Erratum: Charm production in nonresonant e+e- annihilations at sqrt s =10.55 GeV
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Biomedical subjects
Publications and source records attributed to R Ehrlich.
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Transgenic mice containing a swine class I major histocompatibility complex (MHC) gene, PD1, express swine MHC (SLA) antigen. The tissue distribution of PD1 RNA parallels that observed in the swine, indicating that the expression of PD1 is regulated and that trans-acting factors involved in this regulation have been conserved between the species. Although PD1 RNA levels were much greater in transgenic spleen than in thymus, no difference in the chromatin organization of the PD1 gene was detected. In both tissues, a single DNase I hypersensitive site mapped within the 5' flanking region. In vivo treatment of the transgenics with mouse alpha, beta-interferon increases PD1 expression in a number of tissues. In the spleen, this increase parallels that observed for the endogenous transplantation antigen, Kb, but differs markedly from the differentiation antigen, Qa-2. Increases in cell surface expression of both PD1 and Kb occurred equally in splenic T- and B-cell populations following alpha, beta-interferon treatment. In contrast, Qa-2 expression in B cells was enhanced by alpha, beta-interferon, whereas it was unaffected in T cells and thymocytes.
We surveyed 311 children with insulin-dependent diabetes mellitus to evaluate the frequency and characteristics of those children experiencing severe hypoglycemia (defined by an episode of coma, convulsion, or both). The children and their parents completed a questionnaire, and we reviewed the hospital records to confirm reported episodes. Ninety-seven (31%) reported severe hypoglycemia, and a further 50 (16%) reported moderate hypoglycemia requiring the assistance of another person but not resulting in coma or convulsion. In 164 children (53%) there was no history of either moderate or severe hypoglycemia. Sixty-nine (22%) reported the occurrence of more than one severe hypoglycemic episode (range 2 to 20); 52 (16%) reported such an event in a single year. A total of 285 episodes were reported, 39% during sleep and 61% while awake. Children reporting such events tended to have diabetes of longer duration and be younger at the time of the first episode. Hemoglobin A1c concentration at the time closest to the severe episode was significantly lower than in children reporting no hypoglycemia. All families had been taught to use glucagon to reverse severe hypoglycemia at home, but it was available in only 80 of the 97 homes and used in only 30. These data suggest that severe hypoglycemia is common in children with insulin-dependent diabetes mellitus who are treated conventionally. Greater vigilance and education are required both to prevent and to treat severe hypoglycemia in children with insulin-dependent diabetes mellitus.
Deoxyribonucleic acid ploidy as determined by flow cytometric analysis was compared to histological findings and tumor stage for accuracy of prediction of patient survival in a series of Wilms tumors. While anaplastic tumors were more likely aneuploid or tetraploid than diploid, no statistically significant relationship was found between deoxyribonucleic acid ploidy and patient survival in our series. Tumor histology and stage as defined by the National Wilms Tumor Study were more accurate predictors of patient survival than deoxyribonucleic acid ploidy.
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We showed earlier that the region of the bla promoter of Tn3 protected by the RNA-polymerase (RNAP), has the normal size (about 60bp) at RNAP/promoter molar ratio r less than or equal to 2, but rises to about twice this extent as r increases. We confirm here that the species corresponding to normal and extended footprint distinguish by their electrophoretic mobilities. Furthermore, inspection of the complexes by electron microscopy confirms that at r greater than 2, the bla promoter can bind specifically a second RNAP particle, as compared to the 1:1 complex observed at r less than or equal to 2. At r greater than 2, the ability of the bla promoter to initiate transcription in vitro is repressed when compared to the complex 1:1 obtained at r less than or equal to 2. The unexpected decrease in initiation efficiency as the concentration of RNAP particles is increased, together with the striking sequence homology of the bla promoter with promoters of stable RNA, suggest that in vivo, this promoter could be regulated by growth rate.
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The structure of the final initiation complex between E. coli RNA polymerase (RNAP) and the bla promoter from the transposon TN3 has been probed by footprinting experiments and base accessibility to dimethyl sulfate at 37 degrees C. At RNAP/promoter molar ratios "standard" for these experiments (greater than or equal to 10), the contacts on bla extend from -100 to +20, i.e. a length exceeding twice the dimension of the RNAP major axis [33]. Since footprinting at about equimolar amounts of RNAP and bla extends to the usual (-55 to +20) promoter domain, it is very likely that at least two RNAP's participate in the complex observed at tenfold higher RNAP/bla ratios. Under the latter conditions, the extended footprint (-100 to +20) is observed above 30 degrees C, whereas at 15 degrees C, only the -55 to +20 promoter area is contacted. Furthermore, gel retardation experiments show the presence of two complexes of different migration rates. We have reported earlier [21] that at the "standard" RNAP/bla ratio, transcription initiation from the bla promoter is inhibited. The correlation of this inhibition with the postulated two RNAP/bla complex suggests a regulation of bla gene expression by RNAP availability controlled for instance by growth rate. These results can be correlated with those reported in [14, 15] for the tyrT promoter. Interestingly, both promoter share significant sequence homologies.
Congenital hypothyroidism (CH) can be due to an absent gland (athyrosis), an ectopic gland (usually lingual), or an inborn metabolic error (goiter). In this study, radionuclide scanning was compared with ultrasound (US) and serum thyroglobulin (Tg) concentration as a method of determining the cause of CH in 50 newborns. Mean serum Tg values were significantly lower in athyrotic children (7.9 pmol/L) than in either those with goitrous (149.1 pmol/L) or ectopic (60.5 pmol/L) glands, but there was marked overlap among all three groups. With the interpreter "blinded" to the radionuclide diagnosis, a cervical gland could be delineated reliably on US. All 12 goiters and five of five normal glands were identified. In contrast, the correlation between US and radionuclide scanning was poor in patients in whom there was no cervical thyroid tissue. Ultrasound failed to identify 13 lingual glands and was reported as normal in four of 12 children with no radionuclide uptake in the neck and biochemical hypothyroidism. Two children with absent thyroid glands on scanning were biochemically euthyroid. The serum of two others who had normal results of radionuclide studies showed persistent hypothyroidism. Thyroid scanning remains the most accurate diagnostic modality to determine the cause of CH. Serum Tg and cervical US have not been established as reliable alternatives.
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Regulatory DNA sequence elements were functionally identified in the 5'-flanking region of a gene, PD1, which encodes a porcine classical transplantation antigen. Both a positive regulatory element and a novel negative regulatory DNA element were mapped within 1.1 kilobases upstream of exon 1. The negative regulatory element reduced the activity of both the homologous PD1 promoter and a heterologous simian virus 40 promoter. In vivo competition experiments indicated that the functions of the PD1 positive and negative regulatory elements are mediated by distinct cellular trans-acting factors. The PD1 positive regulatory element interacted with cellular factors in common with those binding to the simian virus 40 enhancer. Finally, the negative regulatory element required the presence of a positive regulatory element to function. This interaction between positive and negative regulatory elements represents a novel mechanism for regulating gene expression.
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