The American health care system--introduction.
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Biomedical subjects
Publications and source records attributed to J Lister.
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Although the human U2 and U6 snRNA genes are transcribed by different RNA polymerases (i.e., RNA polymerases II and III, respectively), their promoters are very similar in structure. Both contain a proximal sequence element (PSE) and an octamer motif-containing enhancer, and these elements are interchangeable between the two promoters. The RNA polymerase III specificity of the U6 promoter is conferred by a single A/T-rich element located around position -25. Mutation of the A/T-rich region converts the U6 promoter into an RNA polymerase II promoter, whereas insertion of the A/T-rich region into the U2 promoter converts that promoter into an RNA polymerase III promoter. We show that this A/T-rich element can be replaced by a number of TATA boxes derived from mRNA promoters transcribed by RNA polymerase II with little effect on RNA polymerase III transcription. Furthermore, the cloned RNA polymerase II transcription factor TFIID both binds to the U6 A/T-rich region and directs accurate RNA polymerase III transcription in vitro. Mutations in the U6 A/T-rich region that convert the U6 promoter into an RNA polymerase II promoter also abolish TFIID binding. Together, these observations suggest that in the human snRNA promoters, unlike in mRNA promoters, binding of TFIID directs the assembly of RNA polymerase III transcription complexes, whereas the lack of TFIID binding results in the assembly of RNA polymerase II snRNA transcription complexes.
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The development of elastic fibres in the upper urinary tract was studied in 31 fetuses ranging in ovulatory age from 10 to 24 weeks using special staining techniques for elastic fibres. The number, orientation and distribution of elastic fibres are described and correlated with age, ureteric level, and fetal weight. Significantly, before 10 weeks, elastic fibres were few in number, poorly developed, and randomly arranged. After 12 weeks, these fibres became more numerous at each level of the urinary tract, and were seen to develop specific orientation. The findings are described and potential clinical implications are discussed.
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In order to interpret the interrelation of cholinergic and adrenergic myenteric neural elements in the developing human, histochemical methods were used to demonstrate cholinergic and adrenergic activity independently in consecutive cryostat sections of the esophagus, ileocecal region, and colon of fetuses of 9 to 22 weeks ovulation age. At least some of the neural cells remained plastic, with respect to their transmitter choice, and showed both cholinergic and adrenergic function. These cells were shown to be present first in the ileocecal region (11 weeks) then in the esophagus (12 weeks) and lastly in the colon (14 weeks). Our findings support the hypothesis of a dual gradient of maturation of enteric neurons. The choice of transmitters is influenced by a "microenvironmental" factor, which may also arrest the maturation or cause the death of neurons.
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In order to study the effects of impaired fetal intestinal absorption of amniotic fluid, two series of neonates (551 from Liverpool and 172 from Rome) with different types of congenital gut obstruction were divided into two groups and compared. Group A consisted of patients with complete obstruction at or above the proximal jejunum (within 15 cm of the ligament of Treitz). Patients of group B had either incomplete obstruction at group A level or either incomplete or complete obstruction at a lower level. Maternal hydramnios and fetal growth retardation rates were found to be significantly higher in group A than in group B. Maternal hydramnios was associated with an increased prematurity rate (P less than .001). Fetal growth retardation was not related to the presence of additional anomalies. In group A growth retardation was more frequent in babies born after 37 weeks of gestation (P less than .05). No differences were found between the Liverpool and Rome series of patients. These findings suggest that fetal gut function not only contributes to the control of amniotic fluid volume but also, in the final stages of pregnancy, to normal fetal growth. Maternal hydramnios may be the cause of premature delivery of fetuses with upper gut obstructions.
There are conflicting views in the literature about the relationship between the extent of muscle hypertrophy in infantile hypertrophic pyloric stenosis (IHPS) and the age of the patient and duration of symptoms. This study was undertaken to elucidate the exact nature of these relationships. The degree of muscle hypertrophy was assessed by measurement of the DNA concentration in biopsy specimens, a technique that has been used to quantify organ hypertrophy objectively and accurately. Forty-one patients were studied prospectively over 12 months. The results show that the degree of hypertrophy is not age-related, and that all the patients tend to progress to about the same degree of hypertrophy, which then remains constant regardless of the duration of symptoms.
In order to determine the possible implication of elastin in spasticity of the aganglionic segment in Hirschsprung's disease the elastic fibers in the colon at rectosigmoid level were studied in seven surgical specimens of aganglionic bowel and in seven normal controls. Elastic fibers in both the muscle layers of normal bowel are thin, tend to be straight, and follow the line of muscle fasciculi. In aganglionic bowel, however, the fibers are more numerous and thicker in both layers, and in the longitudinal layer they are laid down in spirals. The total elastin content is increased by approximately 100% as compared with controls. These structural and quantitative changes in the elastin may contribute both to the spasticity and to the increased elasticity of the aganglionic segment.
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The sera of 26 patients with graft versus host disease (GVHD) were analyzed for the presence of autoantibodies. Because the clinical spectrum of GVHD resembles some of the systemic collagen vascular diseases, particular attention was given to antinuclear antibodies and autoantibodies directed against saline soluble cellular antigens. 39% (10/26) of the patients had a positive ANA at a titer of greater than or equal to 1/80. Antibodies to double-stranded DNA were demonstrated in 4 sera (15%), to smooth muscle in 9 (41%) and to nucleoli in 6 (22%). Three sera had precipitating antibodies to saline extracts of rabbit thymus and/or bovine spleen. None of these precipitins showed lines of identity with known autoantibody systems. High titers of ANA were correlated with a previous diagnosis of acute lymphoblastic leukemia and multiple autoantibodies correlated with the severity of GVHD.
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