Structural studies on bacterial luciferase using energy transfer and emission anisotropy. The distance between specific sites on bacterial luciferase was estimated by energy transfer. Luciferase was fluorescently labeled by reaction of an essential sulfhydryl group with N-(1-pyrene)maleimide and N-[p-(2-benzoxazolyl)phenyl]meleimide. Both of the modified enzymes bind 8-anilino-1-naphthalenesulfonate (Ans) with affinities similar to that exhibited by the native luciferase. Using each of the two fluorescent probes as a donor and the bound Ans as an acceptor, the energy transfer efficiencies were determined by the resulting enhancement of fluorescence of the acceptor. The corresponding distance was calculated to be in the range of 21 to 37 A. Energy-transfer studies were also carried out using fluorescence lifetime measurements of bound ANS,  acting as a donor with bound FMN as an acceptor. The corresponding distance was calculated to be between 30 and 58 A. Using samples of luciferase:Ans complex and luciferase modified with N-(1-pyrene)maleimide, the rotational correlation time of the enzyme-dye conjugate as awhole was found to be 47 +/- 2 ns. The observed rotational correlation time is much longer than that calculated for luciferase assuming a spherical structure, thus indicating an elongated form for the luciferase-dye conjugate.


Orientation of chromophores in reaction centers of Rhodopseudomonas sphaeroides: a photoselection study. The relative orientation of the pigments of reaction centers from Rhodopseudomonas sphaeroides has been studied by the photoselection technique. A high value (+0.45) of p=(delta AV--delta AH)/(delta AV + delta AH) is obtained when exciting and observing within the 870 nm band which is contradictory to the results of Mar and Gingras (Mar, T. and Gringras, G. (1976) Biochim. Biophys. Acta 440, 609-621) and Shuvalov et al. (Shuvalov, V.A., Asadov, A.A. and Krakhmaleva, I.N. (1977) FEBS Lett. 16, 240-245). It is shown that the low values of p obtained by both groups were erroneous due to excitation conditions. Analysis of the polarization of light-induced changes when exciting with polarized light in single transitions (spheroiden band and bacteriopheophytin Qx bands) enable us to propose a possible arrangement of the pigments within the reaction center. It is concluded that the 870 nm band corresponds to a single transition and is one of the two bands of the primary electron donor (P-870). The second band of the bacteriochlorophyll dimer is centered at 805 nm. The Qx transitions of the molecules constituting the bacteriochlorophyll dimer are nearly parallel (angle less than 25 degrees). The two bacteriopheophytin molecules present slightly different absorption spectra in the near infra-red. Both bacteriopheophytin absorption bands are subject to a small shift under illumination. The angle between the Qy bacteriopheophytin transitions is 55 degrees or 125 degrees. Both Qy transitions are nearly perpendicular to the 870 nm absorption band. Finally, the carotenoid molecules makes an angle greater than 70 degrees with the 870 nm band and the other bacteriochlorophyll molecules.


Open chain crown-type polyethers and pyridinophane cryptands act as ionophores upon frog motor nerve and isolated rat heart cells. Frog motor nerves and isolated heart cells from neonatal rats were incubated with solutions of open chain crown-type polyether or pyridinophane cryptand. The following alterations in membrane excitability and energy consumption were found: 1. The non-cyclic ligand stabilizes the resting potential of the frog nerve and reduces the pulsation rate of heart muscle cells. It is reversibly bound at the cell surface and does not affect the energy metabolism of the heart cells. (formula: see text) 2. The cryptand 1,12-dioxo-2,11-diaza-5,8,21,24-tetraoxa[12-8(2,11)] (2,6)-pyridinophane) ([2.2.1py]-diamide) is irreversibly bound by the tissues. It facilitates the depolarization of the nerve and shows a positively chronotropic effect upon the heart muscle cells. Single treatment of the cell cultures with 10 microgram [2.2.1py]-diamide per ml medium increased the activities of lactate dehydrogenase and of creatine kinase. When the cell cultures were treated three times at 24 h intervals with 10 microgram complexone/ml, the creatine kinase activity of the heart muscle cells decreased by about 40%. The physiological properties of the ligands are correlated with the stability of their alkali metal ion complexes and with the rate constants of complex formation. It is concluded that [2.2.1py]-diamide can act as a passive carrier for Na+ K+.


Cooperativity of lectin binding to lymphocytes, and its relevance to mitogenic stimulation. The relationship between the binding patterns of soybean agglutinin, peanut agglutinin (both in their native (unaggregated) form and in their polymerized form), and of Phaseolus vulgaris leucoagglutinin, to neuraminidase-treated lymphocytes from different sources, and the mitogenic activity of these lectins, was studied. In all cases investigated, binding of a lectin to lymphocytes which resulted in stimulation was a positive cooperative process. Our findings support the assumption that clustering of receptors and conformational changes in membrane structure are prerequisites for mitogenic stimulation.


Glycoproteins and antigens of membranes prepared from rat thymocytes after lysis by shearing or with the detergent Tween-40. In purification of cell surface antigens an efficient method for preparing membrane from large numbers of cells is needed. Such a method is described for preparing membranes from rat thymocytes after lysis in the non-ionic detergent Tween-40. Cell surface antigens were recovered at a yield of 30-50%, and a purification of 30-40-fold. By contrast enzyme markers for the other cell organelles were present in the membrane fraction in very low yield. The membrane obtained with the detergent method was compared with that resulting from the best of previously describes methods involving cell lysis by shearing. The detergent method compared favourably for simplicity as well as for yield and purification, and both membrane preparations contained similar protein and glycoprotein constituents. The main glycoprotein bands of membranes from thymocytes and thoracic duct lymphocytes were identified after polyacrylamide gel electrophoresis in dodecyl sulphate. In thymocyte membrane, three main bands at apparent molecular weights of 150 000, 84 000 and 25 000 were seen, and of these the 84 000 glycoprotein did not bind to the lentil lectin. In thoracic duct lymphocyte membrane the 25 000 glycoprotein was absent and a band at 95 000 was intensified in comparison with thymocytes.


[Compensatory processes during unilateral loss of vestibular function]. Changes in the compensation of the sequences of the unilateral loss of the labyrinthine function were studied in rabbits. Destruction of the labyrinth was accompanied by ocular nystagmus, increase of frequency of respiration and heart contractions, and EEG-activation. Investigations carried out showed these reactions to be extinguished at different time. At the late periods of labyrinthectomy a considerable asymmetry of nystagmus reaction to the angular accelerations equal in intensity, but opposite in direction was revealed. Stimulation of an intact otolith labyrinth was accompanied by the appearance of positional nystagmus. The results obtained indicated imperfection of the compensatory mechanisms during complete unilateral loss of the vestibular function.


Discrimination between human T and B lymphocytes and monocytes by computer analysis of digitized data from scanning microphotometry. I. Chromatin distribution patterns. Digitized images of Feulgen-stained normal human B and T lymphocytes and monocytes were analyzed by computer and microphotometry. The algorithms assessed the chromatin distribution patterns. A substantial number of parameters descriptive of the chromatin distributions were found to show statistically highly significant differences between B and T cells and monocytes. Although the effects of a number of biologic variables, such as cell cycle phase and immune stimulation, need to be carefully evaluated, the preliminary results indicate potential for automatic classification and subclassification of human B and T lymphocytes in normal and disease states.


Immunologic abnormalities in an animal model of chronic hypoplastic marrow failure induced by busulfan. The immunology of chronic hypoplastic marrow failure (CHMF, aplastic anemia) was studied in an experimental murine model of the disease induced by busulfan. B lymphocytes of peripheral blood, spleen, and bone marrow were reduced to 30%-40% and T lymphocytes of thymus, spleen, marrow, and blood were decreased to 20%-70% of control values. IgG and IgM antibody titer to sheep red blood cells were reduced to one-third of control levels, and splenic IgG, but not IgM, plaque-forming cells were fewer on day 7 after antigen stimulation. The proliferative responses to phytohemagglutinin or concanavalin A were reduced in cultures of peripheral blood lymphocytes, splenic lymphocytes, and thymocytes, and cutaneous delayed-type hypersensitivity induced by dinitrofluorobenze was not detected in mice with CHMF. The results demonstrate disturbance of a variety of cellular and humoral functions and suggest that the disturbance was due to quantitative and possibly qualitative abnormalities of the cell types subserving these functions. The results suggest that residual cell injury, the lesion underlying experimental CHMF, is not confined to the myeloid stem cell but also involved cells of the lymphoid series.


Noninvasive assessment of patients following aortocoronary bypass surgery. A simple, accurate, noninvasive method is required for the objective evaluation of aortocoronary bypass surgery. Stress myocardial imaging with intravenous injection of potassium-43 or thallium-201 was used an average of 4.4 months after direct myocardial revascularization in 77 patients to assess the accuracy of stress myocardial imaging in predicting completeness of revascularization. The results were correlated with maximal treadmill exercise tests, extent of revascularization and status of bypass grafts (occlusion, stenosis and distal disease). We found stress myocardial imaging to be a more sensitive method than the stress electrocardiogram for the detection of incomplete revascularization. The method appears to be a sensitive noninvasive means of evaluating the results of aortocoronary bypass surgery.


Changing patterns of intra-aortic balloon pump assistance. Intra-aortic balloon pump assistance (IABPA) for cardiogenic shock is well established. The response to balloon pumping and patient survival are better after low output from cardiotomy than after myocardial infarction. Elective use of IABPA preoperatively allows an extra margin of safety for patients with acute coronary insufficiency, significant left main coronary artery stenosis, or depressed left ventricular function. However, advances in monitoring techniques during the induction of anesthesia and weaning from cardiopulmonary bypass support, as well as improved methods for myocardial preservation, have reduced the requirements for elective IABPA. Current indications for preoperative IABPA include: patients with acute coronary insufficiency who are totally unresponsive to full medical management and who continue to have pain and electrocardiographic changes at rest, and patients with serious left main coronary artery stenosis who also have acute coronary insufficiency or depressed left ventricular function. The survival of patients with valvular heart disease and left ventricular dysfunction is not improved with preoperative IABPA, while most patients with depressed left ventricular function from coronary artery disease may now undergo revascularization uneventfully, although inevitably some will still require postoperative IABPA.


Angiography in determining the cause and treatment of gastrointestinal bleeding. Angiography is useful in the diagnosis of active gastrointestinal bleeding if the rate is greater than 0.5 mL/min. For upper gastrointestinal bleeding, endoscopy is the preferred initial investigation and angiography is used for diagnosis only if the site of bleeding is still obscure. Angiography is the preferred method for investigation of massive lower gastrointestinal bleeding if results of sigmoidoscopy are negative. Vasopressin infusion is most useful for control of bleeding from esophageal varices, erosive gastritis and diverticular disease of the colon. Embolization with Gelfoam or clot is possible for massive hemorrhage from a single source in poor-risk patients. This is most successful for gastric or duodenal bleeding since the collateral blood supply prevents infarction. Some of the methods and complications of embolization are discussed and examples are given. Standard surgical principles should still apply in most cases.


Influence of aortocoronary bypass surgery on employment. Aortocoronary bypass operations are expensive. Economic benefit might be derived if such operations influenced the ability of persons with symptomatic coronary artery disease to be employed. Follow-up data were obtained for 329 survivors of bypass operations 2 to 60 months (mean, 22.9 months) postoperatively; 178 had been working prior to the operation and 213 were working at the time of follow-up, for a net gain of 35 employed patients. Therefore, bypass surgery does lead to a small but significant increase in the proportion of angina patients who are employed.


Effect of lithium on granulopoiesis in culture. Lithium carbonate therapy is associated with polymorphonuclear leukocytosis. In vitro studies have shown that lithium ions stimulate formation of granulocytic colonies. In a study undertaken to determine how lithium acts, colony-forming cells uncontaminated by monocytes (which elaborate colony-stimulating factor [CSF] in vitro) were obtained by means of a two-step cell separation procedure. The effects of lithium on colony formation were then studied in (a) cultures stimulated by humoral CSF, (b) cultures in which monocytes were relied upon to synthesize CSF de novo and (c) unstimulated cultures. Lithium enhanced the action of CSF but did not stimulate colony formation in the absence of CSF. In monocyte-stimulated cultures, colony formation increased with lithium concentrations up to 1 mmol/L but this increase paralleled that in CSF-stimulated cultures and therefore was not due to increased CSF production by monocytes. At higher concentrations of lithium, colony formation decreased in the monocyte-stimulated cultures but increased in the CSF-stimulated cultures. A lithium concentration of 4 mmol/L gave the greatest enhancing effect on colony formation in CSF-stimulated cultures and a concentration greater than 1 mmol/L inhibited de novo synthesis of CSF by monocytes.


Selection of operation in patients with bleeding esophageal varices. The results of surgical treatment of bleeding esophageal varices over an 8-year period in 155 patients are reviewed. Primary treatment of bleeding was conservative, with intravenous administration of vasopressin and balloon tamponade. Emergency operations were carried out after 48 hours in persons with persistent bleeding who were surgical candidates. Operative mortality was higher in this group (40%) than in those undergoing elective or urgent operations (each 10%). Postoperative encephalopathy occurred in 35% of patients and was correlated closely to late death after establishment of a shunt. The mesocaval shunt is no better than the portacaval but appears to be a good alternative in an emergency. In a controlled trial the distal splenorenal shunt was found to be associated with a lower rate of postoperative encephalopathy than the portacaval shunt, but thus far the long-term survival rates have not differed.


Expectations of myocardial revascularization. Surgical treatment of coronary artery disease has been under development for more than 35 years, during which time it has been met with considerable enthusiasm. As the surgical risk decreases, indications for coronary bypass procedures are being liberalized somewhat and increasing numbers of patients are being referred for surgical treatment. The most immediate benefit of such treatment is prompt relief from angina and improvement in the quality of life. Other benefits for various patient subgroups are improvement in left ventricular function and prolonged life. Further experience and controlled studies gradually will elucidate further indications for coronary artery bypass surgery and will result in improved evaluation of this treatment.


Hyperthermia, antipyretics and function of polymorphonuclear leukocytes. Whether hyperthermia (temperature, 40 degrees C), salicylates, acetaminophen or phenacetin has an adverse effect on polymorphonuclear leukocyte (PMNL) function was examined. Migration experiemnts were carried out in Boyden chambers with bacterial chemotactic factor as the attract, and bactericidal assays were done with Staphylococcus aureus and serum from an AB blood group donor as a source of opsonins. PMNL viability was determined by the trypan blue exclusion method. Neither hyperthermia nor any of the drugs tested affected PMNL viability adversely, but sodium salicylate and phenacetin suppressed PMNL migration. Early staphylococcal killing was greater at 40 degrees C; however, after 2 hours the converse was true. Bactericidal activity was suppressed by acetylsalicylic acid, sodium salicylate and phenacetin. Hence it appears PMNL function is similar at 37 degrees and 40 degrees C but that some commonly used antipyretics have an adverse effect on PMNL activity.


Oral high-dose methotrexate with citrovorum factor rescue in metastastic squamous cell carcinoma of the lung. Thirteen patients with metastatic squamous cell cancer of the lung were treated, in a nonrandomized study, with an oral high-dose methotrexate and citrovorum factor rescue regimen. There was some response and/or stabilization of disease for at least three months in six (46%) of 13 cases. The median survival time of the study group was double (365 vs. 180 days) that of a retrospectively matched control group. This suggests a possible therapeutic effect of this treatment program in metastatic squamous cell cancer of the lung.


Angioimmunoblastic lymphadenopathy: an ultrastructural and immunologic study with review of the literature. Six cases of angioimmunoblastic lymphadenopathy (AIBL) are presented, detailed ultrastructural and immunohistologic studies of several involved organs are described, and the literature is reviewed. The features of the lesion are of normal immune reactive cells containing polyclonal cytoplasmic immunoglobulin. Large numbers of dying and degenerating cells result in accumulations of cell debris, corresponding to the characteristic interstitial material seen by light microscopy. Our studies confirm that the vascular changes are unique to lymph nodes, appear confined to postcapillary venules, and consist of endothelial cell hypertrophy and expansion of the vessel wall by basement membrane-like material, cellular debris and collagen fibers. No deposits of amyloid or antigen-antibody complexes were noted by ultrastructural or immunologic techniques. Our data reveal morphologic and laboratory features of a hyperimmune state but with paradoxical cutaneous anergy and decrease in blood (T) lymphocytes. We postulate that AIBL is an abnormal, but non-neoplastic immune reaction related to the autoimmune disorders, resulting from a loss of suppressor T cells with hyperfunction of the B lymphocyte system.


Ability of thymic lymphocytes to alter CFU kinetics in radiation chimeras. It is known that the poor colony-forming ability of B6 bone marrow transplanted into B6D2F1 hybrids can be improved if B6 lymphocytes are given in addition. It was recently reported that the augmenting lymphocytes decrease the doubling time of differentiating hemopoietic cells. To determine whether thymus cells alter the self-renewal of CFUs in this parent leads to F1 combination, retransplantation and 3H-thymidine 'suicide' were employed as methods to determine the cell-division rate. We have observed that in the presence of thymocytes, parental bone marrow cells are seeded more efficiently in the spleen, and the lag phase of the CFUs growth curve is shortened. However, thymic lymphocytes do not increase the slope of the exponential growth phase of CFUs.


[Hemobilia and hemoperitoneum (discussion of an unusual clinical case)]. A rare case of haemoperitoneum from rupture of haemocholecyst is described. The origin of the haemorrhage, on the basis of the case history, clinical, intra-operative and anatomo-pathological data, was in all probability intrahepatic. In addition to discussion of the incidence of this morbid event, the article refers to the most frequent causes of haemobilia, the physiopathological mechanisms supporting it, the symptomatological triad characterising it even when aspecific, and the available diagnostic possibilities.


Physiologic improvement following coronary artery bypass surgery. In this study the effects of coronary artery bypass surgery on ventricular function were evaluated at rest by quantitative analysis of segmental wall motion on cineventriculography, and during maximal treadmill exercise by measurement of serial cardiac outputs (Fick method) with the use of indwelling pulmonary artery and radial artery catheters. The patient had single vessel coronary disease and exertional angina. Following placement of a bypass graft to the proximally occluded left anterior descenting coronary artery, and despite the presence of arterial hypoxemia secondary to interstitial pulmonary fibrosis, a striking increase in maximal cardiac output occurred, mediated by a rise in both maximal heart rate and stroke volume. In this patient, resting ventricular volumes and ejection fraction were normal both before and after surgery, but preoperative abnormalities in extent of segmental wall motion, identified quantitatively, were restored to normal after bypass grafting. These investigations indicate that bypass surgery can provide substantial physiologic benefits in addition to providing subjective relief of anginal symptoms.


Methotrexate-induced ventriculitis: appearance on routine radionculide scan and emission computed tomography. A 9-year-old boy with acute lymphocytic leukemia underwent intrathecal methotrexate (MTX) treatment over a period of one year because of CNS symptoms. After a sudden rapid deterioration, radionuclide imaging demonstrated marked ventricular wall concentration, presumed related to MTX toxicity. After cessation of MTX treatment, the patient improved, and subsequent radionuclide images reverted to normal appearance.


Nutrition and the immune response.

Nutrition and the immune response. Vitamin E--selenium deficiency in dogs resulted in complete suppression of lymphocyte responsiveness to stimulation with mitogens. Depressing effects on neutralizing antibody synthesis were also noted. A serum factor associated with the inability of lymphocytes to respond has been isolated and partially purified. The suppressor factor can be removed or transformed by both in vivo and in vitro vitamin E supplementation.


Pre- and postoperative pulmonary function abnormalities in coronary artery revascularization surgery. Pulmonary function studies were conducted one to two days prior to, two weeks after, and an average of 116 days after coronary artery revascularization surgery. Preoperation it was found that 11 of 19 patients had mild to moderate obstruction, 8 of 17 had diffusing capacity less than 80 percent of predicted, and 9 of 17 had mild hypoxemia. Many of these abnormalities seemed related to smoking. After surgery, significant reductions in volumes, diffusion and PaO2 were found at two weeks. By the last study, there was improvement in volumes and diffusion, but they remained significantly reduced in comparison to preoperative levels. Arterial oxygen tension (PaO2) had returned to preoperative levels. Correction of diffusion for volume showed there to be no change in any of the study periods suggesting chest wall alteration is a major component of the abnormality. It is concluded that close monitoring of pulmonary function is indicated before and after operation in this patient population even if the patient is asymptomatic.


Repeat aortocoronary bypass grafting. Early and late results. Seventy-nine patients underwent repeat myocardial revascularization between March 1971 and January 1977. The initial procedure was performed at the St. Vincent Medical Center, Los Angeles, in 70 (2.0 percent) of 3,526 patients undergoing surgery for coronary arterial disease and in nine more patients was performed at other hospitals; the second operation followed the first procedure at an interval of from three weeks to 78 months. Five deaths (6 percent) occurred while patients were hospitalized, and six deaths (8 percent) occurred later. Two of the six later deaths were from noncardiac causes. Complications were not different from those that occurred during primary procedures. Thirty-six (60 percent) of 60 patients undergoing repeat surgery since 1973 did not receive any transfusions of blood during or after surgery. Of 48 patients followed-up for periods ranging from 12 to 70 months after the second operation, angina was completely relieved in 18 patients (38 percent), improved in 16 patients (33 percent), unchanged in 11 patients (23 percent), and worse in three patients (6 percent).


Normotopic plus heterotopic atypical teratomas. 6 cases of normotopic plus heterotopic atypical teratomas are presented. The difficulty of making an accurate early diagnosis is stressed. Suggestions for interpreting both clinical and radiograph data are presented.


Genetic heterogeneity at the locus for hypoxanthine-guanine phosphoribosyltransferase. The purine phosphoribosyltransferases have emerged as important enzymes in the metabolic economy of the developing human. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, EC 2.4.2.8) catalyses the conversion of hypoxanthine and guinine into their respective nucleotides. Inherited variation in HGPRT first became evident through clinical observations with the definition of the Lesch-Nyhan syndrome. In this disorder, HGPRT activity in erythrocytes is almost zero, although the fact that sensitive electrophoretic analysis reveals a tiny amount of activity suggests that a protein of altered structure is present. Furthermore, this variant enzyme has been activated by manipulation in the presence of small amounts of normal enzyme. Nevertheless, no cross-reacting material could be detected in lysates of red cells or fibroblasts of patients with the syndrome when tested with antiserum prepared in rabbits to normal erythrocyte HGPRT. We have tested for the presence of cross-reacting material in 18 patients, and all were negative. More HGPRT variants are coming to light. Most of the patients have renal stone disease or gout but no other feature of the Lesch-Nyhan syndrome. In one family four affected males displayed about 5% of normal activity, and the enzyme migrated electrophoretically more rapidly than normal. Cross-reacting material could not be demonstrated in erythrocyte lysates, although it was clear that a variant protein was present. A boy with renal stone disease has been found to have about 1% of normal erythrocyte activity of HGPRT. Cross-reacting material was found in his erythrocytes. The data indicate that mutations which produce diminished enzyme activity in this protein with a distinct subunit structure may or may not so alter the tertiary state of the protein that immunoreactive sites are no longer available to antibody prepared against the normal enzyme. So far whenever a variant normal HGPRT has been found there has been an identifiable clinical illness. The different forms of illness provide for correlation of molecular structure and function in man.


[Angiodysplasia of the gut as cause of massive gastrointestinal bleeding (author's transl)]. Angiodysplasia of the colon with preferential localisation in the region the ileocoecal valve is not infrequently the cause of massive gastrointestinal bleeding. The diagnostic problems of this disease are illustrated by seven cases. Contrary to angiography, coloscopy, which may have to be done as an emergency procedure, frequently does not allow localisation of the haemorrhage. Vascular malformations can be demonstrated by arteriography even in the asymptomatic interval. They frequently escape macroscopic identification even in the resected specimen due to their small size and their localisation in the submucosa. The diagnosis can be established histologically by serial sections with vascular filling if necessary. The treatment of choice is resection of the affected part of the gut. In cases of decreased operability endoscopic laser coagulation can be indicated.


Studies on hypothalamic estradiol binding during estrous cycle and after ovariectomy. Specific binding of 3H-estradiol (1 microgram kg-1 injected s.c. 1 h before sacrifice) in the hypothalamus, anterior pituitary and uterus of cycling and ovariectomized female rats was investigated. Preoptic-anterior hypothalamic area (POA-AH) and median eminence-basal hypothalamus (ME-BH) were separated by gross dissection from the bulk of hypothalamus. Pieces of parietal cortex served as controls. The lowest amount of 3H-estradiol specifically bound to cytoplasmic and nuclear receptors in POA-AH and ME-BH was found in proestrus, while in estrus-metestrus it was the highest. In contrast to hypothalamic estrogen sensitive areas, the lowest uterine binding was found in estrus and the highest in diestrus-proestrus. Changes in estradiol binding in the anterior pituitary were similar to that in the uterus. Ovariectomy made 48 h before 3H-estradiol injection markedly increased the nuclear binding in POA-AH and ME-BH compared to that observed in cycling animals. However, it decreased nuclear binding in the uterus. Cytoplasmic binding seems to be decreased in the hypothalamus as well as in the uterus of ovariectomized animals as compared to the highest level observed during estrous cycle in intact ones.


Failure to demonstrate a natriuretic effect of neurophysin in rats. Partly purified rat neurophysin was tested for its possible natriuretic activity in acutely hypophysectomized saline-loaded rats (hypophysectomized 2 h prior to saline infusion). Such animals were unable to excrete the saline load. When partly purified rat neurophysin was injected i. p. in a dose of 40 microgram per animal (which corresponds to its content in one rat posterior pituitary) before saline loading, the sodium excretion was not different from that found in acutely hypophysectomized animals, but it was significantly lower than in normal saline-loaded rats. It was concluded that any apparent natriuretic effect of rat neurophysin could not be established by the present experiments under the experimental conditions used.


Diurnal rhythm corticosterone in fasted rats. The diurnal rhythm of plasma and adrenal corticosterone level was examined in fed male Wistar rats and in these fasted for 24 and 48 h. In fed animals a remarkable diurnal rhythm of both parameters was found showing a nadir at the beginning and a zenith at the end of light period. After 24 h of fasting the zenith was shifted to the beginning of dark period without any other changes. After 48 h of fasting remarkable shifts were found resulting in a nadir at the beginning of dark period and a zenith at the middle of light period.


Tertiary follicles in heifers treated with melengestrol acetate. Qualitative and quantitative changes of tertiary follicles were studied in ovaries of heifers during and after the treatment with melengestrol acetate (MGA--6-methyl-6-dehydro-16-methylen-17alpha-acetoxyprogesteron), the atretic tertiary follicles being classified into several types. During the administration of MGA an increased number of atretic follicles was found as well as a stimulation of glandular cells of theca interna, while after the withdrawal of the drug an increased number of normal tertiary follicles was observed estrous cycle. On the 7th day of MGA administration most of the atretic follicles were in the stage of early atresia and a few only were in the stage of luteinized cystic atresia. On the 14th day, however, most of tertiary follicles were in late atresia and only a few were in early atresia. Moreover, at the same time the number of follicles classified as luteinized cystic atresia was increased, while that of follicles showing cystic follicular atresia was decreased. After the withdrawal of MGA the most numerous group of follicles was in the stage of early atresia. It was demonstrated that the time changes in the number of follicles with a diameter larger than 5 mm resemble that of normal tertiary follicles. During MGA administration the number of follicles with a diameter of 2 to 5 mm was the largest. These findings show that MGA may effect the feed-back regulation of both the cyclic and basal secretion of gonadotropic hormones. After the withdrawal of the drug there may be higher basal secretion of gonadotropins.


Diurnal variations in plasma calcium, parathormone and calcitonin levels and crop gland activity in pigeon. Circulating levels of plasma calcitonin and parathormone were measured in the pigeon by radio immunoassay in relation to plasma concentrations of calcium. Adult birds undergoing 3 particular phases of crop gland activity (Group 1.--4 days prior to hatching, Group 2.--2 days following hatching, Group 3.--12 days following hatching), were used as experimental animals. Calcium showed a marked circadian rhythm and the levels of plasma calcitonin and parathormone fluctuate similarly with calcium changes. Significant differences between treatment groups were noted for calcium, calcitonin and parathormone, indicating the interacting control of calcium mobilization and utilization by these two hormones during crop gland activity.


The requirement of cytoplasmatic receptors for entry of testosterone into nuclei of rat skeletal muscle. A reconstituted system composed of partially purified nuclear pellet and cytosol from rat quadriceps muscle was used in order to establish whether cytosol is necessary for nuclear uptake of testosterone. It was demonstrated that the presence of cytosol enhances remarkably the total nuclear uptake of this hormone.


Influence of intragastrically administered androgens on hypothalamic differentiation in rats. Male and female rats aged 3 days were injected intragastrically with methyltestosterone and STS 383 synthetic androgen in doses between 0.4-3.2 mg and 0.2-3.2 mg, respectively. The treated females showed disturbances in hypothalamic differentiation as demonstrated by changes of the day of vaginal opening and frequency of oestrus, by a decrease of ovarian weight and a loss of fertility. It is thus possible to investigate perorally active aromatizable androgens for their central activities. STS 383, a new p. o. active androgen showed a higher activity compared with methyltestosterone in this study, whereas in the Hershberger model methyltestosterone was previously found to be 4 times more active than STS 383. A possible dissociation of central and peripheral activities between these two substances is discussed.


Influence of single peroral dose of aminoglutethimide on the rat adrenal cortex. In female albino rats force fed with a single dose of 50 mg of aminoglutethimide (AG) lipoid adrenocortical hyperplasia was found within 24 h. In addition, a marked focal increase in cytoplasmic transparency was found which ultrastructurally appeared to result from optically empty vacuoles and membrane-bound spaces. Later, an increase occurred in the translucency of the cytoplasmic matrix, mitochondrial swelling, destruction of cell membranes and disappearance of adrenocortical cells presenting as cytolysis. Some of the damaged cortical cells contained protein vacuoles with fibrillar structures and occasionally also blood cells. All such changes were associated with a marked infiltration by neutrophilic granulocytes, the most severe of them resembling an acute purulent epinephritis. Ultrastructural examination showed blood monocytes with signs of initial phagocytic activity at sites of disintegration of adrenocortical cells. Focal decrease of dehydrogenase activity was demonstrated in areas of cellular destruction, while no alteration in acid phosphatase activity was detected. Moreover, an absolute increase in corticosterone production form endogeneous precursors in vitro was found which could be partially explained by an increase in adrenocortical size. Formation of 18-hydroxycorticosterone and aldosterone from 4-14C-progesterone was decreased. However, no appreciable changes were revealed in the zona glomerulosa. From these findings it may be assumed that high doses of AG not only block the conversion of cholesterol into pregnenolone, but also injure some other cellular enzymatic systems necessary for the integrity of the adrenocortical cell.


Intragastral disintegration of blood coagula by mechanical vibration. A new method of intragastral disintegration of big blood coagula by mechanical waves is described. Intragastral application of ultrasound was disappointing. A flexural electromagnetic resonator was brought up for clinical trial and showed an effective intragastral thrombotripsy. Even other substances like tablets, food or scybala could be disintegrated. The described method represents a simple, safe and efficient procedure which will enrich the catalogue of possiblities in endoscopic examinations.


Ruptured pancreatic pseudocysts: diagnosis by endoscopy. Report of 3 cases. Report on 3 cases of spontaneous perforation of a pancreatic pseudocyst into the stomach; presenting symptom was in each case an acute upper GI-bleeding. The pseudocyst was endoscopically seen as a well delineated, hemorrhagic protrusion into the stomach. After full perforation the spontaneous ostium had the appearance of a surgical anastomosis. High amylase concentration in the aspirate ave further diagnostic evidence. All 3 patients survived, 2 of them without surgery.


Surgical emergency cases--endoscopic treatment. For gastrointestinal surgery endoscopy gains more and more importance. Besides the desired improvement of pre-, intra- and postoperative diagnosis multiple therapeutic procedures proved to be practicable. Of special interest are those methods, which can be used successfully in emergency cases. Here the foreign body dislodgement, the stopping of hemorrhage and the introduction of tubes in cases of ileus or dehiscence of the suture have to be mentioned. The endoscopic treatment is very often a complementary or palliative one and not so much an alternative. These methods are applied to patients at high risk.


Isolated varices of the gastric fundus--endoscopic diagnosis and surgical treatment. Isolated gastric varices in patients with portal hypertension are a relatively rare source of bleeding into the gastrointestinal tract. Endoscopy is a very valuable method of diagnosis in such cases. The authors report their own observation of gastric varices, well documented with the endoscopic technique before and after surgery. Varices of the gastric fundus are always an indication to surgical management. On the basis of their own experiences made with 5 patients, the authors recommend a direct intervention in form of an extragastric suture or resection of the convolution of the varicose veins, in selected patients simultaneously complete with a portasystemic shunt.


Multiple sclerosis. T lymphocytes in cerebrospinal fluid and blood. Peripheral blood from 21 patients with active and 19 patients with stable multiple sclerosis (MS), and cerebrospinal fluid (CSF) from 7 of the patients with active disease were examined for T lymphocytes by rosette formation with sheep erythrocytes. Increased numbers of T cells were found in CSF in active disease (94.0 +/- 0.7 compared to 71.3 +/- 4.4% in controls). Decreased relative and absolute numbers of T cells were found in peripheral blood in active, but not in stable disease (mean 47 +/- 3 and 957 +/- 93%/mm3 compared to 66 +/- 2 and 1,381 +/- 93%/mm3 in controls).


Surface markers on lymphocytes from human cerebrospinal fluid. Predominance of T lymphocytes bearing receptors for the Fc segment of IgG. Surface markers of cerebrospinal fluid (CSF) cells have been studied in comparison with those of peripheral blood lymphocytes. The great majority (about 95%) of CSF cells bear surface markers of thymus-dependent lymphocytes (E rosettes with uncoated sheep red blood cells), while being devoid of bone-marrow derived cell markers (EAC rosettes with complement-coated red blood cells). In contrast with lymphocytes from peripheral blood, CSF cells form predominantly 'early' and 'sphere'-shaped E rosettes, and bear receptors for the complement-fixing segment of immunoglobulins G. Treatment with concentrated CSF does not affect rosette forming ability of peripheral blood lymphocytes.


Spontaneous clones of cytotoxic T cells in culture. III. Discriminatory lysis of pairs of syngeneic blast induced by different mitogens. When normal spleen cells are cultured for 4 days in polyacrylamide vessels, individual clones of cytotoxic lymphocytes (CL) can be detected. The specificity of these 'spontaneous' CL was investigated by assaying the cytotoxic acitivity of cells from individual clones against pairs of different target. Target cells used were syngeneic blast cells induced by dextran sulfate, lipopolysaccharide (LPS), concanavalin A (ConA) and phytohemagglutin (PHA). It was found that LPS blasts were lysed by a separate set of CL clones from those which lysed PHA blasts of the same H-2 haplotype, and the clones of CL which lysed PHA blasts were a subset of all the clones which lysed ConA blasts. When individual clones of spontaneous CL were assayed against LPS and DS blasts, there were clones which lysed both types of blasts as well as clones which were specific for either LPS or DS blasts. These results have been interpreted as demonstrating that spontaneous CL can recognize and kill subsets of cells which are stimulated by different mitogens.


Presence of "La-like" antigens on human T lymphocytes bearing receptors for IgG. Human peripheral blood T cells bearing receptors for the Fc portion of immunoglobulins were characterized by the formation of double rosettes with sheep red blood cells and IgG-coated chicken erythrocytes (EA). Treatment of cells by anti-"Ia-like" antisera inhibits the binding of EA. Inihbition appeared to be specific since anti-HLA-A and HLA-B antibodies did not inhibit the formation of EA rosettes, whereas F (ab')2 fragments of anti-Ia-like IgG were found to be as potent inhibitors as the whole IgG. This result shows that in human and in mice, Ia-like determinants arepresent, close to Fc gamma receptors, on the surface of the T lymphocytes bearing such receptors.


On reversible changes in the steady state ion-conductance of the Ranvier node membrane under low frequency sound fields. The influence of sound waves on the stationary membrane conductivity of the axon membrane in myelinated nerve was investigated. Sound fields with frequencies within the auditory limit shift the transition voltage Vtr and correspondingly the threshold voltage of the action potential in polarisation direction. The results indicate that these changes of the electrical membrane behavior are due to a direct mechanical interaction between low frequency sound fields and membrane structure.


A contribution to the technique of mouse bone marrow cell culture in semisolid agar. A method of cultivation of mouse bone marrow cells in semisolid agar is described. Colony-stimulating factor was provided either by a "feeder layer" containing kidney cells (from 8-day-old mice) or by the addition of "lung conditioned medium" or post-endotoxin serum. The effect of various factors and media on the formation of colonies was tested. The best growth of colonies was observed in medium RPMI 1640 or in Eagle's minimal essential medium containing 0.2% bactotryptose supplemented with 20% foetal calf serum. Both the morphology of cells found in the colonies and the proliferative state of the cells that give rise to colonies indicate that CFU-C represent the committed progenitor for myelopoiesis.


Disappearance of haemopoietic stem cells from blood after hydroxyurea. Haemopoietic stem cells were examined in the blood of mice which had been injected with hydroxyurea. It was observed that the amount of CFU in the blood quickly decreased and after higher doses of hydroxyurea CFU completely disappeared from blood. Since CFU are rather resistant to the killing effect of hydroxyurea, it is assumed that the observed effect is caused either by an interference of hydroxyurea (due to its effect on the blood-forming tissues) with the migration of CFU into blood or by stimulating the removal og CFU from blood.


[Subpopulations of peripheral lymphocytes in insulin-dependent diabetics (author's transl)]. There is an increasing evidence that autoimmune mechanisms may have a role in the pathogenesis in insulin-dependent diabetics. The numerical and functional study of peripheral blood lymphocytes in diabetes mellitus might indirectly contribute to the understanding of its pathogenesis. In this study, detection of peripheral blood T lymphocytes was measured by rosettes with sheep red blood cells (SRBC), and B lymphocytes were measured by immunofluorescence with specific antiserum to immunoglobulins. The mean (+/- SD) percentage of SRBC was 67.6 +/- 7.2 in 21 normal subjects, 71.5 +/- 7.0 in 15 insulin-dependent diabetics, and 68.6 +/- 6.7 in 30 insulin-independent diabetics. There was no difference in the absolute T-lymphocyte number per mm3 in these three groups. Insulin-dependent diabetics showed a normal percentage and absolute number of B lymphocytes when compared with normal subjects.


Effects of Poly A. Poly U in vivo alterations of proportions of T and B cell subsets. Spleens and thymuses of mice were examined for changes in lymphocyte subpopulations after in vivo treatment with a double stranded synthetic polynucleotide: Poly A.Poly U. The cell populations were characterized on a biophysical basis: the electrical charge of cell surface assessed by the anodic electrophoretic mobility. The proportion of spleen cells exhibiting a high electrophoretic mobility (T lymphocytes) increased markedly on the 3rd day after a single intravenous injection of Poly A.Poly U. In thymuses, early important variations in electrophoretic distribution profiles were observed after Poly A.Poly U injection, suggesting that adjuvant acts on T cells.


Protein synthesis inhibitors and gastric acid secretion. The involvement of de novo protein synthesis in acid secretion by the in vitro bullfrog gastric mucosa was examined using the inhibitors cycloheximide and puromycin. Both inhibitors reduced [3H]leucine incorporation by more than 90%. The inhibition of protein synthesis had no influence on spontaneous acid secretion nor did it effect secretory stimulation by histamine, carbachol, pentagastrin, or theophylline. Oxygen consumption by nonstimulated and theophyllinestimulated tissues was shown to be independent of protein synthesis. The dramatic morphological changes observed in oxyntic cells during a transition from rest to active secretion persisted in cycloheximide-and puromycin-treated tissues. Stereological analysis of the apical membrane surface area density failed to demonstrate any quantitative influence of protein synthesis inhibition. These studies quantitatively confirm that protein synthesis is not required for the biochemical and morphological events involved in acid secretion by the in vitro frog gastric mucosa.


A role for T lymphocytes in the antitumour action of systemic C. parvum. The frequency of tumours arising from s.c. injection of a syngeneic chemically-induced fibrosarcoma (Fsa) was not influenced by systemic administration of C. parvum (day + 3) except when doses less than the TD50 were injected. Then the number of takes was increased. The tumour normally grows progressively however regression was frequent in intact mice treated with C. parvum. Tumour regression did not occur in T cell-depleted mice treated in the same way. Splenic T cell-enriched populations of cells taken from Fsa-bearing C. parvum-treated mice caused tumour regression when adoptively transferred to Fsa-bearing T cell-depleted mice. Although this assay measures systemic rather than intratumoral T cell activity, it is proposed that C. parvum-induced regression of the fibrosarcoma is to a large extent due to enhanced T cell reactivity.


Possible mechanisms in the anti-tumour activity of C. parvum. Normal murine peritoneal macrophages exhibited anti-tumour cytotoxicity following simultaneous incubation with C. parvum and lymphoid cells from C. parvum-treated mice. Both T- and B-lymphocytes appear to be involved in this macrophage activation which is mediated by a soluble factor(s) released by immune lymphoid cells in response to the specific immunising strain of C. parvum. Cells capable of macrophage activation do not appear until 6 days following systemic C. parvum administration despite the appearance of cytotoxic macrophages in vivo by day 3. It was therefore concluded that two mechanisms of macrophage activation might exist (1) an early phase of activation, possibly involving a direct effect on macrophage precursors by C. parvum, and (2) a later phase in which activation is mediated by T- and B-cells responding to the C. parvum stimulus.


Local gangrene: a complication of peripheral Pitressin therapy for bleeding esophageal varices. Two patients developed local gangrene after subcutaneous infiltration of vasopressin (Pitressin, Parke, Davis & Company, Detroit, Mich.) utilized for the control of bleeding from esophageal varices. In the 1st patient, ischemic gangrene resulted in transmetatarsal amputation and also necessitated skin grafts on the forearm. The 2nd patient developed gangrene and clostridial sepsis and expired. The effects of systemically administered Pitressin are reviewed and suggestion to prevent local necrosis are presented.


Alpha1-antitrypsin bodies, PiZ phenotype, and peptic ulcer. An association between chronic peptic ulcer and heterozygous alpha-antitrypsin deficiency has been reported: this study found no evidence of such an association. The prevalence of alpha1-antityrpsin bodies in the liver was compared with the known prevalence of PiZ phenotype in the population: there was no significant difference.


Clinical, biochemical, and histological studies of osteomalacia, osteoporosis, and parathyroid function in chronic liver disease. Twenty of 32 patients with either chronic cholestatic or hepatocellular liver disease had bone pain or recent fractures. On bone biopsy five patients had normal bone, 15 had osteomalacia, five had osteoporosis, and seven had a combination of osteomalacia and osteoporosis. In the presence of osteoporosis, osteomalacia was minimal or absent. There was no biochemical, radiological, or histological evidence of excess parathyroid activity. No significant correlations were demonstrated between the plasma and urinary biochemical findings and the presence of either osteoporosis or osteomalacia and bone biopsy was essential for correct diagnosis. There was no statistical relationship between low serum 25-hydroxy vitamin D values and the presence of osteomalacia. Bone disease was not prevented by regular intramuscular vitamin D2, although biochemical changes were improved. Drugs such as corticosteroids and cholestyramine may be important aetiological factors in hepatic osteodystrophy.


Establishment and characterization of leukemic T-cell lines, B-cell lines, and null-cell line: a progress report on surface antigen study of fresh lymphatic leukemias in man. Permanent human hematopoietic cell lines representing T-cell, B-cell and non T/non B (null-cell) leukemia have been established. Comparative analyses were made for their phenotype characteristics. A number of characteristics common within the 7 T-cell lines studied or distinct from other leukemia-type lines were described. Usefulness, validity and limitation of these findings are discussed in connection to the attempt at classification of ALL, CLL and blastic phase of CML. The great majority of CLL were SmIg+-B-cell leukemia and a single case of T-cell CLL was documented. Except 10% as T-cell ALL and a single case of B-cell ALL, the majority of ALL were found to be the non T/non B ALL. Nevertheless, little evidence was suggested from the present study in favor for a notion that the T-cell ALL and the non T/non B ALL are two distinct diseases.


Etiological, clinical and prognostic significance of the T-B immunological classification of primary acute lymphoid leukemias and non Hodgkin's lymphomas. The discovery of B or T markers on neoplastic cells in acute lymphoid leukemia (ALL) is correlated with a poor prognosis, while a cure expectancy of 50% can be expected for null cell ALL patients of all ages. In the case of Non Hodgkin's malignant lymphoma the patients with the T cell types carry a poor prognosis, while the patients with a B cell type present an 85% cure expectancy, and those with the null cell type a 65% cure expectancy. The correlation between immune markers on the one hand, and WHO cyto-histological typing and clinical presentation on the other, is reported.


Membrane marker analysis of 'lymphoid' and myeloid blast crisis in PH1 positive (chronic myeloid) leukemia. The membrane phenotype of leukaemic cells was analysed during different stages of chronic myeloid leukaemia by a panel of markers. These included antisera against ALL antigen, p23,30 (Ia-like structure) and other T cell, B cell and myeloid markers 'Lymphoid' blast crisis shares the phenotype of common ALL (of non-T, non-B variety). Both leukemias react with anti-ALL serum and have pre-myeloid, pre-B lymphoid and pre-thymocyte characteristics. Their phenotype may reflect the characteristics of the pluripotential stem cell from which they derive. Nevertheless both leukaemias retain their undifferentiated characteristics and lack overt myeloid, B cell and thymocyte differentiation markers. Myeloid blast crisis and AML are negative with anti-ALL serum but some of the poorly differentiated myeloblasts react with anti-p23,30 serum (and negative for SmIg). The anti-p23,30 serum (used in a double marker assay combined with anti-immunoglobulin) detects some (4-11%) intermediate sized agranular p23,30+/SmIg-cells in peripheral blood during the chronic phase of CML as well as in normal foetal bone marrow. These could be myeloid stem cells (from which in CML the myeloid blast crisis arises). The results demonstrate that surface membrane analysis can aid exact diagnosis in different stages of CML.


The pattern of involvement of murine lymphoid tissues by primary lymphomas of different cell lineage. Murine virally induced lymphomas with T cell surface antigens migrate in the lymph nodes and spleen in the same regions as normal recirculating T lymphocytes. Non-T cell lymphomas have different patterns of migration.


Ther persistent PHA-responsive population in the mouse thymus. i. Characterization of the population. Using an in vitro culture technique, mouse thymus graft cells were co-cultured with peripheral blood lymphocytes in the presence of phytohaemagglutinin (PHA). The persistent PHA-responsive thymus graft population (Elliott, 1973) was shown to be able to response to other T-cell mitogens (Con A, pokeweed mitogen, staphylococcal enterotoxin B), but not to E. coli lipopolysaccharide a known B-cell mitogen. The percentage of persistent PHA-responsive cells did not alter during 5 days in culture and was relatively unaffected by either hydrocortisone or anti-lymphocyte serum treatment in vitro. In allogeneic thymus grafts (AKR leads to CBA), persistent PHA-responsive cells could be demonstrated, which were destroyed when incubated with CBA anti theta AKR serum and complement. When thymus graft cells were allowed to sediment on a 0.2-2 per cent BSA gradient, it was seen that the PHA-responsive population sedimented faster than the bulk of thymus graft cells. Some separation could be obtained on this gradient between the persistent and non-persistent PHA-responsive cell populations.


Identity of a T-lymphocyte inhibitor with mouse immunoglobulin in the serum of tumour-bearing mice. A component of the serum of tumour-bearing mice has been shown to be inhibitory to the immunological function of normal mouse T cells. This factor fractionates with monomeric immunoglobulin upon gel filtration. Studies were carried out utilizing goat antisera to the major immunoglobulin chains of mouse Ig (kappa, gamma, alpha and mu) mixed with the immunoglobulin-rich fraction of serum from normal mice and tumour bearers and passed through immunoadsorbent columns prepared with rabbit anti-goat immunoglobulin. Such studies showed that the inhibitory activity in tumour-bearing serum could be removed after treatment with anti-kappa, anti-gamma and anti-mu chain antisera but not by treatment with either anti-alpha chain or goat immunoglobulin. That the inhibitory activity of tumour-bearing immunoglobulin could be attributed to simple quantitative differences in the levels of IgM and IgG in the test samples was discounted by quantification of the amounts of immunoglobulins in normal and tumour-bearing sera.


Embryonic mouse thymocyte development. Enhancing effect of corticosterone at physiological levels. The action of corticosterone on embryonic mouse thymus development has been studied in vitro. Effects of the hormone on lymphoid differentiation varied according to the dose. 0.2-1.0 microgram/ml had an enhancing effect, resulting in an increase in the proportion of Thy-1.2 positive cells as compared with control cultures. Two to fifty micrograms per millilitre had an inhibitory effect, appearing to selectively kill small lymphocytes while leaving large and medium lymphocytes intact. At higher does these immature cells were also killed.


Effect of corticosteroids on the response of lymphocytes to stimulation by galactose oxidase-modified lymphocytes. Human peripheral blood mononuclear cell preparations, after treatment by neuraminidase plus galactose oxidase, stimulated untreated lymphocytes. The increases in tritiated thymidine incorporation in the responder lymphocytes were observed after 48 h of mixed cell cultures. Monocytedepleted lymphocyte preparations were equally effective stimulator cells. Both purified T and B fractions were effective stimulator cells. On the other hand, only the T but not the B fractions could respond to the stimulation. The response of the cells to this type of stimulation was suppressed by 10(4)-10(7) M of the corticosteroid preparation methylprednisolone. When the cells treated with neuraminidase plus galactose oxidase were cultured alone for 48 h, they lost their stimulating capacity. However this loss could not be prevented by the presence in the culture of methylprednisolone. Hence the drug has selective suppressive activity on one type of lymphocyte activity but not the other.


Suppression of lymphocyte responses by cephalosporins. Human peripheral blood lymphocytes were cultured in several concentrations of each of several cephalosporins. Responses to phytohemagglutinin were compared with that of duplicate cultures containing penicillin-streptomycin, chloramphenicol, or no antibiotics. Possible effects of cephalosporins on responses of lymphocytes to concanavalin A and pokeweed mitogen were similarly determined. Significant suppression of responses to phytohemagglutinin and concanavalin A were seen in cultures containing 50 microgram each of cephalothin, cephalexin, or cephradine per ml. Lymphocyte responses to pokeweed mitogen were suppressed by 50 microgram of cephalexin, cephradine, or cefoxitin per ml. A higher concentration (100 microgram/ml) of all cephalosporins except cefoxitin and cefazolin suppressed the phytohemagglutinin response to less than 20% that of controls. Chloramphenicol (50 microgram/ml) did not inhibit the response to any mitogen used. These findings suggest that cephalosporins should not be used for prevention of bacterial overgrowth in certain cell cultures. Since many of the cephalosporins were suppressive in therapeutically attainable concentrations, these results may have potential clinical significance.


Friend virus-induced immunodepression: effect of neuraminidase treatment on Thy-1.2 antigen expression and cytotoxic potential of splenocytes from virus-infected mice. Infection of susceptible strains of mice with Friend leukemia virus (FLV) results in a profound depression of cell-mediated immunity as assessed by lymphocyte-mediated cytotoxicity. This depression occurs early in the disease, before the onset of splenomegaly, and is associated with a decline in the susceptibility of splenocytes from FLV-infected mice to lysis by anti-Thy-1. 2 serum and complement. Treatment of splenocytes from FLV-infected mice with neuraminidase restores, in large part, their susceptibility to anti-Thy-1.2 serum as well as their cytolytic capacity. These studies suggest that one early immunosuppressive consequence of infection with FLV involves alteration of the effector T-lymphocyte cell surface.


The enhancing effect of unsaturated fatty acids on E rosette formation. The number of bound sheep red blood cells (SRBC) per lymphocyte of 16 healthy subjects were assayed prior and after addition of unsaturated fatty acids. Addition of fatty acids to the assay system was found to increase significantly the number of avid T lymphocytes (which bind more than 10 SRBC). It is suggested that increased fatty acid level might change lipid fluidity of the plasma membrane and increase the number of attachment points between the cell surface of the lymphocyte and SRBC. The immunoregulatory effect of fatty acids is discussed.


Subpopulations of T lymphocytes in human extravascular fluids. Surface markers of lymphocytes from various human extravascular fluids (cerebrospinal fluid, aqueous humour, colostrum, breast and ovary cyst fluids, peritoneal and pleural transudates) are compared with those of lymphocytes from peripheral blood. Significantly higher percentages of T cells are found in all extravascular fluids: the great majority of extravascular T lymphocytes show high E rosette-forming ability and bear IgG Fc receptors (T Fc+ cells). Functional implications of the shown high predominance of T Fc+ cells in extravascular fluids are discussed on the basis of presently available information on the immunological role of such cells (cytotoxic? suppressor? amplifier?).


Effect of long-term cyclophosphamide treatment on T and B lymphocytes in normal guinea pigs. The effect of long-term repeated cyclophosphamide administration at low doses on T and B lymphocyte levels in the blood, lymph nodes and thymus of the guinea pig has been studied. A significant depletion of B cell levels occurred in the blood and the lymph nodes. Although there was evidence of depression of T cell levels in both blood and thymus, these changes were not statistically significant, except in the case of total T lymphocyte levels in the blood in one experiment. It is suggested that differences in sensitivity of T and B cells to cyclophosphamide may be related to differences in proliferative turnover and in their capacity to repair damage to DNA.


C3 activator in agammaglobulinemia.

C3 activator in agammaglobulinemia. C3 activator in sera of patients with agammaglobulinemia shows higher levels compared with age-matched healthy controls. This fact may be due to a compensatory function of the alternative pathway of the complement system to make up for the defect of production of antibody in these patients.


Gamma-ray induced double-strand breaks in DNA resulting from randomly-inflicted single-strand breaks: temporal local denaturation, a new radiation phenomenon? The induction of single- and double-strand breaks in DNA by gamma-rays has been measured. The maximum number of nucleotide pairs (a) between two independently induced single-strand breaks in opposite strands of the DNA which cannot prevent the occurrence of a double-strand break was found to amount to about 16. This value did not differ significantly for the four types of bacteriophage DNA investigated (T4, T7 and PM2 DNA, and replicative form DNA of phage phiX174) and was the same in 10(-2) M phosphate buffer containing 0, 0.5 or 1 M NaCl. In 10(-3) M phosphate buffer a was 34 nucleotide pairs. Evidence is presented that the relatively large value of a has to be ascribed at least partly to a temporal local denaturation accompanying the induction of a single-strand scission. A contribution of base damage that labilizes the DNA-helix, between two single-strand breaks to the high value of a can not be excluded.


The radiation response of cultured mammalian V79-S171 cells exposed to a wide concentration range of sulphate salt solutions. The radiation response of Chinese hamster cells (V79) exposed to a wide concentration range of Li2SO4, Na2SO4 or K2SO4 has been examined and compared with the radiation response of cells treated in an identical manner with LiCl, NaCl, or KCl solutions. At hypotonic salt concentrations, cells were radiosensitized by both the chloride and sulphate salts. At high salt concentrations, approximately greater than 0.9 M, a radioprotective effect was observed with both chloride and sulphate salts. At intermediate salt concentrations from about 0.2 to 0.9 M, the cells that were treated with the sulphate salt solutions were radioprotected; cells treated with chloride salt solutions were radiosensitized. The difference in radiation response was attributed to the difference in anions for the two types of salts used.


Cystic hamartoma of Brunner's glands.

Cystic hamartoma of Brunner's glands. A 64-year-old white man was operated on for acute gastrointestinal bleeding. The patient was known to have a duodenal polyp for 15 years. Surgery revealed a small duodenal ulcer and a large cystic hamartoma of Brunner's glands. Incidence, aspects of pathogenesis, clinical features and treatment of this rare tumor are discussed.


Induction of immunoregulatory T cells by adjuvant. The effect of adjuvant on the generation of suppressor cells in the thymus was investigated. C57Bl/6 mice were injected i.p. with complete Freund's adjuvant (CFA), and the capacity of thymocytes and splenic T cells to suppress the in vitro generation of cytolytic T cells was studied. Suppressor thymocytes were detected within two days after CFA inoculation and preceded the appearance of suppressor T cells in the spleen by six days. Characterization of the suppressor thymocyte populations showed that they inhibited primary but not memory T cell responses in vitro. We suggest that the initial step in the regulation of the primary immune response by adjuvant is the generation of suppressor cells in the thymus. Thymic suppressors subsequently migrate to peripheral lymphoid tissue where they inhibit cytotoxic, but no helper, T cell function.


[Symptomatology and diagnosis of vestibular disorders following head injury (author's transl)]. One hundred cases of head injuries were submitted to thorough repeat neuro-otological examinations. The results were evaluated with respect to the diagnostic importance of vestibular symptoms. Positional nystagmus was found to be the most common symptom (51%). In 25% of the cases, spontaneous nystagmus could be demonstrated up to two years following head injury. Pathologic caloric responses were found in only one-third of the patients. Positional and positioning nystagmus were found to be the most important symptoms of a vestibular disorder following head injury, and seem to be the most reliable criteria for the assessment of disability and working capacity.


Descending fibres of the lateral funiculus of the amphibian spinal cord: their course and terminal distribution. Descending fibres of the lateral funiculus (LF) of the spinal cord have been mapped in the adult bullfrog, Rana catesbeiana. Following large and small lesions of the cervical LF, Nauta preterminal and terminal degeneration staining techniques revealed a large bilateral projection to intermediate regions of the lumbar central grey. Dorsal LF fibres were seen only contralaterally, and ventral fibres mainly ipsilaterally, Medical LF fibre and terminal degeneration occurred bilaterally. Terminal fields of ipsilateral fibres often included the large motoneuron somata situated dorsolaterally in the ventral grey. The smaller contralateral contingent of fibres terminated most often in areas of the central grey dorsal or medial to the motoneuron pool.


Cordycepin. An inhibitor of newly synthesized globin messenger RNA. The effect of cordycepin (3'-deoxyadenosine) on newly synthesized globin mRNA in cultured mouse fetal liver erythroid cells is investigated. At cordycepin concentrations that do not inhibit amino acid incorporation into acid-precipitable material, the quantity of pulse-labeled (radioactive) globin mRNA nucleotide sequences is reduced by 90%, as compared to adenosine-treated controls. The reduction of radioactivity in globin-specific RNA sequences is greater than the inhibition of total RNA synthesis in experiments in which the labeling times range from 6 to 60 min. Control experiments demonstrate that cordycepin does not reduce the recovery of total cell RNA or steady state (unlabeled) globin mRNA. The hybridization assay used to detect radioactive globin mRNA sequences is independent of the cellular location or the number of 3'-terminal adenylate residues in the mRNA-containing molecules. These data thus indicate that cordycepin inhibits newly synthesized mRNA as effectively as it inhibits ribosomal and transfer RNA synthesis.


[Architecture of the visual system of Discoglossus pictus (Oth)]. The retinofugal pathways of an "archaic" Anura Discogossus pictus were examinated with Fink-Heimer method following ablation of the retina and after survival times of 5--105 days at 14 degrees C. A description of the diencephalic and mensencephalic architectonics has been done in order to replace the visual system into the general pattern. The scheme of primary optic pathways and centers is similar in Discoglossus and Rana. However, some retinofugal fibers reach the posterolateral part of the ipsilateral tectum opticum. Beside this study, a Golgi study has shown the link which exists between the degeneration territories (neuropils) and the periventricular cell-masses by the way of the dendritic trees of multipolar, bipolar and pear-shaped neurons. An hypothesis about the notion of visual center is formulated. In the tectum, the distribution of degenerations allows to understand the existence of two visual behaviors: avoidance and prey-catching. The signification of the ipsilateral retinotectal pathway is discussed.


Molecular basis of B cell activation: mitogenicity of native and modified digitalis glycosides. Lanatoside C, a digitalis glycoside, has previously been shown to be a potent polyclonal B cell activator for mouse lymphocytes. Since the chemical structure of lanatoside C is well defined we investigated the effect of different chemical modifications on the mitogenic properties of the glycoside in order to determine the molecular basis of B cell activation. The presence of an OH- group at C12 in the steroid nucleus proved to be essential for activation to occur in serum-free medium. Likewise, an intact carbohydrate side chain at C3 appeared to be necessary for retaining mitogenic properties. In serum-supplemented cultures, however, a much more complex response pattern was observed where the prerequisites for activation were not as distinct as in serum-free medium.


Polyclonal activation of CR+ and CR- B lymphocytes: the kinetics of initiation of DNA and immunoglobulin synthesis by lipopolysaccharide. B cells that carry the complement receptor (CR+) were separated from B cells that lack the complement receptor (CR-) by velocity sedimentation or by passage through C-coated Sephadex columns. The kinetics of responses to bacterial lipopolysaccharide (LPS) in both B cell subpopulations were determined in three assay procedures: 1) incorporation of radioactive thymidine into DNA; 2) incorporation of radioactive leucine into immunoglobulin; 3) enumeration of cells forming polyclonal antibody to the 2,4,6-trinitrophenyl hapten. Although both subpopulations of B cells responded to LPS, they differed in the time course. CR- B cells responded with a delay of approximately 24 hr as compared with the response of CR+ B cells. The implications to the ontogenetic status of CR+ and CR- B subpopulations are discussed.


Inhibition of specific effector T cell-target cell conjugates by cell plasma membranes. Conjugate formation between effector T cells raised in vivo in a BALB/c hose had fluorescein diacetate-labeled allogeneic EL4 tumor target cells was observed and scored by using a fluorescence mirroscope. This conjugate formation was found to be specifically inhibited by plasma membrane vesicles isolated from the EL4 cells.


Transfer of concanavalin A between responding lymphocytes and syngeneic stimulating cells in cell-mediated mitogenic response. We have studied the mechanism of the cell-mediated mitogenic response (CMMR), in which proliferative responses are generated in mouse T lymphocytes co-cultivated with syngeneic mitomycin C-treated spleen cells (Mito-SP), when either responder or stimulator cells are briefly pretreated with concanavalin A (Con A) under nonmitogenic conditions. We present evidence that an intact membrane of the stimulator cells is required in CMMR, since the response was abolished by fixation, or by freezing and thawing of stimulator cells. The fate of cell-bound Con A was studied by tracing I-Con A bound to either stimulator or responder. A lymphoblast that developed from untreated CRT stimulated by I-Con A-coated syngeneic Mito-Sp carried about 105 molecules of 125I-Con A. The amount of Con A released into the culture medium was not sufficient for inducing a mitogenic response by itself, nor to bind to cells at the level found in CMMR, suggesting that 125I-Con A was transferred directly from labeled cells to unlabeled cells. Transferred 125I-Con A found in lymphoblasts was undergraded intact Con A, as demonstrated by gel electrophoresis. Autoradiography allowed visualization of the movement of 125I-Con A from stimulator to responder cells within 60 min of cell contact.


Reaginic antibody formation in the mouse. X. Possible role of suppressor T cells in transient IgE antibody responses. The kinetics of IgE antibody response to alum-absorbed dinitrophenyl derivatives of ovalbumin (DNP-OA) was dependent on the dose of immunogen. A persistent IgE antibody response was obtained when high responder BDF1 mice were immunized with a minimum (0.05 microgram) dose. An increase of the immunogen to 10 microgram depressed IgE antibody responses but enhanced IgG antibody responses of both hapten and carrier specificities. Determination of T helper cell activity and B memory cells after immunization with different doses of antigen indicated that minimum immunogen was favorable for developing helper activity, whereas 1 to 10 microgram immunogen were more favorable than a 0.05-microgram dose for developing both IgE and IgG B memory cells. Nevertheless, neither helper T cells nor B memory cells in the spleen explains a transient IgE antibody response to a high (10 microgram) dose of DNP-OA. Evidence was obtained that immunization with 10 microgram OA induced generation of antigen-specific suppressor T cells, which were not detectable after immunization with 0.05 microgram OA. Transfer of suppressor T cells to DNP-OA-primed mice depressed both anti-hapten and anti-carrier IgE antibody responses. The results suggested strongly that suppressor T cells are involved in a transient IgE antibody response to a high-dose immunogen.


Suppressor T cells for IgE and IgG in Peyer's patches of mice made tolerant by the oral administration of ovalbumin. A single oral dose of ovalbumin (Ov) resulted in inhibition of IgE formation in mice subsequently immunized i.p. with Al(OH)3-Ov. Repeated feeding of Ov (on alternate days for 2 weeks) induced the formation of detectable suppressor cells in Peyer's patches and spleen. Suppression was demonstrated by the ability of adoptively transferred Peyer's patch or splenic lymphocytes from Ov-fed tolerant mice to inhibit IgE formation in Ov-immunized syngeneic recipients. Suppressor cells could be induced by feeding mice as little as 100 microgram of Ov on alternate days for 2 weeks. Suppression was specific and Peyer's patch lymphocytes were shown to be more effective suppressors than splenic lymphocytes.


Control of human B lymphocyte responsiveness: enhanced suppressor T cell activity after in vitro incubation. Human peripheral blood mononuclear cells (PBM) lost the capacity to generate immunoglobulin-secreting cells (ISC) in response to pokeweed mitogen (PWM) after a period of preincubation in vitro. When fresh PBM were co-cultured with preincubated PBM their response to PWM was inhibited, indicating that enhanced suppressor activity developed in the aged PBM concomitant with the loss of PWM responsiveness. Suppressor cell activity of aged PBM was present within the T lymphocyte population. The suppressor T cell inhibited PWM responsiveness of autologous and homologous PBM to an equivalent degree. The action of the suppressor cell was abrogated by inhibitors of DNA synthesis or by hydrocortisone. A suppressor T cell population with similar characteristics was found in freshly prepared PBM before in vitro incubation. Expansion of this suppressor T cell population during preincubation required cell division. There was no change in the functional capability of the helper T cell population as a result of similar in vitro culture. These observations indicate that a T cell population capable of suppressing PWM-induced generation of ISC can be selectively expanded by in vitro incubation of normal human PBM without additional mitogenic stimulation. Moreover, these data emphasize that control of B lymphocyte differentiation involves a critical interrelationship between T lymphocyte subpopulations exerting both positive and negative influences.


Electrophoretic mobility distributions of normal human T and B lymphocytes and of peripheral blood lymphoblasts in acute lymphocytic leukemia: effects of neuraminidase and of solvent ionic strength. Human T and B lymphocytes were found to be distinguishable on the basis of electrophoretic mobility, with the T cells having the higher mobility, in agreement with previous reports. The effects of the enzyme neuraminidase on the electrophoretic mobilities of T and B lymphocytes were determined. T lymphocytes showed a greater decrease in electrophoretic mobility after neuraminidase treatment; the relative mobilities of T and B cells were reversed by neuraminidase treatment, and the electrophoretic distinguishability was enhanced. The electrophoretic mobility distributions of lymphoblasts from patients with acute lymphocytic leukemia were found to differ from those of normal cells in their response to neuraminidase treatment and to changes in solution ionic strength. These results imply that the surface structure of the leukemic cells differs from that of either T or B lymphocytes from normal donors.


Lymphocyte isolation from chronically inflamed synovial membranes. A simple two-step procedure was developed for isolation of lymphocytes from chronically inflamed human synovial membranes. In the first step minced inflamed synovial tissues are disrupted enzymatically by deoxyribonuclease and collagenase. The second step consists of nylon-wool column filtration of the isolated cells. 7 min of preincubation of up to 37.4 X 10(6) cells in a column packed with 600 mg nylon-wool in 6 ml prior to filtration did not result in significant selective losses of either T or B cells, whereas 45 min of preincubation did. Recovery of lymphocytes after nylon-wool column filtration ranged from 68 to 95% (mean 80%) and viability was always higher than 90%. Nylon-wool column filtration increased the proportion of lymphocytes by a mean 73%. The method allows rapid identification of synovial tissue lymphocyte subpopulations as well as characterization of their function.


Some requirements for a linear cell dose response in vitro assay for the T-cell progenitors of cytotoxic lymphocytes. To develop a precise assay for the T-cells progenitors of cytotoxic lymphocytes (CL-progenitors), lymphoid were cultured under optimal conditions in Marbrook vessels with mitomycin-treated allogeneic stimulator cells, and the total level of CL produced 5 days later estimated by a modified 51Cr release assay. Conditions were adjusted so an arithmetically linear cell dose response relationship was obtained. Three aspects of the cell dose response curve required attention. (1) At low responding cell inputs a macrophage-like cell became limiting (despite the presence of allogeneic macrophages in the stimulating cell population), leading to a lag in the response. This limitation was overcome by adding a low level of irradiated syngeneic macrophages, or by using irradiated syngeneic spleen 'filler' cells. (2) The slope of the resultant linear dose response region could be reduced if desired by changing from cellophane dialysis membranes to 0.1 mu pore size nuclepore membranes, suggesting a stimulatory role for some higher molecular weight soluble factor produced in the cultures. (3) At higher responding cell inputs a marked and extensive plateau was obtained. CL developing early in the response appeared to be destroying the allogeneic stimulator cells causing the response to be self-limiting. This problem was overcome by using a responding cell concentration lower than commonly employed. Assays using mixed leukocyte cultures in the lag or plateau regions could give misleading vlaues for CL-progenitor activity. It is suggested that some examples of apparent synergism in CL generation may have resulted from these effects, rather than T-cell helper T-cell progenitor interactions.


Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex. Genetic restrictions governing the induction and expression of suppressor T cells (Ts) in tolerance to 1-fluoro-2,4-dinitrogenzene (DNFB) contract sensitivity were studied. Tolerance was induced by using 2,4-dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogen. Two kinds of Ts were found-those produced by DNP-LC syngeneic to the donor of the Ts (syninduced Ts), and those produced by DNP-LC allogeneic to the donor of Ts (alloinduced Ts). Studies employing congenic resistant mouse strains indicated that recognition of DNP-modified-major histocompatibility region determinants on the tolerogenic DNP-LC was essential for the induction of both types of Ts. Non-H-2 genetic background was irrelevant to Ts induction. Mapping studies indicated that induction of both syninduced and alloinduced Ts was associated with  recognition of DNP-modified-MHC region determinants which map to the right of the H-2G region (i.e., H-2D gene products). Tolerization of donor mice with DNP-LC which were H-2D region compatible, but not with H-2K or I region compatible DNP-LC, was both sufficient and required for the induction of hapten-specific syninduced Ts. Tolerization of donor mice with DNP-LC which were incompatible only at the H-2D region was sufficient for the induction of alloinduced Ts. These Ts were capable of suppressing recipient mice only if the recipients shared the H-2D region with the strain providing the DNP-LC tolerogen, and were not capable of suppressing recipients sharing all but the H-2D region with the tolerogen.


On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? In the thymus, precursor T cells differentiate recognition structures for self that are specific for the H-2K, D, and I markers expressed by the thymic epithelium. Thus recognition of self-H-2 differentiates independently of the T cells H-2 type and independently of recognition of nonself antigen X. This is readily compatible with dual recognition by T cells but does not formally exclude a single recognition model. These conclusions derive from experiments with bone marrow and thymic chimeras. Irradiated mice reconstituted with bone marrow to form chimeras of (A X B)F1 leads to A type generate virus-specific cytotoxic T cells for infected targets A only. Therefore, the H-2 type of the host determines the H-2-restricted activity of killer T cells alone. In contrast, chimeras made by reconstituting irradiated A mice with adult spleen cells of (A X B)F1 origin generate virus-specific cytotoxic activity for infected A and B targets, suggesting that mature T cells do not change their self-specificity readily. (A X B)F1 leads to (A X C)F1 and (KAIA/DC) leads to (KAIA/DB) irradiation bone marrow chimeras responded against infected A but not B or C targets. This suggests that cytotoxicity is not generated against DC because it is abscent from the host's thymus epithelium and not against DB because it is not expressed by the reconstituting lymphoreticular system. (KBIB/DA) leads to (KCIC/DA) K, I incompatible, or completely H-2 incompatible A leads to B chimeras fail to generate any measurable virus specific cytotoxicity, indicating the necessity for I-specific helper T cells for the generation of killer T cells. Finally adult thymectomized, irradiated and bone marrow reconstituted (A X B)F1 mice, transplanted with an irradiated thymus of A origin, generate virus-specific cytotoxic T cells specific for infected A targets but not for B targets; this result formally demonstrates the crucial role of thymic epithelial cells in the differentiation of anti-self-H-2 specificities of T cells.


The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help. The thymus determines the spectrum of the receptor specificities of differentiating T cells for self-H-2; however, the phenotypic expression of T cell's specificity for self plus virus is determined predominantly by the H-2 type of the antigen presenting cells of the peripheral lymphoreticular system. Furthermore, virus specific helper T cells are essential for the generation of virus-specific cytotoxic T cells. For cooperation between mature T cells and other lymphocytes to be functional in chimeras, thymic epithelial cells and lymphohemopoietic stem cells must share the I region; killer T-cell generation also requires in addition compatibility for at least one K or D region. These conclusions derive from the following experiments: A leads to (A X B)F1 chimeric lymphocytes do produce virus-specific cytotoxic T-cell activity for infected A but not for infected B cells; when sensitized in an acutely irradiated and infected recipient (A X B)F1 these chimeric lymphocytes respond to both infected A and B. Therefore the predominantly immunogenically infected cells of chimeras the radiosensitive and by donor stem cells replaced lymphoreticular cells. In this adoptive priming model (KAIA/DB leads to KAIA/DC) chimeric lymphocytes could be sensitized in irradiated and infected F1 against KA and DC but not against infected DB targets. In contrast KBIB/DA leads to KCIC/DA chimeras' lymphocytes could not be sensitized at all in appropriately irradiated and infected F1 recipients. Thus these latter chimeras probably lack functional I-specific T helper cells that are essential for the generation of T killer cells against infected D compatible targets. If T cells learn in the thymus to  recognize H-21 or K, D markers that are not at least partially carried themselves in other cells of the lymphoreticular system immunological interactions will be impossible and this paradox situation results in phenotypic immune incompetence in vivo.


Autologous leukemia-specific T-cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia. Short-term culture of acute myelogenous leukemia patient's remission lymphocytes with inactivated autologous leukemic blast cells plus allogeneic lymphocytes, generated effector T lymphocytes which were cytotoxic for the specific autologous blast cell in 11 of 14 patients studied. Experiments using Daudi and Molt 4 lymphoblastoid cell lines as  third-party helper cell suggest that an HLA D locus incompatability is necessary to provide effective help in this system. Cold target inhibition experiments, crossover studies between pairs of patients, and experiments with allogeneic leukemic blast cells as priming stimulus suggest that the target antigen is only present on the specific autologous blast cell.


Complete replacement of serum by albumin, transferrin, and soybean lipid in cultures of lipopolysaccharide-reactive B lymphocytes. Albumin, transferrin, and lipids can replace serum entirely for support of LPS-stimulated murine B lymphocytes in culture. In the presence of these compounds, growth and maturation to IgM and IgG secretion, induced by lipopolysaccharide (LPS), occurs at the same or higher efficiency in serum-free conditions as in conventional serum-containing medium, even at relatively low cell concentrations. In contrast to the rapid disappearance of LPS reactivity in conventional serum-containing medium, responsiveness remains at initial levels in serum-free conditions for 2 days before slowly declining. Overall lymphocyte survival is also markedly prolonged. In the presence of thymus "filler" cells, the serum-free conditions permit growth of every LPS-responsive cell to a clone of Ig-secreting cells at dilutions as low  as a single reactive B cell per culture. The results have several important implications. These include the establishment for the first time of transferrin as a requirement for B lymphocyte responses in culture, and the availability now of conditions for the assay isolation of cell products regulating lymphocyte function, free of interference from undefined serum components.


Induction of partial chimerism in nonirradiated B-lymphocyte-deficient CBA/N mice. Nonirradiated B-lymphocyte-deficient CBA/N mice given T6T6 chromosome-marked normal CBA/CaHN spleen cells became lymphoid chimeras exhibiting donor-type mitoses. Normal CBA/CaHN recipients did not exhibit significant numbers of donor-type mitoses. The lymphoid cell chimerism in the CBA/N host appeared in spleen, lymph nodes, and Peyer's patches, but not in marrow or thymus. Stimulation of CBA/N-recipient spleen cells in vitro suggested that the chimerism involved donor T6T6 cells which were responsive to the B-lymphocyte mitogen, lipopolysaccharide, but not to the T-lymphocyte mitogen, phytohemagglutinin. These data indicate that stable, long-term chimerism of a specific class of lymphocytes is possible in nonirradiated, B-lymphocyte-deficient CBA/N mice.


The induction of secondary cytolytic T lymphocytes by solubilized membrane proteins. Membrane-bound antigens responsible for induction of a secondary allogeneic murine cytolytic T-cell (CTL) response have been obtained in a soluble, biologically active form by deoxycholate solubilization of tumor cell plasma membranes. The active proteins are soluble by the criteria of both ultracentrifugation and gel filtration. The immunological specificity of the induced CTL and removal of the activity from solution by treatment with B6 anti-P815 (anti-H-2d) antiserum and Protein A-Sepharose demonstrate that the CTL-inducing activity is dependent upon solubilized major histocompatibility complex antigens.


[Differences between human and rat blood towards 3,4-dihydroxy-L-phenylalanine and 5-hydroxy-L-tryptophan in vitro. Biochemical and histochemical data (author's transl)]. When incubated with whole human blood at ordinary temperature, 3,4-dihydroxy-L-phenylalanine remains unchanged for at least 30 min. Under the same experimental conditions, 5-hydroxy-L-tryptophan shows a tendency to decrease. When incubated with blood from pentobarbital anaesthetized rats, these aminoacids decrease to about 50% of the added quantity in less than 5 min; thereafter, their level remains stable (3,4-dihydroxy-L-phenyl-alanine) or slowly decreases (5-hydroxy-L-tryptophan).


Intraspinal arachnoiditis and hydrocephalus after lumbar myelography using methylglucamine iocarmate. A 35 year old woman developed a severe meningeal reaction after lumbar myelography using the water-soluble contrast medium methylglucamine iocarmate. Three months after myelography the findings were a transverse spinal cord syndrome corresponding to the middle thoracic segments resulting from well developed leptomeningeal adhesions. This was combined with a noncommunicating hydrocephalus, probably the result of leptomeningeal fibrosis in the posterior fossa. After treatment with a ventriculoatrial shunt the patient is almost free of symptoms. A possible pathogenetic relationship between the contrast medium, the chronic leptomeningeal changes, and the symptoms of our patient is discussed on the basis of the literature.


Time course of clinical and physiological effects of stimulation of the cerebellar surface in patients with spasticity. A double-blind study of the short-term (12--48 hours) effects of cerebellar stimulation was performed on 11 selected patients with spasticity. Six of patients had a good clinical long-term response to chronic stimulation, four had a moderate response, and one had no response. Each patient received stimulation for two periods of 24 hours and was off stimulation for two periods of 24 hours. The periods were randomised over four consecutive days. Neither the patients nor the observer could distinguish between the days on stimulation and the days off stimulation. Simple tests of function of the upper limbs during stimulation, measurements of H responses, tonic vibration responses, vibration-induced suppression of H responses, stretch responses, and co-contraction, showed no differences between the four days. These results are contrasted with acute physiological changes seen in some patients during stimulation and also with the slow progressive improvement in clinical function that characterises the successful clinical response. It is suggested that lack of either acute or short-term changes in response to cerebellar stimulation does not predict the clinical outcome. If the strength of stimulation is changed, at least three days and preferably 10 days should be allowed for the effects to appear. The mechanisms responsible for the alleviation of spasticity are likely to be more complex than those mediating acute and reversible changes in reflex activity.


Electronystagmographic criteria in neuro-otological diagnosis. 2. Central nervous system lesions. Direct current electronystagmographic recordings of spontaneous nystagmus in light, in darkness, and with eye closure have been carried out on (a) 33 patients with acoustic neurinomata pressing on the brain stem, and (b) 10 patients with lesions involving the brain stem at a high level. Patterns of response characteristics of each group have been identified in 21 out of 28 cases of group a, the spontaneous nystagmus present in light was abolished by eye closure and inhibited in darkness, nystagmus being absent in the remaining five; in group b the greater proportion (70-80%) of patients presented with spontaneous nystagmus in light which was abolished by both eye closure and darkness.


Percutaneous epidural stimulation of the spinal cord for relief of pain. Long-term results. Percutaneous epidural stimulation of the spinal cord was carried out in 20 patients with intractable pain. The procedure proved simple, and no major complications were encountered. The long-term results were comparable to the results obtained after a dorsal column stimulator implant by laminectomy. The percutaneous technique allowed extended trial stimulation without committing the patient to a major operation. Those patients in whom stimulation did not alleviate pain could be identified during a 2-week observation period, and the system could be removed easily. Seven patients were placed on chronic autostimulation and only one of those failed to experience continuing pain relief throughout the follow-up time of up to 2 years. It is concluded that percutaneous epidural stimulation constitutes a valid alternative to dorsal column stimulator implantation.


Anterior inferior cerebellar artery aneurysms. Case report. A 54-year-old man experienced a right occipital headache accompanied by a roaring sound, nausea, vomiting, right facial weakness, and stiff neck. Vertebral angiography revealed an aneurysm of the right anterior inferior cerebellar artery (AICA) at the internal acoustic meatus which was later excised with favorable results. The literature is reviewed; operations have been reported in eight other cases. Inconstant waxing and waning cerebellopontine angle symptoms and signs can be found when a history of subarachnoid hemorrhage is lacking.


Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. We have performed brain scanning by computed tomography on 46 consecutive live-born infants whose birth weights were less than 1,500 gm; 20 of them had evidence of cerebral intraventricular hemorrhage. Nine of the 29 infants who survived had IVH. Four grades of IVH were identified. Grade I and II lesions resolved spontaneously,  but there was prominence of the interhemispheric fissue on CT of the infants at six months of age. Hydrocephalus developed in infants with Grade III and IV lesions. Seven of the surviving infants with IVH did not have clinical evidence of hemorrhage. There were no significant differences between the infants with and without IVH in birth weight, gestational age, one- and five-minute Apgar scores, or the need for resuscitation at birth or for subsequent respiratory assistance.


Enlargement of subarachnoid spaces and lateral ventricles in pediatric patients undergoing chemotherapy. This retrospective study investigated the possible adverse effects of cancer therapy on the brain. Cranial computed tomographic scans of 76 patients with non-central nervous system malignancies and 25 patients with leukemia had enlarged lateral ventricles and/or cortical sulci in 19% and 40%, respectively. Leukemic patients, especially those with meningeal involvement, had the most frequent and most severe abnormalities.