PARATHORMONE DOSAGE AND SERUM CALCIUM AND PHOSPHORUS IN EXPERIMENTAL CHRONIC HYPERPARATHYROIDISM LEADING TO OSTITIS FIBROSABodansky, Aaron; Jaffe, Henry L.
doi: 10.1084/jem.53.5.591pmid: 19869866
1. On a low calcium intake hypercalcemia tended to disappear in chronic hyperparathyroidism on a given dose of parathormone (as large as 6 units per kg.), apparently due to the reduction of a readily available calcium reserve. An increase of either the calcium intake or of the daily dose of parathormone caused a rise of serum calcium and symptoms of overdosage. 2. Hypocalcemia developed in chronic hyperparathyroidism in young puppies on a low calcium diet. Tetany occurred at a calcium level which was higher and a phosphorus level which was lower than in tetania parathyreopriva of young puppies. About 0.1 gm. of calcium daily was apparently sufficient to maintain the serum calcium at a normal level. 3. The serum phosphorus in chronic hyperparathyroidism in young puppies continued at or rose above the high level normal for young animals. Toward the end of long periods of treatment on large parathormone doses (about 5 units per kg.) serum phosphorus approached normal levels, pronounced hypercalcemia was absent but hypotonia and other symptoms of hyperparathyroidism were present. 4. A single dose of parathormone caused early in the treatment and on liberal calcium intakes a more marked relative rise of serum calcium than in normal adult dogs, confirming previous observations (5, 8). Later in the treatment and on low calcium intakes this effect was greatly reduced. Serum phosphorus rose after a single injection of parathormone, even when the effect on the serum calcium was slight or absent. 5. The continued effect of parathormone on serum calcium after prolonged periods of treatment, and the modified response of the serum phosphorus indicate tolerance due to some compensation, rather than immunity. 6. The bone lesions, presenting the essential features of ostitis fibrosa cystica (von Recklinghausen's disease) in varying degrees of severity, depending on the relation of the parathormone dose to the calcium intake and to the duration of the treatment, were most prominent on low calcium intakes, which permitted the use of large doses of parathormone without fatal hypercalcemia and without symptoms of overdosage. 7. Clinical and experimental hyperparathyroidism are compared and discussed. Footnotes Submitted: 12 January 1931
STUDIES IN THE SEROLOGY OF SYPHILISEagle, Harry
doi: 10.1084/jem.53.5.605pmid: 19869867
The discovery (1) that there are many substances with the sensitizing properties hitherto believed peculiar to cholesterol and its derivatives, and (2) that sensitizer can be added to antigen in very large quantities, many times those currently used, and yet continue to increase its complement-fixing efficiency with no danger of giving falsely positive tests has made possible the preparation of an antigen much more sensitive than any now available for use in the Wassermann reaction. 100 gm. of dry powdered beef heart muscle are extracted with 500 cc. ether for 15 minutes at 37°C. with shaking. After filtration with suction , the ether filtrate is discarded. The powder is then dried and extracted for 3 to 5 days with 500 cc. of 95 per cent alcohol, with intermittent shaking. The mixture is filtered, and the moist powder washed on the filter paper with two portions of alcohol, each 100 cc. The alcoholic filtrate and washings are combined and evaporated on the steam bath down to 250 to 300 cc. Cholesterol (0.8 per cent), and sitosterol (0.6 per cent) are then added, and dissolved at 65°–75°C. The excess sensitizer which crystallizes out upon cooling is dissolved just before using by immersing the antigen in a 56°C. bath for a few minutes. It is diluted by pouring the saline rapidly into the antigen. A 1:40 dilution is recommended for use in water bath fixation (½ hour at 37°C.), as well as for the short ice box fixation (8°, 4 hours) and a 1:120 dilution for use in the overnight ice box method (16 to 24 hours at 8°C.), as being well beyond its anticomplementary range; the anticomplementary quantities being 1:5 and 1:25 respectively. There is reason to believe that this antigen possesses almost the maximum sensitivity obtainable. The method of preparation insures its being almost saturated with antigen-lipoids; and more sensitizer could not be added without increasing the turbidity of its dilution in saline to a point where it would interfere with the reading of hemolysis. Any further improvement must await the discovery of better sensitizers. Preliminary experiments indicate that this new sensitizer, sitosterol, will find an immediate application, not only in the Wassermann reaction, but also in a more sensitive flocculation test to be described in a following paper. Footnotes Submitted: 6 February 1931
STUDIES IN THE SEROLOGY OF SYPHILISEagle, Harry
doi: 10.1084/jem.53.5.615pmid: 19869868
Serum, in concentrations greater than 1:25, causes a marked inhibition of complement fixation in general and of the Wassermann reaction in particular. The serum protein is probably adsorbed by the colloidally dispersed lipoid-reagin complexes, forming a protective film which prevents the fixation (adsorption) of complement. This inhibition explains the zone phenomenon in complement fixation: a weakly positive serum may give a completely positive reaction in e.g ., 1:5 dilution, and yet, because of this serum inhibition, may appear completely negative when tested as whole serum. The greater sensitivity of the ice box test is due (1) to the fact that the serum inhibition just described is less marked at lower temperature; (2) to the prolonged incubation time, making for greater specific fixation; (3) to a more marked non-specific destruction of complement by antigen; and (4) a spontaneous deterioration in the longer ice box test. Because of the inhibition by serum protein in high concentration, a quantitative Wassermann technique involving the use of graded quantities of serum is worthless when carried out at 37°C. Even the ice box test, which is less susceptible to this inhibiting effect, will yield a positive reaction with whole serum only when the circulating reagin exceeds a surprisingly high threshold (six to ten times the quantity which could be detected in dilute serum). It is well known that a negative Wassermann, even by a very sensitive test, does not exclude syphilis: it now appears that a negative Wassermann does not exclude circulating reagin. Footnotes Submitted: 6 February 1931
SPECIFIC AND NON-SPECIFIC POLYSACCHARIDES OF TYPE IV PNEUMOCOCCUSHeidelberger, Michael; Kendall, Forrest E.
doi: 10.1084/jem.53.5.625pmid: 19869869
1. Three nitrogen-containing polysaccharides have been isolated from autolyzed cultures of Type IV pneumococcus: (1) a type-specific carbohydrate differing markedly from those of Type I, II, and III pneumococcus, and representing a type of substance hitherto not observed among specific polysaccharides, (2) a chemically similar carbohydrate without specific function, and (3) the "C" substance, or species-specific polysaccharide of Tillett, Goebel, and Avery. 2. The chemical differences between the specific polysaccharides of Pneumococcus are discussed, and the relationship of the new examples to chitin is pointed out and its bearing indicated on the unsettled controversy as to whether or not chitin occurs in bacteria. 3. The data of Tillett, Goebel, and Avery on the "C" substance have been extended. Footnotes Submitted: 1 February 1931
STUDIES ON INFLAMMATIONMenkin, Valy
doi: 10.1084/jem.53.5.647pmid: 19869871
India ink or graphite partides injected into an area of inflammation fail to disseminate to the tributary lymph nodes. When injected into a normal peritoneal cavity they rapidly appear in the retrosternal lymph nodes. When injected into an inflamed peritoneal cavity they are fixed in situ and fail to reach the regional lymph nodes. Graphite particles injected in the circulating blood stream enter an inflamed area both as free particles owing to increased capillary permeability and also as phagocyted material within leucocytes. Bacteria ( B. prodigiosus ) injected into inflamed tissue are fixed at the site of inflammation and fail to disseminate to the regional lymph nodes as readily as when injected into normal tissue. Bacteria ( B. prodigiosus ) injected at the periphery of an inflamed area do not readily penetrate into the site of inflammation. The experiments furnish evidence, in addition to that already provided, that fixation of foreign substances by the inflammatory reaction is primarily due to mechanical obstruction caused by a fibrin network and by thrombosed lymphatics at the site of inflammation. Bacteria ( B. prodigiosus and B. pyocyaneus ) injected intravenously rapidly enter an inflamed area. It is suggested that localization of bacteria in a locus minoris resistentiae may be explained as the result of increased capillary permeability with subsequent accumulation and fixation of bacteria from the blood stream at the point of injury. Footnotes Submitted: 27 January 1931
METABOLISM OF S AND R FORMS OF PNEUMOCOCCUSFinkle, Philip
doi: 10.1084/jem.53.5.661pmid: 19869872
In the present paper are given the results of studies on the respiratory and glycolytic metabolism of Pneumococcus Types I, II, and III, and of the R forms derived from these. The metabolism of the S and R forms are compared, and the relationship between changes in virulence, changes in chemical constitution, and changes in metabolism is discussed. 1. There is no respiration in Ringer solution unless sugar is added. 2. The pH (7.8) that is optimal for growth of pneumococcus is also the pH at which the maximum respiration occurs. 3. The intensity of respiration varies with type in the strains used. The respiratory capacity of Type I is 56 per cent of that of Type III, which in turn is 71 per cent of that of Type II. 4. The anaerobic glycolysis is approximately the same for all three groups. 5. Pneumococcus Type I is capable of aerobic glycolysis. 6. Pneumococcus Types II and III do not effect glycolysis aerobically. 7. The energy set free in respiration is considerably greater than that set free in glycolysis. 8. The oxidation quotient for lactic acid is of the same order as found by Meyerhof in muscle and by Warburg for mammalian tissues. 9. The respiratory capacities of Types I and III are changed on conversion of the smooth to the rough form. ( a ) For Type I the respiration is increased 110 per cent. ( b ) For Type III the respiration is diminished 45 per cent. ( c ) For Type II there is only a slight diminution in respiratory activity (16 per cent). 10. The anaerobic glycolysis is increased about 25 per cent on the average for all R forms irrespective of type derivation. 11. Type I on being converted to the R form, loses its capacity for aerobic glycolysis. 12. Type III, on being converted to the R form, gains the capacity for aerobic glycolysis. 13. The oxygen consumption by Pneumococcus compared with that of the human tubercle bacillus and of mammalian tissue, for the same time intervals, weight for weight, is as follows: ( a ) Pneumococcus Type I consumes thirteen times as much oxygen as does the tubercle bacillus (H37). ( b ) Pneumococcus Type II consumes thirty-four times as much oxygen as does the tubercle bacillus. ( c ) Pneumococcus Type II consumes over twenty times as much oxygen as does isolated rat kidney tissue, and almost 100 times as much oxygen as does isolated dog muscle. Footnotes Submitted: 16 February 1931
CONGENITAL PROTEIN HYPERSENSITIVENESS IN TWO GENERATIONSRatner, Bret; Gruehl, Helen Lee
doi: 10.1084/jem.53.5.677pmid: 19869873
Hypersensitivity actively induced in utero is shown to persist for a longer period than passive sensitization. The degree of hypersensitivity, its duration, and its transmissibility appear to be influenced by the time elapsing between the original injection of the parent and parturition. A pregnant guinea pig receiving a parenteral injection of antigen 2 to 4 days prior to parturition transmits a state of hypersensitivity to two succeeding generations. The sensitization of the F I generation is due to the passage of antigen. The sensitization of the F II generation is due to the passage of antibodies formed in the F I generation. This prevents any further transfer of the hypersensitive state. Though hypersensitivity occurs in two successive generations, the phenomenon is congenital and not hereditary. We believe that this phenomenon demonstrated in the guinea pig is fundamentally related to the problem of congenital sensitization of the human being. Footnotes Submitted: 30 January 1931
STUDIES ON THE ETIOLOGY OF TRACHOMAReimann, Hobart A.; Pillat, Arnold
doi: 10.1084/jem.53.5.687pmid: 19869874
A bacillus which corresponds closely with the description of B. granulosis Noguchi was isolated from 1 of 5 typical cases of trachoma in Chinese. Inoculation of suspensions of this bacillus into the eyelids of M. sinensis monkeys produced scarring and contraction of the tarsal cartilages with the development of a few conjunctival follicles in 2 out of 5 animals. The possible relations of the observed lesions with human trachoma have been discussed. Footnotes Submitted: 6 October 1930
STUDIES IN THE BLOOD CYTOLOGY OF THE RABBITCasey, Albert E.
doi: 10.1084/jem.53.5.695pmid: 19869875
1. Statistical analyses have been made of the weekly variations in the blood counts of groups of normal rabbits to find whether there exists any relationship between the numerical changes occurring in the various cell types. Consecutive blood counts and differential white cell determinations on five groups of normal male rabbits comprising 45 animals in all were made at weekly intervals from October, 1927, to June, 1929, the number of observations on each group varying from eight to thirty-five. 2. The following relationships between the varying group means were found to be consistent and significant:—The number of the red blood cells varied with the amount of hemoglobin per cubic millimeter and with the number of lymphocytes. There was an inverse relationship between the amount of hemoglobin and the number of monocytes. The neutrophiles varied in number with the monocytes; the basophiles with the eosinophiles; and the eosinophiles with the monocytes. Other associations not always similar but of high significance as far as the combined values were concerned, were the relations of the red blood cells with the basophiles and the monocytes. The relations of the neutrophiles with the red blood cells and the hemoglobin were very irregular. 3. Significant association of the white blood cells with variations in the red blood cells and the hemoglobin content were observed. The numerical variations in the group means of the total white cells were associated with similar variations in the group means of the neutrophiles, the lymphocytes, the monocytes, the basophiles, and the eosinophiles almost to the degree of their numerical occurrence in the peripheral blood. 4. With the exception of the total white cells, approximately only half the variations in the group levels of the various cells and of the hemoglobin content can be accounted for on the basis of simultaneous associations with each other. 5. The red blood cells, the lymphocytes, and the basophiles as one group, the eosinophiles and the monocytes as another group, and the hemoglobin content and the neutrophiles as a third group, described a definite shift from a high to a low numerical value during the 2 year observation period. From the standpoint of the magnitude of the shift, the basophiles, the eosinophiles, the monocytes, the lymphocytes, and the red blood cells participated in the order mentioned. The neutrophiles were only slightly affected and the hemoglobin content relatively not at all. 6. No significant relationship was ever found, even in the component groups, between the weekly mean values of the following: the hemoglobin with the basophiles, the eosinophiles, or the lymphocytes; the neutrophiles with the basophiles or the eosinophiles; and the lymphocytes with the eosinophiles or the monocytes. Footnotes Submitted: 3 February 1931