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Biomedical subjects

R B Elliott

Publications and source records attributed to R B Elliott.

At least 55 records · Page 3Linked to original sources
PubMed1989

Experience with neonatal screening for cystic fibrosis in New Zealand using measurement of immunoreactive trypsinogen.

Neonatal cystic fibrosis (CF) screening has been performed in New Zealand for a total of 7 years. This study reports the experience with this procedure in New Zealand over a 4 year period and compares it with 2 years when diagnoses of CF were suggested by clinical features only. A total of 72 infants were confirmed as having CF during 4 years of screening. Twenty-eight infants were found to have CF during 2 years in which screening was not performed. There were 29 false positive diagnoses during the screening years and six false negative diagnoses. Three of the false negative diagnoses occurred because of laboratory error, but three occurred because either the first or second measurement of immunoreactive trypsinogen (IRT) was normal. Faecal chymotrypsin was measured in samples from 434 infants at the time of the second IRT and assisted with the diagnosis for one infant which might otherwise have been missed. Only 42.5% of infants were asymptomatic at the time of the confirmatory sweat test. Significant morbidity and mortality was associated with meconium ileus which occurred in 24% of infants with CF. Improved ascertainment of cases of CF has occurred since screening began. Further follow-up is required to determine other benefits of newborn screening.

Age Factors↗
PubMed1988

Ontogenic development of peptide hormones in the mammalian fetal pancreas.

The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human, pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal beta-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell-types.

Animals↗
PubMed1988

Ontogeny of islet cell antibodies, insulin autoantibodies and insulitis in the non-obese diabetic mouse.

The predictive value of insulitis, islet cell cytoplasmic antibodies and insulin autoantibodies for insulin-dependent diabetes was studied in young female non-obese diabetic mice. The ontogeny of the three markers was examined cross-sectionally at days 15, 25, 40 and 90 while islet cell antibodies and insulin autoantibodies were studied longitudinally from day 35 or day 144-168 until approximately day 250. Insulitis was first observed at day 40 (50%) and subsequently at day 90 (70%). Islet cell antibodies and insulin autoantibodies were present at day 15 in 46% and 54% of the animals respectively. The rate of islet cell antibodies was slightly higher at day 25 (60%) than at day 40 (40%) and day 90 (54%) whereas antibodies to insulin were present in all samples from day 25-90. At day 40 and day 90 insulitis and insulin autoantibodies were present together in 42% and 70% of the animals, respectively, while insulitis and islet cell antibodies had a lower rate of concordance (17% and 42%, respectively; diabetes rate, 30%). The concordance rates for islet cell antibodies and insulin autoantibodies were 42% at day 40 and 54% at day 90. Concordance for all three markers was first observed at day 40 (17%) which increased to 38% at day 90. In longitudinal studies, islet cell antibodies and insulin autoantibodies were often present together whether or not diabetes supervened. In the islet cell antibody procedure, immunoreactive cells were shown immunohistochemically to correspond with insulin and/or glucagon cells. However, this staining was not suppressible with insulin- or glucagon- absorbed sera, implying the presence of non-hormonal autoantigens. We conclude that the three markers investigated are expressed early after birth and well before clinical symptoms appear in this animal model. Both islet cell antibodies and insulin autoantibodies preceded insulitis but the prevalence rate for each marker or their degree of concordance was different from the anticipated rate of diabetes in our colony. Consequently, the early expression of the three markers alone is not predictive of diabetes although concordance for the two, or all three markers may be of some value. However, no animal developed diabetes without the prior appearance of both islet cell antibodies and insulin autoantibodies.

Animals↗
PubMed1988

Dietary prevention of diabetes in the non-obese diabetic mouse.

Diabetes prone NOD female mice were fed diets containing different proteins from just before weaning. Only mice receiving meat meal or casein as the protein source developed diabetes at the rate expected from this colony. Lactalbumin and gluten did not precipitate diabetes except in a small number. Casein hydrolysate in lieu of protein protects against overt diabetes, but only if introduced early. The animals which did not show overt diabetes nevertheless had intermittent trace glycosuria and the majority showed mild degrees of periinsular lymphocytic infiltration.

Animals↗
PubMed1988

An immunofluorescent study of insulin-, glucagon-, pancreatic polypeptide- and somatostatin-containing cells in the early ovine fetal pancreas.

Using antisera to insulin, glucagon, pancreatic polypeptide (PP) and somatostatin, the localization and cellular distribution of the four hormones were investigated in the sheep fetal pancreas of day 40-45 gestation by immunofluorescence. All four hormones were immunolocalized at this early gestational period. The endocrine cell types had a characteristic distribution and were present in different numbers. Insulin and glucagon immunoreactive cells were seen in larger numbers compared to fetal PP and somatostatin cells and were located either in the developing islets or as single scattered cells in the epithelium of the embryonic ductules. These cells became more confined to the developing islets at later stages of gestation. In the pancreas of day 40-45 fetuses PP cells were less numerous than glucagon and insulin cells while somatostatin cells were seen rarely. However, PP and somatostatin cells became more numerous at later stages of gestation. Our studies demonstrate the presence of insulin, glucagon, PP and somatostatin within distinct cell types in the early sheep fetal pancreas.

Animals↗
PubMed1987

Lactose malabsorption in Polynesian and white children in the south west Pacific studied by breath hydrogen technique.

Lactose malabsorption was studied by a breath hydrogen technique in 139 Samoan and 68 white schoolchildren. The Samoans were studied in four locations, two in Western Samoa and two in New Zealand, and the white children in both the Cook Islands and New Zealand. The prevalence of malabsorption varied with location: for Samoans it ranged from 41% to 60% in Western Samoa and 0% to 35% in New Zealand; white children had rates of 27% in the Cook Islands and 5% in New Zealand. Environmental factors rather than genetic factors are likely to play the main part in initiating if not perpetuating lactose malabsorption. In both races lactose malabsorption had no effect on the acceptance of, consumption of, and number of gastrointestinal symptoms caused by milk and milk biscuits. Children who had symptoms after consuming a particular dairy product were more likely to say they disliked it than those who reported no symptoms.

Adolescent↗
PubMed1986

Longitudinal study of first phase insulin release in the BB rat.

First phase insulin release was measured in response to intravenous glucose given weekly from approximately day 40 in 6 BB rats which subsequently developed diabetes and in age-matched non-diabetic (n = 15) and normal Wistar rats (n = 8) until day 180. The mean sequential insulin responses in BB rats with and without diabetes were significantly lower (p = 0.008 and less than 0.0001, respectively) than in normal rats from an early age. Five diabetic BB rats showed a progressive decline in first phase insulin release immediately prior to glycosuria, with the impaired phases ranging from 25-50 days. However, protracted periods of low first phase responses were also seen in several aglycosuric BB rats, which showed histological evidence of insulitis and B-cell loss. Our findings demonstrate that, although most BB rats with diabetes show a progressive impairment of B-cell function preceding the disease, this aberrant phase can also be present in BB rats which remain aglycosuric. Impaired first phase insulin release in response to serial intravenous glucose tolerance tests may not be a reliable predictor of Type 1 (insulin-dependent) diabetes in this animal model.

Animals↗
PubMed1986

Immunolocalization of insulin, glucagon, pancreatic polypeptide, and somatostatin in the pancreatic islets of the possum, Trichosurus vulpecula.

Antibodies to insulin, glucagon, pancreatic polypeptide (PP), and somatostatin were used in the immunofluorescence procedure to demonstrate localization of the four hormones in cells of the pancreatic islets of the brushtailed possum, Trichosurus vulpecula. Most pancreatic islets revealed some differences in the topographical distribution and cell number of each endocrine cell type. Insulin immunoreactive cells were observed in most islets where they occurred as groups of cells peripherally and within the islet. In several islets glucagon cells were the predominant cell population and were distributed peripherally as well as centrally. Pancreatic polypeptide cells were fewer in number and usually occurred as single cells within the islet. Cells immunoreactive to antisomatostatin serum were observed in varying numbers in the peripheral and central regions of the islet. The present immunofluorescence study demonstrates differences in the topographical distribution of the four major pancreatic hormones between a marsupial species and several of the eutherian mammals.

Animals↗
PubMed1985

Outcome of pregnancy in the rat with mild hyperphenylalaninaemia and hypertyrosinaemia: implications for the management of "human maternal PKU".

In attempting to determine the effects of mildly elevated maternal phenylalanine (Phe) blood levels on the developing fetal rat brain, a dietary supplement of Phe was given, under taste cover of Aspartame. Phe and tyrosine (Tyr) levels were mildly elevated throughout pregnancy without evidence of malnutrition. Mild hyperphenylalaninaemia with concurrent hypertyrosinaemia induced in rats prior to conception resulted in microcephaly and lasting behavioural problems in the offspring, specifically hyperactivity and learning difficulties. Dams fed Tyr to produce Tyr levels equivalent to the Phe-fed animals showed only the learning difficulties among the offspring. alpha-Methyl Phe, a Phe hydroxylase inhibitor, fed in conjunction with Phe, at the level relevant to these experiments, resulted in raised Tyr levels and does not provide a better method of determining whether mildly elevated maternal Phe levels alone, or Phe and Tyr in combination, cause the abnormality found in the offspring of Phe-supplemented dams. Therapeutic addition of Tyr to diets of mothers with even mild hyperphenylalaninaemia should be approached with caution as mild co-elevation of Phe and Tyr in the fetus may be harmful. In the face of such a possible therapeutic dilemma alternatives, such as dietary additions of other essential amino acids to limit fetal brain damage, need to be explored.

Animals↗
PubMed1985

Rat trypsin: purification, radioimmunoassay and age-related serum levels in normal and spontaneously diabetic BB Wistar rats.

A convenient procedure is described for the purification of rat trypsin. Tissue was homogenized and extracted at pH 4 and the soluble fraction purified by a two-step affinity chromatography. After polyacrylamide gel electrophoresis at pH 8.8, the purified enzyme was resolved into 1 major and 2 minor bands all of which possessed trypsin-like enzyme activity. Antibodies to rat trypsin were raised in rabbits and utilized in establishing a sensitive radioimmunoassay procedure for the enzyme. The assay was adapted to study the levels of the enzyme in the circulation of normal Wistar and spontaneously diabetic Bio Breeding Wistar rats before onset of insulin-dependent diabetes mellitus in a longitudinal fashion. In the normal rat, serum levels of immunoreactive trypsin were higher in younger animals and showed a decline after weaning. This pattern was also seen in the Bio Breeding Wistar rats. In about half the number of Bio Breeding Wistar rats, serum immunoreactive trypsin levels were much higher than in normal rats. These results may imply that in some Bio Breeding Wistar rats the disease may be associated with inflammatory lesions of the exocrine pancreas.

Age Factors↗
PubMed1985

Ontogeny of cells containing insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the bovine pancreas.

Antibodies to insulin, glucagon, pancreatic polypeptide hormone (PP) and somatostatin were used in the immunofluorescence histochemical procedure to study the ontogeny of pancreatic endocrine cells containing the four hormones in the bovine fetus of approximately 100 days gestation to term. Pancreatic sections from the bovine neonate and adult were also examined for the cellular distribution of the four hormones. Immunoreactive cells staining for insulin, glucagon, PP and somatostatin were present in the pancreas of all fetuses studied. Each endocrine cell type displayed a characteristic distribution within the developing pancreas and in the neonate and adult. The presence of the four islet hormones relatively early in bovine fetal life suggests that they may be important in intra- and extra-islet metabolism in the fetus.

Animals↗
PubMed1985

Tests for autonomic neuropathy in diabetic children.

Five simple tests of autonomic nerve function were studied in 38 children (12.0 years, s.d. = 3.3) with insulin-dependent diabetes mellitus and a further 38 age and sex matched controls in order to validate the use of these tests in children. The five tests included one test (immediate heart rate response to standing) previously reported. Compared to controls, diabetics showed a significantly faster heart rate at rest (P = 0.022), a reduced heart rate variation during quite respiration (P = 0.003), a smaller change in heart rate following a single deep breath (P = 0.006), a lower Valsalva ratio (P = 0.084) and a lower maximum R-R/minimum R-R ratio in response to standing (P = 0.033). The heart rate response to the Valsalva manoeuvre is less suitable for use in children than adults as it requires considerable co-ordination and co-operation and it did not correlate with the other tests of autonomic nerve function. The other tests significantly correlated with each other and were quick and easy to perform. They required no special co-operation and required no special equipment other than a standard ECG machine. Three diabetics had abnormalities in four of the tests (mean heart rate, heart rate variations during quiet respirations, change in heart rate produced by a single deep breath and the previously reported immediate heart rate response to standing). None of the controls had abnormalities in more than two of the tests.

Autonomic Nervous System Diseases↗
PubMed1985

Cellular distribution of insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the fetal and adult pancreas of the guinea pig: a comparative immunohistochemical study.

Antibodies to insulin, glucagon, pancreatic polypeptide hormone and somatostatin were utilized to demonstrate the cellular localization of the hormones in pancreatic tissue of fetal guinea pig of advanced gestation by immunofluorescence histochemistry. The topographical distribution of the 4 endocrine cell types was compared with those of the adult pancreas and was found to be significantly different particularly for cells immunostaining for insulin, glucagon and somatostatin. These observations suggest changes in histogenesis of pancreatic endocrine cells during transition from fetal to postnatal and adult life. The presence of the 4 islet hormones in the fetal pancreas of this species implies that they may be important in fetal metabolism and growth.

Animals↗
PubMed1985

Insulin, glucagon, pancreatic polypeptide hormone and somatostatin in the goat pancreas: demonstration by immunocytochemistry.

Insulin, glucagon, pancreatic polypeptide hormone (PP) and somatostatin immunoreactive cells were demonstrated in the islet of the goat pancreas by the immunofluorescence procedure. Islet cells showing immunostaining for the hormones appeared to have a characteristic distribution. The demonstration of PP and somatostatin within the pancreas of the goat suggests they may be significant in modulating intra- and extra-islet function in this ruminant species.

Animals↗