Immunoreactivity in pulmonary echinococcosis. A comparative study of immunodiagnostic tests. A comparison was made of the diagnostic value of five immunological tests-complement fixation (CF), latex agglutination (LA), bentonite flocculation (BF), passive haemagglutination (PHA), and intradermal (ID)-in patients operated on for pulmonary echinococcosis. The sensitivity of all five tests was significantly lower in the patients with pulmonary echinococcosis than in a comparable group with liver echinococcosis. Some 252 patients with miscellaneous nonhydatid diseases and parasitic infections were also tested; nonspecific reactions were highest in the ID and CF tests and lowest in the LA and BF tests. None of the serological tests was significantly more sensitive than the others, although the CF test was somewhat less sensitive and therefore probably has the least diagnostic value in pulmonary echinococcosis. The ID test showed a significantly higher sensitivity than any of the serological tests. The difficulties encountered in the immunodiagnosis of pulmonary hydatid disease are discussed and it is recommended that at least two serological methods (PHA and either LA or BF) and the ID test should be used in each case.


Immunoreactivity in pulmonary echinococcosis. 2. Evaluation of antibody response. The part played by certain factors in determining the antibody response in pulmonary echinococcosis has been studied. Five immunodiagnostic procedures were used-complement fixation, latex agglutination, bentonite flocculation, passive haemagglutination, and intradermal tests-and parasitological and pathological examinations were carried out. The number of hydatid cysts had only a small influence on the qualitative nature of the immune response while the quantitative effect was considerable. The immune response did not vary significantly in relation to the size of hydatid cysts but it was affected by changes within the cysts and the surrounding lung tissue. In patients with cysts full of clear hydatid fluid the proportions with negative results and relatively low antibody titres were highest. In these patients the size of hydatid cyst appeared to be significant-the smaller the size, the lower the antibody level. The immune response is weak or completely absent when the hydatid cyst has a thick fibrous capsule. When suppurative changes are present in the hydatid fluid and/or in the fibrous capsule, and when there is inflammatory involvement of the surrounding lung tissue an easily detectable immune response may be seen at an early stage, sometimes even with a high antibody level, but later it usually decreases and may disappear completely. A hypothesis for the explanation of immunological reactivity in pulmonary hydatid disease is discussed.


Circulating antibodies in human echinococcosis before and after surgical treatment. Antibody levels in 89 patients who had been operated on for hydatid disease were studied over a period of 4 years by complement fixation, latex agglutination, bentonite flocculation, and passive haemagglutination tests. The geometric mean titres were much higher in patients with liver echinococcosis than in those whose lungs were affected. In the first month after operation, an increase in antibody level was observed more often in the former than in the latter. The raised level usually persisted for 3-6 months.In one group of 77 patients, the serological tests either became negative 6 months to 2 years after operation or remained positive during the entire postoperative period. In the other 12 patients, who had recurrent echinococcosis, the tests did not become negative, although there was a reduction in antibody levels during the first and second postoperative years in 6 patients, followed by a rise when the disease recurred. Antibody levels remained high during the entire observation period in the other 6 patients.The prognosis can be considered favourable in patients with low pre-operative titres, or negative tests, provided the tests remain negative up to the end of the first year after operation or become negative within one and a half years. Where there is only a small reduction in antibody titre, the prognosis may still be favourable if the decrease continues to fall up to the end of the second year. Since a drop in antibody titres occurred in certain cases with recurrent infection, it is advisable to defer an opinion on the prognosis until the end of the second year. If the fall in antibody titres is followed by a steady rise, or if they remain high or show slight fluctuations, a recurrence is almost certain.


Multicentre trials of praziquantel in human schistosomiasis: design and techniques. This paper outlines the experimental design and techniques used in the initial multicentre clinical experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium, S. mansoni, and S. japonicum. Trials were conducted in Brazil, Japan, the Philippines, and Zambia.Close professional cooperation between informed representatives of the manufacturers of the drug and WHO led to the use of a standard clinical trial design and agreed technical protocols, although parasitological methods of therapeutic assessment varied with the species of infecting parasite. Double-blind studies of tolerance were conducted at three different dose levels and subsequently, in Brazil and Zambia, single-blind trials of parasiticidal efficacy were carried out. The results of the various trials are reported separately.This type of close professional cooperation is a useful model for initial clinicopharmacological studies of parasiticidal drugs-an area beset with difficulties for both industry and international agencies.


Primary prevention of ischaemic heart disease: WHO coordinated cooperative trial. A summary report. Elevated serum cholesterol concentrations are known to be predictive of ischaemic heart disease. It remained to be proven, however, whether reduction of clinically manifest ischaemic heart disease could be achieved by the lowering of elevated serum-cholesterol levels. In order to create a clear and simple unifactorial study design, a lipid-lowering substance (clofibrate) was administered to this effect in a double-blind trial to middle-aged male volunteers whose serum cholesterol levels were within the upper third of the distribution in their respective populations (Budapest, Edinburgh, Prague). After an average of 5.3 years of observation, and with a reduction of some 9% of the initial serum cholesterol levels, the incidence of ischaemic heart disease was reduced by 20% in the intervention group as compared with the placebo group, thus demonstrating the preventive value of lowering this plasma lipid. There was, however, a significant increase in total mortality and in non-cardiovascular mortality in the clofibrate group, precluding the community-wide use of this drug for reduction of serum cholesterol. The explanation of this is not clear, but possible mechanisms are discussed.


Anatomical accuracy of echocardiographically assessed left ventricular wall thickness. 1. A comparison of direct measurement and M-mode echocardiography in the determination of posterior left ventricular wall thickness was performed in 26 subjects, of whom 21 underwent cardiac bypass surgery; the remainder came to necropsy. 2. In the surgical group a close correlation was demonstrated between direct measurement of posterior wall thickness and the echocardiographic end-diastolic dimension (r = 0.76, P less than 0.001). 3. The necropsy measurement of posterior wall thickness correlated with the echocardiographic end-systolic dimension (r = 0.99, P less than 0.001). 4. These findings confirm that the echocardiographic measurement of posterior wall thickness accurately reflects the anatomical dimension.


[Studies on the relationship between the endotoxin induced fever and the antipyretic effect of reserpine in rabbits (author's transl)]. It has been well documented that fever could be mediated with endogenous pyrogen released from reticuloendothelial system(RES) by administration of bacterial endotoxin(LPS) intravenously to rabbits. On the contrary, reserpine which has various pharmacological activities by depleting catecholamines decreases the normal body temperature as well as endotoxin induced fever. In this paper, we focussed our attention on the effect of reserpine on the production of endogenous pyrogen with relation to the antipyretic effect in endotoxin fever and obtained the following results: Endogenous pyrogen could be detected by intravenous administration of LPS(0.5 micrograms/kg) during the fever. However, endogenous pyrogen was undetectable with intracisternal administration of LPS(0.01 microgram/body) which provoked long-lasting fever. Reserpine (1 mg/kg, i.v.) decreased both body temperature induced by intracisternal administration of LPS(0.01 microgram/body) or intravenous administration of LPS(0.5 microgram/kg), however the degree was more extensive in cases of LPS-induced fever. Pretreatment of rabbits with reserpine (1 mg/kg, i.v.) suppressed the fever induced by an intravenous administration of LPS(0.5 microgram/kg), but did not suppress the release of endogenous pyrogen. These data suggest that endogenous pyrogen may not be an important factor in the pathogenesis of endotoxin fever.


[Immunopharmacological study of buckwheat hypersensitivity (II). Effect of dialysate on antibody formation (author's transl)]. It was reported that dialysate (BWD) separated from the aqueous extract of buckwheat was a haptenic substance capable of neutralizing IgE antibody on mast cells and that the activity was specific to non-dialysate (BWND)-induced hypersensitivity reaction. The effect of BWD on antibody formation was investigated in the present paper. In rats, anti-buckwheat IgE formation was slightly depressed by the administration of BWD, but both anti-DNP IgE and IgG formations in rats immunized with DNP-BWND were unaffected. In mice, anti-buckwheat IgE formation was suppressed by BWD administration. A good correlation was noted between a decrease of surface IgE population on B cells and that of IgE titer in serum. However, the helper function of T cells for adoptive anti-DNP IgE formation was little affected by BWD treatment. Lymphocyte transformation to BWND and other non-specific mitogens using spleen cells obtained from sensitized mice was inhibited in a dose-dependent fashion by the addition of BWD. However, lymphocyte transformation using spleen cells pretreated with BWD was not affected by other non-specific mitogens except for BWND and pokeweed mitogen.


[Progressive systemic sclerosis - long-term treatment with azathioprin (author's transl)]. The study presents the results of an Azathioprin long-term therapy in 19 of 60 patients with progressive systemic sclerosis (PSS). Average treatment was 47 months (6 to 114 months). The patients received 2-2,5 Azathioprin/kg bodyweight daily. In 16 cases no further progression of PSS was noted. One patient showed minor deterioration. In particular no further deterioration in the lung and kidney manifestations were found. Two patients died. A female patient showed signs of osteomyelofibrosis after being treated for 70 months. She died 3,5 years after Azathioprin had been discontinued. The second patient died of right heart failure after recurrent pulmonary emboli. On the whole treatment with Azathioprin over a long period of time seems in most cases to hold the progression of the disease. The unfavourable prognosis can therefore be much improved.


Xenoserum-induced cytolytic "T" cells: polyclonal specificity with an apparent "anti-self" component, and cooperative induction. Mice were primed in vivo by injection of fetal calf serum (FCS) and their spleen cells were incubated in vitro for 5 days in medium containing 10% FCS. This resulted in the development of cytolytic activity, which was most probably due to "T" cells, since effector cells 1) were sensitive to anti-Thy 1 antiserum or monoclonal antibodies in the presence of complement, 2) were not retained on Ig-anti Ig columns, 3) did not develop from "nude" spleen cells. Further arguments for the T cell nature of these effector cells came from their specificity. Blocking experiments using unlabeled competitor cells demonstrated that FCS-induced cytolysis was polyclonal, with clones recognizing allogeneic or syngeneic determinants possibly related to allo or self H-2. In keeping with polyclonality, cytolysis tested on any given target cell was greatly increased by adding Concanavalin A during the cytolysis test. Experiments were made to investigate whether in particular the anti-self cytolytic activity was directed against FCS determinants. We feel that this possibility, although not formally excluded, was made unlikely. The polyclonal specificity at the effector stage stood in sharp contrast to the serum specificity at the induction stage (reported elsewhere). We demonstrated that these two sets of specificities corresponded to two sets of specific cells. A first population of FCS-primed cells had "promoter" activity, in the sense that it could trigger a second population of "precursor" cells to differentiate into polyclonally cytolytic T cells.


Complement receptor analogous factors in human serum: I. Isolation of a molecule inhibitory for complement dependent rosette formation, its identification as alpha 1-antitrypsin and its functional characterization. A glycoprotein was isolated from human plasma which partially inhibited C3 carrying erythrocytes from binding to complement receptor cells (CR+C). Based on its physicochemical characteristics and its antigenicity this glycoprotein was identified as alpha 1-antitrypsin (alpha 1-AT). The activity of alpha 1-AT towards C3 and its fragments was unaffected by heating but it was destroyed by periodic acid. The isolated carbohydrate moiety of alpha 1-AT showed the same effect as the intact molecule. Using F(ab)2 of IgG-anti-alpha 1-AT could be demonstrated on Raji cells and human erythrocytes. Treatment of these CR+C with IgG-anti-alpha 1-AT resulted in a blockade of their C3 receptor activity. The results suggest, that alpha 1-AT interacts through its carbohydrate portion with C3 and its fragments and functions as a complement receptor molecule.


Use of antifibrinolytic therapy in prostate surgery. The prophylactic use of the antifibrinolytic drug, PAMBA, in a small intravenous dose preoperatively, combined with local irrigation postoperatively, effectively reduces blood loss. The drug is safe and relatively free of adverse side effects, but attentive postoperative care is warranted.


A cross-sectional study of the perceived stressfulness of several life events. Adults from different age groups (18-24, 30-40, and 65-86) were tested to determine if they differ in their perception of certain stressful life events. Twenty adults from each age group were asked to rate a series of events according to their perceived relative stressfulness; included were events thought to be particularly salient for elderly adults. Amster and Krauss' list of events and Holmes and Rahe's procedure for quantifying stress were used. Group differences were not found for the elderly salient events; however it was found that elderly adults perceive death-related events as less stressful than do younger adults.


Cross-sectional analysis of cognitive functioning across the life-span. Performance on Piagetian logical concept tasks, standardized intellectual measures, and measures of memory ability, was assessed cross-sectionally. One-hundred-sixty individuals participated. Differential item difficulty patterns were noted on the Piagetian tasks. Curvilinear trends were evident for class inclusion, combinatorial reasoning, and conservation of surface area. Factorial analyses of variance revealed significant chronological age main effects for all tasks except transitivity of weight. Covariance analyses indicated that educational level is generally more closely related to logical concept performance than is chronological age. Dimensional analyses revealed separate factors for general intelligence, classification, relations, and conservation. The youngest and oldest age groups has similar factor patterns; these differed from those of the mature participants.


Four further antibiotics related to olivanic acid produced by Streptomyces olivaceus: fermentation, isolation, characterisation and biosynthetic studies. Four beta-lactam antibiotics with beta-lactamase inhibitory activity MM 22380, MM 22381, MM 22382 and MM 22383 containing the carbapenem nucleus have been isolated from a culture of Streptomyces olivaceus ATCC 31365. Fermentation conditions for their production and methods for their isolation are described. Evidence for a biosynthetic link between these compounds and the previously described olivanic acid derivatives MM 4550, MM 13902 and MM 17880 is presented.


Comparison of antibacterial activity of a new cephalosporin, ceftizoxime (FK 749) with other cephalosporin antibiotics. FK 749 is a distinctive new parenteral cephalosporin antibiotic with a broad antibacterial spectrum which is more potently active against a wide variety of Gram-negative bacilli, including the opportunistic pathogens such as Citrobacter and Enterobacter species and Serratia marcescens, than SCE 963, T 1551 and cefmetazole. The activity of FK 749 against Escherichia coli, Klebsiella pneumoniae, pyogenes was by far superior to that of the three other antibiotics. These test organisms were not resistant to FK 749. The antibacterial activity of FK 749 against Pseudomonas aeruginosa was almost the same as that of ticarcillin but was inferior to that of gentamicin and T 1551. The bactericidal activity of FK 749 against E. coli, K. pneumoniae and Proteus mirabilis was more potent than that of the three other antibiotics. FK 749, like cefmetazole, was extremely stable to beta-lactamases. In studies in mice, the therapeutic effect of subcutaneous injection of FK 749 against various infections due to Gram-negative bacilli was by far superior to that of SCE 963, T 1551 and cefmetazole, was almost the same as that of SCE 963 and cefmetazole against Staphylococcus aureus infection and that of ticarcillin against P. aeruginosa infection.


Purification of beta-lactamase from Streptomyces cellulosae by affinity chromatography on Blue Sepharose. A beta-lactamase from culture supernatant of Streptomyces cellulosae was purified about 1,450-fold to apparent homogeneity in polyacrylamide gel electrophoresis and isoelectric focusing on polyacrylamide gel sheet. The methods used were ammonium sulfate precipitation, CM-52 cellulose ion-exchange chromatography and affinity chromatography on Blue Sepharose CL-6B. The molecular weight was determined to be approximately 27,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This value was in good agreement with the previous value determined by gel filtration on Sephadex G-75. The isoelectric point was pH 9.5. The enzyme behaved primarily as penicillinase and apparent Km value for benzylpenicillin was 500 microM. The beta-lactamase of S. cellulosae interacted strongly with blue dextran and NADP+-agarose but not with Sepharose. In addition, the presence of NADP+ but not NAD+ and ATP diminished sharply the intrinsic fluorescence intensity of the enzyme and the apparent association constant was calculated to be 1.4 x 10(3) M-1. The beta-lactamase decreases its enzymatic activity against benzylpenicillin in the presence of NADP+. From these results, it is suggested that this beta-lactamase has a dinucleotide binding fold.


[Heterotopic pancreas. Report of 8 new cases (author's transl)]. The authors report 8 new cases of heterotopic pancreas and the clinical signs of each case. The emphasise the difficulties of preoperative diagnosis owing to their usually small size and the necessity of surgical treatment justified by the same lesions which affect the normally placed pancreas including cancer.


Absence of increasing incidence of meningitis caused by Haemophilus influenza type b. An epidemiologic survey of meningitis caused by Haemophilus influenzae type b in children aged zero to four years during an 11-year period (January 1965-December 1975) was conducted in the Baltimore, Maryland, metropolitan area to examine recent trends in the incidence of this disease. Cases of H. influenzae meningitis were identified at all 19 hospitals in the city and county of Baltimore and all 41 hospitals in the surrounding area. The population at risk (age, zero to four years) was estimated using yearly birth rates provided by the state of Maryland and U.S. Census information for 1960 and 1970. Yearly age-adjusted incidence was calculated; in contrast to previous studies, there was no significant increase in the annual incidence (range, 12-27; mean, 19.3/100,000 population at risk). Previous reports of recent increases in the incidence of meningitis caused by H. influenzae type b may be due to differences in study techniques.


Nuclear requirement of post-maturational cortical differentiation of amphibian oocytes: effects of cycloheximide. Cycloheximide induced a complex series of alterations in the cortical cytoplasm of amphibian (Rana pipiens) oocytes undergoing steroid induced nuclear and cytoplasmic maturation in vitro. The morphological changes were described and the role of nuclear-cytoplasmic interactions in the induction of these changes was investigated in intact, enucleated and enucleated-reinjected oocytes. Three stages of cortical changes were ascertained on the basis of: localized alterations at the animal pole, redistribution of pigment and localized contractility (furrow formation) primarily along the animal:vegetal pole axis. The extent and type of cortical alterations varied depending upon the time at which oocytes were examined following hormonal stimulation and cycloheximide treatment. Cycloheximide did not produce cortical alterations in non-hormone treated oocytes nor in steroid treated oocytes until after germinal vesicle breakdown. Nuclear and cytoplasmic maturation and the appearance of cortical alterations were all inhibited when cycloheximide was added to oocytes at the time of steroid treatment. Cycloheximide induction of cortical alterations occurred only after the inhibitor was no longer effective in preventing germinal vesicle breakdown. Enucleated oocytes underwent cytoplasmic maturation in response to the steroid but exhibited no cortical alterations following the delayed addition of cycloheximide. Simultaneous administration of cycloheximide and steroid to enucleated oocytes inhibited cytoplasmic maturation and all observable cortical alterations. Reinjection of nuclear material into enucleated oocytes restored the ability of cycloheximide to induce cortical alterations following steroid induction of cytoplasmic maturation. Without steroid treatment, such reinjected oocytes did not exhibit cortical changes in response to cycloheximide. The data demonstrate that the nucleus is required for and contains a factor(s) which controls the cycloheximide response and post-maturation differentiation of the oocyte. The maturational changes in the cortical cytoplasm appear to be dependent on the intermixing of the germinal vesicle nucleoplasm materials with mature cytoplasm following germinal vesicle breakdown. The results further suggest that the cortical effects of cycloheximide are dependent upon the initiation of protein synthesis during this period of oocyte development. The significance of these observations and experimental studies are discussed in relation to current understanding of the molecular mechanisms controlling meiosis induction and the composition of the germinal vesicle.


Retrograde transport of horseradish peroxidase in sensory and adrenergic neurons following injection into the anterior eye chamber. Horseradish peroxidase (HRP) was injected into the anterior eye chamber of rats and mice and frozen sections from both superior cervical and trigeminal ganglia were incubated to demonstrate neurons accumulating the tracer by retrograde axonal transport. Labelled cells were observed only in ganglia ipsilateral to the HRP injection. Within the trigeminal ganglion, peroxidase-containing neurons were restricted to the medial ophthalmic area, whereas labelled cells in the superior cervical ganglion were more widely distributed. With the use of a new and more sensitive technique for the demonstration of HRP in neurons, it was possible to show retrograde transport also of small amounts of peroxidase injected into the anterior eye chamber. In addition, this technique enabled identification of the central and peripheral processes of neurons in the trigeminal ganglion and the dendrites and axons of sympathetic ganglion cells. The rate of retrograde HRP transport in rats was calculated to approximately 4--5 mm/h for both sensory and adrenergic nerves, which is consistent with previous estimates for this protein. It differs from the transport rate reported for nerve growth factor (NGF) and macromolecular toxins in sensory and adrenergic nerves of the same species. These rates were, however, obtained with a different method and in a different population of sensory neurons and are, therefore, not directly comparable. After treatment with 6-hydroxydopamine the number of HRP-labelled cells in the superior cervical ganglion was significantly reduced compared to controls. Cell counts from trigeminal ganglia showed no significant difference between controls and treated animals.


Evaluation of three imaging instruments in dogs with liver hemotomas: concise communication. Single-gamma emission computerized tomography (ECT) was compared with transmission computerized tomography (TCT) and scintillation-camera imaging (SC) in eight dogs with acute, solitary hematomas in the left liver lobe. The superior performance of TCT was attributed to its inherently better spatial resolution than those of ECT or SC, and to the fact that studies with TCT could be performed during apnea. ECT was more sensitive than SC to small changes in the spatial distribution of radionuclides. In addition, the ECT, by virtue of its sectioning capability, was more sensitive than is SC to differences in radionuclide concentrations at same depth in an organ.


Single-photon transaxial emission computed tomography of the heart in normal subjects and in patients with infarction. Resting computerized transaxial tomography was performed after the i.v. injection of thallium-201 in six normal subjects and in five patients who had had myocardial infarctions 3 mo to 4 yr before scintigraphy. Decreased myocardial activity corresponded to the site of previous infarction in all cases and was clearly separated from adjacent myocardium with normal activity. With tomography, the left ventricle was clearly separated from surrounding structures such as the left-ventricular cavity, the lungs, and the liver. This study demonstrates the feasibility for the assessment of myocardial perfusion using single-photon transaxial emmission computed tomography.


[11C]methionine pancreatic scanning with positron emission computed tomography. By the use of [11C]methionine and positron computed tomography (PCT), images of the pancreas were obtained in 32 patients. The injection of between 10 and 20 mCi of this product enables four to six transverse sections to be obtained. Seventeen of the patients studied had no exocrine pancreatic disease, and in all these cases the pancreas was clearly visible. In four cases of pancreatic carcinoma and one of retroperitoneal tumor, there were abnormalities visible. In five cases of chronic pancreatitis, no pancreatic uptake was observed. In a sixth case, concentration was visible, but only in the head of the pancreas. One case of acute pancreatitis, which showed no concentration during the acute phase, returned to normal after recovery. When visible, the pancreas was easily located and distinguishable from the intestinal image, except in two cases that were uninterpretable for technical reasons. No false positive or negative was observed, but a differential diagnosis between cancer and pancreatitis was impossible.


Isolation and purification of in vivo-generated 25-hydroxyvitamin D2 by preparative high-performance liquid chromatography. In order to obtain a standard compound of 25-hydroxyvitamin D2 (25-OH-D2), a method for isolating in vivo-generated 25-OH-D2 from the blood of rats or rabbits was established by using several steps of preparative high-performance liquid chromatography (HPLC). When the unsaponifiable matter of the plasma obtained from rats or rabbits receiving a large dose of vitamin D2 was applied to the preparative HPLC using a Zorbax SIL column, a peak denoted as peak X was observed on the chromatogram. Since the peak X was thought to be due to 25-OH-D2 from the experiments of time course and dose-response, it was purified by subjecting it to successive preparative HPLC using several kinds of columns. From the results of ultraviolet (UV) absorption spectrum, gas chromatography-mass spectrometry (GC-MS) and mass chromatography, the purified peak X compound was confirmed to be 25-OH-D2. The proposed method for isolating in vivo-generated 25-OH-D2 is very convenient, because the time to perform each HPLC is very short though several steps of HPLC are used.


Effects of cadmium on the impedance locus of the abdominal skin of the bullfrog (Rana catesbeiana). An impedance locus consisting of two superimposed semicircular arcs was revealed on the abdominal skin of the bullfrog. The decrease of skin resistance upon epidermal application of Cd (2 mM), which was related to Na active transport, proved to be due solely to the reduction in the size of the high frequency arc.


Amines and the rat exocrine pancreas: (3) Effects of amines on pancreatic secretion. Effects of L-dopa, L-5HTP, a few amines, and related compounds on the pancreatic rate of flow, protein secretion, and bicarbonate secretion were studied in conscious rats. Single injections of L-dopa, DA and apomorphine did not modify the rate of flow, while an increase was seen with infusion of DA. L-dopa stimulated the protein secretion. L-5HTP and 5-HT decreased the rate of flow and protein secretion. Effects of L-dopa and L-5HTP on the protein secretion were prevented by DA- and 5-HT blockers, respectively. Neither L-dopa nor L-5HTP had any effect on the bicarbonate secretion. Secretin and cholinergic agents (acetylcholine and carbamylcholine) strongly stimulated the rate of flow of pancreatic juice. alpha-Agonists (phenylephrine and clonidine) decreased the rate of flow, and the effects were inhibited by an alpha-blocker. The alpha-agonists had no effect on protein secretion. Although, alpha-blockers (phenoxybenzamine and phentolamine) had no effects on the rate of flow, they did decrease the protein secretion. Isoproterenol was a potent secretagogue, and the effect was suppressed by a beta-blocker. Histamine had no effect on the rate of flow. The results were discussed in relation to our previous histochemical and chemical findings, and the species difference between rats and dogs in response to the amines.


An unusual case of T-cell lymphoproliferative disorder. A 54-year-old woman with epigastric pain had leukocytosis of 73,000/microliter consisting mainly of atypical lymphoid cells with convoluted and cleaved nuclei resembling Sézary cells; the bone marrow aspirate was nondiagnostic. Skin biopsy was unremarkable. The patient also had hypercalcemia and hemolysis with a positive direct Coombs' test, both of short duration. The arterial oxygen tension was decreased, but there was no demonstrable lung pathology. The patient subsequently developed rapidly enlarging lymphadenopathy. Lymph node biopsy was interpreted as "undifferentiated pleomorphic lymphoma." Immunologic functional studies revealed that the majority of the peripheral blood atypical lymphoid cells from involved lymph nodes formed rosettes with sheep erythrocytes. The lymphadenopathy regressed transiently after the administration of chemotherapy and the white blood cell count decreased from a maximum of 385,000/microliter to 3,500/microleter, at which point the arterial oxygen tension returned to normal. The unusual features of this patient are discussed in light of the known characteristics of the various types of T-cell lymphorpoliferative disorders.


Superior vena cava syndrome secondary to histiocytosis-X in a child: case report. A case of histiocytosis-X with multifocal bone involvement and mediastinal soft tissue infiltration leading to superior vena cava obstruction, is presented. The incidence and the causes of superior vena cava syndrome in the pediatric group are discussed.


The incidence of post-splenectomy sepsis and herpes zoster in children and adolescents with Hodgkin disease. The occurrence of sepsis due to Streptococcus pneumoniae and Hemophilus influenza and of herpes zoster (HZ) was reviewed in a series of 72 consecutive, previously untreated children and adolescents with Hodgkin disease. There was not a statistically significant difference in the risk of developing sepsis within five years of diagnosis between patients who had (16.6%) or had not (6.2%) undergone splenectomy. Sepsis occurred most frequently among patients treated initially with total nodal irradiation and combination chemotherapy. The estimated risk of HZ during the first five years after diagnosis was 34%. Patients treated initially with irradiation and combination chemotherapy had a significantly greater risk of developing HZ than patients treated initially with only irradiation (P less than 0.05). Although trends were present which suggested that splenectomy and the extent of disease at diagnosis may influence the occurrence of HZ, these did not achieve statistical significance. Survival was not influenced by the occurrence of HZ.


Suppression of immune anti-tumor lymphocytes by macrophages of advanced tumor bearing rats, across a cell impermeable membrane. In experiments using double and triple chamber cultures it was demonstrated that suppressive macrophages from advanced T8-Guérin tumor (diameter 5--6.5 cm) bearing rats produced a dialysable factor which suppressed the killer activity of lymphocytes from non-advanced T8-Guérin tumor (diameter 0.5--0.7 cm) bearing rats, as well as from nonadvanced h 18R tumor bearing rats and from Ehrlich ascites bearing mice, against T8-Guérin ascitic cells and, respectively, against h 18R ascitic and Ehrlich ascitic cells. The dialysable suppressive factor inhibits immune lymphocytes but has no effect on the lymphotokin itself already produced.


Structural studies of natural actomyosin from thermally acclimated frogs. Natural actomyosin was isolated from skeletal muscle of frogs (Rana catesbeiana) acclimated at 25 degrees C and 5 degrees C. It was found that preparations isolated from warm-acclimated frogs may display considerable degradation of myosin heavy chains as compared with preparations isolated from cold-acclimated frogs. However, degradation may be minimized by inclusion of protease inhibitors during purification, indicating enhanced protease activity in preparations of natural actomyosin from warm-acclimated frogs. When purified in the presence of protease inhibitors, natural actomyosin from both warm-acclimated and cold-acclimated frogs exhibits comparable subunit composition of SDS-gel electrophoresis. The overall gel pattern is similar to that obtained from rabbit natural actomyosin except that in the frog, troponin-T and troponin-C appear to co-migrate with tropomyosin and myosin light chain 2, respectively.


A new variant form of phenylketonuria.

A new variant form of phenylketonuria. We report a family (parents and two sets of twin girls) in which the propositus presented as a case of phenylketonuria with a somewhat less severe degree of phenylalanine intolerance than occurs in patients with classical phenylketonuria and whose phenylalanine tolerance was further impaired by giving cotrimoxazole. The trimethoprim component of cotrimoxazole reduces the phenylalanine tolerance of normal subjects but does not augment the degree of phenylalanine intolerance in patients with classical phenylketonuria. The results of the present study of the phenylalanine tolerance and the way in which cotrimoxazole modifies it in the members of this family are compatible with the segregation of an abnormal gene which causes a previously unrecognized type of phenylketonuria when it is present in the homozygous state. The possible relationship of this to other inherited biochemical lesions of the phenylalanine hydroxylase system is briefly discussed.


alpha 1-Antitrypsin phenotypes in cor pulmonale due to chronic obstructive airways disease. The clinical and radiological features of 23 patients with cor pulmonale due to chronic obstructive airways disease were reviewed. Twenty-two patients had evidence of pulmonary vascular disease and 52 per cent had secondary polycythaemia. Eighteen (78 per cent) had radiological evidence of emphysema. Thirteen of the patients (56.5 per cent) had alpha 1-antitrypsin phenotypes associated with serum deficiency and of these the largest single group was the MZ phenotype (34.8 per cent). No difference was found between the clinical features of patients with the MM phenotype or those associated with alpha 1-antitrypsin deficiency, although radiological emphysema was more common in the latter group (92 per cent compared to 60 per cent).


[Single photon radioisotope emission computed tomography image using gamma camera (author's transl)]. Single photon radioisotope computed tomography (RCT) images were obtained using the following devices such as conventional gamma camera, data processer for exclusive use of nuclear medicine (C.D.S.-4096), magnetic tape and medium size electronic computer FACOM 230-28S (48K) for multipurposes, which are routinely used for clinical purpose. To reconstruct the RCT image we made absorption correction by geometric mean of opposing counts considering the thickness of source and used the convolution integral method. The reconstructed images of phantom study resolved one centimeter clearly and were very similar to original. The RCT image of patient was acquired by the rotation of patients using the revolving chair and the handmade implement which settles the center of patient's head. Three dimensional informations were obtained by one examination with a gamma camera which collects two dimensional images. When using a gamma camera, therefore, not only a transaxial but an arbitraly RCT image will be important to contribute for diagnosis.


The Fc binding regions in protein A are not responsible for the polyclonal B cell activating property of protein A. To test whether the polyclonal B cell activating property of protein A is due to its ability to bind to the Fc part of immunoglobulins, experiments were carried out with purified monomeric or dimeric Fc-binding fragments of protein A. Neither monomeric nor dimeric fragments induced polyclonal antibody synthesis in vitro, whereas intact protein A was a strong activator. It is concluded that the Fc binding part of protein A is not responsible for activation of polyclonal antibody synthesis.


Left ventricular function after aortocoronary bypass surgery. Aortocoronary bypass operations without additional myocardial surgery or valve replacement were performed at Ullevål Hospital in 190 patients during the period May 1971 to Dec. 1975. Postoperatively re-examination was made by left-heart catheterization in 124 patients at a mean interval of 18.2 months and right-heart catheterization in 108 patients at a mean interval of 16.0 months after surgery. The mean postoperative values for PCVP at rest, PCVP during exercise, LVEDP before contrast and LVEDP after contrast were significantly lower than the mean pre-operative values. The difference between pre- and postoperative values were largest in patients with elevated PCVP or LVEDP values before surgery, whereas in patients with low pre-operative values the mean values after surgery were unchanged or increased. The results indicate that marked improvement of left ventricular function may occur after aortocoronary bypass operations, even in patients with signs of ventricular failure at rest. A stress test is, however, of importance in evaluating the haemodynamic consequences of coronary surgery. No difference was found in patients with single versus patients with double or triple shunts. Post-operative shunt occlusion was found in 44 of 258 grafts at re-examination. No difference was found between patients with all shunts patent and patients with one or more shunts occluded as regard to mean postoperative PCVP and LVEDP values.


Mitral insufficiency following myocardial infarction. Severe mitral insufficiency following myocardial infarction in 15 patients is reported. The mean interval from infarction to surgery was 2.8 years. All patients were operated on with mitral valve replacement and in 14 aortocoronary bypass and/or resection of left ventricular aneurysm was necessary as well. Rupture of one or more heads of the papillary muscle was found in 5 patients. In another 5 the papillary muscles were discoloured, fibrosed and shortened, and in the last 5 patients the mitral incompetence was caused by a marked dilatation of the atrioventricular ring. Five patients (33%) died, 3 early and 2 late after surgery. All the patients who died had a markedly imparied left ventricular function pre-operatively with end-diastolic pressures from 15 to 26 mmHg.


A high risk subgroup of patients with unstable angina pectoris treated medically or surgically. Among patients consecutively admitted to a coronary care unit (CCU) without a subsequent diagnosis of acute myocardial infarction (AMI), a subgroup fo unstable angina was selected, defined as continued episodes of angina at rest during a 48-hour period, despite medical treatment in the CCU. During a four-year period, 15 patients fulfilled these criteria. Eight patients were medically treated, seven of whom developed an AMI with three subsequent deaths. Six of the infarcts occurred within eight days of admission. In six patients, fulfilling the criteria, surgical treatment was performed. Angiography and surgery in this group were associated with low incidences of myocardial infarction, late infarction and death. In one patient, surgery was declined due to unfavourable anatomical conditions. This patient subsequently developed an AMI and died. It is concluded that the combination of recent onset of angina and continued episodes of angina at rest, despite medical treatment, selects a high risk subgroup of unstable angina. Acute coronary angiography and surgery ought to be considered in this subgroup.


Surgical treatment of angina pectoris. A follow-up study with special reference to clinical results after bypass. A follow-up study of 132 patients with stable angina pectoris, who underwent a bypass operation during the period 1970-1976, is presented. The survival curves and mortality rates for this group and for 180 patients, who had previously undergone indirect revascularization, are given. At the first follow-up after bypass operation, 87% of the patients were subjectively improved, 72% of the vein grafts were patent and 85% of the patients had at least one graft patent. A positive correlation was found between patent grafts and subjective improvement. A similar correlation between subjective and objective improvement (exercise test) was not found.


Flow measurements and simultaneously performed angiography of aorto-coronary bypass grafts during bypass surgery. The function of aorto-coronary bypass grafts is usually assessed by the run-off, determined from postoperatively performed cineangiograms. The reliability of this method was tested by comparing the electromagnetically measured graft flow with the run-off, qualitatively estimated from cineangiograms. The electromagnetic flow measurements and cineangiography were performed simultaneously during bypass surgery. The run-off was classified by three independent observers into three classes (poor, moderate, and good). The average mean flow rates corresponding to the three classes were: poor: Q = (43 +/- 11)ml/min; moderate: Q = (48 +/- 14)ml/min; good; Q = (63 +/- 22)ml/min. Although the differences between the flow rates of the three classes were found significant (except between poor and moderate run-off), there was a wide range of overlapping. Especially in grafts with low flow rates (Q less than 70 ml/min) there were pronounced disagreements between the qualitative estimation of flow and the electromagnetically measured flow. Using videodensitometric flow measurements as a check test, the uncertainties in classification proved to be caused by the lack of reliability of the observer. The flow rates in aorto-coronary bypass grafts can be determined reliably only by means of quantitative methods, e.g., electromagnetic or videodensitometric flow measurements.


Clinical application of cardioplegia in aortic cross-clamping periods longer than 150 minutes. Out of more than 1000 patients operated upon by means of cardioplegia in profound myocardial hypothermia (15 degrees - 20 degrees C) aortic crossclamping time exceeded 150 min in 26 cases. The average clamping time in this group of patients was 169 +/- 22 min (150 to 227 min). The average duration of the cardioplegic coronary perfusion was 35 +/- 21 min (14 to 99 min). The following procedures were performed. Aneurysmectomy of the ascending thoracic aorta combined with valve replacement (n = 7); valve replacement combined with aorto-coronary bypass procedures (n = 9); multiple valve replacement (n = 3); multiple coronary grafting (n = 6) and one complicated reoperation. Three patients (11.5%) died, none intraoperatively and none as the result of a heart failure connected with the operation.


Socio-agricultural factors and parasitic infections in the Caspian littoral region of Iran. Surveys for intestinal parasites in villages in the Babol area of the Caspian littoral region of Iran have been conducted for five years. During this period, mass chemotherapy and individual treatment have been administered. While the overall prevalence of parasitic disease was reduced after these campaigns, reinfection took place repeatedly, and at a rapid rate. This paper re-examines the prevalence of seven helminth species (Ascaris lumbricoides), hookworms (Ancylostoma duodenale and Necator americanus), Hymenolepis nana, Strongyloides stercoralis, Taenia saginata, Trichostrongylus spp. and Trichuris trichiura) on the basis of geographical and socio-agricultural criteria. The considerable differences in the prevalence of these parasitoses--even between neighboring villages--emphasize the variability of human ecology in the region under study.


Cardiovascular disease in Northern Nigeria. The case files of 4,456 medical admissions in 1975--1976 at Ahmadu Bello University Teaching Hospital, Kaduna, Nigeria, included 354 cardiovascular patients. The most common causes were hypertension (45.5%), cardiomyopathy (20.6%) and chronic rheumatic heart disease (14.4%). The mean age of hypertensive and cardiovascular patients was lower than in Europe. The majority of hypertensive patients suffer from essential hypertension. Congestive cardiac failure is the commonest complication of hypertension and cardiomyopathy. Rheumatic valvular disease with mitral incompetence is frequent and sometimes severe in young people. Other cardiovascular diseases included pericardial disease, bacterial endocarditis, cor pulmonale, anaemic heart failure, congenital and syphilitic heart disease. Coronary heart disease was only encountered in non-Africans. Cardiovascular mortality in hospital was high (20%).


The effect of unipolar aeroions on the capacity of mammalian organism. Based on animal experiments authors established that the different polarity high-concentration aeroions have an effect on the vegetative centres of the Central Nervous System (CNS). Through vegetative centres they influence both electro- and neuro-physiological relations of the nervous system and by this means they make an effect on the capacity. Aeroions have some explicitly favourable effect both on the orientation reflex action and the alert system of the brain stem.  These effects can also be registered either by pharmacology tests or sinstrumentally (electronystagmography).


[The electroaerosoltherapy (author's transl)]. The Electroaerosoltherapy (EAT) has got a world-wide diffusion especially in diseases of the respiratory system. The unipolary negatively charged aerosols are very steady and penetrate deeply into the respiratory tract. The ciliary activity is stimulated, the mucus liquified and the bronchial spasms relaxed. The author use a table-apparatus (Barthel-Küster System), which allows the simultaneous therapy, and a combination from an Ionogenerator with a portable aerosol generator (air ion transmitter needle into the aerosol mask). The EAT has no noxious secondaries effects.


The levels of the major risk indicators of cardiovascular diseases in Eastern Finland rior to a community-based intervention programme. (The North Karelia project). The design, implementation and the major results of a study for measuring the prevalent CHD risk indicators in Eastern Finland are presented. The study formed the baseline survey of the North Karelia Project and was conducted in 1972 for a representative random sample of the population aged 25-59 in the county of North Karelia and a matched reference area. Altogether 11.992 persons were examined with a participation rate of 93% in North Karelia and 90% in the reference area. The prevalence rates of the "hard" CHD risk indicators (blood pressure, cholesterol, smoking and triglycerides) are presented and reference is made to the prevalence rates of some other "softer" risk indicators. In general, the level of the "hard" risk indicators is high and this is especially true for the younger males. The two areas resemble each other closely in these respects as was anticipated. In the discussion the results are reviewed from the point of view of the primary preventive programme.


Holter monitoring in dizziness and syncope. Holter monitoring was used to detect the underlying mechanism among 53 patients referred for dizziness, fainting and/or syncope. The complaints were unexplained on clinical grounds in 38, suggestive of SSS in 11, and of pacemaker dysfunction in 4 patients who underwent pacemaker implantation for symptomatic A-V block. Occult dysrhythmias were revealed in 24 of 38 (61%) of the first group; the clinical impression of SSS was confirmed in 8 of 11 (72%) in the second, and ineffective pacing confirmed in 2 of 4 in the third group. Thus, the diagnosis was clarified in 34 of 53 (64%) of patients. It is concluded that Holter monitoring is most useful for detecting the underlying mechanism in the above mentioned conditions, especially in elderly subjects whose syncopal attacks remained unexplained despite routine cardiological and neurological examination. Holter monitoring should be carried out for at least 36 hours before ruling out dysrhythmias as a cause of dizziness and/or syncopal attacks.


Assessment of sinus node function in asymptomatic subjects with sinus bradycardia and in symptomatic patients with sino-atrial disease. Sinus node function was evaluated in 18 patients with sinus bradycardia without complaints (Group I), in 16 patients with sinus bradycardia and/or sinoatrial block with complaints (subgroup IIa) and in 14 patients with the bradycardia-tachycardia syndrome (subgroup IIb). Mean values of corrected sinus node recovery time (CSRT), atrial effective refractory period (AERP) and atrial functional refractory period (AFRP) differentiated significatively asymptomatic subjects of group I from the two subgroups of patients with sinoatrial disease, but failed to differentiate each subgroup from the other one. There was no significative difference in mean sinoatrial conduction time (SACT) between group I and each of the two subgroups. Three patients of subgroup IIa and 1 patient of subgroup IIb had a false negative response after both overdrive and premature programmed atrial pacing. Spontaneous cycle length was directly correlated with the sinus node recovery time and the atrial refractoriness in group I, and with the only sinus node recovery time in subgroup IIb. No direct correlations were observed in subgroup IIa. This suggests a less disturbed sinus node automaticity in bradycardia-tachycardia syndrome.


[Noninvasive diagnosis of ventricular septal defects using echo-pulsed Doppler velocimetry, localization, evaluation of the shunt and the associated lesions]. A preliminary study of 15 patients with ventricular septal defect demonstrates that Echo-Doppler velocimetry allows the non-invasive diagnosis of this malformation in 80% of the cases, as well as its localisation and detection of associated lesions; tin addition evaluation of the shunt is made feasible by non invasive recording of the flow velocity curves of the shunt and of the pulmonary artery according to a technique derived from the basic one. This method turns out to be essential for establishing the aetiological diagnosis of left parasternal systolic murmurs.


Sinoventricular conduction during acute myocardial ischemia. A case with sinoventricular conduction and sinus bradycardia during unstable angina pectoris is presented. Although His bundle electrogram showed atrial and His bundle deflection no P waves could be observed in any surface leads even when effective high right atrial pacing was performed. It may be assumed that the electric or sinus impulses are conducted over the specialized atrial tracts while atrial muscle is in a refractory state due to myocardial ischemia.


Effect of birthplace on the development of amyotrophic lateral sclerosis and multiple sclerosis. A study among Finnish war evacuees. After World War II the southeastern part of Finland was ceded to the Soviet Union and its entire population evacuated to other areas of the country. The prevalences of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) were studied among the evacuees and compared to the corresponding data among the nonevacuated population. The prevalence of ALS among the war evacuees was two times higher than among the nonevacuated population (18.0 and 8.8 per 100,000, respectively). The prevalence of MS among the evacuees was only half of that found among the nonevacuated population, 38.3 and 73.0 per 100,000, respectively. The findings for ALS indicate that birthplace may have an effect on the later development of the disease and that there may have existed some environmental factor(s) which have made the evacuees more liable to contract the disease later in their lives. The low figure of MS for evacuees supports our previous results of an uneven geographic distribution of MS in Finland with the high-risk areas in the western and southwestern parts of the country. No accumulation of MS was found among the evacuees living in the high-risk areas.


Diagnosis of CNS leukemia.

Diagnosis of CNS leukemia. The cytocentrifuge provides a satisfactory method to distinguish malignant from nonmalignant CSF mononuclear elements in leukemic patients with pleocytosis. In patients who have had meningeal leukemia, our data support the concept that absence of all blasts be required to define remission. The finding of rare blasts by cytocentrifuge in patients with prior history of CNS leukemia, however, should be interpreted in light of the entire clinical and laboratory picture.


Use of the Ommaya reservoir in the prevention and treatment of CNS leukemia. Insertion of an indwelling ventricular cannula via the transfrontal approach by the method described, and the use of an attached reservoir is a safe technique in the hands of experienced personnel. Intraventricular chemotherapy prolongs the duration of remission in those individuals who have evidence of meningeal leukemia. The superiority of this method over intralumbar therapy as a preventive measure has not been demonstrated.


Childhood acute lymphocytic leukemia with a second primary neoplasm. The occurrence of de novo cancer in renal transplant patients who have received immunosuppressive therapy has been noted. An increased incidence of second primary neoplasm (SPN) has been reported in adults with various forms of cancer. The incidence of SPN in childhood cancer is lower. Successful therapy in several childhood cancers has resulted in prolonged disease-free survival time with the opportunity for longer patient-years of observation. The development of a SPN, an astrocytoma, in a child with continuous complete remission for more than 6 years is reported. The incidence of SPN in childhood cancer needs to be established.


Subtle clues to diagnosis by histochemistry. Histiocytosis X. Characteristic mononuclear cells with distorted nuclei and abundant pale-staining cytoplasms together with osteoclast-like giant cells are the cytologic hallmarks of histiocytosis X. The demonstration of acid phosphatase within giant cells in paraffin-embedded sections is a valuable aid to diagnosis. The histologic differential diagnosis of histiocytosis X includes some allergic granulomas, Hodgkin's disease, myelomonocytic leukemia, mastocytosis, and malignant histiocytosis. Some technical prerequisites for accurate diagnosis of histiocytosis X are considered briefly.


Description of a bacteriocinogenic plasmid in Beneckea harveyi. A total of 795 strains of marine Vibrio species and Beneckea harveyi, a luminescent marine bacterium, were isolated from various sources in the area of Galveston Island, Tex., and screened for the production of bacteriocin-like substances. More than 8% of the Vibrio isolates produced low-molecular-weight (dialyzable) substances, which were lethal to a test strain of V. parahaemolyticus. Approximately 5% of the B. harveyi isolates produced higher-molecular-weight (nondialyzable) substances which were lethal to a test strain of B. harveyi. One of the B. harveyi strains (strain SY) produced a nondialyzable substance which was lethal to two of 39 strains of B. harveyi. The substance showed no activity toward 17 test strains drawn from the Vibrionaceae and Enterobacteriaceae. Strain SY showed no sensitivity to its own lethal agent and was shown by agarose gel electrophoresis and electron microscopy to harbor a single plasmid of 38 x 10(6) daltons. Variants of strain SY lacking the plasmid were produced by growth in the presence of the antibiotic novobiocin. These variants lacked both the ability to produce the lethal substance and the ability to survive in its presence. The lethal agent produced by strain SY is the first bacteriocin reported in marine bacteria. The term "harveyicin" is proposed to name this lethal substance.


[Non-Hodgkin's lymphomas of low-grade malignancy with particular reference to the lymphocytic lymphomas of B-cell origin (author's transl)]. More than two thirds of all non-Hodgkin's lymphomas (NHL) are of low-grade malignancy. This group comprehends five histological types: lymphocytic, immunocytic, plasmacytic, centrocytic, and centroblastic-centrocytic lymphomas. The lymphocytic lymphomas are second in frequency among the biopsies. The most common lymphocytic lymphoma is the chronic lymphocytic leukemia (CLL). It is characterized by the proliferation of small lymphocytes. The quantity and arrangement of the constantly present paraimmunoblasts and prolymphocytes allow to distinguish three histological subtypes of CLL. CLL, prolymphocytic leukemia, and hairy cell leukemia may be composed of B- or T-cells. Mycosis fungoides, Sézary's syndrome and T-zone lymphomas are T-cell lymphomas. All NHL of low-grade malignancy show a proliferation of small to medium sized lymphoid cells. Some large blast forms may be intermingled among these smaller cells. The inhomogeneity of low-grade malignant lymphomas with regard to the size of predominant cells and the admixture of blast forms determine the higher ("intermediate") degree of malignancy of some types in the group of low-grade malignant lymphomas. The overgrowth of the intermingled blast forms probably leads to the transformation into a lymphoma of high-grade malignancy. This event happens in variable frequency in the various types of low-grade malignant lymphomas. NHL of low-grade malignancy occur almost exclusively in adults, whereas the high-grade malignant lymphomas are found in all age-groups.


T-cell lymphomas.

T-cell lymphomas. T-cell malignancies are related to various stages of T-lymphocyte differentiation and, consequently, bear diverse immunological and cytochemical markers. The processes may have different malignant potential. Thymus, thymus-dependent areas of lymphatic organs, skin and central nervous system are frequently involved. The histological descriptions of the lesions in question are given.


[Immunopathology of malignant lymphomas (author's transl)]. The present work deals in a first part with the functional characterization of subpopulations of the lymphoid system. Methods for identification of these subpopulations are compared and some immunopathologic data of the different non-Hodgkin's lymphomas are presented. In the group of low-grade malignant lymphomas B-cell disorders predominate, whereas lymphomas of the T-lymphocytes are not unusual in patients with lymphoid tumors of high malignancy. Immunological findings are compared with data on tumor cell kinetics and the clinical relevance of immunopathological investigations is discussed.


Cytometric analysis of small lymphocytes in the bone marrow and lymphatic tissues in neonatally thymectomized and nude mice, with particular reference to differentiation of B-lymphocytes. In neonatally thymectomized mice and nude mice, small lymphocytes in the bone marrow, Peyer's patches, lymph nodes and spleen were studied qualitatively and quantitatively by electron microscopy. Marrow lymphocytes which are mostly small lymphocytes are classified into dark and light types. The greater proportion of marrow small lymphocytes are of the dark type. Small lymphocytes in Peyer's patches, lymph nodes and spleen are of the light type. The nuclear and cellular sizes of small lymphocytes were estimated stereologically. The nucleus-cell ratio, the volumetric proportions of mitochondria, Golgi apparatus, tubular complexes and dense bodies to the cell body and the proportions of nucleoli and nuclear bodies to the nucleus were also determined. The quantitative results thus obtained suggest that light small lymphocytes in the bone marrow are cytometrically similar to small lymphocytes in Peyer's patches, lymph nodes and spleen and that dark small lymphocytes in the bone marrow are different from other small lymphocytes. The findings are discussed in particular relation to morphological differentiation of B-lymphocytes.


IgG1 hypergammaglobulinaemia in chronic parasitic infections in mice: evidence that the response reflects chronicity of antigen exposure. The IgG1 molecules in the sera of IgG1 hypergammaglobulinaemic mice chronically infected with the larval cestode, Mesocestoides corti, are a heterogeneous population. Although antibodies to M. corti are present, the question of whether a minority or majority of the serum IgG1 molecules has anti-parasite reactivity remains open. The splenic PFC response to an intravenous injection of SRBC in M. corti-infected mice does not consist of an unusually high proportion of IgG1 anti-SRBC PFC. Moreover, the adoptive anti-DNP PFC response of spleen cells from M. corti-infected mice to DNP-M. corti is not biased towards IgG1 antibody production. Since IgG1 hypergammaglobulinaemia is seen in mice with chronic, "high-dose" infections, an attempt has been made to simulate chronic antigenic exposure with SRBC in uninfected mice. A split, high-dose regime of SRBC injections leads to a high number and high proportion of IgG1 anti-SRBC PFC in the spleen in three strains of mice. The results suggest that the extraordinarily high levels of IgG1 seen in the sera of mice chronically infected with the metazoa, M. corti and Nematospiroides dubius, reflect persistent, high-dose, "strong", T cell-dependent stimulation of the B cell system.


[Early and late outcome after aortocoronary bypass: experience in 500 cases]. Between 1971 and 1976, 500 patients underwent aortocoronary bypass surgery. There were 15 operative deaths (3%) and the total frequency of perioperative infarction was 7%. The operative mortality was 7.4% in unstable angina, as compared with 1.1% in stable angina (P less than 0.01). The proportion of grafts patent at 2 weeks was 92% and at 18 months 87.6%. Postoperative follow-up was complete for 99% of the patients. There were 15 late deaths (3%) and the rates of survival at 2 and 4 years were 94.4% and 92.1% respectively. The actuarial curve of survival after surgery was not significantly different from that of the general population. After a mean follow-up of 27 months 73% of the patients were completely free of angina and 19% were markedly improved. The rate of recurrence of angina averaged 10% per year and the annual infarction rate was 0.7%. Fourteen patients (3%) underwent reoperation during the follow-up period. Thus, coronary revascularization surgery offers effective and sustained relief of incapacitating angina and might also improve survival if the operative mortality is low.


The orientation of immunological research in relation to the global antimalaria programme. Immunological research on malaria has produced a wealth of information on the relationship between Plasmodium and the vertebrate host, introducing new serological tools into epidemiological methodology and experimentally proving the possibility of protecting vertebrates against malaria, thus moving vaccination from the realm of pure hypothesis to the level of feasibility.The alarming malaria situation in the world is reason enough to expand immunological research further to improve diagnostic and epidemiological tools and to develop methods for the protection of man against malaria. The programme of the Scientific Working Group on the Immunology of Malaria, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, complies with these objectives.A projection of potential effects of malaria vaccines on the malaria situation shows considerable promise in areas with relatively low basic reproduction rates; in areas with high basic reproduction rates they would need to complement other malaria control measures and may ultimately add the critical momentum required to render adequate malaria control feasible in tropical Africa.


The possible role of isoantigens in protective immunity to malaria. The possibility that autoimmune responses to modified red cell antigens might be involved in protective immunity to malaria was investigated in Plasmodium berghei infection of August rats. Animals rendered anaemic by phenylhydrazine treatment at the time of immunization showed significantly greater protection than rats given antigen alone, or phenylhydrazine alone. Adoptive transfer experiments indicated that this enhanced response could be transferred with spleen cells.


Gamete vaccines and transmission-blocking immunity in malaria. We have recently proposed an approach to malaria control based on immunization of the host against extracellular malarial gametes, the stage in the mosquito guts, in order to block transmission by the mosquito vector. Our studies with avian and primate models have demonstrated that immunization of the host with extracellular gametes totally suppresses infectivity to the mosquito of a subsequent blood meal. Gametocytes within the erythrocytes are unaffected by the immunity, since resuspending the gametocytes in serum from normal nonimmune animals restores their infectivity to mosquitos. Immunity is mediated by antibodies that are ingested with the blood meal. These antibodies interact with extracellular gametes and prevent fertilization (the fusion of male and female gametes). Thus the infection in the mosquito is blocked, and in this way transmission is interrupted.


Metrizamide density gradients for separation of different developmental stages of malarial parasites. Density gradients with metrizamide, a tri-iodinated benzamido derivative of glucose, have been used to separate erythrocytes infected with three species of murine plasmodia. Uninfected erythrocytes separated well from erythrocytes containing parasites in different developmental stages. With metrizamide solutions, the densities required for isopyknic separation can be obtained without hypertonicity or high viscosity, and the viability and metabolism of parasites and erythrocytes are not detectably modified by exposure to these solutions. This type of separation has many possible applications to biochemical and immunological investigations.


Malaria infections in different strains of mice and their correlation with natural killer activity. Different mouse strains show marked variation in susceptibility to murine malaria parasites. Of those studied, strain A mice showed the highest susceptibility, most animals dying from Plasmodium chabaudi infections. In contrast, C57Bl and CBA mice all recovered from P. chabaudi infections and were then resistant to challenge with a virulent strain of P. yoelii. BALB/c mice recovered from P. chabaudi infections but were not uniformly resistant to P. yoelii challenge. B10.A mice, which share haplotypes (H-2(a)) with strain A mice, were resistant to P. chabaudi infections. Of all the correlates of resistance, one appears to be of special interest: natural killer (NK) activity. This was high in C57Bl mice and in malaria-infected mice considerable increases in spleen cell numbers and in NK activity were observed. In contrast, strain A mice showed low NK activity and in malaria-infected animals spleen cell numbers and NK activity showed little or no increase. It is suggested that NK cells, recruited and activated by T lymphocyte-mediated immune responses to parasite antigens, recruit and activate NK cells and macrophages, and that a product of the reacting cells may produce death of parasites within circulating erythrocytes.


Cellular aspects of immunoregulation in malaria. Malaria infection dramatically induces two nonspecific perturbations in immune responsiveness, polyclonal B cell activation and immunosuppression. Polyclonal activation occurs early in infection and results in secretion of antibodies that lack antiplasmodial specificity. Immunosuppression occurs later in infection and is characterized by blunted humoral and cellular immune responses to heterologous (nonplasmodial) as well as plasmodial antigens. Previous studies have suggested that defects in macrophage function may be responsible for immunosuppression in malaria. In what way these cells might be altered in their immunoregulatory role during infection has not been clearly defined. One function of macrophages that is modified in malaria is the ability to secrete in vitro the monokine lymphocyte-activating factor (LAF). Adherent spleen cells obtained from mice early in Plasmodium berghei or P. yoelii infection secrete supernormal amounts of LAF. Adherent cells obtained later in infection show subnormal LAF-secreting activity and secrete an immunosuppressive substance. These modulations in macrophage function may be related to the quantity of parasite material ingested by these cells and might help explain the conversion of macrophages from a helper to a suppressor role in malaria.


Lethal Plasmodium yoelii malaria: the role of macrophages in normal and immunized mice. Mice were injected with silica or Corynebacterium parvum, which, respectively, inhibit and stimulate macrophages in vivo, in an attempt to study the role of macrophages in lethal Plasmodium yoelii infection and in mice protected by immunization. In the normal infection, macrophages were able to control parasitaemia for up to 1 week, whereas in immunized mice they appeared to inhibit the sterilizing immune response. A model is proposed in which this dual role of activated macrophages may account for the chronic non-sterilizing course of natural malaria infections.


Immunity to Plasmodium yoelii and Babesia microti: modulation by the CBA/N X-chromosome. CBA/N mice carry an X-linked recessive defect expressed in cells of the B cell lineage. The major deficiency in these mice is an almost complete inability to respond to certain thymus-independent antigens, such as pneumococcal polysaccharide type III (S III). We have examined the responses of mice carrying the CBA/N X-chromosome to the malaria parasite Plasmodium yoelii and the piroplasm Babesia microti. We have found that the duration and severity of these infections is increased in mice carrying the CBA/N X-chromosome and that this is associated with a markedly defective IgM antibody response to the parasitized red cell and a failure to produce autoantibodies to bromelain-treated mouse RBCs. An autoimmune response directed at modified determinants on the red cell membrane may be one of the factors involved in the control of these infections.


Basic considerations concerning field trials of malaria vaccines in human populations. Studies in animals have shown that effective immunity can be induced by vaccines employing plasmodial sporozoites, asexual blood forms (e.g., merozoites), and sexual blood forms (gametocytes/gametes). In the future, but only when extensive safety testing has shown them suitable for administration to human subjects, the efficacy of such vaccines in the control of malaria in human populations will need to be assessed. Field trials will pose many complex problems and assessment of the results they yield will demand precise and detailed information first on the frequency, density of parasitaemia, and clinical severity of malarial episodes in vaccinated and control subjects and second, on the changes that occur in the gametocyte reservoir and entomological indices of transmission within the trial area. They will require to be sited in areas where the prevalence, importance and epidemiology of malaria is known with precision and where much additional information on the endemicity of non-malarial illnesses is available. Trials will entail close collaboration with experienced statisticians and meticulous planning, with special emphasis on the design of an efficient records system. The services of experienced clinicians skilled in the diagnosis and treatment of malarial and non-malarial illnesses will also be essential. Surveillance of the indices of malaria transmission will require competent entomological expertise.


Malaria vaccine development.

Malaria vaccine development. Prospects for the development of effective malaria vaccines have greatly improved over the last 15 years. For further progress to be achieved rapidly, the need for clinical research centres, where exposure and re-exposure to infection can be carefully controlled, is paramount. At such centres, it is possible to evaluate the safety and efficacy of vaccine preparations, using different strams and species of parasite, and to undertake studies in both nonimmune and partially immune volunteers. However, as efficacy under these conditions may not be a good indicator of efficacy under other conditions, the results of such studies should be complemented by field trials in endemic areas. It seems probable that vaccines may show degrees of partial effectiveness in relation to different strains, species, intensities of parasite inocula, and hosts.


Oral health of South African Black (Xhosa) mine recruits. The oral health of 100 rural Black Xhosa men commencing employment on the gold mines was examined. Dental caries were present in 68%, the mean DMFT per mouth was 2.5 (s.d. 2.8) while the mean DMFT per carious mouth was 3.7 (s.d. 2.7). Oral hygiene was good and periodontal disease uncommon. Although the frequency of individuals with dental caries has increased since studies on similar groups were made 40 years ago, the severity of the disease in affected individuals has remained static.


Results of 10 years of supervised fluoride toothbrushing in Rygge, Norway. At the annual examination in 1978 of 141 patients born in 1962, DMFS, sound teeth and the number of erupted permanent teeth were registered. The number of filled tooth surfaces per child per year was compared for the period 1967--78. The average number of erupted teeth in 1978 was 27.3 of which 69 were sound (mean = 18.9). The average DMFS score was 14.3 and decayed surfaces equaled 2.0. The mean number of filled tooth surfaces per year dropped from 6.1 in 1968 to 1.2 in 1978. The need for annual recall and examination routines at the dental clinics are questioned. More attention should be paid to preventive care.


In vitro assay for prekallikrein activator (PKA). The assay measures the action of prekallikrein in generating kallikrein. The prekallikrein activator is the limiting reagent. The product kallikrein is an esterase which can be quantitated using benzoyl arginine ethyl ester. The assay is reproducible and results are comparable with other methods. The large scale preparation of prekallikrein is described.


The assay of prekallikrein activator in human blood products. An assay for the determination of prekallikrein activator (PKA) in human blood products is described. Kallikrein released from a prekallikrein substrate preparation by PKA in the sample is determined using the synthetic substrate S-2302 (H-D-Pro-Phe-Arg-pNA). The PKA content of the sample is quantitated by interpolation from a standard line obtained using a reference preparation of plasma protein fraction (PPF). Endogenous kallikrein is estimated and an adjustment made for its contribution to the apparent PKA content of the sample. The results of determinations on a number of PPF, immunoglobulin and coagulation factor preparations are presented and discussed.


Is SP1 (pregnancy specific beta 1 glycoprotein) elevated in cancer patients? Pregnancy-specific beta 1-glycoprotein, SP1, was measured in serum by competitive double antibody radioimmunoassay. Very low levels of SP1 or SP1-like activity were found in only 2 out of 85 sera from patients with cancer of the digestive tract, breast cancer, melanoma, and sarcoma, in 2 out of 11 sera from patients with infectious diseases, and in none out of 15 sera from non-pregnant healthy individuals. SP1 thus does not seem to be ectopically produced in vivo by the types of cancer studied, but is probably highly specific for the normal and malignant trophoblast.


The reactions of 1.0 nanometre diameter plutonium-238 dioxide particles with rat lung fluid. The reactions of 1.0 nm particles of plutonium-238 dioxide with rat lung fluid have been studied both in vivo and in vitro. In both cases two products have been identified, (i) plutonium-labelled pulmonary surfactant and (ii) a heterogeneous plutonium-labelled material isolated by column chromatography. The formation of plutonium-labelled pulmonary surfactant results in the rapid translocation of plutonium from lungs to blood and in a high urinary excretion relative to administered plutonium citrate.


Transformation of mammalian cells by alpha particles. Mammalian cells in culture have been shown here for the first time to be transformed by alpha irradiation. Mouse embryo (C3H 10T1/2) cells were transformed with 5.6 MeV alpha particles from a Tandem Van de Graaff machine. Malignant tumours were induced following inoculation of the transformed cells into syngeneic hosts. Unirradiated control cells failed to produce tumours. The morphology of the transformed foci was similar to that obtained by X-rays and chemicals but different from virally transformed cells. The transformation frequency increased approximately as the cube of the dose to a maximum of about 4 per cent ofthe surviving cells which occurred between 1.5 and 2.5 x 10(7) alpha particles per cm2 (205-342 rad). It appears that alpha particle irradiation may exert a direct effect on the genome of the cell to produce malignancy without any external immunological or hormonal influences.


Quantitative microscopic studies of the distribution and retention of 239Pu in the ilium of the female CBA mouse. Three month old female CBA mice were injected with 50 nCi kg-1 body mass of minimally polymeric 239Pu-citrate and killed at 24 hours, 10 days, 1 month and 3 months after injection. The distribution of 239Pu in the ilia of these mice was analysed using neutron-induced autoradiography of bone sections together with computer-based methods of data reduction. Results of these investigations demonstrate that while 239Pu is initially localized on bone surfaces, by 3 months after injection it is fairly uniformly distributed throughout mineral bone and its included marrow.


Charge transfer in peptides. Pulse radiolysis investigation of one-electron reactions in dipeptides of tryptophan and tyrosine. One-electron oxidation of TyrOH-TrpH or TrpH-TyrOH in aqueous solutions by N3 radicals occurs predominantly at the tryptophyl residue. The corresponding indolyl radicals (absorbing at 510 nm) are subsequently transformed into phenoxyl radicals (absorbing at 390/405 nm): TyrOH-Trp leads to TyrO-TrpH, k5 = 5.4 x 10(4)s-1, (5), Trp-TyrOH leads to TrpH-TyrO, k7 = 7.3 x 10(4)s-1. (7) The first-order radical transformation rates are independent of the (initial) concentration of N3 or peptide and unaffected by urea (as a modifier of hydrogen bond structures). Intermolecular conversion of indolyl into phenoxyl radicals, e.g. by reaction of GlyH-Trp with TyrOH-GlyH, is very slow and inefficient. It is concluded that reactions (5) and (7) occur by intramolecular charge transfer across the peptide bond.


[Pathogenesis of psoriasis].

[Pathogenesis of psoriasis]. Psoriasis is basically an excessive proliferation of the epiderm. This state results mainly from an imbalance in the cyclical nucleotides linked mainly to anomalies of the keratinocyte membranes. The membrane change is due to antibodies whose production may be dependent upon a deficit of a T-lymphocyte sub-population. This deficit may be considered the result of the penetration of virus agent with the help of multiple genetic factors. The various link of this pathogenic chain may be modified by numerous external factors which, by causing a worsening in a pre-existing imbalance, brings about the appearance of lesions.


Quantitative and functional aspects of T-cell populations in human gut mucosa. Lymphocytes were isolated from rectal biopsies and resected gut specimens through a simple mechanical technique, and assayed for T-cell quantitation and mitogenic response to PHA and PPD. T-cells were found in considerable numbers in gut mucosa of all groups, but in each case their percentage was lower than that of the autologous peripheral blood. The mitogenic response to PHA was found in general to be lower in the mucosal lymphocytes compared to those in blood, with the exception of the polyposis group which responded highly. No response of mucosal cells to PPD was seen. Inhibition studies done by means of mixed cultures revealed the presence of a suppressor activity in many mucosal lymphocytes, especially in the inflamed mucosa group, which may partly account for some low responses observed with mucosal lymphocytes. Further studies are under way to better define these quantitative and functional differences seen in gut mucosal cells, and to correlate differences with disease states.


[Physiopathology of rheumatoid psoriasis]. The physiopathology of rhumatoid psoriasis (RP) is poorly known. Besides the genetic factors we study immunological disorders from a series of 51 cases. We found mainly an increase of serum IgA, a decrease of IgM, a low level of circulating immune complexes, sometimes IgG type antiglobulin factor (very seldom IgM type, which explains the sero-negativity) seldom antinuclear antibodies; we found also a diminution of T lymphocytes detected by a decrease of E rosette - forming cells and an increase of the lymphocyte subpopulation forming high avidity EA rosettes, whereas the mitogenic response is normal or slightly decreased in the presence of Con A (not significant). A increased frequency of HLA DRW5 and DRW2 was found but too few cases were studied to make possible a definite conclusion. This immunopathologic profile is compared to that of psoriasis with anthropathy. The relevance of immune disorders in the physiopathology of RP is discussed.


[Treatment of psoriatic rheumatism].

[Treatment of psoriatic rheumatism]. The authors report on the results of a cooperative study done in collaboration with dermatologists and rheumatologists in order to determine the therapeutic incompatibilities resulting from the co-existence of two diseases, both of unknown cause, namely arthropathies and dermopathies. They make an non exhaustive review of the litearature concerning the different medical or physical methods used. They attempt to outline a therapeutic schema according to the different clinical forms and the more or less large extent of the skin disease.


Antigen degradation by macrophages as an obligatory step in the presentation of antigen to T lymphocytes. Evidence is presented which supports the hypothesis of protein degradation taking place in macrophages as a part of the presentation of antigen to T lymphocytes. It is postulated that the ability of T cells to recognize both native and denatured forms of the same protein is dependent upon degradation of both forms of the protein to yield the same peptides and thus results in the stimulation of identical subsets of T cells. The occasional observation of a lack of cross-reactivity could result if the native antigen is particularly resistant to the denaturing conditions found within macrophages.


Cytotoxic effect of anti-lymphocytic globulin on human lymphoid cells. The cytotoxic activity of two anti-lymphocytic globulin (ALG) preparations was investigated by measurement of 51Cr release from human peripheral blood mononuclear cells and tonsil lymphocytes incubated with ALG in the presence of complement. Both types of ALG had a greater complement-dependent cytotoxic effect on tonsil lymphocytes than on peripheral blood mononuclear cells. The ALG preparations were more cytotoxic for a population of tonsil lymphocytes enriched in non-T cells than for one enriched in T cells. This finding does not support the view that ALG has a selective action on T lymphocytes.


Comparison of the binding of radiolabelled human IgG and Fc fragments to murine spleen cells. The binding properties of an IgG1 human myeloma protein, normal IgG, and the Fc and Fab fragments of each were compared in cultures of murine spleen cells. Both 125I-labelled IgG and Fc fragments bound to splenic lymphocytes, whereas Fab fragments did not bind significantly at the highest concentrations tested. On a molar basis, more Fc bound than intact IgG. According to Scatchard plot analysis, the affinity constand of IgG1 was 1.5 x 10(6) +/- 1 x 10(5) L/M and that of the Fc fragments was 7.8 x 10(5) +/- 2.6 x 10(5) L/M. Approximately 25,000 binding sites/cell were calculated for IgG1 and 102,000 for Fc. Deaggregation of the Fc preparation did not change these values, suggesting that the difference in binding of IgG and Fc did not result from Fc aggregation. Unlabelled IgG inhibited about 25% of the labelled Fc binding, whereas unlabelled Fc inhibited approximately 80% of the labelled Fc binding. IgG antigen-antibody complexes, however, inhibited 75% of the Fc binding. In the reciprocal experiment both intact IgG and Fc inhibited the binding of labelled IgG by 100%. The major cell population that bound IgG and Fc fragments in the spleen cell preparation were the B lymphocytes. Removal of macrophages did not significantly affect the binding of labelled Fc fragments. In addition, T-cell-enriched populations bound an insignificant quantity of Fc fragments.


T and B lymphocytes during normal human pregnancy: a longitudinal study. Immunological relationships in pregnancy were investigated in a longitudinal study of twenty-two pregnant women, whose blood samples were taken before pregnancy, during pregnancy, at delivery, and 3--5 months after delivery. Blood samples were also taken from the fathers and the infants, both at birth and after 3--5 months. All the samples were frozen by means of a cryobiological freezing system, and when a whole longtiudinal series had been collected, the material was thawed and tested in a single seance. T and B lymphocytes were studied with rosette tests (E and HEAC rosettes). T and B lymphocytes were found not to change during the course of pregnancy. It is thus concluded that the mother's tolerance of a fetus with a dissimilar tissue type is not exercised via changes in the total count of T and B lymphocytes, although there may well be changes in their subpopulations, with the hypothesis that T-suppressor function increases and B-lymphocyte function decreases.


Age-dependent changes in the electrophoretic mobilities of human blood lymphocytes. The distribution of the anodic electrophoretic mobilities (EPM) of human peripheral blood lymphocytes was determined for lymphocytes isolated from umbilical cord blood and from blood of individuals 6 months to 93 years of age. The distribution was bimodal in infants up to 2 years of age and suggested a small percentage of cells with a mobility of 0.95 micrometer s-1 V-1 cm. this value was chosen to discriminate between low-mobility cells (LMCs) and high-mobility cells (HMCs). The relative percentage of LMCs increased from birth to 2 years and two types of LMCs could be distinguished. The distribution was unimodal and asymmetric in children and adults and nearly Gaussian in aged people. Substantial differences between the distributions of the lymphocyte EPMs were seen on comparison of the histograms for individuals of similar ages. The analysis of the distribution of the lymphocyte EPMs on cell suspensions enriched in, or depleted of T or B cells confirmed the mobility of most T cells to be higher than the mobility of most B cells, whatever the age of the individual. The distribution of lymphocyte EPMs determined in the same adult over a 6 year period showed minor variations.


Generation of cytolytic T lymphocytes in vitro. XII. Detection of memory CTL precursors in peripheral blood of alloimmune mice. The memory cytolytic T lymphocyte (CTL) response of mice was studied in vitro using peripheral blood leucocytes (PBL) of donors previously immunized with allogeneic cells as responding cells, and particulate alloantigen for stimulation. It is shown that alloimmune but not normal PBL respond to particulate antigen and that small numbers of PBL generate high CTL responses provided non-T accessory spleen cells are added to the cultures. The system provides means to analyse the kinetics of the appearance of memory CTL precursors after primary alloimmunization in individual mice.


Occupational rheumatic diseases and upper limb strain in manual jobs in a light mechanical industry. The prevalence of occupational rheumatic diseases and the relation of the diseases to some specific work load factors were investigated. Ninety-three workers from a light mechanical industry were given a clinical, epidemiologic examination. General work methods were analyzed, and cycle time, mode of control, and the number of pieces handled/time unit were registered. The prevalence of tension neck was 61.3% and that of muscle-tendon syndrome 18.3%. The prevalences of other ailments were insignificant. The number of muscle-tendon symptoms correlated with the number of pieces handled. No other work load factors displayed a statistically significant relationship to the diseases. Tension neck had no relation to the weight/height index.


A behavioral version of catecholamine involvement in new learning rewarded by brain stimulation. Numerous studies in the rat indicate that catecholamines (CA) mediate rewarding properties of self-administered electrical stimulation to the brain. One such property is the learning of new response-reinforcement relationships. In the present experiment, amphetamine which potentiates CA at the synapse produces stereotypical responding but does not interfere with the learning of new response-reinforcement relationships. Apomorphine, which mimics dopamine (DA) at DA receptors, also produces stereotypy and interferes with learning. The results suggest that DA released by stimulation mediates the stereotyped responding seen in intracranial self-stimulation (ICS) but norepinephrine mediates reward of newly learned responses.


Subperiosteal hematomas of the orbit in young males: a serious complication of trauma or surgery in the eye region. Three examples of subperiosteal hematomas in the region of the orbital roof of young males are used to demonstrate the unpredictable appearance, the obscure nature, the complications, and the treatment of this process. One occurred in a 14-year-old boy following blunt head trauma and was cured by aspiration. The second occurred in a 16-year-old boy also resulted from blunt head trauma; it was associated with a large subgaleal hematoma and caused permanent blindness of the involved eye. The third case developed in an 18-year-old male as a complication of acute purulent endophthalmitis following an intraocular foreign body. The purpose of this report is to separate subperiosteal hematoma on the roof of the orbit of young males from the other orbital hematomas to show that it is a concise clinical entity with its own typical history, appearance, and treatment.


[Serological response and the viral carrier state in chickens infected with the pathogenic Newcastle disease virus]. Three groups of susceptible chickens were treated with Newcastle Disease vaccine, as follows: group I--orally, strain La Sota; group II--aerosole treatment, strain La Sota and group III--intramusculary, Komarov's vaccine. Varying HI antibody levels were observed following vaccine application. The average antibody titer of group I and II experimental chickens (40 in number for each group) was 25 days post vaccination respectively log2 = 3.47 and log2 = 6.2 while of group III (50 chickens) it was 14 days post vaccination log2 = 8.4. Aerosole challenge with velogenic viscerothropic strain of Newcastle Disease virus caused a sharp change in serum antibody titer. The low antibody titer in group I rose quickly post challenge while in groups II and III, on the contrary, it fell sharply. This characteristic dynamics is proposed for use as an indicator showing the presence of pathogenic virus in vaccinated birds. It was proven that pathogenic Newcastle Disease virus persisted in birds from group I for 40 days and 10% of them were in a state of latent infection (clinically healthy). The virus was isolated after method of organ cultures of tracheal explantates. It was established that the HI antibody level in the blood serum of virus carriers was higher as compared with that of the remaining birds in the group. The use of this fact as an indicator for beginning virusological investigations aiming to reveal latent Newcastle Disease infection is proposed.


[The effect of a synthetic tripeptide nervous tissue cultured in vitro]. Explants from chick embryo PNS (ganglion trigeminale) and from CNS of embryonal rats (hippocampus) and dissociated cells from chick embryo cerebral hemispheres were cultivated in maximow chambers in the presence of various concentrations of placental serum and of a chemically synthesized tripeptide Gly-His-Lys. 1. The presence of tripeptide in the nutrient medium with a low concentration of serum did not compensate the outgrowth of nerve fibers, that take place in the growth medium. 2. In the presence of tripeptide in the nutrient medium with low concentration of serum the index of growth area increased significantly. 3. Within the first days in cell cultures 0,01 microgram tripeptide pro ml medium stimulated the outgrowth of neuronal processes. 4. The experiments indicated, that the tripeptide did not replace the serum. The possible role of tripeptide as a system in controlling neuron-glial ratio in vitro is discussed.


Extra-lysosomal, fluoride-resistant acid phosphatase-active neuronal system subserving nociception in the rat cornea. Perikarya as well as central and peripheral terminals of nociceptive neurons innervating the rat cornea are genuinely labelled by an extra-lysosomal, fluoride resistant iso-enzyme of acid phosphatase. This enzyme seems to be related to the metabolism of transmitter oligopeptides characterizing such neurons.


Levamisole in the treatment of Hodgkin's disease. In vitro and in vivo action of levamisole has been studied in patients with Hodgkin's disease. In vitro levamisole significantly increased the active T cell count of 35 untreated active patients, of those being in complete remission after treatment and of 19 healthy controls; it significantly raised the total T cell count of patients. However, levamisole could not further improve the considerably increased active and total spontaneous rosette formation resulting from in vivo levamisole treatment. Twenty patients with Hodgkin's disease, being in complete remission, were given levamisole for 3 or 6 months, according to 2 different schedules. Levamisole (150 mg) given on 3 consecutive days of every second week for 3 months considerably increased the number of positive skin tests (from 8/60 to 29/60), the numbers of active and total T cells with unchanged absolute lymphocyte count, and decreased the quantity of circulating immune complex. Continuation of treatment for another 3 months resulted in slight, but consistent, decline in all the above parameters; the ratio of active T cells significantly decreased. This decline was even more pronounced if a raised larger dosage of levamisole was administered for 6 months. In the course of the treatment no side-effect or complication was observed. Levamisole is able to improve the weak cellular immune reactivity of patients with Hodgkin's disease, it can, however, result in undesired suppression in the case of too long treatment with high dose.