Birthweight of infants with phenylketonuria and their unaffected siblings.
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Biomedical subjects
Publications and source records attributed to I Smith.
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Data are presented which suggest that Duchenne muscular dystrophy (DMD) may have some origin in a severe deficiency of total muscle adenine nucleotides. Using double-blind techniques, this possibility was tested in 16 DMD patients by giving oral allopurinol, a synthetic inhibitor of the purine catabolic enzyme xanthine oxidase. Sublingual procaine adenylate was also briefly tested. Instances of clinical improvement quickly occurred which were statistically significant; they were accompanied by a significant increase in physical strength. These improvements have been maintained for more than 6 mo by administration of a small amount of allopurinol daily. Procaine adenylate had little effect. These results support the above view of DMD and seem to indicate that existing purines, retained and recycled after allopurinol, can sustain such improvement, and that additional adenylate is unnecessary.
Primordial cysts (keratocysts) have been shown to have a greater tendency to recurrence than other jaw cysts. Some radiological features may assist in establishing the diagnosis. Thirteen mandibular primordial cysts have been studied radiologically in detail. Characteristic features are extension along the medulla with minimal expansion except in young children. Margins are generally sharply demaracated and either smooth or scalloped. Cortical resorption occurs before expansion. The cysts may displace adjacent teeth, particularly when unerupted, but generally do not produce root resorption. They may displace the neurovascular bundle. Antero-posterior dimensions in this series ranged from 28 to 77 mm, with a mean of 50 mm.
Spontaneous mutants of Bacillus subtilis resistant to thiostrepton (TSP) exhibit relaxed synthesis of RNA when starved for required amino acids. Intact cells of tsp mutants cannot synthesize the regulatory nucleotides, ppGpp and pppGpp, after amino acid deprivation. Because ribosomes isolated from spontaneous revertants to thiostrepton sensitivity and from wild-type stringent strains can synthesize (p)ppGpp whereas ribosomes isolated from tsp strains cannot synthesize these regulatory nucleotides in the presence of stringent factor, it appears that the lesion is expressed at the level of the ribosome. Genetic mapping, via three-factor transformational crosses, has shown that tsp is closely linked to rif, in the order cysA14, tsp, rif-I, strA. The phenotype of the tsp mutants indicates that they are of the relC type. Their map position indicates that they are different from a previously described B subtilis rel mutation. Ribosomes from the latter strain can synthesize (p)ppGpp in cell-free extracts.
Spontaneous mutations causing resistance to the EF-Tu-specific antibiotic kirromycin have been isolated and mapped in Bacillus subtilis. Three-factor transductional and transformational crosses have placed the kir locus proximal to ery-1 and distal to strA (rpsL) and several mutations affecting elongation factors EF-G and EF-Tu, in the order: cysA strA [fus-1/ts-6(EF-G)] [ts-5(EF-Tu)] kir ery-1 spcA. Purified EF-Tu from mutant strains is more resistant to kirromycin as measured by in vitro protein synthesis and also shows a more acidic isoelectric point than wild-type EF-Tu. This indicates that the kir locus is the genetic determinant (tuf) for EF-Tu and that there is a single active gene for this enzyme in B. subtilis.
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Allosterism allows individual assay of both isoenzymes, one abundant in muscle, of pyruvate kinase (PK), recently reported superior to serum creatine phosphokinase (CPK) in detecting patients with and female carriers of X-linked recessive (Duchenne) muscular dystrophy (DMD). Extensive comparative studies did not support these findings and confirmed the marked superiority of CPK over rariants of PK or other enzymes in sensitivity, stability and convenience. Deducting the adenylate kinase increment (AKI) further refined the CPK assay, eliminating the effect of haemolysis in diagnosis and enabling studies of blood cell content. Both leucocytes and erythrocytes liberated PK and lactate dehydrogenase (LDH) after brief chilling or disruption. Only erythrocytes showed a CPK content, however, constantly adjusted to match that of serum as if by free cell membrane passage, but less accomodating to a sudden large influx of CPK than of LDH, where an apparent buffering effect could account for differences in clinical response.
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A prospective survey is described of 200 consecutive patients who had outpatient laparoscopic sterilizations by coagulation and division of the Fallopian tubes. The procedures were acceptable to patients, free of morbidity or complications and made minimal demands on the existing hospital services.
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In seven hypertensives receiving beta-blocker drugs, and additional reduction in standing blood pressure occurred between 60 and 90 minutes after 40 mg phentolamine by mouth. The occurrence of the postural hypotensive effect was delayed in relation to the reported time of peak plasma concentration of unchanged phentolamine. Supine blood pressure and heart rate were unaffected. Phentolamine has no clinically useful anti-hypertensive effect in conjunction with beta-blockers in patients with essential hypertension.
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Four temperature sensitive mutants of B. subtilis were isolated by localized mutagenesis in the major ribosomal gene cluster, and charcterized genetically and biochemically. Three are mutations which cause temperature sensitivity in the elongation factor Ef-G, and one which has a similar effect on the elongation factor Ef-Tu. They map in a cluster near strA, with the temperature sensitive mutations in Ef-G mapping between the strA gene and the temperature sensitive mutation in Ef-TU.
The nucleotide of Bacillus stearothermophilus 5 S RNA is pC-C-U-A-G-U-G-A-C-A-A-U-A-G-C-G-(G-A-G-A-G-G-)-A-A-A-C-A-C-C-C-G-U-U-C-C-C-A-U-C-C-C-G-A-A-C-A-C-G-G-A-A-G-U-U-A-A-G-C-U-C-U-C-C-A-G-C-G-C-C-G-A-U-G-G-U-A-G-U-U-G-G-G-G-C-C-A-G-C-G-C-C-C-C-U-G-C-A-A-G-A-G-U-A-G-G-U-C-G-U-U-G-C-U-A-G-G-COH; the nucelotide sequence of Bacillus subtilis 5 S RNA is pU-U-U-G-G-U-G-G-C-G-A-U-A-G-C-G-A-A-G-A-G-G-U-C-A-C-A-C-C-C-G-U-U-C-C-C-A-U-A-C-C-G-A-A-C-A-C-G-G-A-A-G-U-U-A-A-G-C-U-C-U-U-C-A-G-C-G-C-C-G-A-U-G-G-U-A-G-U-C-G-G-G-G-G-U-U-U-C-C-C-C-C-U-G-U-G-A-G-A-G-U-A-G-G-A-C-G-C-C-G-C-C-A-A-G-COH. Comparison of the sequence of B. stearothermophilus 5 S RNA to the sequence of B. subtilis 5 S RNA and to that of Bacillus megaterium 5 S RNA (Pribula, C. D., Fox, G. E., Woese, C. R., Sogin, M., and Pace, N. (1974) FEBS Lett. 44, 322-323) indicates that the 5 S RNA isolated from the thermophile contains unique nucleotide sequences not found in 5 S RNAs isolated from the two mesophilic species of genus Bacillus.