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Biomedical subjects

J M Goddard

Publications and source records attributed to J M Goddard.

At least 19 recordsLinked to original sources
PubMed1997

Targeted disruption of Hoxd-10 affects mouse hindlimb development.

Targeted disruption of the Hoxd-10 gene, a 5' member of the mouse HoxD linkage group, produces mice with hindlimb-specific defects in gait and adduction. To determine the underlying causes of this locomotor defect, mutant mice were examined for skeletal, muscular and neural abnormalities. Mutant mice exhibit alterations in the vertebral column and in the bones of the hindlimb. Sacral vertebrae beginning at the level of S2 exhibit homeotic transformations to adopt the morphology of the next most anterior vertebra. In the hindlimb, there is an anterior shift in the position of the patella, an occasional production of an anterior sesamoid bone, and an outward rotation of the lower part of the leg, all of which contribute to the defects in locomotion. No major alterations in hindlimb musculature were observed, but defects in the nervous system were evident. There was a decrease in the number of spinal segments projecting nerve fibers through the sacral plexus to innervate the musculature of the hindlimb. Deletion of a hindlimb nerve was seen in some animals, and a shift was evident in the position of the lumbar lateral motor column. These observations suggest a role for the Hoxd-10 gene in establishing regional identity within the spinal cord and imply that patterning of the spinal cord may have intrinsic components and is not completely imposed by the surrounding mesoderm.

Animals↗
PubMed1996

Postoperative pain in children.

An audit project was designed to assess and improve the provision of postoperative analgesia in a children's hospital. Pain assessment for all children and analgesia standards for our institution were introduced prior to data collection. Data were collected on consecutive samples of 316 and 325 children undergoing surgery as inpatients during 10-week periods. Change was initiated between the two periods in response to our findings; our action plan involved education, changes to documentation, the widespread use of diclofenac in children over 2 years of age and recommendations for the prescription of analgesia. The initial prescription of analgesia increased from 95% to 98% (p = 0.019), administration of analgesia to children experiencing bad or severe pain increased from 57% to 71% (p = 0.032) and the number of children experiencing severe pain reduced from 17% to 11% (p = 0.050). Application of audit, by a clinical nurse specialist, enabled us to achieve and demonstrate improvements in the prescription, administration and effectiveness of postoperative analgesia.

Adolescent↗
PubMed1996

The hazards of anaesthetic gas scavenging systems.

The function of scavenging equipment is to remove waste anaesthetic gases from the operating theatre and thus reduce the potentially harmful effects these agents may have on staff. However, these systems can pose a serious risk to patients which is not well recognised. We describe two cases where harm to patients could have occurred as a result of faulty or inappropriate equipment being used and inadequate checking of scavenging systems.

Adult↗
PubMed1996

Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve.

Mice were generated with targeted disruptions in the hoxb-1 gene. Two separate mutations were created: the first disrupts only the homeodomain and the second inactivates the first exon as well as the homeodomain. The phenotypes associated with these two mutant alleles are indistinguishable in surviving adult mice. The predominant defect in these mutant mice is a failure to form the somatic motor component of the VIIth (facial) nerve, possibly through a failure to specify these neurons. The phenotype of hoxb-1 mutant homozygotes closely resembles features of the clinical profile associated with humans suffering from Bell's Palsy or Moebius Syndrome. These animals should therefore provide a useful animal model for these human diseases.

Animals↗
PubMed1996

Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.

Mammals produce two isozymes of angiotensin-converting enzyme (ACE). Somatic ACE plays an important role in the control of blood pressure. The function of testis ACE, produced by male and germ cells, is not known. To examine the roles of these isozymes, we used targeted homologous recombination to introduce a modified ACE allele into a mouse line. Mice homozygous for this mutant allele lack both ACE isozymes and have markedly reduced blood pressures. Contrary to a previous report, we found heterozygous male mice to have normal blood pressures. Homozygous mutant mice also have severe renal disease. The renal papilla is markedly reduced, and the intrarenal arteries exhibit vascular hyperplasia associated with a perivascular inflammatory infiltrate. These animals cannot effectively concentrate urine. They also have an abnormally low urinary sodium to potassium ratio despite reduced levels of aldosterone. Homozygous mutant male mice sire significantly smaller litters than wild-type male mice; however, no defect in sperm number, morphology, or motility was detected. ACE-deficient animals demonstrate the role of this enzyme in systemic blood pressure, renal development and function, and male fertility.

Animals↗
PubMed1993

Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear.

We derived mice that carry a targeted insertion of a neor gene in the int-2 (Fgf-3) proto-oncogene coding sequences. The mutation was found to be recessive and mice that were homozygous for the insertion did not often survive to adulthood. The mutant mice had defects in the development of the tail and inner ear that could be correlated with disruption of int-2 expression in the posterior primitive streak and hindbrain or otic vesicle. While the tail phenotype was 100% penetrant, we found that the inner ear phenotype had reduced penetrance and variable expressivity. The variable expressivity could not be attributed to variability in the genetic background of the mutant allele or to leaky expression from the mutant allele. Thus, we conclude that even in a uniform genetic background, stochastic variation in the expression of a developmental circuit can result in dramatic differences in phenotypic consequences.

Animals↗
PubMed1993

Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain.

Targeted disruption of the murine hox-A1 gene results in severe defects in the formation of the hindbrain and associated cranial ganglia and nerves. Carbocyanine dye injections were used to trace afferent and efferent projections to and from the hindbrain in hox-A1-/hox-A1- mutant mice. Defects were observed in the position of efferent neurons in the hindbrain and in their projection patterns. In situ hybridization was used to analyze the transcription pattern of genes expressed within specific rhombomeres. Krox-20, int-2 (fgf-3), and hox-B1 all display aberrant patterns of expression in hox-A1- mutant embryos. The observed morphological and molecular defects suggest that there are changes in the formation of the hindbrain extending from rhombomere 3 through rhombomere 8 including the absence of rhombomere 5. Also, motor neurons identified by their axon projection patterns which would normally be present in the missing rhombomere appear to be respecified to or migrate into adjacent rhombomeres, suggesting a role for hox-A1 in the specification of cell identity and/or cell migration in the hindbrain.

Animals↗
PubMed1992

Pulmonary collapse during anaesthesia in children with respiratory tract symptoms.

A frequent dilemma facing the anaesthetist is the child with respiratory tract symptoms. The risks of anaesthesia and surgery in these patients have not been clearly established. We present three cases which illustrate a potentially serious complication which may arise. Our patients each had symptoms of cough, but were systemically healthy. Two of the children had absent clinical signs, whilst the third had a normal chest X ray. However, during surgery and anaesthesia each child developed significant pulmonary collapse, associated with desaturation on oximetry.

Anesthesia, General↗
PubMed1992

Pediatric risk of mortality scoring overestimates severity of illness in infants.

OBJECTIVE: To validate Pediatric Risk of Mortality (PRISM) scoring in infants and children admitted for intensive care. DESIGN: Validation cohort. SETTING: A five-bed pediatric ICU and three cots providing intensive care for surgical neonates, within a 159-bed tertiary care children's hospital. PATIENTS: All patients admitted for intensive care during an 18-month period, January 1990 to July 1991. METHODS: Admission (first 24 hrs) PRISM scoring was introduced as a routine procedure. Discretion was allowed in requesting arterial blood gas measurements and clotting studies. All other parameters were intended to be measured on all patients. MEASUREMENTS AND MAIN RESULTS: PRISM scores were obtained on 380 (88%) of 433 patients. Median age was 15 months. A complete PRISM score was obtained in 24% of cases and a score as intended (i.e., allowing discretionary omissions) was obtained in 56% of patients. Comparison of observed and predicted mortality rates using chi square goodness-of-fit tests showed a significantly better observed outcome for all patients (chi 2(5) = 12.04, p < .05). In-depth analysis indicates that the model works well for children (chi 2(5) = 1.80, p > .75), but that observed outcome is significantly better than predicted for infants (chi 2(5) = 17.46, p < .01). Underscoring of children is not the cause of this finding. CONCLUSIONS: In our center, PRISM scoring overestimates severity of illness in infants. PRISM scoring is not institutionally independent and therefore, at present, a comparison between units may not be justified. A reappraisal of the parameter ranges for infants is suggested.

Blood Coagulation Tests↗
PubMed1986

Onchocerciasis in Sierra Leone. I. Studies on the prevalence and transmission at Gbaiima village.

A longitudinal survey--parasitological, clinical, immunological and entomological--of onchocerciasis is being conducted in Gbaiima village in Sierra Leone. The estimated Annual Transmission Potential (ATP) is 5863. More than 80% of the annual transmission occurs between October and December. Four species of the Simulium damnosum complex are known to breed in a nearby river. The relative role of these species as vectors has yet to be determined. The total population (598 persons) aged one year and over were examined. Based on microfilarial and nodular rates the prevalence of onchocerciasis was 68.6%. In persons above 15 years of age this prevalence was 88.9%. Microfilarial and nodular rates were related to age. Severe skin lesions occurred in 1.0% of persons. 24 adults (7.5%) were blind (but the cause of the blindness was not determined).

Adolescent↗
PubMed1986

Surface components of Onchocerca volvulus.

A technique employing Sephadex G25 gel filtration has been developed for the rapid isolation and purification of live microfilariae of Onchocerca volvulus from subcutaneous nodules and skin samples. Microfilariae, adult worms and L3 larvae have been surface radiolabelled using the Iodogen technique. Two proteins have been characterised on the surface of uterine microfilariae: these have apparent molecular weights of 14,800 and 15,000. A MW 15,000 protein was the only molecule labelled on the surface of skin microfilariae. Ten proteins were labelled on adult male worms: these have molecular weights of 15,000, 17,500, 20,000, 22,000, 24,000, 29,000, 32,000, 37,000, 42,000, and 50,000. Some, if not all, of these proteins were also identified on female worms. Seven proteins were labelled on the surface of L3 larvae: these have molecular weights of 17,500, 48,000, 50,000, 52,000, 54,000, 57,000, and 105,000. Three of the adult surface proteins were precipitated by selected human infection serum: these are the MW 17,500, 32,000 and 42,000 molecules. The microfilarial surface proteins were not precipitated by human infection serum. The antiserum used in these experiments was shown by Western blot analysis to contain high levels of antibody with specificity for microfilarial and adult antigens. Indirect immunofluorescent assays showed these sera to contain antibody which bound to the surface of adult worms and eggs but not microfilariae. The possibility that skin microfilariae absorb host serum albumin was investigated: Western blot analysis and surface immunofluorescence assays using a specific anti-human albumin serum gave negative results. Fluorescent lectin binding studies revealed the presence of stage-specific carbohydrate moieties exposed on the surface of adult worms and eggs. Microfilariae do not have surface carbohydrate determinants.

Animals↗
PubMed1986

Isolation and characterization of Caenorhabditis elegans DNA sequences homologous to the v-abl oncogene.

DNA sequences homologous to the v-abl oncogene were isolated from a Caenorhabditis elegans genomic library by their ability to hybridize with a v-src probe. The DNA sequence of 2465 nucleotides of one clone was determined. This region corresponds to the 5' protein kinase domain of v-abl plus approximately equal to 375 base pairs toward the 3' end. Four potential introns were identified. The homology between the deduced amino acid sequence of the C. elegans clone and that of the 1.2-kilobase-pair protein kinase region of v-abl is 62%. The tyrosine residue corresponding to the tyrosine that is phosphorylated in the v-src protein is conserved in the C. elegans sequence. When 95 amino acids around this tyrosine were compared with the corresponding sequences of Drosophila c-abl, v-abl, and v-src, the identities were 83%, 79%, and 56%, respectively. Hybridization of the cloned DNA with C. elegans poly(A)+ RNA revealed a major transcript of 4.4 kilobases.

Amino Acid Sequence↗