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Biomedical subjects

G L Barnes

Publications and source records attributed to G L Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rotavirus infection and prevention.

The major advance in knowledge about rotavirus infection and prevention has been in vaccine development. Several large studies of tetravalent rhesis rotavirus vaccine have had encouraging results, and a first-generation vaccine is likely to be licensed by the 25th anniversary of the discovery of rotavirus (in 1973). Epidemiologic studies have highlighted a diversity of less common G types and non-group A strains, observations to be taken into account in further vaccine development. Disconcerting anecdotal reports of central nervous system involvement need to be cautiously interpreted. New information on pathophysiology raises the intriguing concept of viral toxin involvement. Oral immunoglobulin has been used for prophylaxis and also for treatment during active infection.

Central Nervous System Diseases↗
PubMed1997

Phase 1 trial of a candidate rotavirus vaccine (RV3) derived from a human neonate.

OBJECTIVE: To conduct a phase 1 safety and tolerability trial of an oral rotavirus vaccine candidate RV3 in healthy volunteers. METHODOLOGY: Double blind placebo controlled trial of a single 1 mL oral dose (6.5 x 10(5) fluorescing focus units [FFU]/mL) in 10 healthy young men, 10 3-4 year old children and 10 3 month old infants with a 4 week surveillance period. The study was undertaken at a children's hospital and nearby community in Melbourne, Australia. RESULTS: All subjects successfully completed the trial. There were no significant side-effects attributable to the vaccine preparation in any age group. No shedding of vaccine virus was detected by enzyme immunoassay. There was evidence of an immune response in serum and/or gut secretions in two of five vaccinees in each age group. CONCLUSION: RV3 rotavirus vaccine appears to be safe and well tolerated. Evidence of immunogenicity in some subjects after a single dose encourages further trials to determine immunogenicity after three doses, after reduction of viral dose, and without prior administration of buffer.

Administration, Oral↗
PubMed1996

Valproic acid-induced somite teratogenesis in the chick embryo: relationship with Pax-1 gene expression.

The repeated pattern of the axial skeleton results from the segmentation and re-segmentation of the mesodermally derived somites. During these early events of somite development, the vertebrate embryonic axial skeleton is most susceptible to the teratogenic effects of a variety of pharmaceutical and environmental agents. One example is the anticonvulsant drug valproic acid (VPA), which has been shown to cause craniofacial and minor and major skeletal defects in human and animal embryos. We hypothesize that a candidate set of molecular targets of teratogens are the Pax family of pattern-forming genes, specifically Pax-1, which has been previously demonstrated to be an important regulator of axial skeletal patterning at the somite level. In this study, early developmental stage chick embryos were treated with VPA and dose-dependent malformations in somite development were observed. Two classes of anomalies were evident: class I included discrete sites of somitic fusions or mis-segmentation, and Class II included large areas of disorganized somite patterning. Northern blot analysis revealed a decreased level of Pax-1 expression in VPA-treated embryos. Whole mount in situ hybridization analysis showed that somite anomalies correlate spatially with regions of decreased Pax-1 expression. Finally, comparison of the VPA-induced somitic anomalies with those caused by gene-specific perturbation of Pax-1 gene expression through the use of an antisense oligonucleotide revealed significant similarities. Taken together, these results support the hypothesis that Pax-1 is a molecular target in VPA axial skeletal teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1996

Chicken Pax-1 gene: structure and expression during embryonic somite development.

Recent mouse genetic studies have implicated Pax-1, a paired-box-containing gene, in sclerotomal differentiation and vertebral body formation. To investigate Pax-1 function in somitic sclerotomal differentiation in the chick embryo, we have cloned the chicken Pax-1 gene, and its full length cDNA, and characterized its temporal and spatial expression pattern during somite development. Sequence analysis shows that chicken Pax-1 is highly homologous to murine and human Pax-1 genes with respect to the putative DNA-binding paired-box domain and the octapeptide domain. Northern analysis using probes derived from the paired-box domain and a unique non-paired box sequence of chicken Pax-1 detected 2-kb mRNA transcript. The expression profiles of Pax-1 were examined by in situ hybridization and Northern analysis. The first detectable expression of Pax-1 is seen in the most caudal epithelial somite. As the somite matures, Pax-1 expression takes on a medial distribution, thus corresponding to but preceding the emergence of the sclerotome. In the more mature, rostral somites (stage V and older), Pax-1 expression is found to be progressively localized first to the ventral-medial regions, and then to the caudal-ventral-medial quadrant of the mature somite. This pattern strongly supports the notion that Pax-1 expression is involved in somitogenesis and sclerotomal differentiation, and that it is subsequently a characteristic of the caudal half of the sclerotome, the presumptive precursor of vertebral cartilage. Northern analysis substantiated this expression profile and further revealed that the level of somitic Pax-1 expression increases as a function of embryonic development. Finally, we subjected chicken embryos to controlled heat shock treatment to perturb somite formation and segmentation. The pattern of Pax-1 expression in the anomalous somitic structures generated by controlled heat shock further supports a functional role for Pax-1 in somite development.

Amino Acid Sequence↗
PubMed1996

Serum, fecal, and breast milk rotavirus antibodies as indices of infection in mother-infant pairs.

Sixty-eight mother-infant pairs were followed for 12-17 months after birth. Rotavirus infections in children were detected by EIA of weekly fecal antigen and anti-rotavirus IgA levels, by EIA of anti-rotavirus IgG in sera at birth, 6, or 12-17 months of age, and by anti-rotavirus EIA IgA and neutralizing antibody (NA) in monthly samples of maternal breast milk. Primary rotavirus infection was detected in 26 children (in 15 [58%] by fecal excretion, 12 [46%] by IgG seroconversion, and 22 [85%] by elevations of IgA anti-rotavirus antibodies [IgA coproconversion] in consecutive fecal specimens). Rotavirus "challenge" was detected by rises in levels of NA in breast milk in 9 (47%) of 19 mothers, including 5 (26%) from pairs in which there was no other evidence of rotavirus infection. Reinfections were detected in 2 children by rotavirus excretion and in 4 by coproconversion. IgA coproconversion is the most sensitive technique for detection of symptomatic and asymptomatic rotavirus infection in young children.

Age Factors↗
PubMed1996

Multiple-gene rotavirus reassortants responsible for an outbreak of gastroenteritis in central and northern Australia.

Two rotavirus strains, E210 and E212, implicated in epidemics of gastroenteritis in children in central and northern Australia during 1993-1994, exhibited the unusual combination of a 'short' RNA electrophoretic pattern and subgroup II specificity. The outer capsid protein VP7 was found by PCR typing and sequence analysis to be related to that of serotype G2 viruses. Both strains displayed a novel pattern of reactivity to G2-specific monoclonal antibodies that correlated with sequence variation in the antigenic regions of VP7. The VP4 serotype of E210 and E212 was determined as P1B in an enzyme immunoassay, consistent with other G2 viruses. Analysis of the VP6 gene indicated significant identity (98-99%) with other human subgroup II viruses. Northern hybridization analysis of E210 RNA using total genome probes derived from the prototype strains RV4 and RV5 indicated that E210 was derived from multiple gene reassortment between rotaviruses belonging to different genetic types.

Amino Acid Sequence↗
PubMed1995

Histidine-rich protein B of embryonic feathers is present in the transient embryonic layers of scutate scales.

Based on its amino acid composition and N-terminal sequence, a polypeptide (HRP-B) has been identified as a member of the avian histidine-rich protein (HRP) family. An antiserum against HRP-B has been used to localize this polypeptide in developing feathers and scales of chick embryos. HRP-B was first detectable in the barb ridge cells of feathers at 13 days of incubation and progressively appeared in the distal/proximal and peripheral/central gradients observed previously for the feather-type beta keratins in developing feathers. The HRP-B polypeptide was detected only in the embryonic layers of scutate scales. It first appeared at 16 days of incubation and was not found in the differentiated beta strata of these scales. At no time during the development of reticulate scales or apteric skin regions did the epidermal cells or cells of the embryonic layers express HRP-B. The transient expression of HRP-B by the embryonic layers of the scutate scale epidermis is discussed in light of the feather-forming potential of the presumptive epidermis of the scutate scale-forming region.

Amino Acid Sequence↗
PubMed1995

Patients with enteric adenovirus gastroenteritis admitted to an Australian pediatric teaching hospital from 1981 to 1992.

During the period 1981 to 1992, 4,473 fecal specimens collected from children hospitalized with acute gastroenteritis at the Royal Children's Hospital, Melbourne, Australia, were examined by electron microscopy. A monoclonal antibody enzyme immunoassay for enteric adenovirus (EAd) types 40 (Ad40) and 41 (Ad41) was used when adenoviruses were visualized. Fecal samples were positive for adenovirus by both electron microscopy and enzyme immunoassay in 138 patients (3.1%). Ad40 was identified in 19 children (14%), and Ad41 was identified in 119 children (86%). These EAd were identified during each of the 12 years surveyed. EAd were present year-round, but the annual number of hospitalizations was not constant. Yearly prevalence varied from 0.7% (1981) to 6.5% (1985). This was associated with monthly fluctuations in Ad41 activity, with overall peak monthly prevalence in May (late autumn). By contrast, Ad40 numbers remained low and constant year-round. The frequency of Ad41 relative to Ad40 increased from 25% in 1981 to exceed 75% after 1983. Children admitted with EAd infection were more likely to have diarrhea for more than 5 days (P < 0.001) but less likely to be febrile or dehydrated (P < 0.05) than children with rotavirus infection. EAd are responsible for enteric symptoms of only a fraction of hospitalized children with infectious diarrhea but result in a more-protracted illness than rotavirus. Their relationship to persistent diarrhea requires further investigation.

Adenoviridae↗
PubMed1994

Is cow's milk protein intolerance a cause of gastro-oesophageal reflux in infancy?

To test the hypothesis that cow's milk protein intolerance (CMPI) might cause or contribute to gastro-oesophageal reflux (GOR), 10 of 14 infants with abnormal GOR on prolonged oesophageal pH monitoring who had failed to respond to conventional antireflux therapy were placed on a hypo-allergenic diet for 1 month. In no child was there significant improvement in pH monitoring indices, and only two showed any symptomatic improvement. Therefore, in these children, CMPI did not appear to contribute to GOR. It is probable that CMPI is rare as a cause of passive GOR, although our results do not exclude CMPI as a cause of active vomiting.

Animals↗
PubMed1994

Plant sources of acid stable lipases: potential therapy for cystic fibrosis.

Exogenous lipase used in the treatment of pancreatic insufficiency may be destroyed by stomach acid. This study was undertaken to search for a readily available source of acid stable lipase. Eleven plant sources (avocado, walnut, pinenut, coconut, lupin, lentils, chickpea, mungbean, oats, castor beans and eggplant) were screened for lipolytic activity using a newly developed radio-isotopic labelled substrate method. The results obtained by this method were confirmed by thin layer chromatography. Two of the sources (castor bean and dehulled oats) showed significant lipolytic activity at pH 5.6, castor beans containing 1.5 U/mg of extracted solid and oats 400-1200 U/mg of extracted solid. Castor beans are difficult to obtain and so may be an impractical commercial source of lipase; however, oats are abundant. If simple methods of enzyme purification and concentration can be developed, oats may prove to be a practical source of acid stable lipase for use in the treatment of patients with pancreatic insufficiency, especially those who have cystic fibrosis.

Chromatography, Thin Layer↗
PubMed1993

Region-specific patterns of beta keratin expression during avian skin development.

The transient embryonic layers primarily composed of a periderm and subperiderm cover most regions of the chick embryo and are the first suprabasal cell layers covering the body ectoderm. This study presents evidence for regional variation in the expression of beta keratin in the embryonic layers. Here we show that the embryonic layers covering the anterior metatarsal region of the chicken hindlimb (scutate scale forming region) produce several members of the beta keratin family of polypeptides, designated beta (beta) 1-7. These specific polypeptides are later expressed in this region exclusively in the thick, cornified beta strata of mature scutate scales. In contrast to this sequence of events, the embryonic layers overlying the epidermis of the ventral foot pad (reticulate scale-forming region) and those covering the epidermis in apteric regions of the body produce beta keratin polypeptides beta 1-3 and beta 2,3, respectively, but no subsequent expression of these proteins occurs in the mature epidermises of these regions. Furthermore, we find that the embryonic layers of the skin overlying the anterior metatarsal region of birds homozygous for the mutation "scaleless" (sc/sc), which completely lack scutate scales, produce the same members of the beta keratin family, beta 1-7, as the embryonic layers and beta strata of normal scutate scales. Thus, the accumulation of specific beta keratin polypeptides in the developing anterior metatarsal region appears to occur in two distinct phases; first, an early region-specific expression in cells of the embryonic layers followed by a second phase of expression which occurs in conjunction with appendage morphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Rotavirus gastroenteritis in infants aged 0-6 months in Melbourne, Australia: implications for vaccination.

The aim of this study was to determine the occurrence of rotavirus infection in infants under 6 months of age who were admitted to hospital in a developed country for treatment of gastroenteritis. Between April 1980 and April 1990, 595 such infants were admitted to the infectious diseases ward at the Royal Children's Hospital, Melbourne, Australia. Faecal specimens were collected within 6 h of admission and were tested for viral, bacterial and protozoal enteric pathogens. Rotaviruses of several serotypes were found in specimens from 15.1% of the infants, adenoviruses in 12.4% and other pathogens in 10.8%. Rotaviruses were found equally often in infants in each 1 month age group. No pathogens were able to be identified in 61.7% of cases. These results show that rotavirus is an important pathogen in infants under 6 months of age who are admitted to hospital with gastroenteritis. Rotavirus vaccination will need to be given during the first 1-3 months of life in developed countries, as is recommended for developing countries. The large group in whom no pathogens were isolated requires further consideration.

Acute Disease↗
PubMed1992

Severity of rotavirus infection in relation to serotype, monotype and electropherotype.

The aim of this study was to determine whether the severity of symptoms associated with rotavirus infection was related to the serotype of the infecting virus. Severity of clinical symptoms in 108 children admitted to hospital for treatment of rotavirus diarrhoea was retrospectively assessed using a scoring system for frequency and duration of vomiting and diarrhoea, degree of fever, acidosis and dehydration, and presence of electrolyte imbalance. Children were 6-30 months old and were fully weaned at onset of symptoms prior to admission to hospital. No other enteric pathogens were detected during the course of the illness. Serotypes and monotypes were identified using a panel of monoclonal antibodies. Gel electrophoresis of rotavirus RNA was performed to determine electropherotypes. Children surveyed were infected with serotype 1 (47), serotype 2 (15) or serotype 4 (46) rotaviruses. Comparisons of severity of clinical symptoms according to infecting serotype revealed no statistically significant differences between serotype 1, 2 or 4 infections. In addition, no differences were detected between different rotavirus strains within each serotype (as judged by electropherotype) including monotypes 1a or 1c. This study failed to reveal differences in virulence between rotavirus strains of different VP7 serotypes infecting young children.

Child, Preschool↗
PubMed1992

Normalization of vitamin B12 absorption after ileal resection in children.

Impaired Vitamin B12 absorption after significant ileal resection has been reported to be permanent, although partial recovery after ileal bypass can occur. Three children are presented in whom Vitamin B12 malabsorption returned to normal 6-8 years after ileal resection. This was due probably to adaptation of the remaining small bowel, although spontaneous resolution of bacterial overgrowth is a possible explanation. An abnormal Schilling test after ileal resection does not automatically imply the need for life-long Vitamin B12 injections.

Child↗