Biomedical subjects

D Cox

Publications and source records attributed to D Cox.

At least 37 records · Page 2Linked to original sources

PubMed2001

Driving mishaps and hypoglycaemia: risk and prevention.

Driving is a complex, multi-task activity that can be affected by cognitive impairment resulting from episodes of severe hypoglycaemia. Intensive insulin therapy increases the likelihood of severe hypoglycaemia but there have been few studies examining effects on driving skills. A survey carried out recently indicated that patients with type 1 diabetes had twice the incidence of driving accidents than their non-diabetic spouses or patients with type 2 diabetes. The motor accidents were associated with more frequent low blood glucose while driving and less frequent self-monitoring. In driving simulation tests it was found that driving has an intrinsic metabolic demand that can contribute to hypoglycaemia. Driving performance began to deteriorate at around 3.6 mmol/l but drivers frequently did not recognise and failed to treat the hypoglycaemia. Those who did self-treat had more driving relevant symptoms and less neuroglycopenia quantified by EEG alpha-theta differences. Patients should be recommended not to begin driving if blood glucose is below 4.5 mmol/l and should not continue to drive if they suspect that blood glucose has fallen below 4 mmol/l while driving. If hypoglycaemia is suspected patients should immediately pull off the road, measure blood glucose if possible, treat themselves as necessary and not resume driving until glucose and cognitive-motor function return to normal. The problems of driving and hypoglycaemia should be discussed with patients with diabetes and behavioural interventions instigated. To this end, Blood Glucose Awareness Training (BGAT) and Hypoglycaemia Anticipation, Awareness and Treatment Training (HAATT) have been developed and shown to markedly reduce incidence of driving mishaps.

Accidents, Traffic↗

PubMed2000

Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes.

OBJECTIVES: The study was done to determine the role of partial agonist activity in the lack of effectiveness of the oral GPIIb/IIIa antagonist orbofiban. BACKGROUND: Orbofiban, an oral GPIIb/IIIa antagonist, was found to increase the mortality of patients with acute coronary syndromes (ACS) in the OPUS-TIMI-16 trial, despite the fact that it is a very potent anti-platelet agent and that IV agents have proven very effective. METHODS: Patients (n = 520) with ACS were randomized to orbofiban 30 mg, 40 mg or 50 mg twice daily or 50 mg once daily or placebo. Platelet activity was assessed in 175 patients by examining GPIIb/IIIa receptor conformation, expression of CD63 antigen, and platelet aggregation. RESULTS: Plasma concentrations of orbofiban at the highest dose (74 +/- 6 ng/ml peak, 61 +/- 5 ng/ml trough) exceeded the IC50 for platelet aggregation to adenosine diphosphate (ADP) (29 +/- 6 ng/ml) and thrombin-activating peptide (61 +/- 18 ng/ml). Orbofiban induced a conformational change in GPIIb/IIIa detected as the displacement of the monoclonal antibody mAb2; such conformational changes have been linked to partial agonist activity. Consistent with this, platelet expression of CD63 ex vivo was significantly increased at five time points during the study. In vitro, orbofiban increased platelet aggregation to a submaximal concentration of epinephrine (67 +/- 19% vs. 27 +/- 9%, n = 5) and increased thromboxane formation when the platelet GPIIb/IIIa were clustered using monoclonal antibodies to the receptor. CONCLUSIONS: Orbofiban is both an antagonist and a partial agonist of platelet GPIIb/IIIa. At low concentrations of the drug, this partial agonist activity may enhance platelet aggregation. Along with suboptimal plasma drug levels, these findings may help explain the lack of efficacy seen with orbofiban in patients with ACS.

Acute Disease↗

PubMed2000

Peptide and peptide mimetic inhibitors of antigen presentation by HLA-DR class II MHC molecules. Design, structure-activity relationships, and X-ray crystal structures.

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.

Antigen Presentation↗

PubMed2000

A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis.

Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio-macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes. Expression of Rab11 25N, a GTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(gamma)R-mediated phagocytosis, where Fc(gamma)R is the receptor for the Fc portion of IgG. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.

3T3 Cells↗

PubMed2000

Rac1 and Cdc42 are required for phagocytosis, but not NF-kappaB-dependent gene expression, in macrophages challenged with Pseudomonas aeruginosa.

Macrophages respond to Gram-negative bacterial pathogens by phagocytosis and pro-inflammatory gene expression. These responses may require GTPases that have been implicated in cytoskeletal alterations and activation of NF-kappaB. To determine the role of Rac1 and Cdc42 in signal transduction events triggered by Pseudomonas aeruginosa, we expressed GTP binding-deficient alleles of Rac1 or Cdc42, or Chim-GAP, a Rac1/Cdc42-specific GTPase-activating protein domain, in a subline of RAW 264.7 cells, and challenged the transfected cells with a laboratory strain of P. aeruginosa, PAO1. Expression of Rac1 N17, Cdc42 N17, or Chim-GAP led to a marked reduction of phagocytosis. In contrast, nuclear translocation of p65 NF-kappaB was unaffected by expression of the same constructs. Incubation of macrophages with PAO1 led to NF-kappaB-dependent expression of inducible nitric-oxide synthase, COX-2, and tumor necrosis factor-alpha, which was unaffected by inhibition of Rac1 or Cdc42 function. Isogenic strains of PAO1 that lacked surface adhesins were poorly ingested; however, they induced pro-inflammatory gene expression with an efficiency equal to that of PAO1. These results indicate that the signal transduction events leading to phagocytosis and pro-inflammatory protein expression are distinct. Rac1 and Cdc42 serve as effectors of phagocytosis, but not NF-kappaB-dependent gene expression, in the macrophage response to P. aeruginosa.

Animals↗

PubMed2000

Suppression of the humoral immune response of Atlantic salmon, Salmo salar L. by the 64 kDa serine protease of Aeromonas salmonicida.

Bacteria-free supernatants of broth cultures of Aeromonas salmonicida inhibited the humoral immune response, but not the cell-mediated immune response, of Atlantic salmon to bacteriophage MS2. The immunosuppressive factor was the 64 kDa serine protease secreted by A. salmonicida. The suppressive activity was not due to degradation of epitopes of MS2, and although serine protease degraded the heavy chain of salmon IgM in vitro there was no evidence for significant degradation in vivo. The principal lethal toxin of A. salmonicida, the glycerophospholipid: cholesterol acyltransferase did not inhibit the immune response of salmon.

Aeromonas↗

PubMed2000

Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations.

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.

Adult↗

PubMed2000

Long-term efficacy and safety of oral Viagra (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal.

The long-term efficacy and safety of oral Viagra (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10-100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to placebo or continued treatment with sildenafil. Sildenafil was taken as needed (not more than once daily) approximately 1 h prior to sexual activity. The main outcome measures were a global efficacy question, a sexual function questionnaire, an event log of erections, and adverse event recording. In the open-label phase, 200 of 216 patients (93%) reported improved erections with sildenafil; 28 patients (12%) discontinued treatment. In the double-blind phase, the significant improvements in the frequency and duration of erections were maintained in the sildenafil group but returned to pre-treatment values in patients on placebo (P values < 0.0001 versus placebo). The most frequent adverse events in the sildenafil group during the double-blind phase were flushing (7%), headache (6%), and dyspepsia (5%). Of the 192 patients enrolled in the 1-y extension, 90% completed the study; only two patients (1%) were withdrawn due to lack of efficacy. In men with ED of psychogenic or mixed aetiology, oral sildenafil is effective and well-tolerated both at the initiation of therapy and during long-term treatment. For most patients, sildenafil treatment must be continued for improvements in erectile function to be maintained.

Adolescent↗

PubMed2000

Hospitals without walls: a journey through the health-care system.

The paper describes aspects of a journey through the health-care system following a domestic accident. The journey commenced in the accident and emergency department and, over a 3 month period, traversed the operating theatre, intensive care and an orthopaedic ward before moving into a Hospital in the Home programme and community health and district nursing services. The paper explores the experiences of the accident victim, a 56-year-old man, and his wife who is an experienced nurse and university lecturer. The paper supports the 'seamless delivery' concept of integrated care while, at the same time, sounding notes of caution. The principal messages in this paper are about the relationships that nurses build with patients and their families over long periods of care, the paradoxical sense of 'outsideness' that can occur when the home becomes medicalized and the importance of the home as a healing environment.

Accidents, Home↗

PubMed2000

Effects of lactate-buffered and lactate-free dialysate in CAVHD patients with and without liver dysfunction.

BACKGROUND: Continuous modalities of renal replacement deplete patients of bicarbonate, which is traditionally replaced indirectly by lactate in dialysate or replacement fluids. We have compared a new lactate-free dialysate (unbuffered dialysate with separate bicarbonate replacement of dialytic bicarbonate loss) with standard lactate-buffered dialysate in terms of acid-base control, lactate accumulation, and hemodynamic stability in patients undergoing continuous renal replacement therapy in an intensive care unit. METHODS: A nonrandomized crossover cohort study involving 54 patients with multi-organ failure (of whom 19 had significant hepatic dysfunction) was performed. All patients completed 24-hour continuous hemodiafiltration against both lactate-buffered and lactate-free dialysate. Arterial pH, blood gases, bicarbonate, and lactate, venous sodium, blood pressure, and inotrope requirements were measured before and at six hourly intervals during the first 24 hours of dialysis against each dialysate. RESULTS: Lactate-free dialysate provided more rapid control of acidosis than lactate buffered with less total administration of buffer than that given during the lactate-buffered period (total mmol bicarbonate vs. total mmol lactate + bicarbonate). Lactate accumulation was slight in both periods, but was higher during lactate-buffered continuous venovenous hemodiafiltration (CVVHD). The mean arterial pressure rose during lactate-free dialysis with decreased inotrope doses and fell during lactate-buffered dialysis with increased inotrope requirement. Results in patients with liver dysfunction were not significantly different from those without it. CONCLUSIONS: Over the time scale of 24 hours, lactate derived from continuous dialysis circuits is efficiently cleared from the blood of most patients with multi-organ failure, but with less effect on systemic acidosis than is produced by equivalent amounts of bicarbonate.

APACHE↗

PubMed2000

The expression of Myf5 in the developing mouse embryo is controlled by discrete and dispersed enhancers specific for particular populations of skeletal muscle precursors.

The development of skeletal muscle in vertebrate embryos is controlled by a transcriptional cascade that includes the four myogenic regulatory factors Myf5, Myogenin, MRF4 and MyoD. In the mouse embryo, Myf5 is the first of these factors to be expressed and mutational analyses suggest that this protein acts early in the process of commitment to the skeletal muscle fate. We have therefore analysed the regulation of Myf5 gene expression using transgenic technology and find that its control is markedly different from that of the other two myogenic regulatory factor genes previously analysed, Myogenin and MyoD. We show that Myf5 is regulated through a number of distinct and discrete enhancers, dispersed throughout 14 kb spanning the MRF4/Myf5 locus, each of which drives reporter gene expression in a particular subset of skeletal muscle precursors. This region includes four separate enhancers controlling expression in the epaxial muscle precursors of the body, some hypaxial precursors of the body, some facial muscles and the central nervous system. These elements separately or together are unable to drive expression in the cells that migrate to the limb buds and in some other muscle subsets and to correctly maintain expression at late times. We suggest that this complex mechanism of control has evolved because different inductive signals operate in each population of muscle precursors and thus distinct enhancers, and cognate transcription factors, are required to interpret them.

Animals↗

PubMed2000

A comparative analysis of primary stenting and optimal balloon coronary angioplasty in acute myocardial infarction. Six month results from the STENT PAMI trial.

OBJECTIVE: To compare the outcome of balloon PTCA with final coronary stenosis diameter (SD) < or =30 %, with elective coronary stenting. METHODS: We performed a comparative analysis of the 6 month outcomes in patients treated with primary stenting and those who obtained an optimal balloon PTCA result treated during the first 12 hours of AMI onset included in the STENT PAMI randomized trial. RESULTS: The results were analysed into 3 groups: primary stenting (441 patients, SD=22+/-6 %), optimal PTCA (245 patients), and non-optimal PTCA (182 patients, SD= 37+/-5 %). At the end of the 6 months primary stent group presented with the lowest restenosis(23 vs. 31 vs. 45 %, p=0.001, respectively). Ischemia-driven target vessel revascularization rate (TVR) (7 vs. 15.5 vs. 19 %, p=0.001, respectively). CONCLUSION: At the 6 month follow-up, primary stenting offered the lowest restenosis and ischemia-driven TVR rates. Compared to optimal balloon PTCA. Non-optimal primary balloon PTCA pts (SD=31-50 %), had the worst late angiographic outcomes and should be treated more actively with coronary stent implantation.

Angioplasty, Balloon, Coronary↗

PubMed2000

A study of mild fetal pyelectasia - outcome and proposed strategy of management.

Mild fetal pyelectasia, defined as a renal pelvic anteroposterior (AP) diameter of 4-10 mm, has become a frequent finding on fetal ultrasonography. The natural history of such dilatation is unclear, resulting in confusion as to appropriate postnatal investigation and management. The aim of this study was to examine the urinary tract outcome of a series of infants with mild fetal pyelectasia demonstrated on routine morphology ultrasonogram between 16 and 21 weeks' gestation. Of the 37 cases identified, 13 (35%) went on to require medical or surgical intervention for significant urinary tract anomalies. These anomalies included pelvi-ureteric junction obstruction, dysplastic kidney, vesicoureteric reflux and posterior urethral valves. On initial scan all cases had an AP diameter of 4-8 mm and did not predict those infants who would go on to require intervention. An AP diameter of greater than 7 mm on repeat scans performed after 27 weeks' gestation had a positive predictive value of 0.92 and a negative predictive value of 0.76 for significant urinary tract anomaly requiring intervention. The specificity was 0. 94 and sensitivity 0.70. A protocol of one repeat antenatal ultrasound at 28-34 weeks' gestation would be able to identify those infants who would require postnatal investigation, using a measurement of >/=7 mm. The fetus with a normal repeat ultrasound would not require postnatal follow-up.

Female↗

PubMed2000

Glycoprotein IIb/IIIa receptor number and occupancy during chronic administration of an oral antagonist.

Long-term treatment with oral glycoprotein (GP)IIb/IIIa antagonists has failed to produce significant clinical benefit. We have examined the pharmacology of xemilofiban in the evaluation of oral xemilofiban in controlling thrombotic events (EXCITE) trial. The EXCITE trial was a multicenter study of xemilofiban in 7232 patients undergoing percutaneous coronary intervention. Thirty-two patients randomized to xemilofiban (10 or 20 mg three times daily) or placebo were followed for up to 6 months. GPIIb/IIIa receptor number and occupancy were quantified using two monoclonal antibodies mAb1 and mAb2. mAb1 was used to quantify receptor number. mAb2 recognizes an epitope that is lost due to a ligand-induced conformational change in GPIIb/IIIa and is a marker of receptor occupancy. Platelet aggregation was performed by light transmission. In vitro, the active metabolite of xemilofiban (SC-54701) inhibited mAb2 binding (IC(50) of 0.5 +/- 0.1 x 10(-8) M) but not mAb1. In vivo, long-term therapy with xemilofiban did not alter GPIIb/IIIa receptor number. mAb2 binding was inhibited throughout the treatment period and recovered slowly after drug withdrawal. Maximum inhibition of ADP-induced aggregation occurred at 4 to 7 h after the first dose of study medication. However, inhibition of platelet aggregation was low (between 24 and 45%) before dosing on days 60 and 180. There was no significant rebound increase in platelet aggregation after drug withdrawal. Long-term xemilofiban therapy does not alter platelet GPIIb/IIIa receptor number. Inhibition of platelet aggregation was poor at the end of each dosing interval and this may explain the failure of xemilofiban to alter clinical events.

Adenosine Diphosphate↗

PubMed1999

Quantifying GPIIb/IIIa receptor binding using 2 monoclonal antibodies: discriminating abciximab and small molecular weight antagonists.

BACKGROUND: Dosing of glycoprotein (GP) IIb/IIIa receptor antagonists is frequently based on the inhibition of platelet aggregation, which may be influenced by the agonist used or concurrent medications. Here we describe a monoclonal antibody-based technique to quantify total and ligand-occupied GPIIb/IIIa receptors. METHODS AND RESULTS: In vitro binding of monoclonal antibodies, LYP18 (Mab1) and 4F8 (Mab2), to the GPIIb/IIIa complex, was characterized using purified receptor and to platelets by flow cytometry. Patients undergoing coronary angioplasty received a single 20 mg dose of the oral GPIIb/IIIa antagonist, xemilofiban, or matching placebo, and antibody binding was compared with inhibition of platelet aggregation. Mab1 and Mab2 were bound to purified GPIIb/IIIa and to unoccupied, inactivated receptor on platelets. Mab2 identified the beta3 subunit, whereas Mab1 was complex-specific. Neither antibody interfered with the other's binding, suggesting that they identified distinct sites. Mab1 identified 53 300+/-5423 GPIIb/IIIa sites per platelet, whereas Mab2 identified 50 120+/-5066 sites per platelet. Mab1 binding was inhibited by abciximab in a dose dependent manner (IC50, 0.85+/-0.1 microg/mL), whereas Mab2 binding was unaffected. In contrast, the 2 small molecular weight antagonists, SC-57101A (IC50, 0.22+/-0.06 micromol/L) and eptifibatide (IC50, 0.35+/-0.14 micromol/L) inhibited Mab2 but not Mab1 binding. In patients treated with xemilofiban, Mab1 binding was unaltered but Mab2 binding decreased from 37 930+/-2061 sites per platelet at baseline to 8318+/-870 sites per platelet 6 hours after dosing (P<0.0001). Platelet aggregation to adenosine diphosphate (20 micromol/L) fell to 3+/-3% of baseline in line with the inhibition of Mab2 binding (correlation coefficient 0.8, P<0.0001). CONCLUSIONS: Mab1 and Mab2 bind to GPIIb/IIIa and are differentially displaced by abciximab and small molecular weight antagonists. These antibodies may be used to monitor receptor number and occupancy during administration of a GPIIb/IIIa antagonist.

Abciximab↗

PubMed1999

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.

Adenosine Monophosphate↗

PubMed1999

A requirement for phosphatidylinositol 3-kinase in pseudopod extension.

Phagocytosis requires actin assembly and pseudopod extension, two cellular events that coincide spatially and temporally. The signal transduction events underlying both processes may be distinct. We tested whether phagocytic signaling resembles that of growth factor receptors, which induce actin polymerization via activation of phosphatidylinositol 3-kinase (PI 3-kinase). Fcgamma receptor-mediated phagocytosis was accompanied by a rapid increase in the accumulation of phosphatidylinositol 3,4,5-trisphosphate in vivo, and addition of wortmannin (WM) or LY294002, two inhibitors of PI 3-kinase(s), inhibited phagocytosis but not Fcgamma receptor-directed actin polymerization. However, both compounds prevented maximal pseudopod extension, suggesting that PI 3-kinase inhibition produced a limitation in membrane required for pseudopod extension. Availability of plasma membrane was not limiting for phagocytosis, because blockade of ingestion in the presence of WM was not overcome by reducing the number of particles adhering to macrophages. However, decreasing bead size, and hence the magnitude of pseudopod extension required for particle engulfment, relieved the inhibition of phagocytosis in the presence of WM or LY294002 by up to 80%. The block in phagocytosis of large particles occurred before phagosomal closure, because both compounds inhibited spreading of macrophages on substrate-bound IgG. Macrophage spreading on IgG was accompanied by exocytic insertion of membrane from an intracellular source, as measured by the dye FM1-43. These results indicate that one or more isoforms of PI 3 kinase are required for maximal pseudopod extension but not phagocytosis per se. We suggest that PI 3-kinase is required for coordinating exocytic membrane insertion and pseudopod extension.

Androstadienes↗

PubMed1999

An action plan for mouse genomics.

The mouse has become the leading animal model for studying biological processes in mammals. Creation of additional genomic and genetic resources will make the mouse an even more useful model for the research community. On the basis of recommendations from the scientific community, the National Institutes of Health (NIH) plans to support grants to generate a 'working draft' sequence of the mouse genome by 2003, systematic mutagenesis and phenotyping centres, repositories for mouse strain maintenance, distribution and cryopreservation and training fellowships in mouse pathobiology.

Animals↗