the drug of choice for the treatment of bipolar depression. Its action may be due, in part, to its ability to dampen phosphatidylinositol turnover by inhibiting myo-inositol monophosphatase. Beryllium has been identified as a potent inhibitor of partially purified myo-inositol monophosphatase isolated from rat brain (Ki = 150 nM), bovine brain (Ki = 35 nM), and from the human neuroblastoma cell line SK-N-SH (Ki = 85 nM). It is over three orders of magnitude more potent than LiCl (Ki = 0.5-1.2 mM). Kinetic analysis reveals that beryllium is a competitive inhibitor of myo-inositol monophosphatase, in contrast with lithium which is an uncompetitive inhibitor. Inhibition of exogenous [3H]inositol phosphate hydrolysis by beryllium (IC50 = 250-300 nM) was observed to the same maximal extent as that seen with lithium in permeabilized SK-N-SH cells, reflecting inhibition of cellular myo-inositol monophosphatase. However, in contrast with that observed with lithium, agonist-induced accumulation of inositol phosphate was not observed with beryllium in permeabilized and non-permeabilized SK-N-SH cells and in rat brain slices. Similar results were obtained in permeabilized SK-N-SH cells when GTP-gamma-S was used as an alternative stimulator of inositol phosphate accumulation. The disparity in the actions of beryllium and lithium suggest that either (1) selective inhibition of myo-inositol monophosphatase does not completely explain the action of lithium on the phosphatidylinositol cycle, or (2) that uncompetitive inhibition of myo-inositol monophosphatase is a necessary requirement to observe functional lithium mimetic activity.

Animals↗
PubMed1993

Overexpression of trypanosomal triosephosphate isomerase in Escherichia coli and characterisation of a dimer-interface mutant.

In this paper, the successful expression of trypanosomal triosephosphate isomerase (TIM) from Trypanosoma brucei brucei to high yield in Escherichia coli, using a T7-polymerase-based expression system, is described. Overexpressed trypanosomal TIM is fully active. The measured physicochemical properties of this recombinant TIM and TIM purified from trypanosomes are indistinguishable. Crystals of recombinant TIM have been grown in the presence of 2.4 M ammonium sulphate under the same conditions as for trypanosomally expressed TIM. The recombinant TIM crystal structure has been refined at 0.23 nm resolution; no differences were detected between this structure and the original crystal structure. A TIM mutant was made in which a unique dimer-interface histidine residue (His47) was changed into an asparagine. This variant ([H47N]TIM) could be expressed and purified to homogeneity by a procedure which was somewhat different from the purification of recombinant wild-type TIM. It is shown that the [H47N]TIM dimer is considerably less stable than wild-type trypanosomal TIM. The catalytic activity of [H47N]TIM is concentration dependent. The dilution-dependent inactivation is reversible. His47 is involved in a water-mediated hydrogen bond with Asp385 of the other subunit. The lower stability of the [H47N]TIM dimer implies that this water-mediated hydrogen bond is important for the stability of the TIM dimer.

Amino Acid Sequence↗
PubMed1993

Attitudes of medical students to HIV and AIDS.

OBJECTIVE--To assess the knowledge and attitudes of medical students to HIV/AIDS and whether attitudes correlate with knowledge and clinical experience. To determine if students felt adequately prepared to deal with medical and psychological aspects of HIV/AIDS. SUBJECTS AND METHODS--The subjects consisted of 190 London and 99 Cambridge medical students at the end of their genitourinary medicine attachment, plus 230 Cambridge medical students at the end of their second pre-clinical year. Between March 1991 and February 1992 all were asked to complete an anonymous questionnaire, covering factual knowledge and attitudes towards HIV/AIDS. MAIN RESULTS--Cambridge genitourinary medicine students, despite spending less time studying HIV infection than their London counterparts gave more correct answers to the factual questions, although this difference did not reach significance (52.4% vs. 47.5%, p = 0.14). One third of students believed that many health care workers were at high risk of acquiring HIV at work and one fifth thought doctors should have the right to refuse to treat people with HIV. Fourteen percent of Cambridge genitourinary medicine students indicated that most British people with HIV have only themselves to blame, by comparison with 4% of London students (p = 0.003). Thirty-nine per cent of Cambridge genitourinary medicine students expressed reluctance to care for someone with AIDS by comparison with 10% of London students (p = 0.0001). CONCLUSIONS--It is important that medical educators convey accurate information about HIV, including the actual risks posed by occupational exposure and try to ensure that medical students spend sufficient time seeing patients with HIV/AIDS during their training.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A randomized controlled trial of home exercise on the rheumatoid hand.

OBJECTIVE: To study differing home hand exercise interventions to determine effects on grip strength, and secondarily any immediate or short term effects on range of motion, pain, deformities, hand disease activity, and dexterity. METHODS: Randomized controlled trial of 12 weeks of home hand exercise performed for 10-20 min twice daily. Study exercise interventions were range of motion exercises, balanced resistive exercises, and range of motion plus balanced resistive exercises. RESULTS: Aside from transient, mild to moderate discomfort, exercises were well tolerated. Range of motion exercises were associated with improved right hand joint count. Range of motion plus balanced resistive exercises were associated with increased left hand dexterity. Home hand exercise (exercise groups combined) significantly increased left grip strength. CONCLUSIONS: Temporary use of home hand exercise has acceptable side effects and is an effective means of increasing grip strength.

Ambulatory Care↗
PubMed1992

Structure and expression of class II alpha genes in miniature swine.

Two overlapping genomic clones corresponding to the swine DRA class II gene were isolated and characterized. Restriction mapping and partial sequence data of the exon-containing fragments allowed identification and orientation of the five exons encoding the alpha chain. Two full length cDNA clones corresponding to the transcribed DRA gene from two different haplotypes of the swine MHC were sequenced. Nucleotide sequence alignments revealed that the two swine DRA cDNA were very similar and closely related to the human DRA equivalent. An additional glycosylation site, compared with those of human DRA, was found in the second external domain of the protein. Northern analyses showed that porcine DRA and DQA genes were the only two class II alpha genes expressed in the spleen, despite the presence of DPA and DZA genes in the genome. In addition to transfected cells expressing homologous pairs of alpha and beta chains from SLA-DR, stable transfectants expressing nonhomologous pairs of alpha and beta chains from DR and DQ loci were obtained, suggesting that such associations may contribute to the functional heterogeneity of class II products.

Animals↗
PubMed1992

Endothelin-3-induced microvascular incompetence and mitochondrial damage in rat myocardium.

1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer-perfused rat hearts were perfused with endothelin-3 (ET-3) in phosphate buffer. 2. ET-3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe. 3. These results indicate that ET-3 can substantially reduce microvascular perfusion in the heart and can also cause damage to the myocyte.

Animals↗
PubMed1990

Class II genes of miniature swine. IV. Characterization and expression of two allelic class II DQB cDNA clones.

Two cDNA clones coding for allelic miniature swine MHC class II Ag DQB chains have been isolated, characterized, and shown to be expressed after transfection into mouse fibroblasts. The two alleles differ at the nucleotide level by an overwhelming proportion of replacement substitutions, suggesting the influence of selection for polymorphism. Most of the resulting predicted amino acid replacements are in regions commonly polymorphic in mouse Ab and human DQB sequences, corresponding to the predicted Ag recognition site. Nucleotide and amino acid sequence comparisons to homologous mouse and human sequences show more similarity between swine and man than between either swine and mouse or man and mouse. This tendency is most pronounced when comparing the 3' untranslated regions. However, an examination of unique cross-species sharing of amino acid residues suggests a closer relationship between both man and miniature swine and man and mouse than between miniature swine and mouse. The simplest explanation we can envision for these findings is that the mouse DQB gene homologue (Ab) has been subject to a higher substitution rate than either swine or human DQB genes. An additional cytoplasmic exon expressed in mouse Ab gene products and in putative human DQB2 gene products is lacking in both swine and human DQB cDNA clones. Its absence suggests either that the expression of this exon in mouse Ab genes was activated after mammalian speciation or that the expression of this exon was independently inactivated in swine DQB and human DQB1 genes. Alternatively, the mouse Ab gene may be derived from the same primordial gene as human DQB2, whereas the pig DQB gene may be derived from the same primordial gene as the human DQB1 gene.

Alleles↗