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K Griffin

Publications and source records attributed to K Griffin.

At least 19 recordsLinked to original sources
PubMed2001

Overlapping expression of zebrafish T-brain-1 and eomesodermin during forebrain development.

T-box transcription factors are important determinants of embryonic cell fate and behaviour. Two T-box genes are expressed in the developing telencephalon of several vertebrate species, including amphibia, birds and mammals. Here we report the cloning of zebrafish T-brain-1 (tbr1) and eomesodermin (eom). As a prelude to genetic studies of neuro-ectodermal fate determination we studied their expression pattern during embryogenesis and early larval development. Eom is expressed in the presumptive telencephalon from around the 4-5 somite stage in bilaterally symmetric groups of cells; the number of positive cells increases dramatically with time and encompasses the entire dorsal telencephalon by the 22 somite stage. Tbr1 is expressed from the 18 somite stage in a subset of eom-expressing cells. By 24 hpf eom and tbr1 are expressed in largely overlapping domains in the dorsal telencephalon, tbr1 is expressed in postmitotic cells whereas eomes is also expressed in proliferative ventricular zone cells. Both genes are also found in a small domain of the diencephalon bordering the telencephalon. A detailed analysis of the expression of tbr1 and eom in the brain of 4 day old larvae shows that the two T-box genes are differentially expressed in various cell populations of the developing brain.

Amino Acid Sequence↗
PubMed2000

Stabilisation of Salmonella vaccine vectors by the induction of trehalose biosynthesis.

The growth of an aroA mutant of Salmonella typhimurium (SL3261) in minimal medium containing 0.5 M NaCl resulted in the intracellular accumulation of 2.2 micromol trehalose/mg total protein. The vacuum drying of these bacteria in the presence of trehalose allowed the recovery of 35% of the viable cells that were present before drying. In contrast, bacteria cultured in control medium accumulated 0.4 micromol trehalose/mg total protein and only 5% of the viable cells were recovered after vacuum drying with trehalose. Similar results were obtained when S. typhimurium SL3261, expressing the vaccine antigen (F1-antigen) of Yersinia pestis, was cultured in minimal medium with or without 0.5 M NaCl and dried in the presence of trehalose. Although these results indicate the potential for trehalose stabilisation of vaccine strains of S. typhimiurium, growth in minimal medium containing 0.5 M NaCl resulted in the loss of invasion competence of the bacteria.

Animals↗
PubMed2000

Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon.

Fibroblast growth factors (Fgfs) form a large family of secreted signalling proteins that have a wide variety of roles during embryonic development. Within the central nervous system (CNS) Fgf8 is implicated in patterning neural tissue adjacent to the midbrain-hindbrain boundary. However, the roles of Fgfs in CNS tissue rostral to the midbrain are less clear. Here we examine the patterning of the forebrain in zebrafish embryos that lack functional Fgf8/Ace. We find that Ace is required for the development of midline structures in the forebrain. In the absence of Ace activity, midline cells fail to adopt their normal morphology and exhibit altered patterns of gene expression. This disruption to midline tissue leads to severe commissural axon pathway defects, including misprojections from the eye to ectopic ipsilateral and contralateral targets. Ace is also required for the differentiation of the basal telencephalon and several populations of putative telencephalic neurons but not for overall regional patterning of forebrain derivatives. Finally, we show that ace expression co-localises with anterior neural plate cells that have previously been shown to have forebrain patterning activity. Removal of these cells leads to a failure in induction of ace expression indicating that loss of Ace activity may contribute to the phenotypes observed when anterior neural plate cells are ablated. However, as ace mutant neural plate cells still retain at least some inductive activity, then other signals must also be produced by the anterior margin of the neural plate.

Animals↗
PubMed1999

Renal injury and salt-sensitive hypertension after exposure to catecholamines.

We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor beta by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r(2)=0.99) and the degree of BP lability (r(2)=0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r(2)=0.74), and the final glomerular filtration rate (r(2)=0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged.

Adrenergic alpha-Agonists↗
PubMed1998

Goal-directed transesophageal echocardiography performed by intensivists to assess left ventricular function: comparison with pulmonary artery catheterization.

OBJECTIVES: Transesophageal echocardiography (TEE) is a valuable procedure for assessing left ventricular (LV) function, but it has not been widely applied in critical care because of the limited number of intensivists who are trained in echocardiography. This prospective study was designed to evaluate the feasibility of training intensivists to perform a goal-directed, limited-scope TEE to assess LV function in critically ill patients using a pediatric monoplane TEE probe. A secondary goal was to compare the usefulness of the TEE data with that of data obtained by a simultaneous pulmonary artery catheter (PAC). DESIGN: Prospective, blinded. SETTING: University teaching hospital. PARTICIPANTS: One hundred consecutive, intubated, intensive care unit patients. INTERVENTIONS: Five surgical intensivists with no previous background in echocardiography were trained under the supervision of two cardiologists to perform limited-scope TEE using a monoplane pediatric probe. One intensivist (A) reviewed the PAC data and recorded a diagnostic impression and therapeutic plan. A second intensivist (B), blinded to the PAC data, then performed TEE to determine cardiac volume, LV wall thickness, and LV global and regional wall motion. Intensivists A and B reviewed the data from both PAC and TEE, and intensivist A then formulated a new diagnosis and therapeutic plan. MEASUREMENTS AND MAIN RESULTS: Intensivists performed 48 TEE examinations under direct supervision of a cardiologist, and 52 without supervision, but reviewed poststudy. The average duration of TEE was 12 +/- 7 minutes. The intensivists' interpretations of TEE data were deemed correct in 93% of cases for LV wall thickness, 87% for intracardiac volume status, 81% for regional LV wall motion abnormalities, and 77% for global LV function. When the TEE and PAC technologies were compared, it was found that the TEE data disagreed with the PAC evaluation of intracardiac volume in 55% of cases and with the PAC assessment of myocardial function in 39% of cases. The post-PAC therapeutic recommendations were different from the post-TEE therapeutic recommendations in 58% of patients. CONCLUSIONS: Training intensivists in limited-scope, goal-directed TEE, using a pediatric monoplane probe to evaluate LV function, can be done rapidly and safely, and yield data pertinent to management of critically ill patients even in the early stages of skill acquisition.

Adult↗
PubMed1998

"Nothing about me, without me": participatory action research with self-help/mutual aid organizations for psychiatric consumer/survivors.

Participatory action research with self-help/mutual aid organizations for psychiatric consumer/survivors is reviewed. We begin by tracing the origins of and defining both participatory action research and self-help/mutual aid. In so doing, the degree of correspondence between the assumptions/values of participatory action research and those of self-help/mutual aid for psychiatric consumer/survivors is examined. We argue that participatory action research and self-help/mutual aid share four values in common: (a) empowerment, (b) supportive relationships, (c) social change, and (d) learning as an ongoing process. Next, selected examples of participatory action research with psychiatric consumer/survivor-controlled self-help/mutual aid organizations which illustrate these shared values are provided. We conclude with recommendations of how the key values can be promoted in both the methodological and substantive aspects of future participatory action research with self-help/mutual aid organizations for psychiatric consumer/survivors.

Humans↗
PubMed1998

Miscarriage.

Explore the source record for details and available documents.

Abortion, Spontaneous↗
PubMed1997

Thermodilution cardiac output measurement during simultaneous volume infusion through the venous infusion port of the pulmonary artery catheter.

OBJECTIVE: To determine the effect on thermodilution cardiac output (TDCO) measurements of continuous volume infusion through the right atrial venous infusion port of the pulmonary artery catheter. DESIGN: Prospective, blinded, randomly allocated crossover. SETTING: Surgical intensive care unit in a university hospital. PARTICIPANTS: Forty-nine hemodynamically stable patients between the ages of 43 and 84 in the intensive care unit and with a pulmonary artery catheter in place. INTERVENTIONS: Each patient received two room-temperature infusions (250 or 500 mL/hr) of 5% dextrose. Consecutive TDCO measurements were taken during each infusion and during a control period (no infusion). The sequence of infusion rates and control period was randomly determined. At both infusion rates, most patients exhibited a decrease in TDCO measurement of between 0.1 and 3.0 L/min. Although some patients exhibited an increase in measured TDCO, this increase was primarily between 0.1 and 0.5 L/min. MEASUREMENTS AND MAIN RESULTS: The mean TDCO measurements at infusion rates of 0, 250, and 500 mL/hr were 6.77, 6.49, and 6.47 L/min, respectively. Measured TDCO decreased on volume infusion by 0.3 +/- 0.13 L/min (mean +/- SD, p < 0.02). CONCLUSION: Rapid continuous infusion of fluid through the venous infusion port of the pulmonary artery catheter significantly limits the accuracy of simultaneous TDCO measurements. Optimally, TDCO measurements should be avoided during rapid volume infusion.

Adult↗
PubMed1997

Medical planning--casualty treatment times at first and second line.

OBJECTIVE: To establish the average time taken to treat a seriously wounded battle casualty at First and Second Line (Role 1 and Role 2) according to the British Army Casualty Treatment Regimes under simulated conditions, and, in doing so, to assess whether British medical facilities are capable of meeting the medical planning directives of the Allied Command Europe Rapid Reaction Corps (ARRC). DESIGN: A casualty evacuation exercise, using standard ARRC medical planning data, deploying the war establishment of personnel and equipment of an armoured Battle Group Regimental Aid Post (RAP) and an armoured Field Ambulance. SUBJECTS: 200 simulated casualties, using 120 healthy soldiers dressed in expendable clothing and carrying a description of their injuries and clinical status. MAIN OUTCOME MEASURED: The time taken to treat simulated seriously wounded casualties at Role 1, the RAP and at Role 2, the Field Ambulance Dressing Station (DS). RESULTS: The mean treatment time at Role 1 was 28 minutes and at Role 2 was 17 minutes. CONCLUSION: Within the (large) caveat of simulation, as presently configured, the Field Ambulance (DS) is well able to cope with the casualty load expected of it by ARRC medical planners but the RAP of the armoured Battle Group is not.

Ambulances↗
PubMed1996

Biochemical analysis of mutant T7 primase/helicase proteins defective in DNA binding, nucleotide hydrolysis, and the coupling of hydrolysis with DNA unwinding.

We characterized nine helicase-deficient mutants of bacteriophage T7 helicase-primase protein (4A') prepared by random mutagenesis as reported in the accompanying paper (Rosenberg, A. H., Griffin, K., Washington, M. T., Patel, S. S., and Studier, F. W. (1996) J. Biol. Chem. 271, 26819-26824). Mutants were selected from each of the helicase-conserved motifs for detailed analysis to understand better their function. In agreement with the in vivo results, the mutants were defective in helicase activity but were active in primase function. dTTP hydrolysis, DNA binding, and hexamer formation were examined. Three classes of defective mutants were observed. Group A mutants (E348K, D424N, and S496F), defective in dTTP hydrolysis, lie in motifs 1a, 2, and 4 and are possibly involved in NTP binding/hydrolysis. Group B mutants (R487C and G488D), defective in DNA binding, lie in motif 4 and are responsible directly or indirectly for DNA binding. Group C mutants (G116D, A257T, S345F, and G451E) were not defective in any of the activities except the helicase function. These mutants, scattered throughout the protein, appear defective in coupling dTTPase activity to helicase function. Secondary structural predictions of 4A' and DnaB helicases resemble the known structures of RecA and F1-ATPase enzymes. Alignment shows a striking correlation in the positions of the amino acids that interact with NTP and DNA.

Amino Acid Sequence↗
PubMed1996

Selection, identification, and genetic analysis of random mutants in the cloned primase/helicase gene of bacteriophage T7.

T7 gene 4 specifies two overlapping proteins 4A, a 566-amino acid primase/helicase, and 4B, a 503-amino acid helicase whose initiation codon is the 64th codon of the 4A protein. The 4A' gene, which has a leucine codon replacing the 4B initiation codon, specifies a single 566-amino acid protein that can provide the primase and helicase functions required for normal T7 growth. We selected N-methyl-N'-nitro-N-nitrosoguanidine mutants in the cloned 4A' gene that no longer support the growth of a phage that completely lacks gene 4. Genetic mapping of the 76 mutations found them to be distributed throughout the protein, including both the N-terminal and C-terminal halves of the molecule thought to represent primase and helicase domains, respectively. Complementation tests with partially and completely defective phage showed that all but five of the mutants lacked helicase function but retained primase function. The other five, which lacked both functions, all made short proteins, including one missing only 60 amino acids. No mutations lacked only primase function, and none mapped within the first 105 amino acids, which includes the 63-amino acid region unique to 4A that contains elements required to recognize primase sites. Forty-six mutations were sequenced and included 27 missense mutations affecting 25 amino acids. Many mutations in the N-terminal half of the protein affected its solubility in cell extracts. Mutations in the C-terminal half clustered in or near five helicase consensus sequences. Biochemical analysis of nine of the mutant proteins is described in the accompanying paper (Washington, M. T., Rosenberg, A. H., Griffin, K., Studier, F. W., and Patel, S. S. (1996) J. Biol. Chem. 271, 26825-26834).

Amino Acid Sequence↗
PubMed1995

Adherence to very-low-fat diet by a group of cardiac rehabilitation patients in the rural southeastern United States.

This 28-week observational study measured adherence to and acceptability of the diet and nutrition component of an Ornish-type program among patients in a rural southern setting. Ten volunteers followed a very-low-fat (10% of energy), total vegetarian diet and participated in a program of exercise, stress management, and group support. Patients made significant dietary changes and found the diet "acceptable." Three patients consumed less than 10% of energy from fat and two additional patients consumed less than 20% of energy from fat. Eighty-five percent of the patients' meals adhered to a near vegetarian diet. Weight loss ranged from 0.1 to 11.7 kg (0.25 to 26 lb). Lipid values were unchanged. At 12 months, without the benefit of the structured program, one patient reported 100%, six reported 85%, and two reported 50% adherence to the dietary principles. We conclude that motivated patients with coronary artery disease can follow a very-low-fat, near vegetarian diet but experience difficulty without a structured program.

Coronary Disease↗
PubMed1995

Analysis of FGF function in normal and no tail zebrafish embryos reveals separate mechanisms for formation of the trunk and the tail.

To analyse the roles of FGF activity and brachyury during gastrulation we have directly compared the consequences of inhibition of FGF-receptor signalling with the phenotype of the zebrafish brachyury mutant, no tail (ntl). We show that expression of ntl is regulated by FGF and that inhibition of FGF receptor-signalling leads to complete loss of the trunk and tail. Since the ntl mutant lacks the tail and notochord but has an otherwise normal trunk, this demonstrates that trunk development is dependent upon an unidentified gene, or set of genes, referred to as no trunk (ntk) which is regulated by FGF. We propose a model to explain the FGF-dependent regulation of ntl and ntk that accounts for the above phenotypes. Consistent with this model, over-expression of eFGF led to suppression of anterior fates and development of trunk and tail derivatives only. In addition, widespread activation of convergence and extension movements resulted in the formation of multiple axis-like structures. Expression of eve1 and cad1 was also regulated by FGF activity, suggesting that during gastrulation FGF activity is normally restricted to the germ ring where these genes, and ntl, are expressed. Taken together these data suggest that the germ ring acts as a posteriorising centre during AP patterning, mediated by FGF activity in this tissue.

Animals↗
PubMed1989

The benzodiazepine receptor ligands RO 5-4864 and RO 15-1788 do not block the inhibition of PAF-induced platelet aggregation seen with the hetrazepine WEB2086.

The hypothesis was tested that the hetrazepine WEB 2086 acts as an inhibitor of PAF-induced platelet aggregation via interaction with the platelet benzodiazepine receptor(BDZR). WEB 2086 is a potent inhibitor of rabbit platelet aggregation and ATP secretion induced by 370 nM PAF. The two BDZR ligands RO 5-4864 and RO 15-1788 (7-96 microM) are inactive as PAF antagonists. When platelets were pretreated with either BDZR ligand, and then exposed to various concentrations of WEB 2086, there was no alteration of the dose-response relationship of the hetrazepine on PAF-induced aggregation, as reflected by threshold concentration, ED50, or maximum inhibition seen with WEB 2086. Pretreatment of platelets with the BDZR ligands also failed to block the inhibitory action of WEB 2086 on PAF-induced ATP release. The data are consistent with the notion that WEB 2086 acts as a PAF antagonist through its action at a specific PAF receptor, and is dissociated from, and independent of, interaction with the benzodiazepine receptor.

Adenosine Triphosphate↗
PubMed1989

Activity of clavulanate-potentiated penicillins against methicillin-resistant Staphylococcus aureus.

It has been suggested that combinations of penicillins with clavulanate may be useful in treatment of infections by methicillin-resistant strains of Staphylococcus aureus (MRSA). To determine the potentiating effect of clavulanate on the antibacterial activity of penicillins, we studied MRSA in vitro by an agar-dilution method. A total of 124 clinical isolates of MRSA were tested for sensitivity to benzylpenicillin, amoxycillin, and ticarcillin alone and in combination with 1.25, 2.5, 5.0 and 10.0 mg/l of clavulanate. Most of the strains were not typable by the international reference set of bacteriophages of human staphylococci but showed typical properties of nosocomial strains. A reduction in the MIC90 of benzylpenicillin and amoxycillin to 25 mg/l was seen in the presence of 2.5 mg/l of clavulanate. The effect was less pronounced with ticarcillin. In spite of some increase in the susceptibility of MRSA to benzylpenicillin and amoxycillin produced by clavulanate, these combinations seem to be inappropriate in infections due to MRSA.

Clavulanic Acids↗
PubMed1988

Characterization of the rec-1 gene of Haemophilus influenzae and behavior of the gene in Escherichia coli.

The rec-1 gene of Haemophilus influenzae was cloned into a shuttle vector that replicates in Escherichia coli as well as in H. influenzae. The plasmid, called pRec1, complemented the defects of a rec-1 mutant in repair of UV damage, transformation, and ability of prophage to be induced by UV radiation. Although UV resistance and recombination were caused by pRec1 in E. coli recA mutants, UV induction of lambda and UV mutagenesis were not. We suggest that the ability of the H. influenzae Rec-1 protein to cause cleavage of repressors but not the recombinase function differs from that of the E. coli RecA protein.

Bacterial Proteins↗