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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 307 records · Page 17Linked to original sources
PubMed1986

Subacute combined degeneration of the cord, dementia and parkinsonism due to an inborn error of folate metabolism.

A 2-year-old girl with 5,10-methylenetetrahydrofolate reductase deficiency developed subacute combined degeneration of the cord and a leuco-encephalopathy which was confirmed at necropsy. Total folate concentrations in serum, red cells and CSF were markedly reduced whereas vitamin B12 concentrations were normal. In addition the patient had Parkinsonism and reduced concentrations of homovanillic acid, 5-hydroxyindoleacetic acid and total biopterins in cerebrospinal fluid. Folic acid administration was accompanied by fits and acute deterioration in the movement disorder. At necropsy the basal ganglia showed no detectable abnormality.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1986

Pteridines and mono-amines: relevance to neurological damage.

Patients with phenylalanine hydroxylase deficiency show increased concentrations of biopterins and neopterins, and reduced concentrations of serotonin and catecholamines, when phenylalanine concentrations are raised. The pterin rise reflects increased synthesis of dihydroneopterin and tetrahydrobiopterin, and the amine fall a reduction in amine synthesis due to inhibition by phenylalanine of tyrosine and tryptophan transport into neurones. The pterin and amine changes appear to be independent of each other and are present in the central nervous system as well as the periphery; they disappear when phenylalanine concentrations are reduced to normal. Patients with arginase deficiency show a similar amine disturbance but have normal pterin levels. The amine changes probably contribute neurological symptoms but pterin disturbance is not known to affect brain function. Patients with defective biopterin metabolism exhibit severely impaired amine synthesis due to tetrahydrobiopterin deficiency. Pterin concentrations vary with the site of the defect. Symptoms include profound hypokinesis and other features of basal ganglia disease. Neither symptoms nor amine changes are relieved by controlling phenylalanine concentrations. Patients with dihydropteridine reductase (DHPR) deficiency accumulate dihydrobiopterins and develop secondary folate deficiency which resembles that occurring in patients with defective 5,10-methylene tetrahydrofolate reductase activity. The latter disorder is also associated with Parkinsonism and defective amine and pterin turnover in the central nervous system, and a demyelinating illness occurs in both disorders. In DHPR deficiency cerebral calcification may develop in a similar distribution to that seen in congenital folate malabsorption and methotrexate toxicity. Symptoms are ameliorated by therapy with 5-formyltetrahydrofolate but exacerbated by folic acid.

Amines↗
PubMed1986

Radioimmunoassay of pineal 5-methoxytryptophol in different species: comparison with pineal melatonin content.

A sensitive, specific, reproducible and practical radioimmunoassay for the determination of 5-methoxytryptophol (ML) in pineal glands of different species has been developed. High-affinity specific antisera were produced by immunization of sheep with ML-bovine serum albumin. Iodinated ML, used as the radiolabel, was synthesized by direct iodination of ML using 1, 3, 4, 6, -tetrachloro-3, 6-diphenylglycouril as the oxidant. Sensitivity of the assay was 0.005 pmol/tube. The validity of the assay was checked using classical techniques. Cross-reactivity with other indoles was negligible. Parallel inhibition curves were obtained for rat, hamster, sheep and tortoise pineal homogenates. Using thin-layer chromatography, tortoise pineal immunoreactivity also co-chromatographed with standard ML. Samples (n = 5) with ML concentrations of 0.013, 0.052 and 0.209 pmol/tube had intra-assay coefficients of variation of 9.8, 5.7 and 7.6% respectively. Their respective interassay coefficients of variation were 17.7, 16.5 and 11.4% (n = 8). The pineal concentration of ML was found to be species dependent. Afternoon ML levels were 0.052 +/- 0.002 (S.E.M.) pmol/gland in the rat (n = 16), 0.539 +/- 0.089 pmol/gland in the hamster (n = 16), 1.73 +/- 0.225 nmol/g in the sheep (n = 10) and 7.15 +/- 0.465 pmol/gland in the tortoise (n = 4). The ratio of ML:melatonin content in the pineal gland also showed a large interspecies variation with values of 0.02 in the rat, 0.22 in the sheep, 2.7 in the hamster and 17 in the tortoise.

Animals↗
PubMed1986

A prospective comparison of iotrolan, iohexol and iopamidol for lumbar myelography.

The provisional results are presented of a comparative blind trial of iotrolan, iohexol and iopamidol for lumbar myelography. The aim of the trial was to assess the relative safety, tolerance and radiologic efficacy of the media. From the data available to date the incidence of side effects is similar for all three substances. Iotrolan does not provide specific imaging advantages.

Contrast Media↗
PubMed1985

Mitoxantrone as first-line chemotherapy in advanced breast cancer: results of a collaborative European study.

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is a substituted anthraquinone with a spectrum of activity similar to doxorubicin in experimental tumors. One hundred and seventy three patients with advanced breast cancer and no prior cytotoxic therapy for advanced disease entered a phase II study of mitoxantrone, 14 mg/m2 i.v. repeated every 3 weeks. At the time of this analysis 116 patients were evaluable. Eight patients achieved a complete response and 27 a partial response, the overall response rate being 30% (95% confidence limits: 22-39%). The median time until response was recorded was 15 weeks. The median duration of response was 74+ weeks and the median time to progression or death for all 116 patients was 22+ weeks. Mitoxantrone was well tolerated with myelosuppression as the dose-limiting toxicity. The most frequent non-haematological toxicities were nausea and vomiting (65%) but they were rarely severe. Total alopecia occurred in only 6% of the patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative mitoxantrone doses of 174-256 mg/m2. Thus, mitoxantrone offers comparable efficacy and less acute toxicity than the most active single agents currently available in the treatment of advanced breast cancer.

Adult↗
PubMed1985

Clinical role of pteridine therapy in tetrahydrobiopterin deficiency.

In most patients with deficiency of tetrahydrobiopterin (BH4) continuous administration of BH4 or of a synthetic analogue such as 6-methyltetrahydropterin (6-MPH4) lowers plasma phenylalanine concentrations to the therapeutic range. The effective dose of BH4 varies from 1 to 2 mg kg-1 daily in patients with defective biopterin synthesis, to 5 mg kg-1 or more in patients with dihydropteridine reductase (DHPR) deficiency. The cost of 2 mg kg-1 day-1 of BH4 is comparable to the cost of a low phenylalanine diet. Higher doses of pterins given orally (20 mg kg-1) raise the levels of tetrahydropterin in cerebrospinal fluid (CSF) to normal in patients with defective biopterin synthesis in whom initial concentration of biopterin species are low. In some, but not all, such patients pterin therapy also raises CSF amine metabolite concentrations and ameliorates symptoms. High dose therapy does not appear to be effective in raising CSF pterin levels in patients with DHPR deficiency who already accumulate dihydrobiopterin (BH2) in CSF. Central folate deficiency is an additional cause of neurological deterioration in patients with DHPR deficiency who require supplementation with folate as folinic acid. It is suggested that the accumulation of BH2 in such patients competitively interferes with folate metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1985

A randomised trial of cyclophosphamide pretreatment ('priming') before short-duration chemotherapy for small cell lung carcinoma.

Forty-five patients with small cell anaplastic carcinoma of the bronchus were treated with four four-weekly courses of a combination of cyclophosphamide, vincristine and methotrexate. Randomisation was carried out to determine whether they received in addition 1 g/m2 of cyclophosphamide 1 week before the three-drug therapy. Patients with limited disease received radiotherapy after their chemotherapy. Myelosuppression was similar in the two groups, but the additional cyclophosphamide did not improve remission duration or survival. Confining the chemotherapy to four courses did not give shorter survival times to those reported in other studies.

Adult↗
PubMed1985

Immunoglobulin profile of the preterm baby.

Immunoglobulin concentrations were determined in 64 consecutively born preterm babies at birth and serially throughout each baby's stay in the neonatal unit. No significant IgG generation was found during the first 15 weeks of life, regression analysis giving an exponential decay model. Concentrations fell to 2 g/l or less in 10 (16%) babies (gestational age 25 to 32 weeks), and were as low as 1 g/l in four babies (gestational age 25 to 29 weeks). The effects of gestational age and birthweight on the concentration of IgG at birth were highly interdependent and significant. Most babies had no detectable IgA at birth, and no effect of gestational age or birthweight, or both, on either initial IgA or IgM concentrations could be shown.

Aging↗
PubMed1985

Amino acid and protein requirements in a preterm infant with classic phenylketonuria.

A preterm infant with classic phenylketonuria required rather less than 90 mg/kg of phenylalanine and between 270 and 290 mg/kg tyrosine daily to achieve a rate of weight gain of around 20 g/kg per day. Using Lofenalac as the low phenylalanine food, the intake of tyrosine, an essential amino acid for patients with phenylketonuria seemed to be limiting in respect of growth.

Amino Acids↗
PubMed1984

The complete DNA sequence and regulatory regions of the Bacillus licheniformis spoOH gene.

We have determined the sequence of a 1228 base-pair cloned DNA fragment from Bacillus licheniformis capable of specifically complementing mutations in the spoOH gene, which is required for the early stage of sporulation in B. subtilis. The sequence has only one long open reading frame consisting of 168 codons. In vivo and in vitro transcription mapping studies indicate the size of complementary RNA to be around 1 kb with the 5' initiation site at base 79 and the 3' termination site in the area of base 1138. This indicates the presence of a 5' untranslated RNA and a fairly long 3' extension. The promoter sequence of this gene is 5'TATAAT3' at -10, and 5'TTGACG3' at -35, a typical E. coli-like promoter sequence, and is transcribed in vitro specifically only by RNA polymerase containing delta 55 and not delta 37-containing holoenzyme.

Amino Acid Sequence↗
PubMed1984

Bacillus subtilis spo0H gene.

A 2.8-kilobase fragment of the Bacillus subtilis chromosome containing a functional spo0H gene was cloned by using a modification of the helper system described by T. Gryczan and co-workers (T. Gryczan, S. Contente, and D. Dubnau, Mol. Gen. Genet. 177:459-467, 1980). The chromosomal segment specifically complements spo0H mutations in recE4 strains and when integrated into the chromosome of Rec+ strains maps in the spo0H region of the B. subtilis genome. A deletion within the transcribed region of the cloned spo0H gene was constructed which abolishes its spo0H+-complementing activity. DNA sequences containing this deletion were introduced into a B. subtilis Rec+ strain containing the spo0H75 mutation. The absence of recombination between the deletion and the spo0H mutation indicates that both reside in the same gene. There is homology between the B. subtilis spo0H gene and a 1.2-kilobase chromosomal fragment from Bacillus licheniformis which also complements B. subtilis spo0H mutations. In vivo transcription mapping experiments have shown that the B. subtilis spo0H gene is transcribed during vegetative growth as well as during sporulation.

Bacillus subtilis↗
PubMed1984

Blood spots on Guthrie cards can be used for inherited tetrahydrobiopterin deficiency screening in hyperphenylalaninaemic infants.

We describe a method of screening for dihydropteridine reductase deficiency and dihydrobiopterin synthesis deficiency--the two inherited defects that cause tetrahydrobiopterin deficiency--using blood spots on Guthrie cards. Dihydropteridine reductase deficiency may be identified positively, and a biopterin value of less than 6.0 micrograms/l in the presence of hyperphenylalaninaemia indicates further investigation for dihydrobiopterin synthesis deficiency.

Adolescent↗