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Biomedical subjects
Publications and source records attributed to S Simon.
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A retrospective study was performed to determine the course of limb-length discrepancies occurring in patients with monoarticular and pauciarticular juvenile rheumatoid arthritis. Data were assessed on thirty-six patients followed to skeletal maturity, on fifteen patients who had not reached skeletal maturity but who had been followed for four years or more, and on forty-nine patients followed for three years or less. In seventy-two of the total of 100 patients the onset of the disease occurred before they were five years old, and ninety patients had involvement of the knee. All patients in whom the disease developed before the age of nine had overgrowth of the involved extremity, but that overgrowth never exceeded 3.0 centimeters. The major discrepancy developed within the first three or four years and either increased very slowly thereafter, remained level, or decreased. Of the thirty-six patients who were followed to skeletal maturity, in twenty-nine a discrepancy of 1.5 centimeters or more developed at some time during the period of assessment. Twelve of the thirty-six patients had diminution of the discrepancy to the extent that epiphyseal arrest was not required. Fifteen eventually had an epiphyseal arrest. Rapid premature closure of the epiphyseal growth plate occurred only in those patients in whom the disease developed after the age of nine years. This led to immediate shortening of the involved side and on occasion to marked limb-length discrepancies.
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In the parents of 250 diabetic children the occurrence of juvenile and maturity onset diabetes was found to be more frequent than in the parents of 230 medical students. Assuming a multifactorial poligeneic heredity, the role of common genes predisposing to diabetes cannot be neglected in the manifestation of the two types of the disease. In the families where juvenile diabetes had occurred, the probability of occurrence of juvenile diabetes is considerably higher than that of maturity onset diabetes. This might be in connection with the fact that the provocative factors are different in juvenile and maturity onset diabetes.
We have determined the low temperature EPR spectra and room temperature ligand dissociation rate constants of human NO-hemoglobins F and A as a function of pH and inositol hexaphosphate levels in order to assess the contribution of a quaternary structural equilibrium in the two proteins to their spectral and functional properties. Our results are consistent with an increased stability of a ligated low affinity structure in the fetal protein; the functional properties of this structure appear to be essentially the same in the two hemoglobins, even though its stability relative to a high affinity conformation is different. The pH dependence of the NO dissociation constant in both adult and fetal hemoglobin can be assigned primarily to the pH-dependent equilibria of high and low affinity forms as monitored by EPR.
The simultaneous occurrence of HLA B8 and BW15 and B8 antigens is significantly more frequent in diabetic children than in the general population. BW15 alone shows no significant difference but may be considered as a potentiating factor. The relative risk of the manifestation of diabetes in the highest when HLA B8 and BW15 occur simultaneously. In the nearest diabetic relatives of diabetic children the occurrence of B8 and B8 and/or BW15 antigens is significantly more frequent than in the diabetic child population.
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The occurrence of diabetes mellitus and Addison's disease together is discussed by the authors. The female patient described here had diabetes at the age of four; Addison's disease appeared when the patient was 19 years old. Four years prior to the appearance of Addison's disease, an ophthalmoscopic examination revealed microaneurysms. The examination of the fundus of the eye was negative when Addison's disease, was diagnosed. An HLA-B8 antigen positivity was established. The authors discussed the pathogenetic relationship of HLA-B8 antigen positivity, diabetes mellitus, and Addison's disease.
Rabbits generally numbering 27 or 36 in each experiment were injected in 1970 with doses of the pyrogenic preparation Pyrago (HUMAN) and in 1971-72 and 76 with doses of the International Pyrogen Standard (I.P.St.). The maximum temperature rises were registered, randomized and interpreted according to the requirements of the BP, USP, P. Hung. and P. Nord. 0.29 degrees C mean temperature rises proved to be non-pyrogenic according to BP and P. Hung; whereas according to the USP and P. Nord. in some percents 'to be rejected' qualifications were also established. At more increasing mean temperature rises 0.49 degrees C and 0.58 degrees C, increasing pyrogenic and decreasing 'passable' qualifications were obtained. Beginning with 0.70 degrees C and at 0.86 degrees C and 1.08 degrees C, 'passable' groups disappeared. Exclusion of the rabbits showing low sensitivity (before randomization) barely influenced the results with 3.5 ng kg-1 I.P.St. in the experiment in which the mean temperature rise was 0.49 degrees C. If, however, the mean temperature rise was higher (0.57 degrees C or 0.69 degrees C), such a selection practically resulted in the disappearance of 'passable' qualifications in the triplet groups and a great predominance of 'to be rejected' qualifications in the large groups.
The pH dependence of several functional properties of human fetal and adult hemoglobins have been studied to determine the relative stabilities of the high and low affinity (R and T) quaternary conformations of the two proteins under different conditions. Fetal aqumethemoglobin undergoes changes in sulfhydryl reactivity, absorption spectrum, and circular dichroism in the presence of insitol hexaphospahte which are consistent with a transition from the R to T quaternary state, but only at pH values below 6.8. In adult hemoglobin this transition can be induced pH values below 7.2. Even in the absence of phosphates, the ultraviolet (uv) circular dichroism spectrum of fetal aquomethemoglobin at low pH indicates the presence of some T conformation. The initial value for the second-order rate constant for combination of fetal deoxyhemoglobin with carbon monoxide is comparable to that for adult hemoglobin in the absence of organic phosphates and is not reduced by organic phosphates as much as that for the adult protein. The apparent first-order rate constant for dissociation of CO from fully liganded fetal hemoglobin, measured by replacement with NO, increases threefold in the absence of organic phosphates, and fourfold in the presence of organic phosphates, with decreasing pH; the midpoint of the pH dependent transition occurs around 6.8. A similar increase in the apparent first-order rate constant for O2 dissociation as measured by replacement with CO, can also be seen with decreasing pH. NO-hemoglobin F can be converted to the T state even when fully liganded simply by lowering the pH, as judged by uv circular dichroism, visible difference spectrum in the region of the alpha and beta bands, and a dramatic increase in the rate of NO dissociation, measured by replacement with CO in the presence of dithionite. These results are all consistent with a model for fetal hemoglobin in which the organic phosphate site may be functionally weakened by replacement of a residue involved in ionic interactions with the negatively charged phosphate groups, but in which the low affinity T conformation is intrinsically more stable than that of adllt hemoglobin. According to this model,the differences between fetal and adult hemoglobin can be accounted for primarily in terms of the relative stabilities of R and T conformations in each of the proteins with differences in the intrinsic properties of the individual conformations contributing effects of only secondary importance.
The formation of planar bilayer membranes from lipid monolayers as described by Montal and Mueller (Proc. Natl. Acad. Sci. 1972. 69:3561) is analyzed. Bilayers absolutely free of alkane solvents or other nonpolar hydrocarbons can be formed on polytetrafluoroethylene (PTFE) (e.g. Teflon) septa only if certain boundary conditions are satisfied. Measurements have been made of the contact angles between monolayer-coated water and PTFE in the presence and absence of alkane solvents. The measurement suggest that the boundary conditions for formation of stable bilayers can be satisfied only when a nonpolar solvent is present. We conclude that the bilayer must be surrounded by a torus of alkane solvent, petroleum jelly, or silicone grease depending upon the details of technique used to form the bilayer. The non-polar solvent used in the formation of the bilayer may or may not be present in the bilayer depending upon the water solubility and size of the solvent molecule relative to the size of the alkyl chain of the lipid. Detailed sketches describing the formation of bilayers from monolayers are presented.
Rabbits, 27 or 36 in each experiment, were injected with the International Pyrogen Standard (I.P.St.) in different seasons. The maximum temperature rises were registered, randomized and interpreted according to the requirements of the B.P. (1973), U.S.P. (1970), P. Hung. (1970) and P. Nord. (1962). Although the dose of 3.5 ng kg(-1) I.P.St. proved to be non-pyrogenic as tested in summer, when tested in winter the same dose was qualified pyrogenic (to be rejected) by up to one third of the combinations by the criteria of the four Pharmacopoeias. In the spring experiment "to be rejected" qualifications predominated as based on the response of large groups of rabbits. Exclusion of the rabbits showing low sensitivity (before randomization) barely influenced the results with 3.5 ng kg(-1) I.P.St. in the experiment in which the mean temperature rise was 0.49 degrees. If, however, the mean temperature rise was higher (0.57 or 0.69 degrees), such a selection practically resulted in the disappearance of "passable" qualifications in the triplet groups and a great predominance of "to be rejected" qualifications in the larger groups. The dose 7.0 ng kg(-1) consistently proved to be pyrogenic in large groups of rabbits.
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