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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 271 records · Page 15Linked to original sources

Survey of neonatal screening for primary hypothyroidism in England, Wales, and Northern Ireland 1982-4.

National screening for congenital hypothyroidism was established in the United Kingdom in 1982. During 1982-4, 488 infants with primary congenital hypothyroidism were detected by the 25 regional screening laboratories in England, Wales, and Northern Ireland. In addition, one infant had signs of cretinism at birth and was investigated before the screening test was done and four infants were known to have been missed by the screening programme; among these four infants the initial thyroid stimulating hormone concentrations were normal in two with inherited defects of synthesis of thyroxine, not measured in one, and false negative in one. The overall incidence of primary hypothyroidism was 1:3937 births (boys 1:6640, girls 1:2756). The incidence seemed to be reduced in infants born to black mothers (two cases only) and increased in those born to Asian mothers (61 cases). Congenital anomalies other than those of the thyroid glands were reported in 36 children (7%), and 15 (3%) died from various causes before the age of 4. Infants who were considered to show unequivocal evidence of hypothyroidism started treatment at a median age of 17 days (5th and 95th centiles 10 and 42 days) compared with a median age of 14 days (5th and 95th centiles 9 and 21 days) for infants with classic phenylketonuria also detected by national screening.

Asian People↗

First-line chemotherapy rechallenge after relapse in small cell lung cancer.

Response to second-line therapy in relapsing patients with small cell lung carcinoma (SCLC) is often claimed to be evidence in favour of non-cross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were retreated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 2-4 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.

Aged↗

Bovine and human pineal glands contain substantial quantities of endothelial cell stimulating angiogenic factor.

Using a quantitative assay the amount of a low Mr endothelial cell stimulating angiogenesis factor (ESAF) has been determined in human pineal glands and bovine brain, retina, pineal gland, liver and kidney. Pineal glands contain approximately ten times as much ESAF as the retina or grey and white matter from the cerebral cortex and a hundred times as much as highly vascular tissues such as liver and kidney. The relevance of these findings to the highly vascular nature of the pineal gland is discussed.

Angiogenesis Inducing Agents↗

Seeing gel wells well.

Indicator dyes have been incorporated in the stacking gel monomer used in acrylamide gels to render readily visible and delineate the sample wells. Some dyes, such as bromphenol blue, migrate during the electrophoresis, whereas others, such as the ortho-unsubstituted phenol red, become chemically bound to the polymerized gel. The method can be used for agarose gels.

Coloring Agents↗

Use of a versatile lacZ vector to analyze the upstream region of the Bacillus subtilis spoOF gene.

We have constructed a versatile vector, pIS112, in which lacZ translational fusions can be made in Escherichia coli and then analyzed in Bacillus subtilis in three contexts, without recloning: in multicopy during propagation of the plasmid, in single copy integrated via a Campbell-type mechanism into the wild-type locus of the cloned fragment, or in single copy integrated into a heterologous locus. Upstream regions are reconstituted in the integration into the wild-type locus, but not into the heterologous locus, allowing the identification of upstream regulatory sequences. We have used this vector to analyze the expression of the early sporulation gene, spoOF, which, during early stationary phase, is induced 10-fold from a basal vegetative level. When a region, -50 to -150 bp relative to the transcriptional start site, is removed in the spoOF-lacZ gene, stationary phase induction of beta-galactosidase is lost. The same deletion in the upstream region of the functional spoOF gene results in cells which sporulate very poorly, although they are not blocked at the onset of sporulation, as in an spoOF null mutant. This suggests induction of spoOF expression during the beginning of stationary phase is necessary for wild-type sporulation.

Bacillus subtilis↗

Behavior disturbance in 8-year-old children with early treated phenylketonuria. Report from the MRC/DHSS Phenylketonuria Register.

Using the Rutter Behavior Questionnaire, schoolteachers assessed the frequency of common abnormal behavior in 544 8-year-old children with phenylketonuria who were born in the United Kingdom and in whom the diagnosis was made by routine testing in infancy, either during the early years of screening (cohort 1, births 1964 to 1971) or after a national reorganization of the program (cohort 2, births 1972 to 1977). All children received treatment before 4 months of age. Two matched control subjects were assessed for each patient. Compared with the controls, patients in cohorts 1 and 2 receiving a strict low-phenylalanine (phe) diet (average phe concentration less than 600 mumol/L) were 1.5 and 1.7 times, respectively, more likely to have deviant behavior; those receiving a less well controlled diet were 2.5 and 1.9 times, respectively, more likely to show such behavior. Patients more often had mannerisms, hyperactivity, and signs of anxiety and were less responsive and more solitary than were controls. On the other hand, they were not more aggressive, untruthful, or disobedient, nor absent from school more frequently. The increased frequency of deviant behavior may be the result of both psychologic stress and neurologic impairment.

Child↗

The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies.

Proteins secreted by strains of Mycobacterium tuberculosis during short-term, zinc-sufficient batch culture were identified in order to define antigens likely to be relevant to the pathogenesis of human disease. [35S]Methionine-labelled proteins in supernatants of 4-7 d cultures were separated by PAGE under both denaturing and non-denaturing conditions, and the position of labelled material was determined. Secreted protein patterns of M. tuberculosis were quite similar to those of Bacillus Calmette-Guérin (BCG) but differed by the absence of the 46 kDa dimeric protein specific to BCG and by the presence in large amounts of a 23 kDa protein which, when denatured, gave 13 kDa subunits. This 13 kDa subunit protein constituted up to 20% of secreted proteins in classical strains of M. tuberculosis of phage type B but was not detected in phage type I strains from South India. This may be relevant to the different pathogenicity of these strains. Western blot analysis showed that antigens defined in supernatants of short-term (3 d) cultures of M. tuberculosis constituted a small subset of those seen in supernatants of organisms cultured for longer periods. One of the secreted proteins has the interesting property of binding to fibronectin. The available monoclonal antibodies and antisera have been used to identify lines on immunoblots corresponding to the secreted/released antigens of M. tuberculosis. The present findings suggest that there are major secreted antigens to which antibodies do not yet appear to have been produced experimentally.

Antibodies, Monoclonal↗

Structure and expression of the Bacillus subtilis sin operon.

The newly identified sin gene affects late growth processes in Bacillus subtilis when it is overexpressed or inactivated in the chromosome. S1 nuclease mapping of the sin gene transcripts in vivo reveals the existence of three transcripts (RNAI, RNAII, and RNAIII). By correlating 5' ends of sin gene transcripts with DNA sequence, we have identified three different promoterlike sequences (P1, P2, and P3) for these transcripts. 3'-End mapping of these transcripts identified three prominent termination sites at the end of the sin gene. These termination sites are localized on two hairpin structures previously identified from the DNA sequence. The most abundant transcript, RNAIII, coded only for the sin gene, while the polycistronic transcripts RNAII and RNAI coded for the sin gene and ORF1 that precedes the sin gene. S1 mapping and translational lacZ fusion studies indicated that ORF1 and the sin gene are regulated differently. ORF1 expression is under developmental control, increasing at the end of vegetative growth, and requires functional spo0A and spo0H gene products. The sin gene is expressed at an almost constant and relatively low level throughout growth and remains largely unaffected by spo0A and spo0H mutations.

Bacillus subtilis↗

Bacillus sporulation gene spo0H codes for sigma 30 (sigma H).

The DNA sequences of the spo0H genes from Bacillus licheniformis and B. subtilis are described, and the predicted open reading frames code for proteins of 26,097 and 25,447 daltons, respectively. The two spo0H gene products are 91% identical to one another and about 25% identical to most of the procaryotic sigma factors. The predicted proteins have a conserved 14-amino-acid sequence at their amino terminal end, typical of sigma factors. Antibodies raised against the spo0H gene product of B. licheniformis specifically react with RNA polymerase sigma factor protein, sigma 30, purified from B. subtilis. We conclude that the spo0H genes of B. licheniformis and B. subtilis code for sigma 30, now known as sigma H.

Amino Acid Sequence↗

Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency.

We previously described demyelination in the brain and subacute combined degeneration of the spinal cord in a patient with 5,10-methylenetetrahydrofolate reductase deficiency. To assess the role of methionine, S-adenosylmethionine, folate, and neurotransmitter amine metabolism in the demyelination process, we measured these metabolites in CSF from this patient; the findings are compared with those obtained from three patients in whom neurologic deterioration had been halted by the administration of betaine. Folate concentrations were low, and amine and biopterin metabolism were abnormal in all patients. Methionine and S-adenosylmethionine concentrations were undetectable in the first patient. In those receiving betaine, methionine concentrations were proportional to the dose administered and S-adenosylmethionine concentrations were near normal. The results provide the first evidence for an association between defective S-adenosylmethionine metabolism and demyelination in humans.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Timing of strict diet in relation to fetal damage in maternal phenylketonuria. An international collaborative study by the MRC/DHSS Phenylketonuria Register.

64 infants born to women with phenylketonuria (PKU) were grouped according to the mother's dietary treatment in pregnancy. 17 infants, whose mothers were receiving a strict low phenylalanine diet and had blood phenylalanine concentrations below 600 mumol/l at the time of conception, had normal birthweights and head circumferences and no malformations. In the 29 infants whose mothers were receiving either a relaxed diet or a normal diet at conception but who started a strict diet at some time during pregnancy, birthweights and head circumferences were below those in healthy infants and there was an excess of malformations; the findings closely resembled those for the 18 infants whose mothers received no treatment during pregnancy. The birthweights and head circumferences of the 64 infants were inversely related to the maternal phenylalanine concentrations around the time of conception. Only a strict diet started before conception is likely to prevent fetal damage.

Birth Weight↗