Orientation of chromophores in reaction centers of Rhodopseudomonas sphaeroides. Evidence for two absorption bands of the dimeric primary electron donor. Chromatophores from Rhodopseudomonas sphaeroides were oriented by allowing aqueous suspensions to dry on glass plates. Orientation of reaction center pigments was investigated by studying the linear dichroism of chromatophores in which the absorption by antenna bacteriochlorophyll had been attenuated through selective oxidation. Alternatively the light-induced absorbance changes, in the ranges 550-650 and 700-950nm, were studied in untreated chromatophores. The long wave transition moment of reaction center bacteriochlorophyll (P-870) was found to be nearly parallel to the plane of the membrane, whereas the long wave transition moments of bacteriopheophytin are polarized out of this plane. For light-induced changes the linear dichroic ratios, defined as deltaav/deltaah, are nearly the same for untreated and for oxidized chromatophores. Typical values are 1.60 at 870 nm, 0.80 at 810nm, 1.20 at 790 nm, 0.70 at 765 nm, 0.30 at 745 nm , and 0.50 at 600 nm. The different values for the absorbance decrease at 810 nm (0.80) and the increase at 790 nm (1.20) are incompatible with the hypothesis that these changes are due to the blue-shift of a single band. We propose that the decreases at 870 and 810 nm reflect bleaching of the two components of a bacteriochlorophyll dimer, the "special pair" that shares in the photochemical donation of a single electron. The increase at 790 nm then represents the appearance of a monomer band in place of the dimer spectrum, as a result of electron donation. This hypothesis is consistent with available data on circular dichroism. It is confirmed by the presence of a shoulder at 810 nm in the absorption spectrum of reaction centers at low temperature; this band disappears upon photooxidation of the reaction centers. For the changes near 760 nm, associated with bacteriopheophytin, the polarization and the shape of the "light-dark" difference spectrum (identical to the first derivative of the absorption spectrum) show that the 760 nm band undergoes a light-induced shift to greater wavelengths.


Transfer of spleen cells from young to aging NZB X NZW F1 hybrid mice. Effect on mortality, antinuclear antibody, and renal disease. Multiple injections of spleen cells from young NZB x NZW F1 hybrid mice with a mean age of 9 weeks were administered to syngeneic recipients at 10-day intervals beginning at 3 months of age. The recipient mice had a dealyed appearance of antinuclear antibody, decreased cumulative incidence of antinuclear antibody positivity up to 7.3 months of age, lower cumulative mortality up to 8 months of age, and a lesser degree of glomerular sclerosis at 8 months of age. By 9 months of age no significant differences in these parameters remained. Transferred cells were most effective during the 4- to 6-week period immediately following initiation of injections. The beneficial effects appeared to reflect an early but temporary suppression of the autoimmune process by the transferred lymphoid cells.


The interaction of alpha-1-antitrypsin with soluble and sepharose-bound elastase. The products resulting from the interaction of alpha-1-antitrypsin with elastase were examined with polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate, and by affinity chromatography. Five products of the reaction can be identified by polyacrylamide disc gel electrophoresis. Two products are complexes between alpha-1-antitrypsin and elastase (73 800 and 58 300 daltons). Two additional products are identical to fragments of alpha-1-antitrypsin which can be washed from a column of Sepharose-bound elastase immediately after alpha-1-antitrypsin is applied to the column. The larger component about 50 000 daltons, reacts with antiserum to alpha-1-antitrypsin, and does not inhibit enzymes. Together, these two products have an amino acid analysis similar to alpha-1-antitrypsin. These two fragments are probably hydrolytic products of the interaction of elastase with alpha-1-antitrypsin which is biologically inactive. The fifth product is probably a fragment of alpha-1-antitrypsin missing from the low molecular weight complex. The components of the complexes can be separated from each other by a mild nucleophilic attack. Small quantities of alpha-1-antitrypsin can be displaced from the elastase affinity column by phenyl methane sulfonyl fluoride. In conclusion, porcine pancreatic elastase forms two complexes with alpha-1-antitrypsin. One or both complexes can be split by alkali.


Effect of furosemide on unidirectional fluxes of sodium and chloride across the skin of the frog, Rana pipiens. 1. The diuretic furosemide, when added to the outside solution at a concentration of 5-10-4 M, increases the electrical potential difference (PD) across the isolated frog skin, but the short-circuit current (Isc) is unchanged. Lower concentrations had no significant effect on these electrical parameters. 2. When SO42- or NO3- are substituted for Cl- in the Ringer's solution furosemide has no effect on the PD or Isc. 3. Simultaneous unidirectional fluxes of Na+ and Cl- show that furosemide (5-10-4 M outside) reduces both the influx and outflux of Cl-, while the Na+ fluxes are not altered. 4. Furosemide (5-10-4 M) on the corium side of the frog skin had no significant effect on either PD, Isc or undirectional fluxes of Cl-. 5. It is suggested that furosemide reduces passive Cl- transfer, possibly by interacting with the Cl-/Cl- exchange diffusion mechanism which has been observed in this tissue. These observations further suggest that perhaps the diuretic action of furosemide may be mediated by such an effect on passive Cl- permeability which is linked to the active Cl- transport mechanism in the renal tubule.


Analogy tests and psychopathology at follow-up after open heart surgery. A study of 100 coronary bypass and cardiac valvular surgery patients investigated whether preoperative brain damage, as measured by the Conceptual Level Analogy Test (CLAT), is a major risk factor for postoperative psychiatric symptoms and mortality. Three cognitive psychological tests, including the CLAT, and psychatric interviews were given preoperatively, postoperatively, and at 18-month follow-up. Surgical outcome was specified as: Catastrophic Outcome (death or severe stroke), Psychiatric Complications, or Good Outcome (survival with no psychiatric complications). Inhospital outcome related significantly to analogy test scores, as did both surgical procedure and diagnosis of rheumatic heart disease. However, long-term outcome was unrelated to medical diagnosis and only weakly related to surgical procedure, but highly significantly related to preoperative analogy scores. The CLAT was a more consistent predictor of both short- and long-term outcome than any of the other ten variables considered (medical and surgical variables, inhospital outcome, demographic measures, other psychological tests).


Vestibular dysfunction in emotionally disturbed children. Twenty-five emotionally disturbed children were tested on the Lafayette Clinic Cognitive Perceptual Motor (CPM) battery. The children were next examined for vestibular function by measuring ocular nystagmus for three different rotation rates. Under conditions of eye closure, children found to have two or more marked CPM deficits demonstrated a significantly reduced amplitude of postrotatory nystagmus as compared to CPM nondeficit children, and for the slowest rate of rotation (30 degrees/sec), a significantly decreased duration of nystagmus.


The action of various sera on colony formation and DNA synthesis of murine thymocytes in culture. Murine thymus cells were caltivated up to 10 days in a semi-solid medium. Both macroscopically visible colonies and DNA synthesis (identified by 3H-thymidine incorporation) were counted with and without added sera. According to their origins the sera exerted different modifications of the cultivated cells behaviour. Changes of colony number and of thymidine incorporation were quite independent on each other.


An animal model for the study of human alpha-1-antitrypsin deficiency. Turkeys with "round heart disease" often have a deficiency in alpha1 globulin. Within their liver cells, PAS +, diastase resistant granules are present, and are remarkably similar to those of persons with inherited AAT deficiency. The electrophoretic patterns made according Fagerhol's method showed differences between the serum of healthy birds and the turkeys suffering from "round heart disease".


Acute lymphoblastic leukemia: a study of 25 cases by scanning electron microscopy. Cells from 25 cases of acute lymphoblastic leukemia (ALL) were studied under the scanning electron microscope (SEM). In 24 of the cases, the vast majority of circulating leukaemic cells had few microvilli. Villous cells were rarely encountered and prominent ridge-like profiles and ruffled membranes were not seen. Only six cases were studied by immunological techniques and four of the cases were of the null type while in two the cells bore detectable T-markers. It seems that ALL is almost always associated with the presence of cells with few microvilli in the peripheral circulation, differing in this respect from most cases of CLL. Although circulating leukaemic lymphocytes with few microvilli are sometimes seen in CLL, the most frequent cell type encountered is a more villous lymphocyte. Differences between leukaemic cells from patients with ALL, CLL and non-lymphoblastic leukaemias are discussed. It appears that SEM may help to distinguish lymphoblastic and nonlymphoblastic leukaemic cells in many instances and can be used as a useful adjunct to other modes of microscopy in the diagnosis of acute leukaemia.


The small bowel enema:  description and experience of a technique. A method of examining the small bowel, involving duodenal intubation is described. Good visualization of all parts of the small bowel is obtained using an air-barium double contrast technique. The technique is compared and contrasted with the more conventional methods of small bowel examination, and its advantages and disadvantages discussed. The authors relate their experience with the technique, indicating the abnormalities which can be shown, and list the type of clinical problems where the technique may be most usefully employed.


Lymphocytic infiltration of the brain in sleeping sickness. Cerebrospinal fluid mononuclear cells from 40 patients with advanced Gambian sleeping sickness were examined for intracytoplasmic immunoglobulin and for B- and T-lymphocyte markers. About 5% of mononuclear cells were plasma cells. Most of the lymphocytes present were B cells. These findings suggest that the considerable lymphocytic infiltration of the nervous system seen in advanced sleeping sickness is not a cell-mediated immune reaction to trypanosomes. Immune complexes may play a part in producing the brain damage characteristic of this disease.


Separation of mononuclear leukocytes and polymorphonuclear leukocytes from equine blood. The present study describes a two step technique for the separation of mononuclear leukocytes or mononuclear and polymorphonuclear leukocytes from whole equine blood. First, the leukocyte rich plasma was obtained by sedimentation of erythrocytes in the undiluted blood. Subsequently, separation of the different populations of white blood cells was performed by centrifugation with different gradients overlaid with the leukocyte rich plasma. The optimal separation of the mononuclear cells was obtained by the centrifugation of the leukocyte rich plasma overlaying the gradient containing 24 parts of 9.5% ficoll and ten parts of 34% isopaque. The mononuclear leukocytes (95% lymphocytes and 5% monocytes) formed a monolayer band at the plasma-ficoll-isopaque interface and other blood cells migrated to the bottom of the tube. For the separation of mononuclear and granular leukocytes from the blood, the gradient containing 24 parts of 10% ficoll and ten parts of 34% isopaque was used. The separated monuclear leukocytes responded to stimulation with phytohemagglutin and viability of both mononuclear and polymorphonuclear leukocytes was not affected by ficoll-isopaque separation.


Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia. The 50 patients in this survey were classified by a panel of neurologists into 4 clinical sub-groups: Group Ia ("typical" Friedreich's ataxia, complete picture), Group Ib ("typical" Friedreich's ataxia, incomplete picture), Group IIa ("atypical" Frriedreich's ataxia, possible recessive Roussy-Levy syndrome), Group IIb (heterogeneous ataxias). The clinical symptoms and signs were analyzed for each of these groups. A constellation of signs constantly present in Friedreich's ataxia and obligatory for diagnosis was described. Other important symptoms, such as the Babinski sign, kyphoscoliosis and pes cavus were found to be progressive, but not essential for the diagnosis  at any given time. Finally, a host of other symptoms can only be called accessory. The progression of scoliosis was found to be an important tool in the differential diagnosis of ataxias. Our study also indicates, in contrast to the opinion of some authors, that absent deep tendon reflexes in the lower limbs and early dysarthria are essential in "typical" Friedreich's ataxia.


The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. The cytotoxic effect of methotrexate (MTX) for mouse bone marrow cells has been studied by in vitro of the granulocyte precursor cell (CFU-C) in a medium containing dialyzed fetal calf serum and dialyzed L-cell supernatant. The formation of 50-cell colonies was inhibited to 50% of control by 10(-8) M MTX. Further increases in MTX concentration rapidly abolished colony formation by CFU-C. The potential of leucovorin and nucleosides to rescue the CFU-C from MTX toxicity was studied. Toxicity of 10(-7) M MTX was completely reversed by equimolar concentrations of leucovorin, but with higher MTX concentrations, relatively more leucovorin was required. While 10(-5) M MTX was rescued by 10(-3) M leucovorin, rescue of the toxic effect of 10(-4) M MTX by 10(-3) M leucovorin was not observed. In contrast to the rescue by Leucovorin, toxicity of all MTX concentrations up to 10(-4) M was completely prevented by 10(-5) M thymidine with 10(-5) M adenosine, inosine, or hypoxanthine. Single nucleosides or thymidine with guanosine were ineffective, as were lower concentrations (less than or equal to 10(-6)M) of the effective combinations. Thus, while leucovorin reversed the MTX toxicity to CFU-C competitively, rescue by nucleosides was noncompetitive. The significance and possible usefulness of these findings for chemotherapeutic protocols are discussed.


The stimulation by methotrexate of human chorionic gonadotropin and placental alkaline phosphatase in cultured choriocarcinoma cells. Treatment of the BeWo line of choriocarcinoma cells with methotrexate in doses that inhibit DNA synthesis causes a tenfold increase in synthesis of human chorionic gonadotropin and a threefold increase in activity of placental alkaline phosphatase. No concomitant increase in lactic dehydrogenase activity occurs under these conditions. This effect of methotrexate can be blocked by simultaneous addition of thymidine or folinic acid, neither of which alone increases human chorionic gonadotropin synthesis or placental alkaline phosphatase activity in BeWo cells.


Biochemical and pharmacokinetic effects of leucovorin after high-dose methotrexate in a murine leukemia model. The administration of calcium leucovorin, either concurrently or after high dosages of methotrexate in L1210 leukemic mice, has both pharmacokinetic and biochemical effects in tumor cells and drug-limiting proliferative  normal tissue in small intestine. A reduction in the maximal level of accumulation and retention of exchangeable drug (unbound to dihydrofolate reductase) in tissue could be demonstrated when calcium leucovorin was given simultaneously with methotrexate at equal or greater dosages than the latter. The dose dependence for calcium leucovorin-introduced drug loss is similar in both tissues and showed the expected variation when the time interval between methotrexate and calcium leucovorin doses was increased. With 400 mg methotrexate per kg, greater than 96 mg calcium leucovorin per kg were required maximally to affect overall drug retention in tissue 2 hr after drug, whereas only 24 mg calcium leucovorin per kg were required 16 hr after drug. Calcium leucovorin, given after methotrexate, induced synchronous recovery of DNA synthesis (measured by labeled deoxyruridine incorporation) in both small intestine and L1210 cells. An initial cycle of synthesis was induced in the presence of exchangeable levels of drug. Two hr after methotrexate, 12 mg/kg, calcium leucovorin induced an immediate but only partial (20 to 25% of control rate) recovery of synthesis with dose dependence from 3 to 12 mg calcium leucovorin per kg. Less synthesis was induced after 96 mg/kg and almost none after methotrexate, 400 mg/kg. With calcium leucovorin, 24 mg/kg, given 2 hr after methotrexate, 12 or 96 mg/kg, a major cycle of synthesis occurred when total drug levels approached the equivalence of the dihydrofolate reductase content. The magnitude of this cycle of synthesis in both L1210 cells and small intestine was the same as that seen in animals recovering from methotrexate alone. However, this is based on the assumption that an approximately equivalent relationship between DNA synthesis and labeled doexyuridine incorporation in each tissue during the period of maximal incorporation within the cycle. The major effect of calcium leucovorin, then, was to induce an earlier resumption of DNA synthesis as a consequence of the pharmacokinetic effect in each tissue. With calcium leucovorin, 24 or 400 mg/kg, given 16 hr after methotrexate, an identical effect on drug retention was observed in both L1210 cells and small intestine. Although there was a difference in the time course for recovery in small intestine at each dosage of calcium leucovorin, the recovery of DNA synthesis as drug levels approached the dihydrofolate reductase content was similar in magnitude. In L1210 cells, however, substantial recovery of synthesis to a comparable level and with a similar time-course occurred only after leucovorin, 400 mg/kg. Little or no recovery of DNA synthesis was observed after calcium leucovorin, 24 mg/kg, during the same time period. This dosage schedule (methotrexate, 400 mg/kg, s.c...


Identification of the epidermal "Stiftchenzellen" of frog tadpoles by electron microscopy. Differentiated surface epidermal cells observed in the skin of tadpoles of Rana temporaria by electron microscopy have been identified with the Stiftchenzellen originally described by Kölliker in 1885. The cells have apical microvilli or a single apical projection and appear to have synaptic associations with nerve fibres in the epidermis. The distribution, dimensions and structure of the cells are in agreement with descriptions from le cells are sensory in nature. In addition, there are fine structural resemblances to the gustatory cells of fish and of amphibians which suggest that the Stiftchenzellen are chemoreceptors.


Atherosclerosis of the aorta and coronary arteries in five towns. Material and methods. This chapter outlines the way in which the problems of obtaining and assessing population-related material and analysing the data were tackled. Some of the limits of the approach used, namely, the examination of nearly all deaths from several demographically defined communities, are discussed.


Atherosclerosis of the aorta in five towns. Fatty streak was always present in both the thoracic aorta and the abdominal aorta in the youngest subjects studied (aged 10-14 years). Fibrous plaque was present in a small proportion of these young subjects, but a rapid increase in prevalence occurred as early as the fourth decade. Complicated and calcified lesions appeared as early as the age of 20-25 years but a rapid increase in prevalence was seen after age 40 for complicated lesions and after age 50 for calcified lesions. There were differences in the prevalence of severe lesions among the five towns. There was little increase in the extent of atherosclerosis in the thoracic aorta before the age of 40 and in the abdominal aorta before the age of 20. The increase was more rapid after those ages. When atherosclerosis had affected about 50% of the intimal surface of the thoracic aorta and 70% of the intimal surface of the abdominal aorta, the increase slowed down considerably. In contrast to other types of lesion, the extent of fatty streak increased only up to 30 years of age, when it occupied 25-30% of the intimal surface. Then it declined and in the older age groups did not exceed 4-5% in men or women. The extent of fibrous plaque and complicated lesions was at all ages greater in men than in women, while the extent of fatty streak and calcified lesions in older age groups was greater in women. There were marked differences in the extent of atherosclerotic lesions in the five towns.


Atherosclerosis of the coronary arteries in five towns. Two atherosclerotic lesions (fatty streak and fibrous plaque) were seen in coronary arteries as early as in the 10-14 age group. Then their frequency increased with age, more rapidly in the left anterior descending coronary artery than in the left circumflex artery. After the age of 55 years fatty streak was still the sole type of lesion in 0.3% of men and an even higher proportion of women. In contrast to the findings in the aorta, the mean extent of fatty streak in the average coronary artery did not exceed 3-4% in all age groups. Fibrous plaque was found in over 90% of men over 40 and women over 50 years of age. The extent of fibrous plaque was greatest by about the age of 65 years in both sexes and showed little change thereafter. The first complicated and calcified lesions appeared in a small proportion of subjects after the age of 20. The frequency of complicated lesions did not exceed 50%, being much lower than that of calcified lesions. Complicated lesions occupied a very small area (mean extent 0.6% in men and 0.3% in women); the extent of calcified lesions in older age groups reached 9-10% of the intimal surface in both sexes. Coronary stenosis appeared after age 20 years in men and 10 years later in women, and its frequency increased with age. There were considerable inter-town differences in the prevalence and extent of atherosclerotic lesions.


High and low atherosclerosis groups.

High and low atherosclerosis groups. Aortic and coronary atherosclerosis were studied in two groups, the "high atherosclerosis group" and the "low atherosclerosis group". The latter may be considered as showing basic levels of atherosclerosis in the different communities. The development of lesions in the two groups occurred in parallel, but earlier in the high group. Sex differences in the two groups were similar to those in the whole material. Generally speaking, inter-town comparisons were similar in each group and similar to those for deaths from all causes, a notable exception being the prevalence of coronary stenosis. The findings indicate that the groups can be used as reference groups, but only for material drawn from the same source.


Atherosclerosis and sudden death.

Atherosclerosis and sudden death. The prevalence of complicated and calcified lesions and coronary stenosis, the mean heart weight, and the extent of atherosclerosis in the aorta and coronary arteries were greater in the "sudden heart death" group than in the high atherosclerosis group. In the "other sudden death" group, which included sudden deaths without myocardial infarction or coronary occlusion, all the above variables, except heart weight, were found to be lower than in the low atherosclerosis group and were close to those in the standardized average atherosclerosis group. The mean heart weight in the "other sudden death" group was lower than in the "sudden heart death" group but significantly higher than in the three reference atherosclerosis groups.


Atherosclerosis in relation to cholelithiasis and cholesterolosis. The frequency of cholelithiasis and cholesterolosis was remarkably similar in Prague and Malmö subjects. When the possible effects of associated hypertension or diabetes mellitus were taken into account, subjects with cholelithiasis showed the same extent of raised and calcified lesions of the coronary arteries, the same prevalence of large myocardial scars, and the same distribution of heart weight as subjects without cholelithiasis. In general, they showed rather fewer raised and calcified lesions of the aorta, less coronary stenosis, and fewer fresh myocardial infarctions than subjects without cholelithiasis. Subjects with cholesterolosis were similar to those without this condition in respect of raised lesions of the aorta and coronary arteries. Men with cholesterolosis had slightly more aortic calcification and slightly less coronary calcification. Women with cholesterolosis had slightly less coronary stenosis than those without cholesterolosis. There was a slight tendency for those with cholesterolosis to show an increased frequency of fresh myocardial infarction and large myocardial scars and to have a higher heart weight.


Atherosclerosis and hypertension.

Atherosclerosis and hypertension. Autopsy studies of atherosclerosis of the aorta and the coronary arteries were carried out in 3134 subjects with essential hypertension. A comparison was made with low, average, and high atherosclerosis groups. Essential hypertension was found to accelerate the development of all types of aortic lesion, except fatty streak, as compared with the standardized average atherosclerosis group, and to accelerate the development of fibrous plaque but not complicated and calcified lesions as compared with the high atherosclerosis group. The extent of fibrous plaque in the coronary arteries was greater in the essential hypertension group than in the low and standardized average atherosclerosis groups but did not differ from that in the high atherosclerosis group. The extent of complicated and calcified lesions and the prevalence of coronary stenosis were higher in the high atherosclerosis group than in cases of hypertension. Geographical differences in atherosclerosis among hypertensives in different towns reflected the findings for the whole material. Symptomatic hypertension was found to accelerate aortic atherosclerosis at least to the same extent as essential hypertension. It was conductive to coronary atherosclerosis but not to the same extent as essential hypertension. Coronary stenosis and various manifestations of coronary heart disease were rare in symptomatic hypertension.


Atherosclerosis and diabetes mellitus.

Atherosclerosis and diabetes mellitus. Diabetes mellitus occurred most frequently in Prague (8.4%) and Malmö (8.6%), and less often in Tallin (3.4%), Yalta (3.3%), and Ryazan (2.1%), these differences not being connected with differences in age distribution. The extent of raised and calcified lesions in the coronary arteries and calcified lesions in the aorta in the pure diabetes group was similar to that in the high atherosclerosis group and significantly higher than in the standardized average atherosclerosis group. Raised and calcified lesions in the aorta and raised lesions in the coronary arteries were more extensive in the diabetes group than in the high atherosclerosis group. In all diabetes groups, stenosis of the coronary arteries and myocardial lesions occurred much more frequently than in the average atherosclerosis group but were less common than in the high atherosclerosis group. Coronary thrombosis also occurred more frequently in the high atherosclerosis group. Diabetes per se and hypertension were found to have approximately the same effect on the development of atherosclerosis, but hypertension had a greater effect than diabetes on the development of aortic atherosclerosis. There were no significant differences in the frequency of coronary stenosis and myocardial lesions in diabetics and hypertensives. Diabetics of more than 10 years' standing generally showed more coronary but not more aortic atherosclerosis than those who had had diabetes for less than 10 years. In insulin-treated diabetics coronary atherosclerosis tended to be more extensive than in those treated by diet or by tablets, but there was no difference in the frequency of coronary stenosis and thrombosis and myocardial and cerebrovascular lesions.


Atherosclerosis and malignant tumours.

Atherosclerosis and malignant tumours. Aortic and coronary atherosclerosis were studied in subjects with a malignant disease and compared with those in the three atherosclerosis reference groups. In general, subjects with a malignant disease had little atherosclerosis, except for men with lung or prostatic cancer; in particular, men with lung cancer tended to have more extensive aortic atherosclerosis. Atherosclerosis was less extensive in subjects with tumours specific to females. The ratios between the different types of lesions was preserved and the change was therefore quantitative rather than qualitative. No proof of a real negative influence on atherosclerosis by malignant diseases was found but wasting could be one factor influencing the development of atherosclerosis in tumour subjects. Such subjects, except those with lung and prostatic cancer, could have been included in the low atherosclerosis group which was an index of the mean basic level of atherosclerosis in the populations studied.


Atherosclerosis and rheumatic heart disease. The extent of aortic atherosclerosis in subjects with rheumatic heart diseases was similar to that in the standardized average atherosclerosis group of subjects. The extent of coronary atherosclerosis, particularly in men, was similar to that in the low atherosclerosis group. In the aorta, this finding was accounted for by the greater extent of complicated and raised lesions; in the coronary arteries, it was accounted for by the lesser extent of fibrous plaque. Coronary stenosis, fresh myocardial infarction, and large myocardial scar occurred much less frequently in rheumatic subjects than in the high atherosclerosis group. There was no difference in the frequency of stenosis between the rheumatic and low atherosclerosis groups.


Atherosclerosis and cirrhosis of the liver. Atherosclerosis of the aorta and coronary arteries and myocardial infarction were studied post mortem in 390 males and 190 female cirrhotic subjects in the 5 towns. Comparison with the reference groups revealed that calcification of the aorta and coronary arteries was more frequent (in the case of males) and more extensive (in the case of males and females) in cirrhotics than in noncirrhotics. Raised and complicated lesions were not increased. Coronary stenosis (in females), fresh myocardial infarction (in both sexes), and large myocardial scar (in both sexes) were less frequent in cirrhotics. "Obesity" was similar in cirrhotics and non-cirrhotics.


Atherosclerosis and peptic ulcer.

Atherosclerosis and peptic ulcer. Aortic and coronary atherosclerosis and the frequency of coronary stenosis and myocardial lesions were studied in subjects with peptic ulcer, in two subgroups with acute and chronic peptic ulcer, and in subjects who had undergone a stomach operation. In all these respects the groups were similar to each other. Men with peptic ulcer had the same amount of aortic atherosclerosis as the standardized average coronary atherosclerosis group but less coronary atherosclerosis, while women with peptic ulcer had less aortic and much less coronary atherosclerosis. The prevalence of coronary stenosis, fresh myocardial infarction, and myocardial scar was very low in those with peptic ulcer, especially in women.


Atherosclerosis in relation to tuberculosis and chronic lung disease. The relation between atherosclerosis and tuberculosis and other chronic lung diseases was studied in extensive autopsy material. Aortic atherosclerosis in subjects with such conditions was generally similar in extent to that in the standardized atherosclerosis group and more extensive than that in the low atherosclerosis group, while coronary atherosclerosis was less extensive than in the standardized average group and, especially in women, approximated to that in the low atherosclerosis group. The prevalence of coronary stenosis and myocardial lesions was very low in subjects with tuberculosis and other chronic lung diseases. The presence of such diseases seemed to increase the development of atherosclerosis in the thoracic part of the aorta in relation to the abdominal part.


Atherosclerosis of the aorta and coronary arteries in coronary heart disease. Aortic and coronary atherosclerosis and the prevalence of coronary stenosis and thrombosis were studied in subjects who had died of fresh or recurrent myocardial infarction or had suffered from myocardial infarction in the past. In general, severe atherosclerosis of the coronary arteries with stenosis and calcification was almost a prerequisite for the development of coronary heart disease. The frequency of coronary heart disease varied widely both in different countries and in different towns in the same country. Considerable variations were found among the various towns in the frequency of stenosis and thrombosis in those who had died of coronary heart disease. This finding indicates that although atherosclerosis is indeed a prerequisite for the development of myocardial infarction, other factors may play a significant role in its occurrence. The weight of the heart in persons (excluding hypertensives) with coronary stenosis or a first fresh myocardial infarction was considerably greater than that in the low atherosclerosis group.


Atherosclerosis and myocardial lesions in subjects dying from fresh cerebrovascular disease. TAKING INTO ACCOUNT AGE, SEX, GEOGRAPHICAL DISTRIBUTION, OBESITY, AND ASSOCIATED CAUSE OF DEATH, IT WAS CONCLUDED THAT: (1) the extent of aortic calcification was much lower in cerebral haemorrhage than in cerebral infarct. In deaths due to cerebral haemorrhage aortic calcification was at about the same level as in those due to cancer of the stomach, while in deaths due to cerebral infarct it was at the same level as in those due to coronary heart disease; (2) the prevalence of large myocardial scar was low in deaths due to cerebral haemorrhage (at about the same level as in those due to prostatic cancer), while in deaths due to cerebral infarct it was more frequent (at the same level as in deaths due to diabetes); (3) the extent of coronary calcification and prevalence of coronary stenosis and fresh myocardial infarction were low in the cerebral haemorrhage and cerebral infarct deaths, but a little lower in the former; and (4) the extent of raised lesions of the aorta and coronary arteries was similar in the cerebral haemorrhage and cerebral infarct deaths, the level of aortic lesions being high and overlapping in level with those in the coronary heart disease and hypertensive deaths, and the levels of coronary lesions being much lower and well below those in the coronary and diabetic hypertensive deaths.


Aortic, coronary, and myocardial lesions in relation to various factors. The relative extent of raised and calcified coronary aortic lesions, prevalence of coronary stenosis and of fresh and old myocardial infarction, and mean heart weight were expressed on a continuous scale for 4 disease groups (coronary heart disease, cerebral infarction/haemorrhage, hypertension/diabetes, cancer). Within these groups the relative position for each of the lesions was calculated by subgroups of disease in order to show the elevating or depressing effect of hypertension, diabetes, obesity, and combinations of disease. The strength of association between 33 factors (town 5, disease 24, obesity, heart weight, age, and sex) and the lesions was calculated. An analysis of variance was carried out and the proportion of the variance of the different lesions accounted for by town, disease, etc., is shown. The extent of raised aortic lesions is strongly associated with age and hypertension. It is positively associated with coronary heart disease and inversely associated with cancer. Town factors have a small positive association which is larger than that due to obesity. 33 factors taken together account for 50% of the variance. Age alone accounts for 37% and sex for only 0.3%. The extent of calcified aortic lesion is strongly associated with age, town, hypertension, coronary heart disease and diabetes mellitus. It is inversely associated with cancer, more strongly in cancer of the bronchus and the liver than in other cancers. It is inversely associated with obesity. 33 factors together account for 30% of the variance and age alone accounts for about 13%. The extent of raised coronary lesions is strongly associated with age, coronary heart disease, sex, diabetes mellitus, hypertension and obesity. It is inversely associated with cancer, more strongly in cancer of the prostate and the liver than in other cancers. Town factors have a small association. 33 factors taken together account for about 43% of the variance. Age alone accounts for 25%. The extent of calcified coronary lesions is associated with coronary heart disease and age. There is a low association with hypertension and diabetes, an inverse association with cancer, and a low inverse association with obesity. 33 factors together account for 20% of the variance. Coronary heart disease alone accounts for 12% and age alone accounts for 8%. The prevalence of coronary stenosis is strongly associated with coronary heart disease, age, and sex. There is a small association with town factors, obesity, and hypertension, and an inverse association with cancer. All the factors together account for about 30% of the variance. Coronary heart disease alone accounts for 23% and age 10%.


Atherosclerosis and body build.

Atherosclerosis and body build. In a large autopsy series the relation between various measures of body build and aortic and coronary atherosclerosis, coronary stenosis, and myocardial lesions was studied. Stature was not associated with any of these variables. Various measures of obesity all showed an association between obesity and the above-mentioned variables. Obese people were found to have more coronary atherosclerosis, coronary stenosis, and myocardial lesions than thin people, a difference that persisted, in a reduced form, when hypertensives and diabetics were excluded. When compared with the standardized average atherosclerosis group to exclude the effect of "wasting diseases", and when hypertensives and diabetics were excluded, neither the extent of atherosclerotic lesions nor the prevalence of coronary stenosis were increased in obese subjects. Obese men but not obese women, however, had more myocardial lesions, especially fresh myocardial infarction.


Atherosclerosis and myocardial disease in relation to physical activity of occupation. This study supports the data of other authors in finding that the proportional mortality of sudden heart death and coronary heart disease is greater in men aged 40-59 years with sedentary occupations than in those with strenuous occupations. Clear evidence was found of an association between the extent of raised coronary lesions (mainly fibrous plaque and calcified lesions in the left anterior descending coronary artery and complicated lesions in each artery) and inactivity of occupation. The evidence for a similar association with the prevalence of coronary stenosis, myocardial lesions, and the extent of raised lesions of the aorta was suggestive but less clear. There was no evidence of an association between the physical activity of occupation and the extent of calcified lesions in the aorta or coronary arteries. Prevalence and extent of atherosclerotic and myocardial lesions were compared in each of 6 cause of death groups, between those who had been in strenuous, medium, and sedentary occupations.


Alcohol consumption and atherosclerosis. A study was made of the material obtained in 737 autopsies carried out on men aged 30-69 years (including 88 visitors) who had died in Yalta from various diseases, accidents, and violence. Information on the consumption of alcohol was obtained by questioning the subjects' near relations, neighbours, and associates, as well as from medical records. The most reliable part of this information-the average number of days per month on which the subject consumed alcohol-was taken as the basic criterion for grouping the observations. People taking alcohol on 16 or more days per month had more extensive atherosclerotic raised lesions in the aorta than those drinking on not more than 3 days per month. This difference was most significant in the case of calcified lesions. Fatty streak in the aorta was more extensive in the medium group (drinking on 4-15 days per month) than in either of the extreme groups. As regards the coronary arteries, a significant difference positively associated with alcohol consumption was established only in the case of calcification. The few differences concerning myocardial and cerebral infarction had a negative association with alcohol consumption.


Atherosclerosis in smokers.

Atherosclerosis in smokers. Cigarette smoking was found to be associated with an increased extent of raised lesions of the aorta and aortic calcification. The apparent association with aortic calcification was mainly due to co-existing alcohol consumption. The apparent association of smoking with the extent of coronary calcification was also related to co-existing alcohol consumption; smoking alone tended to be negatively associated with this lesion. There was no clear association between smoking and coronary stenosis, myocardial infarction, and heart weight.


Immunofixation. III. Application to the study of monoclonal proteins. We have shown how immunofixation can be successfully used to study proteins exhibiting electrophoretic polymorphism. An analogous situation is seen in the disorders of the immune system that result in the production of variable quantitites of homogeneous immunoglobulins. Immunoelectrophroesis has been heavily used--sometimes unsuccessfully because of poor resolution--to study these materials. The appearance of a monoclonal immunoglobulin band is identical in both immunofixation and standard gel electrophoresis, a feature that allows unambiguous identification of a protein as to its heavy-chain class and light-chain type. Because antigen and antibody are placed in contact almost immediately after electrophoresis, interfering diffusion does not occur and even extremely small bands can be demonstrated and characterized.


Severe combined immunodeficiency with B lymphocytes: in vitro correction of defective immunoglobulin production by addition of normal T lymphocytes. A 6 1/2-month-old male with severe combined immunodeficiency (SCID) had a low percentage and number of T cells (11%; 241/mm3) and a high percentage and number of B cells (52%; 1187/mm3) and null cells (37%; 868/mm3). In vitro studies were performed to determine if this child's primary defect involved differentiation of both T and B lymphocytes or if failure of B lymphocytes to differentiate into immunoglobulin producing cells was secondary to T lymphocyte abnormalities. Immunoglobulin production by lymphocytes in response to polyclonal mitogens (pokeweed mitogen and foetal calf serum) was measured by pulse-labelling cells with 3H-leucine and then precipitating cytoplasmic and secreted immunoglobulins with polyvalent anti-human immunoglobulin and S. aureus (Cowan strain I) protein A. The patient's lymphocytes did not synthesize immunoglobulins in vitro in response to mitogens. They did not suppress synthesis of immunoglobulins by normal lymphocytes. However, addition of normal purified T cells, which themselves did not synthesize immunoglobulins, enabled the patient's B lymphocytes to become immunoglobulin synthesizing and secreting cells. Gamma, mu, and light chains were secreted. This suggests that the primary abnormality was in the T-cell axis at the level of lymphoid stem cells or prothymocytes and that failure of B lymphocytes to become immunoglobulin-producing cells was secondary to this defect.


The effects of purified mitogenic proteins (Pa-1 and Pa-2) from pokeweed on human T and B lymphocytes in vitro. Purified proteins (Pa-1 and Pa-2) from pokeweed have been compared with commercial pokeweed mitogen (PWM-G) and other mitogens in their ability to stimulate human lymphocytes. With cultures of T and B cells separated from tonsil lymphocytes, thymidine uptake, blast transformation and immunoglobulin (Ig) synthesis have been measured. IgM and IgG was measured in supernates of stimulated cultures by radioimmunoassay. Pa-1, Pa-2 and PWM-G were found to be potent mitogens for unseparated tonsil lymphocytes or nylon column purified T cells. Pa-2 was found to be active at lower concentrations than Pa-1, and PWM-G was less potent than the purified mitogens. These three mitogens all stimulated unseparated lymphocytes to secrete large quantities of Ig (20-100 mug/ml) during 7 days in culture. With increasing amounts of mitogens severe decreases in immunoglobulin synthesis were observed at day 6 even with doses which were still optimal for stimulation of thymidine uptake at days 3 and 6. With purified B cells (less than 2% T cells) Pa-1 was the best mitogen for thymidine incorporation. However, the secretory response was very variable. In some experiments B cells did not secrete Ig in response to mitogens; in others Pa-1 was clearly more effective at stimulating secretion than Pa-2 or PWM-G and in some experiments B cells were stimulated by all three. In one experiment Pa-1 stimulated prolymphocytic leukaemia cells to blast transformation and the secretion of IgM. It is concluded that Pa-1, Pa-2 and PWM-G are much better activators of Ig synthesis in human cultures than either PHA or LPS and that Pa-1 is the most reliable B-cell stimulant of the three.


Lymphocyte subpopulation in neoplastic and non-neoplastic thymus and in blood of patients with Myasthenia gravis. The lymphocyte subpopulations in the thymus and in the blood were investigated in ten myasthenic patients who had been thymectomized. Histologically, the thymuses tested comprised three cases of thymoma including two cases with malignant characteristics, five cases of hyperplastic thymus with lymph follicles and germinal centres, and two cases of persistent thymus without lymph follicles. Virtually all lymphoid cells in the three thymomas formed spontaneous rosettes with sheep red blood cells as did normal thymocytes from non-myasthenic patients. There was no significant proportion of immunoglobulin Ig-bearing lymphocytes. While the majority consisted of cells forming spontaneous rosettes with sheep red blood cells, there was a certain proportion (2-17%) of Ig-bearing lymphocytes in four of five hyperplastic thymuses, in one of two persistent thymuses, and in a residual atrophic thymus of a thymoma. The myasthenic patients tested were for the most part normal, as compared with healthy individuals, in the proportion of rosette-forming lymphocytes and Ig-bearing lymphocytes in the blood collected immediately before and one to three months after thymectomy. The presence of Ig-bearing lymphocytes in the thymus was not necessarily related to the appearance of circulating antibody to striated muscle. The antibody to striated muscle was demonstrated in all myasthenic patients with thymoma.


Immune status and BCG vaccination in newborns with intra-uterine growth retardation. In severe intra-uterine growth retardation there are low IgG levels, low numbers of B cells and low percentage as well as numbers of T cells in cord blood. Following BCG vaccination given soon after birth, Mantoux conversion and leucocyte migration inhibition response to BCG was defective.


Lymphocytotoxins in acute and chronic hepatitis. Characterization and relationship to changes in circulating T lymphocytes. Serum lymphocytotoxicity (LCT) was detected in 49% of fifty-one patients with acute viral hepatitis and 72% of twenty-nine patients with chronic hepatitis. LCT was not detected in ten chronic carriers of hepatitis B surface antigen. Characterization of LCT revealed it to be active at physiologic temperatures and to be reactive against both T and B lymphocytes. The occurrence of LCT was transient in acute hepatitis and intermittent in chronic hepatitis. There was a significant inverse relationship between the percentage change in LCT over time and peripheral blood T-cell proportions amongst the patients studied. These findings indicate the importance of liver damage in the appearance of LCT and suggest that LCT may contribute to depressed lymphocyte function in liver disease.


Double-stranded DNA-binding capacity of serum in acute and chronic liver disease. Serum antibodies to double-stranded 'native' DNA have been measured in acute and chronic liver diseases using the Farr technique. Elevated levels of DNA binding were found in all groups of patients, with the highest levels in acute viral hepatitis and lowest in primary biliary cirrhosis. All patients with hepatitis B surface antigen-positive chronic active hepatitis had elevated levels, hence persistent elevation of DNA binding after acute type B hepatitis might be an unfavourable prognostic marker indicating progression to chronic active hepatitis, DNA antibody levels will not offer diagnostic help in liver diseases, or help to follow the response of patients with 'lupoid' hepatitis to corticosteroid therapy. Production of DNA antibody may be a response to release of DNA from damaged hepatocytes.


A subpopulation of human B lymphocytes that rosette with mouse erythrocytes. A proportion of human peripheral blood lymphocytes form rosettes with mouse erythrocytes (M-RFC). It is confirmed that the proportion of such rosette-forming cells is high in chronic lymphocytic leukaemia (CLL). Analysis of normal lymphocyte populations revealed that M-RFC belong to the B-lymphocyte subclass exclusively. Analysis of their surface markers showed: (a) complement receptors in 50% as compared to 71% of the total B-cell population; (b) a distribution of surface immunoglobulins G, A, M and E typical of the lymphocyte sources; (c) lack of sheep erythrocyte receptor. No differences in the ratio of M-RFC to total B cells was found between lymphocyte population from tonsils, bone marrow and peripheral blood although a significantly higher ratio was seen in cord blood and in chronic lymphocytic leukaemia. Investigation of the properties of mouse erythrocyte rosette formation revealed the following: (a) incubation of lymphocyte mouse erythrocyte mixtures at 37degreesC before centrifugation inhibited rosette formation when CLL lymphocytes were used; (b) treatment of mouse erythrocytes with neuraminidase or trypsin increased their adhesiveness to lymphocytes; (c) treatment of lymphocytes with neuraminidase promoted M-rosette formation but trypsin treatment had an inhibitory effect; (d) cyanide and fluoride at concentrations which strongly inhibited E-rosette formation had no inhibitory effect on M rosettes; (e) M-rosette formation was inhibited by anti-immunoglobulin serum but not by anti-lymphocyte serum; and (f) M-rosette formation was also inhibited by the presence of staphylococci. E-rosette formation was unaffected. The nature of the bond in mouse rosettes is discussed in the light of these findings. The evidence indicates that the lymphocyte receptor may be a part of an immunoglobulin molecule.


Clinical reliability of posterior fossa scintigraphy. Radioisotope imaging of the brain is considerably less useful in posterior fossa lesions than in supratentorial diagnosis, due to the peculiar technical difficulties and biological characteristics of infratentorial lesions. Exceptions are acoustic neurofibromas and probably meningiomas, which can be reliably detected. The importance is stressed of making skull and chest radiographs at the time of the examination, in order to enhance the diagnostic accuracy of the scintigraphic result.


Timing of permanent tooth emergence in two Greenland Eskimo populations. Mean times of emergence of the permanent teeth (except the first and third molars and mandibular central incisors) were studied cross-sectionally in an unmixed East Greenland population in 1957 and in present West Greenland Eskimo children. In spite of differences in racial and environmental conditions, practically no difference was found between the two samples in the timing of dental development in general, taking into account the average difference in emergence times of the individual teeth. Both samples showed advanced dental development in comparison with two unmixed Caucasoid and two unmixed Mongoloid populations. The mutual similarity in timing of tooth emergence between the East and West Greenland Eskimo children considerably greater than the similarity between each of the Eskimo samples and any of the other four populations.


Anomalous origin of left coronary artery from pulmonary artery. An anomalous origin of the left coronary artery from the pulmonary artery in a 26-year-old man was corrected by the ligation of the artery at its anomalous origin, followed by the construction of an aortocoronary bypass with a venous graft. The flow of blood to the myocardium was measured for the purpose of comparing the effect of the bypass method with that of the ligation method. The result suggested that the bypass method provided a greater flow of blood to the myocardium than did ligation alone.


Participation of thyroid D-aspartate oxidase in iodide oxidation and incorporation into thyroid proteins. It was found that the H2O2 generating system containing D-aspartate oxidase isolated from the thyroid gland and D-aspartate, takes part in oxidation of iodides. The molecular I2 formed under experimental conditions is subsequently incorporated into thyroid proteins. Thiosemicarbazide, thiourea, methylthiouracyl, sulphathiazole, thiocyanate and azides were found to have an inhibiting effect on iodide oxidation. Methimazole inhibits both the oxidation of iodide and incorporation of 131I into protein. The iodide incorporation was inhibited by catalase. The findings of these investigations suggest an indirect participation of D-aspartate oxidase in the synthesis of the thyroid hormone by supplying the essential substrate for the iodide oxidation, H2O2.


Re-evaluation of the role of aldosterone in mechanism of natriuresis induced by extracellular fluid volume expansion. Acute experiments were performed in thiobarbiturate (Inactin, PROMONTA) anaesthesia in 21 male rats. It was found that the attenuation of the antinatriuretic effect of aldosterone by a spironolactone Aldactone (BOEHRINGER) in a dose of 10 mg per rat in 1 h i.v. enhanced urine (V) and sodium (UNaV) excretion following the extracellular fluid volume expansion (ECFV) with intravenous infusion of saline. Max. V = 81.44 +/- +/- 7.46 mul min-1 was obtained in Aldactone treated rats as compared to 54.95 + 7.24 mul min-1 in controls: UNaV = 9.89 +/- 1.26 muval min-1 vs. 6.17 +/- 0.73 muval min-1, respectively. The urinary Na/K ratio was also significantly higher in the same samples of Aldactone treated rats (6.15 +/- +/- 1.22 vs. 2.68 +/- 0.19). It is concluded that endogenous aldosterone blunts nriuresis induced by the ECFV expansion.


Inactivation of Oxytocin and its analogues by subcellular fractions of hen tissues. The enzymic inactivation of oxytocin by liver, kidney, uterus and pancreas homogenate subcellular fractions of hens was studied. Oxytocin was most rapidly degraded by the soluble fraction of tissues examined. All the subcellular fractions of liver and kidney inactivated oxytocin, but only the microsomal and soluble fractions of uterus and pancreas showed the oxytocin-inactivating activity. The location of enzymes inactivating oxytocin in subcellular fractions of hen tissues was investigated with the aid of synthetic analogues of oxytocin (deamino-oxytocin and deamino-carba1-oxytocin). The carboxamidopeptidase activity, hydrolyzing the amide bonds in the linear portion of oxytocin was located in the soluble fraction of hen liver, kidney and uterus. No carboxamidopeptidase activity in the pancreatic soluble fraction was found. These results showed that aminopeptidase activity is bound to heavy subcellular particles in the hen tissue. An action of unknown endopeptidases was observed in the microsomal fraction of uterus and pancreas.


Thyroparathyroid conditioning of hydrocortisone and glucagon-induced hypocalcemic effect in rats. A single dose of 2.5 mg hydrocortisone induced hypocalcemia in both intact and parathyroidectomized rats. This effect disappeared in the thyroparathyroidectomized group and did not reappear after the substitution with parathormone. A single dose of 0.2 mg glucagon produced a significant hypocalcemic effect in intact, but not in parathyroidectomized rats. In the latter group, however, the hypocalcemic effect of glucagon reappeared after the administration of parathormone. It was concluded that the hypocalcemic effect of hydrocortisone may be conditioned by the presence of calcitonin secreting thyroid and that of glucagon - by the presence of parathyroids.


Analysis of variables in treatment of anovulation with human gonadotrophins. Twenty seven women with anovulation were given 121 courses of gonadotrophins monitored by excretion of estrogen and pregnanediol. The FSH, ovulating dosage of HCG, time interval between FSH and HCG and subsequent supporting doses of HCG were varied in a statistical design. None significantly affected ovulation or pregnancy rates. The preparation with an FSH:LH ratio of 1 required a lower dosage to initiate an estrogen response than that with a ratio of 5. After adjustment it still produced a faster rise in estrogen excretion. The amount of estrogen also varied with the time interval between FSH and HCG, the ovulating dose of HCG and supporting doses of HCG. The amount of pregnanediol varied with the ovulating dose of HCG and the length of the luteal phase varied with the ovulating dose of HCG and supporting injections of HCG. The dosage of FSH needed to initiate a response increased on average by 8% from one course to the next. Simplicity, economy and risk of multiple pregnancy are discussed in relation to these variables.


Plasma oxytocin and oxytocinase levels in third trimester of pregnancy and at labour. In women during the third trimester of normal pregnancy and at labour the level of oxytocin and progesterone in plasma were determined by means of radioimmunoassay and the activity of oxytocinase was measured spectrophotometrically. The plasma oxytocin levels measured from the 25th week of pregnancy showed a gradual increase with the peak values at the 39th and 40th week. At labour, the oxytocin values remain at the same level as these found at the end of pregnancy. The increase in oxytocin levels at contractions compared to its values found between contractions was not statistically significant. Oxytocinase levels showed also an ascending character until the 38th week of pregnancy. Later, a decrease was found which continued until the termination of pregnancy. At labour, there was a decrease in progesterone level in plasma which was about at the limit of significance.


Effect of long-term fluoride administration on thyroid hormones level blood in rats. The effect of 2 months fluoride administration (0.1 and 1.0 mg daily/rat) on thyroxine and triiodothyronine level in blood and T3-resin uptake ratio was investigated in rats. In addition, free thyroxine index was calculated from serum thyroxine level and T3-resin uptake ratio. It was found that fluoride administration caused: 1. decrease in thyroxine and triiodothyronine level in plasma; 2. decrease in free thyroxine index values; 3. Increase in T3-resin uptake ratio. From these observations as well as from previous experiments it was concluded that fluoride given continuously to the rats may influence the thyroid gland rather indirectly by changing thyroid hormone transportation in the blood.


Species specificity of guinea pig erythropoietin. Various stimuli (hypoxic hypoxia, bleeding, carbon monoxide hypoxia and cobalt administration), well known to increase erythropoietin plasma level in many species including man, failed to increase the erythropoietin activity in plasma of guinea pigs when measured in the polycythaemic mice assay. Nevertheless, the plasma of these guinea pigs stimulated the erythropoiesis in polycythaemic guinea pigs which, however, failed to respond to rat erythropoietin. From this it was concluded that not only the erythropoietin, but also the erythropoietin responsive cells in the bone marrow of guinea pigs are species specific. Bilateral nephrectomy in guinea pigs exposed to hypoxia prevented the increase in the erythropoietin plasma level, thus suggesting that, similarly as in other species, also in guinea pigs the kidney is the main organ of erythropoietin elaboration. The species specificity of guinea pig erythropoietin - erythropoiesis system is an interesting exception among mammals, since the erythropoietin of a large number of species belonging to this class was demonstrated to lack species specificity.


Influence of different cytotoxic drugs on T and B lymphocytes in children with all during remission maintenance therapy. The influence of four different cytotoxic drugs (MTX, CYC, 6MP, and ARA-C) on T, B, and O-lymphocytes was investigated in 20 children with ALL in complete remission during cyclic remission maintenance therapy. Each of the four drugs causes a marked reduction of the absolute number of T and B cells whereas the relative number lies within the normal range with the exception of CYC, which leads to a depression of the percentage of both T and B cells. The percentage of O cells is markedly increased by CYC and slightly increased by MTX, 6MP, and ARA-C. The data are interpreted with care since the function of the immune system and especially tumor rejection depends on the interaction between the different lymphocyte subpopulations.


"Early T cells" and "late T cells"; suggestive evidence for two T cell lineages with separate developmental pathways. Peripheral lymphocytes from mice have been analyzed by a combination of cell electrophoresis and size distribution analysis and the data have been processed with a computer into two-dimensional distribution patterns (fingerprints). The fingerprints of lymph node cells revealed the existence of at least three major classes of small lymphocytes. Cells with similar physical properties were found in the spleen and thoracic duct lymph. The data also allowed calculation of the quantitative ratios of the three cell types. In the normal mouse, the two electrophoretically faster cell classes represent essentially two subclasses of T cells. The quantitative ratios are here always in agreement with the known percentages of B and T cells. Lethally irradiated mice that have been reconstituted with syngeneic bone marrow or fetal liver cells often lack one of the T cell subclasses. This has two important implications. 1) It indicates that the widely used syngeneic or allogeneic bone marrow chimeras may be incomplete in respect to their T cell repertoire and that experiments with these models should be interpreted with caution. 2) The deficiency was found to correlate strictly with a deficiency in a physically defined subset of small cortical thymocytes that has been described previously. This correlation suggests strongly that the fast peripheral T cells and the "early small cortical thymocytes" represent two developmental stages of a distinct cell lineage ("early T cell lineage"), while the thymic pool of "late small cortical thymocytes" gives rise to electrophoretically slow peripheral T cells, which may be called "late T cells). The possibility that both T cell lineages are derived from different classes of prethymic stem cells in the reconstitlting stem cell preparation is discussed. The proportion of "early T cells" in the lymph nodes decreases with age. The ratio of "late" and "early T cells" is similar in the spleen and in the lymph nodes, and both cell classes contain a significant proportion of cells that are not affected by the early effects of adult thymectomy. Thus, they do not correspond to T1 and T2 cells.


Immune conservation: a possible consequence of the mechanism of interferon-induced antibody suppression. The effect of interferon preparations on the development of single clones of antibody-forming cells generated against sheep red blood cells in mouse spleen cell cultures has been studied. It was found that the presence of interferon had no effect on either the number or the size of clones which developed early in the in vitro antibody response. At the peak of the response (day 3), a decrease in the number but not in the size of clones was observed in interferon-treated compared to control cultures, while by day 4 both the size and number of clones were significantly decreased. These findings indicate that interferon appears to affect only nonactivated B cell precursors by preventing them from becoming activated and commencing clonal expansion. Early responding precursors, which are in cell cycle, presumably having been previously activated in vivo, are refractory to interferon-induced suppression in vitro. The way in which this immunosuppressive activity of interferon might be of great advantage to an animal as a means of "immune conservation" during viral infections is discussed.


Surface molecules of cultured human lymphoid cells. Cell surface molecules of cultured human lymphoid cells were selectively labeled by lactoperoxidase-catalyzed iodination and examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two major iodinated species with apparent mol. wts. of 27 000 and 35 000 daltons were detected on autoradiographs of the labeled proteins of human lymphoid cell lines believed to be of thymus-independent (B) cell origin. Neither molecule was detected on putative thymus-dependent (T) lymphoid cell lines. Metabolic labeling studies showed that both molecules are glycoproteins. Rabbit antisera against cultured B lymphoid cells made specific by absorption for B cells reacted with several labeled species from iodinated B cells including the 27 000 and 35 000 mol. wt. glycoproteins. These molecules were also detected on tonsillar lymphocytes but not on peripheral blood lymphocytes. Reciprocal absorption with B cells of rabbit antisera against cultured T cells gave antisera specifically cytotoxic for T cells. However, these sera did not precipitate iodinated proteins from Nonidet P-40 lysates of T cells.


Immune response of New Zealand mice to trinitrophenylated syngeneic mouse red cells. NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism.


In vivo sensitization of T cells to hapten-conjugated syngeneic structures of major histocompatibility complex. I. Effect of in vitro culture upon generation of cytotoxic T lymphocytes. Murine T cells were sensitized in vitro towards fluorescein isothiocyanate (FITC)-conjugated syngeneic spleen cells. The lytic activity of the effector cells generated was restricted to FITC-conjugated, H-2-compatible target cells. 2,4,6-Trinitrophenyl (TNP)-conjugated syngeneic targets were not lysed. A method is described for the in vivo sensitization of murine T cells towards TNP (or FITC)-conjugated syngeneic spleen cells. The procedure is based on the observation that a local graft of hapten-conjugated syngeneic spleen cells results in the development of sensitized prekiller T cells within the draining lymph node (LN). By mere in vitro incubation of such LN cells immunological specific anti-TNP (or anti-FITC)-reactive cytotoxic T lymphocytes (CTL) are generated. The in vitro differentiation of CTL requires 48-72 h; it is dependent on cell proliferation and is abolished by treatment of the LN cells with mitomycin C. Thus there is a separation between the sensitization of CTL precursors (which effectively takes place in vivo) and the phase of cell differentiation into CTL (which effectively takes place only in vitro). Similar to in vitro-sensitized CTL, the specificity of in vivo-sensitized CTL is dictated by the hapten used for the induction of the immune response and is restricted to hapten-conjugated syngeneic target cells.


Lack of effect of thymectomy on spontaneous recovery from tolerance to levan. Adult CBA mice were made tolerant with 1 mg levan and tested subsequently for sponteneous recovery by plaque-forming cell assay in response to immunizing challenge. Weakening of tolerance was first detectable only after 100 days, while return to full normal responsiveness required 400 days. Thymectomy 2 weeks prior to tolerization neither retarded nor diminished the recovery process. Loss of tolerance which had been induced by 1 mg dextran B512 was much slower in onset (greater than 250 days), yet not delayed by thymectomy (full recovery was not followed). These findings in relation to other considerations imply that associative recognition by T cells is not required for B cell responses to these "thymus-independent" antigens.


Functional half-life of virgin and primed B lymphocytes. The functional half-life, a measure of the persistence of lymphocytes in an antigen-free environment, has been estimated and found to be about 7 days for virgin 2,4,6-trinitrophenyl (TNP)-reactive mouse B cells, and 2--3 times longer for TNP-primed B cells. Using allotype-congenic mice, lymph node cells were transferred from virgin or primed CBA/Igb donors to normal CBA/Iga recipients, and the proportion of donor B cells estimated at intervals...


Structural aspects of immune recognition of lysozymes. III. T cell specificity restriction and its consequences for antibody specificity. We have studied the relationship between the determinants encountered by T cells on an antigenic molecule and the specificities of the antibodies eventually produced by the B cells with which these T cells cooperate. The number of  epitopes on the hen lysozyme (HEL) molecule available to T cell receptors was functionally limited by inducing T cell tolerance to HEL in rabbits. Highly cross-reactive lysozymes were then used to challenge the HEL-unresponsive rabbits. Only T cells which recognize new epitopes on the challenge lysozymes could act as helpers in generating an anti-lysozyme response. Amino acid differences between Japanese quail lysozyme (JEL) and HEL are segregated within a single quadrant of this small antigen molecule. HEL-tolerant rabbits challenged with JEL produced antibodies which were totally cross-reactive with the tolerogen HEL. This result is in contrast to the result obtained in nontolerant rabbits which produced antibodies to JEL which were only 50-70% cross-reactive with HEL. We conclude that T cells restricted to the JEL-unique epitopes were only capable of cooperating with B cells specific for common epitopes shared between JEL and the tolerogen HEL. Turkey lysozyme (TEL), on the other hand, bears different amino acids which are distributed over several regions on the surface of the molecule. Any one HEL-tolerant rabbit developed a restricted response to TEL; in some rabbits the anti-TEL was highly HEL cross-reactive, while in others little cross-reactivity with HEL was observed. Each of four HEL-tolerant rabbits injected with the minimally altered bob-white quail lysozyme possessed the reactive T cells necessary to mount a limited response to this challenge lysozyme, suggesting a diverse library of T cell specificities. Recognition of the small differences between the challenge lysozymes and the T cells of these tolerant rabbits to make a fine discrimination between minimally changed epitopes.


T cell requirements for the expression of the lipopolysaccharide adjuvant effect in vivo: evidence for a T cell-dependent and a T cell-independent mode of action. The in vivo adjuvant effect of lipopolysaccharide (LPS) in mice was investigated with the soluble synthetic polypeptide antigen (T, G)-A--L, the antibody response to which is determined by the Ir-1A gene. With this specific antigen it can be demonstrated that the LPS adjuvant effect has the following modes of action: a) a T cell-dependent enhancement of primary and secondary IgM antibody response; b) a T cell-dependent enhancement of IgG secondary andibody response; and c) a T cell-dependent induction of switchover from IgM to IgG andibody in some strains of Ir-1A low responders. Although T cells are necessary for some aspects of the adjuvant effect, these data do not distinguish between a mechanism involving a direct interaction between LPS and T cells or a direct interaction of LPS and B cells with a general requirement for T cells for expression of IgG antibody.


T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice. Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node and spleen cells from appropriately immunized donors. In contrast to lymphoid cells, immune serum did not transfer this autoimmune disease nor did serum have any facilitating or inhibitory effect on the capacity of lymphoid cells to transfer EAE. Transfer of EAE was effected in normal mice, lightly irradiated (350 rad) and lethally irradiated (850 rad) and bone marrow-protected mice, but not in mice which had been given 850 rad total-body irradiation. There was a striking augmentation of severity of transferred EAE in the lightly irradiated recipients, possibly attributable to selective radiosensitivity of suppressor T cells. Cell-mediated immunity but not circulating antibody to basic protein of myelin was demonstrated in recipients with transferred EAE. The immune lymphoid cells responsible for transfer of EAE were T lymphocytes. Thus transfer was successful after passage of sensitized cells through anti-immunoglobulin columns and was abrogated following treatment with anti-Thy-1 serum and complement. Neonatally thymectomized mice failed to develop either EAE, cell mediated immunity or humoral antibody against myelin basic protein (BPM). Inhibition of EAE and immune responsiveness was solely due to the removal of the source of thymus lymphocytes, because reconstitution of neonatally thymectomized mice with T lymphocytes completely restored these functions. It is concluded that T lymphocytes are required for the production and adoptive transfer of EAE, for the development of cell-mediated immunity to BPM and for the production of antibody to BPM.


T lineage lymphocytes in nude mice born from homozygous nu/nu parents. T lineage cells are found in the spleen of neonatal nu/nu mice born from nu/nu x nu/nu matings, and also in old, healthy nude mice obtained from the usual nu/+ x nu/nu matings. Their presence in neonatal nude mice which were never in contact with mother or normal littermate thymus products shows that commitment of stem cells towards the T lineage does not require the influence of the thymus.


Transplantation tolerance at the T-lymphocyte receptor level. I. Spontaneous release of T-cell receptors by lymphocytes from tolerant mice. Spleen and lymph node T cells from CBA mice when cultivated in vitro almost immediately started to shed receptors for A alloantigens. In contrast, cultivated T lymphocytes from CBA mice tolerant of A alloantigens for 657 or 692 days began releasing receptors for the formerly tolerated A alloantigen after a delay of 8 h. This delay in receptor shedding coincided with that observed when nontolerant lymphocytes were treated with antisera to T-cell receptors. The results suggested a close similarity of mechanisms and indicated that transplantation tolerance may be maintained by active suppression of otherwise reactive T cells mediated by anti-receptor antibody. Lymphocytes from untreated tolerant mice and those treated with a nonspecific anti-receptor serum showed normal responses, as measured in terms of receptor release, to third-party alloantigens, as did cells from untreated normal mice. Precultivated normal lymphocytes treated with anti-receptor antibody and complement failed to release the appropriate receptor specificity but similarly treated tolerant lymphocytes were almost resistant, presumably because they expressed only few receptors at the time of treatments.


Transplantation tolerance at the T-lymphocyte receptor level. II. Interaction of T-cell receptors with alloantigen and with anti-receptor antiserum. CBA T lymphocytes deprived temporarily of receptors for alloantigens A[RS(A)] cultivated in vitro for 30 h with anti-receptor antibody-forming (AxCBA)F1 spleen cells were capable of resynthesizing RS(A) if primed F1 cells exceeded parental T cells by a factor of 25 or less, but not if the excess was 50-fold or more. This indicated that resynthesis of CBA T-cell RS(A) was successful if primed F1 cells formed insufficient amounts of anti-CBA T-cell RS(A) antibody. Abortive or successful receptor resynthesis was measured by two parameters, (a) reappearing RS(A) formed PAR together with A alloantigens of (AxCBA)F1 spleen cells and (b) budding receptors bound anti-receptor antibody. CBA B lymphocutes did not interfere with these reactions. A search for putative T suppressor cells in the F1 cell population was unsuccessful. PAR formation and anti--RS antibody consumption by reappearing receptors differed temporally: receptors forming PAR were present after a delay lasting 8 h; receptor structures fixed anti-RS antibody as early as 5 h after being cultivated. With due caution, these results might reflect processes operating in maintenance of transplantation tolerance, suggesting that this condition is a serum-mediated suppression of long duration. The suppression would encompass continued neutralisation of receptors for the alloantigen to be tolerated by anti-T-cell receptor antibody formed by the F1 chimeric cells within an animal with acquired transplantation tolerance.


Meiotic origin of triploidy in the frog detected by genetic analysis of enzyme polymorphisms. A female frog heterozygous at two unlinked loci, specifying electrophoretic forms of mannosephosphate isomerase (MPI) and malate dehydrogenase (MDH) was crossed to male frogs homozygous for different alleles at each locus. In the offspring approximately ten percent proved to be triploid according to nucleolar and chromosome counts of tail tip cells. Most of these triploids had both maternal alleles at the MDH and MPI loci suggesting that the first meiotic division was repressed. Others seemed to represent a repressed second meiotic division and one animal, a pentaploid, could only have resulted from inhibition of both meiotic divisions of the egg. Densitometer tracings of starch gels stained for 6 phosphogluconate and isocitrate dehydrogenases, expected to be heterozygous in a particular cross, demonstrated that the triploids had twice as much maternal as paternal gene product for each locus, similar to patterns found in triploids produced by nuclear transplantation.


Anemia--a common but never a normal concomitant of aging. Diagnosis is often overlooked because symptoms develop slowly and insidiously and many patients don't complain about them. Then too, the giddiness, apathy, confusion, clumsiness, and similar problems may be considered simply signs of "old age." Iron deficiency anemia is the most common type in old people. It's usually due to gastrointestinal bleeding, but there may be a second, less obvious cause. The classic picture of low serum iron, high total iron-binding capacity, and low iron-binding saturation is sometimes distorted. Usually, many studies are needed to confirm the suspicion of a vitamin B12 or folic acid deficiency. A raised mean corpuscular volume in itself signals the need for further investigation. In patients with macrocytosis, the bone marrow must be examined. Tests for intestinal malabsorption must be considered too. Repeated blood tests are essential in patients being treated for any type of anemia. Iron deficiency may hide evidence of folate or B12 deficiency. And iron therapy may lessen bleeding from colonic cancer, delaying diagnosis until it's too late to operate.


Depressed cell-mediated immunity in coeliac disease. Fourteen coeliac patients on a gluten free diet (GFD) and 10 on a normal diet were studied by lymphocyte transformation in response to PHA to assess the integrity of cell-mediated immunity (CMI). Transformation was depressed in the majority taking a normal diet, with improvement after a GFD. In some patients the depression may have been due to a serum factor, as transformation was more nearly normal when the lymphocytes were cultured in pooled AB serum than in their own serum. There was no correlation between transformation and nutritional deficiencies. Mantoux tests were performed in some of these and other coeliac patients and there was a very significant reduction in the incidence of positive tests compared with controls. These findings provide evidence of depressed CMI in coeliac patients taking a normal diet with improvement on a GFD and may be of relevance to the high risk of malignancy in coeliac disease, further strengthening the case for a strict GFD.


Anergy to dinitrochlorobenzene and depression of T-lymphocytes in Crohn's disease and ulcerative colitis. Skin reactivity to dinitrochlorobenzene (DNCB) and levels of circulating T-lymphocytes were measured in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 12 normal control subjects. Diminished reactivity to DNCB was demonstrated in 87% of patients with Crohn's disease (P less than 0-001) and in 53% with ulcerative colitis (P less than 0-02), as compared with only 8-5% of controls; anergy was more frequent in Crohn's disease than in ulcerative colitis (P less than 0-05). Levels of circulating T-lymphoctes were also depressed in both Crohn's disease and ulcerative colitis (P less than 0-001) as compared with controls, with the values lower in Crohn's disease than in ulcerative colitis (P less than 0-02). There were no correlations of DNCB response with extent, duration, or severity of disease nor with T-cell levels within any patient group. These data provide further support for the concept that there is impairment of cell-mediated immunity among many patients with chronic inflammatory bowel disease, including both Crohn's disease and ulcerative colitis.


Effect of hydrocortisone on response of human lymphocytes to galactose oxidase stimulation. Hydrocortisone at 10(-4)M concentration could inhibit the response of human lymphocytes to galactose oxidase stimulation. Removal of the hydrocortisone after 4 h of culture did not reverse this inhibition. On the other hand, removal of monocytes greatly enhanced it, so that it could be observed at 10(-6)M concentration. Next, tonsil cells were separated into two fractions relatively rich in either T or B cells. Both fractions could respond to galactose oxidase and the response could be inhibited by hydrocortisone.


Influence of diftalone on tolbutamide test and i.v. glucose tolerance test. In 16 healthy volunteers tolbutamide tests or i.v. glucose tolerance tests were performed with and without previous oral administration of 1000 mg diftalone. Blood sugar and serum insulin were assayed in regular intervals. Both with and without previous administration of diftalone blood glucose after tolbutamide did not show any difference. IRI response to tolbutamide, measured by planimetrical integration showed a statistically significant augmentation (0.05 greater than p greater than 0.01) after diftalone. Glucose assimilation (K-value) after diftalone was decreased (0.05 greater than p greater than 0.01) yet within normal range. For the accompanying insulin levels however no statistically significant difference was observed. In addition a normalisation of pathological tolbutamide test after diftalone could be noted in five patients with subclinical diabetes. Our results indicate that diftalone seems to have the following three actions: 1. Enhancement of the tolbutamide action. 2. direct augmentation of IRI secretion, 3. a peripheral action on glucose metabolism.


The effects of U.V.-light, ionizing radiation and the carcinogen N-acetoxy-2-fluorenylacetamide on the development in vitro of one- and two-cell mouse embryos. The development of one- and two-cell mouse embryos to morula-blastula stages was followed in vitro after treatment with low doses of U.V.-light, ionizing radiation or N-acetoxy-2-fluorenylacetamide. Exposure of one-cell embryos to either radiation source 18 and 24 hours after human chorionic gonadotropin injections prevented maturation, most embryos being arrested at the one-cell stage and a few at the two-cell stage. Two-cell embryos, however, were not sensitive to low doses of either U.V. or X-irradiation and developed normally. Treatment of early one-cell embryos with the carcinogen, N-acetoxy-2-fluorenyl-acetamide (0-7 muM), also arrested development, whereas exposure of late one-cell embryos did not completely prevent maturation to morula-blastula stages. Exposure of two-cell embryos to the same concentration of carcinogen had no effect on their development to blastulas. Results with all three agents showed that mouse embryos at the one-cell stage are more sensitive than those at the two-cell stage, as judged by their ability to develop in vitro.


Recovery response of dividing cells in the thymus of whole-body gamma-irradiated mice. Mice were irradiated with different doses of gamma-rays 30 min after the administration of 32P-orthophosphate. The dose-response curves determined at 72 hours after exposure showed an inflection point in the total activity present in the DNA in thymus and spleen. In the low dose-range, the dose-response curves have D0 = 55 rad (n = 2-5) for thymus and DO = 95 rad (n = 2-5) for the spleen. Thirty minutes after the administration of 32P-orthophosphate, the dividing cells from thymus were partially synchronized by the administration of 80 mg per kg body-weight hydroxyurea. At different time-intervals, the mice were irradiated with 80 rad, and the total activity of DNA was determined at 72 hours after synchronization. A significant maximum of recovery was found at 5 hours (S phase) after the administration of hydroxyurea. In similar conditions, the dose-response curves corresponding to the G1, S and M phase of the division cycle were also determined. The synchronization of dividing cells induced by hydroxyurea failed in the spleen.


Investigation of the interaction of alkyl sulphates with serum albumin using the thiocyanate radical ion (SCN)2. The reaction of the radical anion -(SCN)2-, produced during pulse radilysis of aqueous KCNS solutions, have been used to study the binding of a range of alkyl sulphates to bovine (BSA) and human (HSA) serum albumin. At neutral pH, -(SCN)2- reacts chiefly with trytophan residues. Approximately ten high-affinity binding sites are detectable for compounds of chain length greater than C7. The results are interpreted in terms of a model in which one hydrophobic region in the protein, containing the tryptophan residues, can accommodate the ten ligand molecules. Electrostatic interactions with positively-charged groups surrounding the hydrophobic area are also involved in binding.


Survival of human T and B lymphocytes after X-irradiation. The survival of unstimulated human T and B lymphocytes after X-irradiation in vitro was measured by Trypan Blue dye exclusion over a period of four days. B cell numbers were observed to decline rapidly even after relatively low doses, but T cell numbers fell much more slowly. A comparison of the percentage survival 96 hours after irradiation shows that in this system T cells are between approximately 2 and 5 times more resistant than B cells. Data for interphase death after 48 hours are compared with cytogenetic data for interphase loss of PHA-stimulated human lymphocytes and are shown to be in broad agreement at radiation doses below 400 rad. It is suggested that at higher doses mitotic delay may be increasingly important leading to selection of non-irradiated cells at 48 hours.


Reaction of ethanol radicals with ribonuclease. Ribonuclease was irradiated under conditions such that ethanol radicals were the main reactive species in solution. Sephadex gel filtration of the irradiated solution demonstrated that ethanol radicals had reacted with the ribonuclease and had become firmly bound to the enzyme molecule. The number of ethanol molecules bound to ribonuclease was a function of dose and correlated with the loss of enzymatic activity and with the changes in the molecular configuration of the enzyme molecule.


A comparison of physical and cytogenetic estimates of radiation dose in patients treated with iodine-131 for thyroid carcinoma. Physical and cytogenetic estimates of the whole-body radiation doses have been compared in 11 patients receiving large doses of iodine-131 for the treatment of thyroid carcinoma. The physical estimate was based on the measurement of thyroid uptake, of the plasma activity variation, and of urinary activity. The cytogenetic estimate was obtained from the analysis of chromosome aberrations in peripheral blood lymphocytes. Good agreement between the estimates was observed in patients whose thyroid glands had previously been ablated by radioiodine. In patients who had varying degrees of thyroid function, there were considerable differences between the estimates with the cytogenetic value always being higher. It is suggested that these differences might be due in part to non-uniform irradiation of lymphocytes by local sources of activity in the thyroid and in the liver.


An analysis of the interaction of a platinum complex and radiation with CHO cells using the molecular theory of cell survival. A mathematical analysis is developed from the concepts of the molecular theory of cell survival to explain the cytotoxic action of a platinum complex on CHO cells and its synergistic interaction with radiation. In the analysis, it is assumed that both inter- and intra-strand cross-links induced by the Pt complex in the DNA contribute to cell killing and that the synergistic effect arises from the interaction between an intra-strand cross-link and a radiation-induced single-strand break on complementary strands of the DNA. The analysis is shown to be compatible with experimental results. Further, a mechanistic model is developed in an attempt to explain in more detail the processes which appear to be involved in the expression of the cytological damage.


Skin response to X-irradiation in the guinea-pig. Skin reaction to X-irradiation has been studied in the albino guinea-pig; early response in limited-field irradiations of the flank is comparable to that commonly seen in rodents, swine and man, and is dose-dependent with a dynamic range from mild erythema to moist desquamation. The peak early skin reaction is seen between 14 and 21 days after irradiation, and declines before 30 days except at the highest doses used. Fractionation of the X-ray dose at 24 hours results in a 'sparing' of about 340 rad. Permanent partial epilation is detectable at doses in excess of 1400 rad, and complete epilation at 1 year occurs in 50 per cent of irradiated fields at 1740 rad. Twenty-four hour two-dose fractionation results in a 'sparing' of about 500 rad for epilation. Palpable dermal 'fibrosis' is detectable at 3 months after irradiation in fields given more than 2070 rad, and at 1 year after irradiation in fields given more than 1800 rad; 50 per cent of fields showed palpable 'fibrosis' at 1 year at 1930 rad. Unlike domestic swine and man, skin fields in the guinea-pig showed no dimensional contraction after X-ray doses which produced gross early skin damage.


Effect of gamma-irradiation on dye-DNA binding. The effect of gamma-rays on the binding of proflavine and acridine orange to DNA was investigated by spectrophotometry. The effect of irradiation was observed on the buffered solutions of the free dye and free DNA. A dose of about 35 krad caused a hyperchromicity of 30-40 per cent to the DNA peak at 258 nm, while the same dose introduced a hypochromic effect to the monomer peaks of the dyes by 30 per cent. This implied that gamma-rays have an effect of decreasing the monomer concentration of free-day molecules in solution. From the results, we conclude that more dye is bound to the changed conformation of dye-bound DNA on irradiation. Scratchard-binding isotherms drawn for the unirradiated and irradiated complexes of Pf-DNA showed interesting differences. Similar isotherms could not be obtained for the acridine orange-DNA system.


The relationship between early and late radiation damage in rodents' skin. A study is made of the relationship between early and late damage after irradiation of the feet or ears of rats. In one type of experiment in which large groups of animals were given the same dose, there was a good correlation between the early and late forms of damage. In another experiment, the relationship between these two forms of radiation damage was found to be unaltered by a single dose of X-rays given 8 months earlier. Thus, both types of experiment point to the early and late forms of reaction in the skin of rodents resulting from a common cause. Other relevant experimental data and their relationship to clinical observations are discussed.


[Dynamics and metabolism in coronary heart disease before and after revascularization intervention]. In summary, rapid atrial pacing prior to surgery may be able to assess LVF and the degree of coronary insufficiency by measuring lactate production. Functional contraction abnormalities of the left ventricle are described by the anginal depression of the LVF, whereas a preanginal depression should be a sign of organic, fibrotic impairment of myocardial function. In cases of the former, after successful bypass surgery, a normal LVF may be observed. Moreover, myocardial metabolism is normalised. In the latter group, despite clinical improvement, functional abnormalities can persist.


Positive contrast ventriculography in cats with experimental obstructive hydrocephalus. Cerebrospinal fluid pathways were studied in both normal and experimental obstructed hydrocephalic cats by positive contrast ventriculography. Either water soluble or insoluble contrast material was injected into the lateral cerebral ventricles, and radiographs were taken of the head and spinal cord. In the normal cat, the contrast material freely flowed throughout the spinal fluid spaces. The contrast material accumulated in the cisterna magna, and from there extended into the cranial and spinal subarachnoid spaces. In the kaolin-induced hydrocephalic cat, the outlets from the fourth ventricle were obstructed, and direct communication between the ventricular system and the subarachnoid spaces no longer existed. In these cats, the contrast material passed directly down the central canal of spinal cord and its movement was followed throughout the entire length of the canal. At the lower lumbar-sacral regions, the material perforated the cord and flowed into the subarachnoid space. At all levels, the central canal was enlarged and local dilatations were seen extending dorsally.


The effects of response contingent vestibular stimulation on the behavior of autistic and retarded children. The purpose of the present experiment was to examine the reinforcing effects of repetitive vestibular stimulation. While both autistic and retarded children would push a button for vestibular stimulation, frequency of stimulation was an important parameter for autistics but not for retardates. These results were interpreted as evidence for central rather than peripheral locus of control of motility disturbances in autistic children.