Citations

The chief points presented in this paper are: 1. Following the ingestion of buckwheat (plant or seed) varicolored guinea pigs, white swine and goats exhibited symptoms of photosensitization, the degree of sensitization being in the order given. 2. Rabbits, dogs, white mice and rats did not manifest symptoms of photosensitization. 3. The symptoms and reactions were: agitation, itching, scratching of the ears, weakness, urticaria with sloughing and symptoms similar to those in anaphylaxis. 4. Microscopic examinations showed the lack of marked pathologic change. The lesions, such as petechial hemorrhage of the lungs, brain, liver, stomach and kidneys, suggest that profound toxemia has been present. 5. Lesions were not found which appeared to be suggestive of malignant neoplasms. 6. Irradiation by a quartz mercury vapor lamp apparently develops a resistance to photosensitization, probably because of increased pigmentation induced by ultra-violet light. 7. From the nature of the physiologic and pathologic reactions produced under various filters and from a consideration of the percentages of transmission of solar energy in the visible spectrum, it would seem that the region of photosensitization lies between 580 millimicrons (yellow) and the red end of the spectrum. This conclusion, moreover, is substantiated by the fact that irradiation by a quartz mercury vapor lamp (which radiates no energy in the visible spectrum at a wave-length greater than 579 millimicrons) produces no symptoms or reactions. 8. Spectrophotometric determinations of alcoholic extracts of grass (non-toxic) and of buckwheat (toxic) show the presence of two additional bands in the absorption spectrum of buckwheat with maxima at about 540 and 600 millimicrons, respectively, together with the common absorption zones at 430 to 490 millimicrons and 630 to 690 millimicrons. 9. Spectrophotometric determinations of blood serums of sensitized animals show, besides the usual absorption bands peculiar to oxyhemoglobin (with maxima at 540 and 580 millimicrons respectively), two zones with maxima at 600 and 660 millimicrons respectively. 10. The fluorescence of chlorophyll per se, as suggested by previous investigators, is not, in all probability, the cause of the sensitization induced by buckwheat. 11. Hematoporphyrine is not the photodynamic substance in all probability. 12. Phylloporphyrine may be the photodynamic substance. In this regard, also, the possibility of cholehematin is not to be ruled out.

1. Distilled water dialyzes through the collodion tube and causes hemolysis. Clotting of the hemolyzed blood in the collodion tube occurs later. 2. Bile salts accelerate the appearance and development of white thrombi in the heparinized animal. The masses of white thrombi are very loose, soft, fragile and easily broken into clumps of platelets. They are poor in fibrin or the fibrin is abnormal, since they have less retractility than those obtained from the use of physiologic sodium chloride solution or calcium chloride or serum. Despite the increase in number and size of white thrombi, normal clotting does not occur. 3. When the collodion tube is surrounded by 1 or 2 per cent d-glucose solution, tiny and numerous white thrombi appear as radiating figures. The masses of white thrombi are rather loose and fragile. The clotting time of the heparinized blood does not appear to be shortened. 4. When a 1 to 2 per cent solution of calcium chloride is used as the dialyzing fluid outside the collodion tube, or when it is injected into the circulation, the formation of white thrombi is accelerated. They grow very rapidly. In spite of the action of heparin, the white thrombi formed are not so fragile as when bile salts are placed outside of the collodion tube. Fibrin seems to form easily. Obstruction of venous cannula takes place speedily and if the clots in the cannula are not removed, the white thrombi in the collodion tube remain small and become red by sedimentation of red cells. 5. Intravenous use of 10 per cent solution of magnesium sulfate without heparin retards the coagulation of circulating blood and permits the blood to flow through the extracorporeal loop from three to four times as long as normal. The formation of white thrombi, as well as red, is retarded. Magnesium sulfate (1 per cent) in physiologic sodium chloride solution placed outside the collodion tube markedly retards the formation of white and red thrombi in the heparinized animal. Magnesium sulfate (10 per cent), 50 mg. for each kilo of body weight each hour, administered intravascularly in the heparinized animal definitely prevents the first stages of thrombosis, and consequently prevents clotting. 6. It is possible by the combined use of adequate amounts of magnesium sulfate and of heparin intravenously to prevent all stages of thrombus formation for from 1 to 3 hours.

The effects of environmental temperature on thrombosis in circulating blood were tested in the extracorporeal loop by the method previously described. Cold (7° to 15°C.) about the collodion tube retards the clotting of circulating blood. Obstruction of the arterial cannula occurs after from 15 to 25 minutes. Heat (40° and 55°C.) tends to hasten clotting; obstruction by red clot takes place after from 4 to 6 minutes and from 2 to 4 minutes, respectively. In the latter case no characteristic thrombus structure may be seen. These results were what might be expected. The formation of white thrombi occurs even under the influence of cold, and they continue to form and grow as long as the circulation continues. When the carotid artery is partially occluded and the blood stream slowed, after the injection of the anticoagulant, the blood has a tendency to form red thrombi on the foreign surface of the vascular loop. The thrombi are deposited chiefly in the arterial half of the apparatus, especially at the bottom of the arterial end of the collodion tube, just as in the case of Aschoff's sand experiments. In spite of incoagulability of heparinized blood, red clots, with interwoven fibrin bands, are found. Also very tiny white thrombi may form in other parts of the collodion tube. The effect of complete obstruction of the carotid artery and jugular vein on thrombus formation was studied after the use of anticoagulant. When the carotid artery is obstructed the formation of white thrombi is negligible and sedimentation of erythrocytes and deposition of fibrin appear throughout the apparatus; then the blood, at a standstill, clots very slowly. When the jugular vein is obstructed, dislodgment of platelet thrombi probably results from the pulsating movement, and sedimentation of erythrocytes follows, forming mixed thrombi. The dislodged white thrombi tend to gather in the bottom of the tubes of the widest caliber, especially in the collodion tube.

A new method has been described for the study in vivo of thrombus formation in blood circulating extracorporeally in an artificial loop. This method permits of control of many factors, and hence of intensive study of thrombus formation under many and varied conditions. It admits of separate study of the formation of white thrombi and of the deposition of fibrin, which may apparently be independent processes.

1. Effects of anticoagulants, heparin and hirudin, on extracorporeal thrombosis were studied in thirty-three experiments by means of the extracorporeal vascular loop. In spite of adequate single doses of the anticoagulants white thrombi are formed and obstruction to flow may follow in the course of time, but the formation of red thrombi is markedly retarded. 2. The new method throws some light on the mechanics of thrombosis. The influences of foreign surfaces, of irregularities on the surface of the vessels, of whirlpools and of eddying motion of the blood current and of slowing and of stagnation with consequent prolonged contact with foreign surfaces are demonstrated, and these are analyzed in respect to the laying down of platelets and leucocytes. 3. The structure of white thrombi formed after anticoagulant injection is almost identical with that described by Welch. In one respect, however, the present results appear to differ from his: the formation of fibrin is postponed and retarded, and hence the collections of platelets are deposited in greater amount.

Thrombus formation has been studied in normal rabbits with an experimental method of establishing extracorporeal circulation. In the normal animal circulation in the extracorporeal loop usually ceases in from 6 to 10 minutes, or at most, in very large and vigorous animals, in 25 minutes.1 Cessation of the circulation is due most frequently to obstruction of the venous cannula (sometimes of the arterial cannula) by a mass of white thrombi and secondary fibrin formation around it. The site of the clot is determined somewhat by the swiftness of the blood stream. In the collodion tube red mural thrombi are obtainable as a rule. They are flat and present a wide base resting on tiny white thrombi. After the complete obstruction of the circulation, the blood in the apparatus clots very rapidly. When the obstruction occurs very quickly either in the arterial or venous cannula, or when the blood stream is very slow, the clotting in the loop may occur before platelets are laid down in large numbers or before the formation of the white thrombi is evident. Mixed thrombi are found in the jugular vein, and have their inception in the white thrombi, in the cannula or from the injured intima. They extend in the direction of the blood flow.

AbstractBackground: One of the numerous proteins causing amyloidosis is transthyretin (TTR), a protein usually responsible for the transport of thyroxine and retinol-binding protein. Variants within TTR cause it to aggregate and form insoluble fibers that accumulate in tissue, leading to organ dysfunction.Methods: TTR was immunoprecipitated from serum by use of a polyclonal antibody and subsequently reduced with tris(2-carboxyethyl)phosphine. The purified TTR was then analyzed by fast-gradient liquid chromatography–dual-electrospray ionization Fourier-transform ion-cyclotron-resonance (FT-ICR) mass spectrometry. DNA sequencing was performed on all samples used in this study.Results: Because of the inherent limitations in achieving high mass measurement accuracy based on the most abundant isotopic mass, we applied a fitting procedure that allowed determination of monoisotopic mass. Wild-type TTR (mean molecular mass, 13 761 Da) and its associated variant forms could be distinguished because of the high molecular mass accuracy afforded by FT-ICR (≤3 ppm) except for instances involving isobaric species or when isotopic distributions overlapped significantly. The [M + 11 H+]11+ charge state for all samples was used to determine the mass accuracies for both wild-type and variant forms of the protein. We correctly assigned seven of seven TTR variants. Moreover, using a combination of proteomic and genomic technologies, we discovered and characterized a previously unreported cis double mutation with a mass only 2 Da different from wild-type TTR. Furthermore, DNA sequencing of the TTR gene for all individuals in this study completely agreed with the intact protein measurements.Conclusions: FT-ICR mass spectrometry has sufficient mass accuracy to identify genetic variants of immunoaffinity-purified TTR. We believe that 91% of known TTR variants could be detected by this technique.

1. In acute experimental hydronephrosis chloride retention occurs as well as retention of water, urea, and phenolsulfonephthalein. 2. If both water and chlorides are retained there may be no appreciable rise in the plasma chloride content. 3. When chlorides are retained, but not water, the chloride content of the plasma rises strikingly. 4. After the removal of the ureteral obstruction in acute hydronephrosis all renal functions, water, urea, and chloride excretion, may be rapidly restored in equal degree, or the chlorides may be retained temporarily while there is free excretion of water and urea. 5. In chronic hydronephrosis adequate daily excretion of urea and chlorides may be maintained by a compensatory polyuria. 6. Chloride retention or an abnormal chloride excretion may occur in certain renal lesions when there is no change in the urea, phenolsulfonephthalein, or water excretion.

Seven autoplastic transplantations and one homoplastic transplantation of the spleen of dogs were made. One autotransplantation was successful, the gland being normal at the end of 88 days.

Our experiments on dogs showed that the thyroid gland which was autoplastically transplanted, by means of various methods of blood vessel anastomosis, could live in good condition and functionate favorably several months after the operation, even after the interruption of the circulation for 1½ hours. They further showed that the circulation through the transplanted blood vessels as well as glands was as good as normal, and that permanent successful results of the homoplastic transplantation of the gland are as yet not possible.