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Biomedical subjects

M A Hall

Publications and source records attributed to M A Hall.

At least 109 records · Page 6Linked to original sources

HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer.

HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease.

Celiac Disease↗

Celiac disease is associated with an extended HLA-DR3 haplotype which includes HLA-DPw1.

HLA-DP polymorphism was examined among celiac disease patients and controls. Restriction fragment length polymorphism (RFLP) genotyping showed a significant association of DPw1 in celiac disease (32/80) compared with controls (6/53, p = 0.0002). DPw1 typing by RFLP was verified using DPB1-amplified DNA and an oligonucleotide probe specific for the DPw1-associated DPB1 gene. The RFLP-assigned DPw1 genotype corresponded closely to the binding pattern of the sequence-specific oligonucleotide probe, although discrepancies did occur. The association between celiac disease and DPw1, however, remained. Oligonucleotide probe specificity was confirmed by sequencing DPB1-amplified DNA from four DPw1-genotyped celiacs. DPw1 is only present in celiacs who genotype DR3a-positive. Of DR3a controls 24% are DPw1-positive compared with 5% of non-DR3a controls (p = 0.03), suggesting that an extended DR3a, DPw1 haplotype occurs in the control population. This haplotype forms a large proportion of the DR3a haplotypes predisposing to celiac disease. Alternatively, DPw1 may represent an independent risk factor inherited in linkage with HLA-DR3 and -DQw2. Although predisposition to celiac disease is likely to be mediated by a specific DQ alpha/DQ beta heterodimer, a direct role for the DPw1 antigen cannot be discounted.

Base Sequence↗

Sequence analysis of HLA-DR4B1 subtypes: additional first domain variability is detected by oligonucleotide hybridization and nucleotide sequencing.

The stimulating capacity of HLA-DR4 variants in mixed leukocyte culture correlates with variation in the polymorphic regions of the first domains of their DR beta 1 chains. Variability between amino acids 67 and 86 appears largely to determine HLA-DR4,Dw type. We have used a combination of a DR4B1-specific primer set in the polymerase chain reaction and specific oligonucleotide probes to examine DR4,Dw-associated nucleotide polymorphisms. Phenotype and gene frequencies are reported among 44 normal DR4 Caucasoids. Oligonucleotide probes were selected which enabled definition of Dw4-, w14-, w10-, w13-, and w15-associated sequences. Unexpectedly, several subjects were positive for Dw15 sequences which are usually characteristic of Oriental populations. Dw15 assignment was confirmed by nucleotide sequencing of DR4B1 polymerase chain reaction products. A pair of oligonucleotides informative for the glycine or valine dimorphism at position 86 was used to identify two novel DR4B1 alleles, designated 13.2 and 14.2. Nucleotide sequencing shows that these represent recombinants between third hypervariable regions associated with Dw13 and Dw14 and a codon for glycine at position 86 which is usually found associated with Dw4 and Dw15 sequences.

Alleles↗

Coeliac disease.

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Adolescent↗

Time course of vitamin E repletion in the premature infant.

Plasma and erythrocyte (RBC) tocopherol-isomer concentrations were determined serially in forty-two premature infants (25-35 weeks gestation) from birth to 8 weeks of age. For comparison purposes vitamin E status was also determined in six term infants over the first 8 d following birth and in a group of thirteen adult volunteers. Vitamin E intakes in term and preterm infants were calculated from recorded food intakes and blood transfusions. In term infants plasma vitamin E concentration rose from 1.9 mg/l (day 1) to 8.2 mg/l by day 8. In comparison preterm plasma vitamin E concentration, 0.3 mg/l (day 1), did not change appreciably by day 8 (0.7 mg/l). Likewise RBC vitamin E concentration increased in term infants from 1.3 mg/l (day 1) to 2.7 mg/l (day 8), while in preterm infants it remained unchanged, 1.5 mg/1 (day 1) v. 1.3 mg/l (day 8). Over the 3 weeks following birth, RBC vitamin E concentrations in the premature infants increased to adult values, while plasma vitamin E concentration did not reach the adult range until 8 weeks post-term. These slow changes in plasma vitamin E status occurred even though the vitamin E intake of these infants was similar to that proving adequate for term infants.

Adult↗

Strain-gauge fontanometry--an advance in non-invasive intracranial pressure measurement.

The validation of a fontanometer based on the strain-gauge principle is described. Fontanelle pressures correlated well with invasively determined cerebrospinal fluid (CSF) pressures in a group of neonates and infants with hydrocephalus. This device, which can be zeroed in vivo, has the additional advantage of a fast response time and allows reliable measurements of spontaneous pulsations and induced changes in CSF pressure. Unlike previously reported devices, the accuracy of this transducer was shown to be independent of external forces.

Humans↗

Patterns of immune response among survivors of group B streptococcal meningitis.

Serum samples from 10 infants surviving type III, group B streptococcal (GBS) meningitis were collected acutely and longitudinally for 6 months to determine patterns of antibody response to the capsular polysaccharide and their in vitro functional correlates. Five infants who failed to develop specific antibody at a mean of 3.8 weeks after diagnosis had an increase of greater than or equal to 1.0 microgram/ml after another 4-8 weeks. This IgM-predominant type-specific antibody declined to baseline 2-4 months later. Opsonophagocytosis of type III GBS increased from 0 to 88% in parallel with peak antibody response. Three infants developed increased antibody and opsonophagocytosis at 15-31 weeks after diagnosis, while two had no detectable response. Despite increasing complement levels, opsonophagocytosis of type III GBS was poor with low specific antibody levels These results suggest that survivors of GBS meningitis transiently develop specific antibody and associated efficient opsonophagocytosis, but functional competence does not persist despite maturation to adult levels of complement proteins.

Aging↗

The application of oligonucleotide probes to HLA class II typing of the DRB sub-region.

A plan for DRB typing at the sequence level is detailed. Only one polymerase chain amplification reaction is needed and the application of a limited number of short oligonucleotide probes allows an almost complete definition of DRB alleles. The scheme was tested on 40 homozygous cell-lines selected to cover a wide range of specificities, and 40 RFLP-typed controls. The results are presented and discussed. The simplicity and accuracy of this scheme are emphasized.

Alleles↗

Plasmid profiling of members of the family Enterobacteriaceae, lactobacilli, and bifidobacteria to study the transmission of bacteria from mother to infant.

Plasmid profiles of isolates of the family Enterobacteriaceae, lactobacilli, and bifidobacteria cultured from vaginal, oral, and rectal swabs collected from women soon after admission to a maternity hospital were compared with those of strains detected in the feces of their infants. Lactobacilli inhabiting the vaginas of the mothers did not appear to colonize the infant digestive tract, but evidence for the transmission of fecal isolates of the Enterobacteriaceae and bifidobacteria from mother to infant was obtained in four out of five cases. Many of the bifidobacteria isolated were plasmid-free but could be distinguished with biochemical profiles.

Bifidobacterium↗

Hyperinsulinaemic hypoglycaemia in small for dates babies.

Blood glucose concentrations were measured prospectively in 27 small for dates infants in the first 48 hours after birth: 10 infants became hypoglycaemic. Of these, five had inappropriately raised plasma insulin concentrations. Plasma free fatty acids were lower and carbohydrate intake higher in these five infants, further supporting the diagnosis of hyperinsulinism. The hypoglycaemia recurred in four of the five hyperinsulinaemic infants, but in none of those who were not hyperinsulinaemic. Hyperinsulinism is common in small for dates babies. It is important to recognise this because hypoglycaemia is likely to recur and appropriate treatment is needed to prevent long term sequelae.

C-Peptide↗

Factors influencing the presence of faecal lactobacilli in early infancy.

The faecal flora of 46 preterm infants and 52 born at full term was studied at 10 days of age; 46 born at full term and 37 preterm infants were also studied at 30 days. Viable counts of coliforms, lactobacilli, and bifidobacteria were made; gas liquid chromatography was used to identify the anaerobes. Lactobacilli, but not bifidobacteria, were found in high counts in the stools of most of the infants born at full term by 30 days of age. The mode of delivery, but not the method of feeding, had a significant influence on early colonisation. A selective deficiency of lactobacilli compared with coliform organisms was found in preterm infants. Previous treatment with antibiotics and being nursed in an incubator were also significantly associated with a lower rate of early colonisation with lactobacilli. Our findings indicate that lactobacilli may be an important part of the normal stool flora in early infancy, and that modern methods of neonatal care are associated with delayed or deficient colonisation.

Anti-Bacterial Agents↗

Ethylene: receptors and action.

The characterisation and purification of the ethylene binding protein from developing cotyledons of Phaseolus vulgaris is described. Polyclonal antibodies to this protein recognise homologous proteins in peas, tomatoes and Arabidopsis. Direct binding assays and results from immunological studies indicate that more binding protein is present in abscission zones of Phaseolus than in petioles; ethylene treatment increases binding site abundance in abscission zones. Binding sites for ethylene in peas. Arabidopsis and rice are described indicating that there exist two classes differing only in their rate constants of association and dissociation. Arabidopsis mutants wholly insensitive to ethylene may be receptor deficient and their possible use in receptor studies is assessed. It is proposed that those binding sites with high rate constants of association are functional receptors. The sites with low rate constants of association may be receptors but may also represent receptor precursors or internalised receptors.

Antibodies↗

Recurrent acute proptosis in atypical systemic lupus erythematosus.

A patient is described who developed acute proptosis, a rare complication of systemic lupus erythematosus, 16 years after the onset of the disease. Treatment with intravenous methylprednisolone produced rapid improvement, but swelling recurred a few days later. Intravenous corticosteroid was again effective and was continued orally without further episodes of proptosis. This patient is unusual in the long period of mild disease before the development of systemic complications, and in having antibodies to nuclear ribonucleoprotein but persistently normal titres of DNA-binding antibodies in her serum.

Acute Disease↗

Antibiotic exposure delays intestinal colonization by Clostridium difficile in the newborn.

Two antibiotic regimens commonly used in neonatal intensive care were compared for the rate at which Clostridium difficile appeared in the faeces. Over a nine month period neonates with suspected sepsis admitted to a Special Care Baby Unit (SCBU) were randomly allocated to receive either cefotaxime or penicillin and netilmicin. A contemporaneous group also admitted to SCBU but without sepsis served as non-treated controls. Four hundred and sixteen stool specimens from 158 neonates without diarrhoea were analysed every five to seven days until discharge. The results showed that these antibiotics did not encourage gut colonization by C. difficile, that they might even be protective in this respect and that monotherapy with cefotaxime was no more likely to generate C. difficile overgrowth than the penicillin-aminoglycoside regimen.

Anti-Bacterial Agents↗

Carbohydrate fermentation by gut microflora in preterm neonates.

To study organic acid excretion, urine was collected from 52 preterm infants at weekly intervals and analysed by capillary gas chromatography-mass spectrometry. Twelve of 22 babies born before 33 weeks' gestation excreted 2,3-butanediol, as did six born between 33 and 36 weeks. Six very immature babies also excreted acetoin, the metabolic precursor of the diol. Other products derived from carbohydrate included methylmalonic and ethylmalonic acids in one baby, and D-lactic acid in five. Acetoin has never been found in urine before, and the other four acids have been found only rarely. Excretion of these metabolites by preterm babies can be explained by increased intestinal permeability, unabsorbed lactose in the colon, and colonisation with certain opportunistic micro-organisms prevalent in neonatal units, including klebsiella, serratia, and enterobacter. The findings support evidence from breath hydrogen analysis that carbohydrate fermentation takes place in the gut of preterm infants.

Acetoin↗