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Biomedical subjects

K Wallis

Publications and source records attributed to K Wallis.

At least 19 recordsLinked to original sources

Review article: glucagon-like peptide 2--current applications and future directions.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is an important peptide growth factor secreted from the human intestine. The trophic properties of GLP-2 are very specific to the gut where it is pivotal in the regulation of mucosal morphology, function and integrity. AIMS: This review details the current understanding of the molecular biology of GLP-2, its mechanisms of action and physiological properties. A major focus is the discussion of recent clinical data evaluating the use of GLP-2 as a therapeutic agent. METHODS: Relevant articles were identified using Medline searches and from the reference lists of key papers. RESULTS AND CONCLUSIONS: In the treatment of short bowel syndrome, GLP-2 has been shown to be highly effective in improving fluid absorption. In Crohn's disease, GLP-2 is superior to placebo in the induction of remission. Early data also suggest that the effects of GLP-2 on bone metabolism can provide a new treatment approach for patients with osteoporosis. In the future, the positive effects of GLP-2 on intestinal barrier function, splanchnic perfusion and mucosal healing could be utilized to expand its therapeutic application to other causes of intestinal injury. However, important safety aspects need to be considered when using this potent growth-promoting agent for a long term.

Amino Acid Sequence↗

FGF-8 in the ventral pharynx alters development of myocardial calcium transients after neural crest ablation.

Cardiac neural crest ablation results in depressed myocardial calcium transients and elevated proliferation in myocardium at a stage when cardiac neural crest cells are not in contact with the myocardium. To test the hypothesis that cardiac neural crest-derived cells, which migrate into the caudal, ventral pharynx at stage 14, block a signal from the ventral pharynx, we cultured stage 12 chick heart tube or myocardial strips in the presence or absence of ventral pharynx. We found that myocardium cultured with ventral pharynx that had not yet contacted neural crest cells had significantly reduced calcium transients and an increased rate of proliferation. Ventral pharynx from intact embryos at a stage when neural crest-derived cells had reached the pharynx had no effect on myocardial calcium transients. Ventral pharynx from neural crest-ablated embryos continued to suppress myocardial calcium transients at this later stage. Myocardium cultured with FGF-2 also showed a significant reduction in calcium transients. An FGF-2-neutralizing Ab reversed the deleterious effect of the ventral pharynx on myocardial calcium transients and proliferation. We therefore examined the expression of FGF-2 and similar FGFs in the ventral pharynx. Only FGF-8 was expressed in a temporospatial pattern that made it a viable candidate for altering the myocardial calcium transient during stages 14-18. In explant cultures, neutralizing Ab for FGF-8 rescued development of the myocardial calcium transient in neural crest-ablated chick embryos.

Animals↗

Amniotic band syndrome: the association between rare facial clefts and limb ring constrictions.

The pathologic cause of both rare craniofacial clefts and congenital limb ring constrictions is the subject of some debate. Uncommon though these two conditions are, they have often been anecdotally reported in association. This study sought to determine the frequency of congenital limb anomalies in general and limb ring constrictions in particular amongst a population of patients with rare craniofacial clefts. Eighty-five cases of nonsyndromal, rare, craniofacial cleft were identified from a population of 280 patients assessed at the Women's and Children's Hospital, North Adelaide, with a diagnosis of rare craniofacial cleft classifiable by the Tessier system. Twenty-two patients (25.9 percent) displayed congenital limb anomalies. Eleven of these (12.9 percent) showed evidence of limb ring constrictions, a frequency much greater than in the general population. The group with limb ring constrictions demonstrated a significantly greater complexity of involvement with craniofacial clefting than the non-limb ring constriction group (4.27 clefts/patient versus 2.3 clefts/patient, p < 0.01). The distribution of craniofacial cleft locations in patients with evidence of limb ring constrictions was found to differ significantly from those with other or no limb anomalies (p < 0.01). The clefts in cases in which limb ring constrictions coexist are largely restricted to the paramedian 2-12, 3-11, 412 axes. This study confirms an association between rare craniofacial clefts and limb ring constrictions. The two conditions may therefore possess common etiology.

Abnormalities, Multiple↗

Abnormal patterning of the aortic arch arteries does not evoke cardiac malformations.

Ablation of the cardiac neural crest results in abnormal development of the aortic arch arteries leading to altered patterning of the great arteries. The cardiac outflow tract is also affected after neural crest ablation because normally a subset of neural crest cells migrates from the pharyngeal region to form the outflow septum. Using neural crest ablation, it has not been possible to separate the occurrence of aortic arch maldevelopment from cardiac outflow tract dysmorphogenesis. In order to determine whether normal aortic arch artery development is a prerequisite for normal outflow tract development, we have used a combination of antisense treatment with backtransplantation of cardiac neural folds to produce abnormal patterning of the aortic arch arteries. Paralogous groups of Hox messages with their anterior expression domains in pharyngeal arches 3, 4 and 6 were targeted. Antisense targeted to paralogous group 3 Hox message caused aortic arch 3 located within the pharyngeal arch to regress in a manner similar to aortic arch 2, while antisense targeted to paralogous group 5 Hox message caused the appearance of an additional pharyngeal arch containing a novel and completely independent aortic arch artery. Antisense treatment targeting paralogous group 4 Hox message led to no detectable cardiovascular phenotype in the first 6 days of development. While regression of arch artery 3 was associated with abnormal branching patterns of the aorta and pulmonary trunk, this did not involve abnormal separation of the aorta and pulmonary trunks, the semilunar valves or the subvalvular region of the outflow tract. Because none of these changes in pharyngeal or aortic arch artery development was accompanied by abnormal development of the cardiac outflow tract, it appears that normal patterning of the aortic arch arteries is not a prerequisite for normal heart development. Using reverse transcription polymerase chain reaction (RT-PCR) we were unable to detect changes in any of the Hox messages except group 4, thus, using this particular experimental strategy, we are unable to demonstrate or refute that expression of hox genes by cardiac neural crest cells controls aortic arch patterning. Development of the cardiac outflow tract was normal in each instance. This suggests that abnormal aortic arch patterning does not necessarily lead to cardiac malformations.

Animals↗

Current materials and techniques used in a burn scar management programme.

A range of materials is now available for use in a burn scar management programme. The use of these materials is detailed and suggestions are made based upon the experience gained from close clinical observation of children treated over a 7-year period at the Adelaide Children's Hospital Burn Clinic. Lightweight pressure garments are still needed to keep these various media in contact but are not included in the discussion.

Bandages↗

Nucleoside requirements for the in vitro growth of bovine aortic endothelial cells.

The nutritional needs of cultured fetal bovine aortic endothelial cells were studied with regard to their nucleotide metabolism. When Medium 199 containing calf serum was supplemented with up to 5 microgram/ml of the deoxyribo- or ribonucleosides found in DNA or RNA, the rate of endothelial cell growth increased. The effect was entirely attributable to the pyrimidine nucleosides. The combination of deoxythymidine and deoxycytidine was much more effective than either deoxyribonucleoside used alone or than the combination of uridine and cytidine. Addition of deoxythymidine and deoxycytidine (each at 1 microgram/ml) to the medium supported the growth of endothelial cell cultures from initially sparse populations (ca. 50 cells/cm2), even at low concentrations (1%) of fetal bovine serum. The pyrimidine deoxyribonucleosides on their own were unable to stimulate cell growth; other bonafide growth stimulatory factors, such as those present in serum, serum dialysates, or retinal extracts, were needed in the medium to signal the initiation of DNA synthesis and cell replication. The significance of these findings with respect to improving cell performance under in vitro conditions and controlling endothelial cell growth in vivo are discussed.

Animals↗

3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle.

The amounts of succinyl-CoA--3-oxo acid CoA-transferase (EC 2.8.3.5) decrease progressively in skeletal muscle in streptozotocin-diabetic rats, reaching after 10 days about 50% of the value in normal rat muscle. Electrofocusing studies indicate the occurrence of partial proteolysis of the enzyme in diabetic muscle. However, several functional parameters relating to acetoacetate utilization, including substrate inhibition, are quite similar for muscle transferase preparations from normal and diseased rats. The development of pathological ketoacidosis is discussed in the light of these observations.

Acetoacetates↗

Subcellular localization of acetoacetate coenzyme A transferase in rat hepatomas.

Succinyl coenzyme A:acetoacetate coenzyme transferase (EC 2.8.3.5), an initiator of ketone body usage and absent in normal liver, has been shown to be located in mitochondria from Morris hepatoma 7288ctc using differential and density gradient centrifugation. Furthermore, tumor mitochondrial subfractionation revealed that this transferase is associated with the matrix-soluble proteins. Comparison of the amounts of total transferase activity in several other hepatomas with the amounts found in the corresponding isolated mitochondria suggests that the results with the 7288ctc tumor pertain generally. The mitochondrial localization of coenzyme A transferase indicates the probable use of ketone bodies as energy sources for the hepatomas.

Acetyl Coenzyme A↗

Haemoglobin G-Szuhu, beta80 Asn-Lys, in the homozygous state in a patient with abetalipoproteinaemia.

An 11-year-old Jewish girl of Turkish extraction with abetalipoproteinaemia was found to be homozygous for haemoglobin Szuhu (beta80 Asn leads to Lys). Except for the abnormal haemoglobin, no other haematological or biochemical abnormalities were found in her consanguineous parents and one sister. In the propositus, erythrocyte morphology showed the acanthocytosis known to be in association with abetalipoproteinaemia. Increased autohaemolysis was also found, which reverted to normal after treatment with vitamin E. This case represents the first reported association of abetalipoproteinaemia with an abnormal haemoglobin, and the first homozygous Hb G-Szuhu.

Abetalipoproteinemia↗

Acetoacetate coenzyme A transferase activity in rat hepatomas.

The presence of succinyl-coenzyme A:acetoacetate CoA transferase (CoA transferase) (EC 2.8.3.5), an initiator of ketone body utilization in nonhepatic tissue, was examined in liver from normal, partly hepatectomized, neonatal, and tumor-bearing rats, as well as in a series of transplantable rat hepatomas ranging widely in growth rate. While levels of CoA transferase are extremely low in normal, host, and regenerating liver, considerable amounts of activity are detectable in neonatal liver and in the hepatomas. In fact, the content of CoA transferase in the series of Morris hepatomas increases progressively with increase in tumor-growth rate. The fastest-growing tumor studied (7288Ctc) contains about the same amount of CoA transferase activity as rat skeletal muscle (i.e., an activity of about 0.1 mumole of acetoacetate used per min per g tissue). These results clearly indicate that the faster-growing hepatomas have adequate capacity to utilize ketone bodies in bioenergetic or biosynthetic activities. Furthermore, the enzymes from normal and hepatoma 7288Ctc tissues are quite similar with respect to (a) size of about 10(5) daltons, (b) reaction mechanism requiring formation of an enzyme:CoA intermediate (from ping-pong kinetic data), and (c) various kinetic parameters (such as Michaelis constants, product competitive inhibition constants, and acetoacetate substrate inhibition). The enzymes from rat skeletal muscle and Morris hepatoma 7288Ctc have the same isoelectric point (7.6), which differs from that for the rat heart enzyme (6.8).

Acetoacetates↗

Comparative studies on 3-oxo acid coenzyme A transferase from various rat tissues.

1. Tissue activities, intracellular distribution as well as selected kinetic and molecular properties of succinyl-CoA-3-oxo acid CoA transferase (EC 2.8.3.5), which is an initiator of ketone body usage, were examined in rat kidney, heart, brain, skeletal muscle and liver. 2. The activities of the transferase in these tissues are similar to reported values and are somewhat affected by the homogenization medium. Higher recoveries of activity are obtained when a phosphate buffer is used during the homogenization; Tris solutions containing sucrose and mannitol lead to only slightly lower recoveries, but can be used in studies to determine the subcellular localization of the transferase activity. 3. A close correlation was observed between the relative activities of citrate synthase (a mitochondrial marker enzyme) and CoA transferase in the cytoplasmic, particulate and mitochondrial fractions from the five tissues. 4. The K(m) values for acetoacetate (measured in two different ways), the ratio of V(max.) values for the two enzyme-catalysed half-reactions, and succinate product inhibition are quite similar for the enzyme from each tissue. 5. The enzymes are also similar in molecular weight (with an approx. mol.wt. of 100000 as determined by gel filtration). All show an active band in isoelectric-focusing studies with pI 7.6, except for the enzyme from heart (pI 6.8). 6. The results demonstrate a mitochondrial origin for CoA transferase in these rat tissues and support the proposition that CoA transferase is a ketolytic enzyme, i.e. an enzyme uniquely involved in the complete oxidation of ketone bodies. The structural and functional similarities of these transferases suggest that factors other than differences in K(m) values account for differences in the utilization of ketone bodies by various tissues.

Acetoacetates↗