A randomized study of instructional variations in nutrition counseling and their efficacy in the treatment of hyperlipidemia. The important of the educational diagnosis in instructing patients in a fat modified diet was examined in a double blind study. The educational diagnosis depended upon the assessment of three independent instructional parameters: the amount of structure, the teaching mode, and the language code preferred by the patient. Group I (67 patients) received traditional personalized counseling for 3 months. Group IIa (40 patients), whose instruction was matched to their preferred education attributes, was randomized against group IIb (36 patients), whose instruction was mismatched. Group IIIa (33 patients), receving matched instruction was randomized against group IIIb (35 patients), receiving high structure in the symbolic mode of instruction. The greatest reduction in serum cholesterol was seen in group I. At 3 months, no significant difference in serum cholesterol reduction could be shown between groups IIa and IIb, or IIIa and IIIb. However, the mean cholesterol reduction became significantly greater (P less than 0.05) in IIa than IIb at the 6 month visit. Seven day food diaries showed no significant differences in dietary intake and 1 and 3 months between matched and unmatched groups. The data did suggest that patients preferring high structure in the symbolic mode had a greater serum cholesterol reduction that other diagnostic groups. Analysis of variance showed an interaction between the preferred and instructional level of structure as related to the change in total fat, and saturated fat of the diet after 3 months.


Counterimmunoelectrophoresis of blood cultures. Temporal Relationship of positive Gram stain to positive counterimmunoelectrophoresis. Counterimmunoelectrophoresis (CIE), Gram staining, and quantitative measurements were performed on simulated blood cultures at hourly intervals after inoculation with Streptococcus pneumoniae, Klebsiella pneumoniae, or Haemophilus influenzae. The CIE became positive either at the same time as the Gram stain or within the ensuing five hours. In no case was CIE positive when the Gram stain was negative. The numbers of colony-forming units milliliter necessary for a positive CIE result varied with the types of microorganisms. The procedure of CIE appears useful as a rapid screening technic for identification of bacteria in blood cultures when microorganisms are seen in Gram-stained smears.


Counterimmunoelectrophoresis for rapid identification of blood-culture isolates. A total of 303 blood cultures that were positive by examination of Gram-stained smears were tested immediately by counterimmunoelectrophoresis for detection of bacterial antigens. Antigen was detected in all 82 blood cultures containing Streptococcus pneumoniae and 11 of 22 with Klebsiella pneumoniae, two of two with Haemophilus influenzae, and one of one with Neisseria meningiditis. False-positive cross-reactions in 265 tests occurred only with pneumococcal Omniserum in two cases of nongroupable streptococcal bacteremia and with Klebsiella antiserum in one case of Escherichia coli bacteremia (1.1%). A specific identification of the microorganisms at least 24 hours earlier than by subculture technics was accomplished in 91% of the cultures containing the aforementioned bacteria. The procedure was not useful for detecting antigen in blood cultures containing Staphylococcus aureus.


Lipoprotein-X and other tests in the diagnosis of obstructive jaundice in the infant. The infant with elevated direct-reacting bilirubin levels requires an early specific diagnosis to identify those who would require early surgical intervention and those in whom the bilirubin levels will eventually return to normal. This study compares the accuracy of three tests: the serum lipoprotein-X (LP-X), the I131 rose bengal (IRB) excretion and the serum alpha-fetoprotein (AFP) in making a specific diagnosis in 15 patients. When used individually the accuracy of the tests varies from 56-100%. The LP-X and IRB excretion are more specific and when in agreement are 100% acurate in the diagnosis of the neonatal hepatitis syndrome (NHS) or extrahepatic biliary obstruction (EHBO). This study suggests that both the LP-X and IRB excretion should be used in the investigation of the infant with conjugated hyperbilirubinemia.


Aortocoronary bypass grafting in the management of patients with coronary artery disease. There is widespread agreement that aortocoronary bypass grafting generally lessens the symptoms and functional limitations of patients with angina pectoris. Evidence for prolongation of life or prevention of myocardial infarction, arrhythmias and ventricular dysfunction is inconclusive. Harmful effects associated with surgical management of coronary artery disease can be documented in terms of operative mortality, perioperative myocardial infarction, graft occlusion and progression of occlusive disease in the native circulation. In this review of published experience, the accomplishments and the limitations of myocardial revascularization are considered in various clinical settings. Critical assessment of evolving information leads to the conclusion that widespread application of this procedure beyond the alleviation of symptoms refractory to medical therapy is not justified by present data.


Granulocyte transfusion therapy: state of the art. Previously, granulocyte transfusion therapy was impractical due to insufficient yields obtained from normal donors. With the advent of such technical advances as continuous-flow centrifugation (CFC) and filtration leukapheresis (FL), the procurement of sufficient amounts of normal donor neutrophils becomes feasible. These techniques have allowed normal granulocytic cells to be infused into patients with a wide variety of granulocytopenic disorders related to infections which, without therapy, could prove fatal. In conditions in which normal granulopoiesis has become insufficient or when used to assist antibiotics in their fight against infection, granulocyte transfusion has been shown to be of definite clinical value.


Maternal serum alpha-fetoprotein levels as an index of fetal risk. In a prospective study on an obstetric population (1,059 cases) an association was found between elevated levels of maternal serum AFP at weeks 16 to 22 and the occurrence of premature labor or the need for emergency cesarean section in the third trimester. There was no association with other late fetal complications including perinatal death, perinatal asphyxia, and intrauterine growth retardation. The sensitivity of the test in respect of premature labor was 14 per cent but the high incidence of false-positive results reduces the practical value of the test.


Lack of hydrophilic lens discoloration in patients using dipivalyl epinephrine for glaucoma. Five glaucoma patients used topical dipivalyl epinephrine for periods of up to 84 weeks without discoloration of their soft contact lenses. Thus, patients who need both soft contact lenses and antiglaucoma therapy with topical epinephrine may use the dipivalyl analogue without lens spoilage.


Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin. A model for pulmonary fibrosis in the rat has been developed using intratracheal administration of bleomycin. The histopathologic features of the reaction are similar to those reported in the hamster model. Increases in vascular permeability are seen in the lung within 24 hours and persist over a 2-month period. Extractable collagen, as measured by hydroxyproline, increases during this time by a factor greater than 1.5 times the reference control values of normal lung. During this same period, a prominent eosinophilia develops. The continued treatment of bleomycin-injected rats with indomethacin markedly diminishes the amount of extractable lung collagen at 60 days and the histopathologic evidence of pulmonary fibrosis. The eosinophilia over the first 3 weeks is also markedly suppressed. Less dramatic effects were seen with the permeability changes. These findings indicate that the rat is a reliable and useful model for the study of blemoycin-induced pulmonary fibrosis and that treatment with indomethacin ameliorates the lung changes.


Personal mythology as a paradigm for a holistic public psychology. Viewing personal myths as cognitive structures, this paper examines the existing literature on cultural mythology, considers its relationship to personal mythology, and proposes an understanding of personal myths as a means of enhancing individuals' control over their lives. Its applicability to therapeutic counseling and its role in a holistic public psychology are discussed.


Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. II. The effects of histamine on heart cAMP-dependent protein kinase activity, cAMP levels, phosphorylase activity, and contractile force was investigated in the perfused guinea pig heart. To accurately determine the protein kinase activity ratio in guinea pig heart, it was necessary to measure kinase activity in whole homogenates immediately after homogenization of the tissue. Histamine produced a rapid dose-dependent increase in cAMP and the protein kinase activity ratio followed by increased in contractile force and phosphorylase activity. There was a good correlation between the degree of protein kinase activation and the increase in phosphorylase and force. The beta-adrenergic blocking agent propranolol did not reduce the effects of histamine, but metiamide, a potent H2-receptor antagonist, greatly attenuated all the effects of histamine. The data support the hypothesis that increases in heart cAMP-dependent protein kinase activity produce corresponding increases in contractile force and phosphorylase activity.


Lymphocyte responsiveness to phytohemagglutinin and to worm and egg antigens in human schistosomiasis japonica. Using a whole blood culture technique, lymphocyte responsiveness was assayed as 3H thymidine incorporation in 41 individuals infected with Schistosoma japonicum. In comparison with controls, response to phytohemagglutinin (PHA) was suppressed but was unrelated to egg excretion levels or duration of infection. Reactivity to whole worm antigens was significantly greater in individuals with a higher level of egg excretion and presumably greater infection intensity. The response to egg antigens significantly decreased with age and duration of infection. Some individuals with a depressed responsiveness to PHA maintain a high reactivity to parasite antigens, suggesting that different subpopulations of lymphocytes may be involved in these measurements.


Sensitivity and background staining of the unlabeled antibody enzyme (PAP) method. new approaches to the investigation of the effects of non-immune serum, primary antiserum concentration and pronase digestion using formalin fixed paraffin embedded material. The effect of primary antibody concentration, non-immune serum, and pronase digestion on the stainability of immunoglobulin containing cells (plasma cells) and background stainability was investigated using the peroxidase-antiperoxidase (PAP) method and antigens consisting of formalin fixed paraffin embedded maxillary mucosa, colonic mucosa, inflammatory synovia and soft-tissue plasmocytoma. The effect of primary anti-serum concentration and non-immune serum on cell and background stainability was smaller, but pronase digestion clearly improved positive stainability and reduced background stainability.


An immunoperoxidase assay for serum ragweed-specific IgE. A solid-phase enzyme immunoassay for allergen-specific IgE antibodies in serum is descirbed. In this technique these antibodies are allowed to bind to the allergen previously adsorbed to the wells of polystyrene microtiter plates. After a washing step the tubes are incubated with rabbit antihuman IgE labelled with horseradish peroxidase. Following a second washing step, the enzyme bound to the tubes is assayed spectrophotometrically using O-phenylene diamine as the substrate. The standard curves obtained with this method and with the RAST technique are illustrated. For the assay of serum antiragweed IgE antibodies, concordance between the results obtained with the RAST test and this immunoperoxidase assay was observed in 85 or 95 (90%) patients with symptoms of ragweed hayfever. The coefficients of variation ranged from 4.4% (2SD +/- .010) TO 14% (2SD +/- .008). The advantages of using peroxidase as the enzymatic marker for the assay of allergen-specific IgE are discussed.


Pathology of Legionnaires' disease.

Pathology of Legionnaires' disease. The acute lesion in Legionnaires' disease pneumonia is an acute fibrinopurulent bronchopneumonia in which the alveoli are filled with many neutrophils and macrophages and abundant fibrin. There is only slight necrosis. Although characteristic, the lesion is not specific for this agent. However, the association with this lesion of myriad small pleomorphic rods, which stain well with Dieterle's silver-impregnation method but poorly or not at all with Gram-type stains, is uncommon except in Legionnaires' disease pneumonia. Final diagnosis requires isolation of the organism or immunofluorescent studies of the tissue, sera or both. The full spectrum of the pneumonia is not known, but organization has been reported once. No definite anatomic correlate for the extrathoracic manifestations of Legionnaires' disease has been identified nor has the organism been found at extrathoracic sites.


Microbiology of Legionnaires' disease bacterium. Legionnaires' disease bacterium in tissue does not readily react with the Gram stain but can be seen by other stains and direct immunofluorescence. It is a slow-growing, aerobic, gram-negative rod that can be cultivated over a narrow temperature range on Mueller-Hinton agar supplemented either with complex biological mixtures or certain ferric salts and cysteine. The bacterium produces unique, branched-chain fatty acids, catalase, oxidase (weakly), and gelatinase and uses starch while ignoring other carbohydrates. Pigment production is related to tyrosine in the medium. In-vitro studies suggest susceptibility to all antibiotics except vancomycin, but a class 1 beta-lactamase has been demonstrated. Analysis of DNA confirmed the unrelatedness of this bacterium to previously recognized prokaryotes. Diagnosis of the disease has depended largely on serologic test findings and the demonstration of the bacterium in tissue and, occasionally, on isolation. Additional, simpler, and more rapid diagnostic tests should soon be available.


Four serogroups of Legionnaires' disease bacteria defined by direct immunofluorescence. Thirty-five strains of Legionnaires' disease bacteria were shown to belong in four distinct serologic groups on the basis of findings obtained with direct fluorescent antibody testing. Thirty of the strains were placed in group 1, three in group 2, one in group 3, and one in group 4. Immunoelectrophoretic studies showed both unique and common antigens among the representative strains of the four serogroups.


Immunochemical, serologic, and immunologic properties of major antigens isolated from the Legionnaires' disease bacterium. Observations bearing on the feasibility of a vaccine. Two antigens were isolated from each of three strains of the Legionnaires' disease (LD) bacterium. One antigen was serotype-specific; the other cross-reacted with strains of LD bacteria of different serotypes. The serotypic antigens contained all the major branched-chain fatty acids characteristic of LD bacteria and were a lipid-protein-carbohydrate complex. Electrophoresis resolved the serotypic antigen of Knoxville 1 strain into four protein bands and one glycoprotein band with molecular weights ranging from 0.5 to 7.2 x 10(5). The specificity of the serotypic antigens was established by immunofluorescent staining, and double gel diffusion confirmed the absence of cross-reactions between the serotypic antigens of different types and the partial identity of the serotypic antigens from serologically related strains. The cross-reacting antigens formed precipitin bands with all the homologous and heterologous sera tested. Induction of immunity by vaccination with serotypic antigens was shown in three animal models using guinea pigs and mice. Passive-transfer of immunity (IgG) was also shown in mice and guinea pigs. These observations raise the possiblity of a vaccine for protection against infection of LD bacteria.


Ultrastructure of the Legionnaires' disease bacterium. A study using transmission electron microscopy. The Legionnaires' disease (LD) bacterium appeared ultrastructurally identical in human lung, egg yolk membrane, and artificial media, seen as a blunt or tapering rod measuring 0.3 to 0.9 micron in diameter and greater than or equal to 2.0 micron long. Greatly elongated forms were commonly found in cultures and yold sac membranes after 5 to 7 days of growth but were only rarely seen in human lung. The LD bacterium was clearly prokaryotic. Prominent features included electron-lucent nucleoids interspersed among areas of well-defined ribosomes; cleanly circumscribed cytoplasmic vacuoles or granular inclusions; and a double envelope enclosure, each portion consisting of a triple-layered "unit" membrane, approximately 75 A wide. Division always occurred as a pinching, nonseptate process typical of bacteria with a double, gram-negative type of envelope. No definite structure was seen in the periplasmic space that might represent the peptidoglycan layer. These features of the LD bacterium confirm earlier reports of the gram-negative staining reaction of organisms obtained from cultures and preliminary evidence of their gram-negative ultrastructure. We found no unique features that would aid in the ultrastructural differentiation of the LD bacterium from other small gram-negative bacilli.


Direct in-vitro isolation of the Legionnaires' disease bacterium in two fatal cases. Cultural and staining characteristics. Two cases of Legionnaires' disease were diagnosed by direct isolation of the organism, from pleural fluid obtained before death in one case and lung tissue obtained after death in both cases. The organisms were recovered on a commercially prepared, enriched chocolate agar (Gibco, Madison, Wisconsin). Subcultures grew on commercially prepared, enriched chocolate agar (Baltimore Biological Laboratories, Cockeysville, Maryland) and on in-house enriched chocolate agar prepared with GC Medium Base (Difco, Detroit, Michigan). No growth was obtained on enriched chocolate agar prepared with trypticase soy agar. The organisms were poorly visualized in Gram-stained sections of formalin-fixed lung tissue. In Giemsa-stained sections poorly stained intracellular and extracellular slender rods were seen. However, with a silver impregnation stain, either a modified Dieterle or a modified Warthin-Starry procedure, many large, blunt-ended rods were seen. Smears prepared from minced formalin-fixed lung tissue and stained with a fluorescent antibody conjugate contained large numbers of well-stained organisms.


The effect of indoxole on the corneal immunologic response. To study the effect of locally administered indoxole (with polysorbate 80) on the inflammatory and immunologic responses, we made unilateral intracorneal injections of rabbit eyes with bovine gamma globulin (BGG). The indoxole was injected subconjunctivally one day before, and 1, 2, 3, and 5 days after the BGG injection. The homolateral lymph nodes, uveal tracts, and corneas of rabbits killed on postinjection days 6 and 12 were tested for antibody-forming cells (AFC) by a modification of the Jerne plaque technique. On day 6 the indoxole-treated eyes were more inflamed and had a greater number of AFC in the tested tissues than the control eyes, but in neither of these respects was there any essential difference between the treated and control eyes on day 12. The possible mechanisms by which indoxole achieved its effect were explored.


Detecting enteropathogenic strains of Escherichia coli of porcine origin. 2. Relationship between O and K antigens and the production of enterotoxin in strains isolated from the piglet after weaning. The production of enterotoxin by biological tests (Yl adrenal cells and the suckling mouse) has been examined in 96 strains of Escherichia coli, isolated from sick piglets after weaning. There is a good correlation between the presence of the capsular antigen K88 and that of the thermolabile fraction (LT) of the enterotoxin (69.2 per cent of the enteropathogenic strains studied). However, the presence of the thermostable fraction (ST) of the enterotoxin of strains which, according to their serological grouping, possess in theory the two fractions LT + ST or only the ST fraction is only confirmed in a small number of strains (16 per cent) by the biological test.


Study of factors influencing the effectiveness of two treatments, penicillin-streptomycin and rifamycin, against experimentally induced staphylococcal mastitis in lactating cows. The effectiveness of two antibiotic preparations, a combination of Penicillin-Streptomycin and Rifamycin SV, was measured on persistent subclinical infections produced experimentally by two strains of Staphylococus aureus in the bovine mammary gland. Effects of different parameters upon the efficiency of these treatments were analysed. The combination Penicillin-Streptomycin cured 23 quarters of 46 treated (50 %) against 14 out of 55 for the Rifamycin SV (25 %). This difference was significant (P less than 0.02). Whatever the antibiotic preparation used the highest cure rate was observed for the cows in first lactation (60 % against 24 %) and beyond the second month of lactation (43 % against 10 %). The factors dependent on the cow were related to these two parameters. Front quarters were cured in higher percentage (43 %) than rear quarters (29 %), although the difference was not statistically significant. The influence of other parameters on the cure rate, such as previous cleared infections and number of CFU and somatic cells in the quarters at the time of treatment, depended on the treatment used. The bacteriological results showed that cures could be correctly evaluated only after a minimum interval of three weeks post treatment. From the data a standardised model is proposed for the evaluation of the effectiveness of treatments.


Immunoperoxidase localization of Sporothrix schenckii and Cryptococcus neoformans. Staining of tissue sections fixed in 4% formaldehyde solution and embedded in paraffin. An indirect immunoperoxidase staining method has been successfully applied to 4% formaldehyde solution tissue sections fixed in and embedded in paraffin for the localization of Sporothrix schenckil and Cryptococcus neoformans without prior trypsinization of tissue sections. A comparison of this method with an analogous immunofluorescence staining technique has been made.


Effect of Graves' disease on idiopathic thrombocytopenic purpura. The association between hyperthyroidism and thrombocytopenia is a known although infrequent clinical condition. Distinct mechanisms are probably active in each particular case, but the thyrotoxic state has been implicated as having a key effect on the fall in the number of platelets. We describe a patient with coexisting Graves' disease and idiopathic thrombocytopenic purpura who showed special refractoriness to treatment of the bleeding condition in the thyrotoxic state, but who promptly responded to treatment when the thrombocytopenia relapsed 2 1/2 years later, while he was euthyroid. Thus, in this case, a clear exacerbating effect of the thyrotoxic state on the thrombocytopenia was observed. We suggest evaluation of the thyroid condition in patients suffering from refractory thrombocytopenia.


[Conduction of disorders after total correction of Fallot's tetralogy. Electrocardiographic and electrophysiological study]. The conduction defects observed after total correction of Fallot's tetralogy in 133 children, and their association with the long term outcome were studied with comparison of pre and postoperative electrocardiograms and, in 26 cases, His bundle recording. 23 early complete heart blocks were recorded which were nearly always transient. Only 4 (3.6%) became permanent. 58 had a right bundle branch block (48.4%) and 19 a bifascicular block (15.8%). The early operative mortality (9.7%) appeared to be related to transient complete heart block with 26% deaths in this group. Late mortality was high in patients with permanent heart block (2 out of 4) and also with bifascicular block (3 out of 17). His Bundle recordings showed lengthened H-V intervals in 3 patients, all of whom had transient complete heart block early post-operatively. In conclusion, complete heart block, even when transient, and bifascicular blocks are related to early and late mortality. The indications of permanent pacing, formal for patients with permanent complete heart block, are arguable for patients with bifascicular blocks preceded by postoperative complete heart blocks with long H-V intervals.


[Glucocorticosteroid, catecholamine and protein-bound iodine (PBI) plasma levels in swine following electrocutaneous stimulation]. Application of electrocutaneous stimuli for short-time excitation of swine, accompanied by high locomotor activity, led in animals weighing between 30 kg and 45 kg to steep rises of catecholamine and glucocorticosteroid plasma concentrations, while little change was recordable from protein-linked iodine. Increase in plasma glucose and RQ in animals with higher rises in plasma-borne catecholamines and glucocorticoids was higher than that in animals with lower catecholamine deflection. Both the results reported in this paper and findings obtained from other studies into swine are likely to suggest major involvement of the sympathico-adrenomedullary system in the buildup of transport stress. Interdependence was found to exist between the intensity of the adrenergic reaction, on the one hand, and rises in plasma glucose and RQ as well as drop of pH, on the other. Those findings from various tests seem to support the conclusion that under conditions of severe excitation and high locomotor activity the differentiated resistance of swine to stress is atributable to different intensities of sympathico-adrenergic reaction of the animal concerned.


[Painful disseminated fibromatosis (systemic hyalinosis): a new hereditary collagen dysplasia]. A case of systemic hyalinosis is reported and the main features of this unusual affection are quoted. The systemic hyalinosis is a syndrome exhibiting the following symptoms : a distressing arthogryposis syndrome, a diffusely stiff skin, some subcutaneous and submucosal fibrotic nodular lymps, repeated suppurative original infections and a facial dysmorphy. Biopsies of nodules show an active proliferation of the connective tissue associated with some peculiar hyalin changes of the collagen fibres. Most cases including the present one die in the first years. The pathogenesis is presently unknown. The systemic hyalinosis seems to be an autosomic recessive heritable disorder and is reasonably settled in the large group of the hereditary diseases of the connective tissue.


Antisera against polypeptide chains derived from M and N blood group glycoproteins. The polypeptide chains, containing only small amounts of hexosamines, were obtained from M and N blood groups glycoproteins by four cycles of periodate oxidation-Smith degradation, and were used for immunization of rabbits. The antisera obtained precipitated with the Smith-degraded glycoproteins, they reacted much weaker with the desialylated glycoproteins and they did not precipitate the untreated glycoproteins. In the quantitative microprecipitation assay the antisera precipitated better with the antigens of the same blood group specificity (M or N than those used for immunization. This blood group specificity was significantly increased by the cross-absorption of antisera.


Isolation and partial characterization of I antigen from I adult erythrocyte membranes. The i-active substance was isolated from i adult and I int erythrocyte membranes by butanol-water extraction and was purified by SDS-gel filtration and thin layer chromatography of peracetylated samples. The i-active substances from both types of erythrocytes showed also IF activity. In antigen isolated from i adult red cells the IF activity was lower than i activity. On the other hand, the antigen of I int red cells showed higher IF than i activity. The chemical characterization of isolated antigens indicated their glycosphingolipid character.


Further investigation of Ii phenotypic variants. I and i subtypes were investigated in erythrocytes with depressed expression of I antigen. It was confirmed that both, I and i antigens are heterogeneous. The depressed i status was found in all abnormal I phenotypes, but no direct correlation between i status and I subtype was found.


Serological investigations on ribitol-containing lipopolysaccharides from Proteus mirabilis. Lipopolysaccharides containing or noncontaining ribitol derived from several Proteus mirabilis strains were studied using passive hemagglutination, hemagglutination-inhibition and semi-quantitative precipitin tests. The results indicate that ribitol plays a role in the serological specificity of the respective lipopolysaccharides.


Immunochemical characteristics of Shigella sonnei and serotype 6 Shigella flexneri lipopolysaccharides and enterobacterial common antigen. Immunochemical studies on Shigella sonnei and serotype 6 Shigella flexneri 0 antigens (lipopolysaccharides) and enterobacterial common antigen (ECA) isolated from Shigella sonnei were carried out. Oligosaccharide structure of 0-specific chain of serotype 6 Shigella fiexneri lipopolysaccharide was defined and beta-L-rhamnosyl-1,3-N-acetyl-D-galactosamin as immunodeterminant of type VI specificity was recognized. The structures of core regions of lipopolysaccharides isolated from R mutants of both Shigella subgroups were established. On the base of the serological and structural results it has been suggested that these core regions are identical and very close to RI core structure of E. coli C. The effective method of isolation and purification of enterobacterial common antigen from Shigella sonnei was elaborated and its immunological properties as well as chemical character defined.


Localization of structural differences between serum and colostral ovine and bovine IgG1 and IgG2 immunoglobulins. Physicochemical and serological studies on immunoglobulins, their Fab and Fc fragments, L and H chains, showed that the strongest differences occurred in case of IgG2, and that the differences were localized in the Fc region.


The effect of some unspecific stimuli on defence mechanisms in weaned pigs. The studies were performed to find out whether a prophylactic use of unspecific stimuli affects appreciably the selected biologic indices in weaned pigs. The variables used in the experiment were found to exert a favourable effect on the state of health and growth of pigs but they had no essential influence on the level of immunoglobulins and increase in the titre of antibodies against E. coli (0141, 0149), isolated from pigs kept in the same pigsty.


Passive sensitization of mice and rats with IgE antibodies. The strain-dependent variation in susceptibility to passive sensitization of the skin and peritoneal mast cells with homologous IgE antibodies was observed in inbred strains of mice. Strain 129 showed low susceptibility to passive sensitization and high efficiency of normal serum in blocking mouse reagin-induced PCA in rats. Balb/c and C3H/A strains showed higher susceptibility to passive sensitization and the efficiency of normal serum in blocking rat PCA lower than strain 129. The serum factor responsible for rat PCA inhibiting effect was heat-labile. The anaphylactic response of peritoneal mast cells of inbred strains to the challenge with anti-mouse IgE and anti-rat IgE in vitro was low in Balb/c mice, as compared with the response of C57BL/6J and 129 mice. The results suggest, that non-specific IgE present in the serum or bound to the mast cells may be one of the factors determining the susceptibility of mouse strains to reagin-induced passive sensitization. However, the results obtained with C57BL/6J strain suggest the existence of other factors effecting this susceptibility.


Effect of complexes of lidocaine with transient metals on histamine release from rat mast cells. The effect of complexes of lidocaine with zinc, copper and cobalt on histamine release from peritoneal rat mast cells induced by various secretagogues was investigated. The complexes of lidocaine with metal ions inhibited histamine release induced by compound 48/80 and ionophoreous antibiotics: A23187 and X537A. The ionic complex of lidocaine with zinc was found to be the most potent against 48/80--induced histamine release and exerted the significant inhibition in the concentration of 10(-5) M. The action of coordination complex of lidocaine with zinc was somewhat weaker. The significant inhibitory effect on 48/80-induced histamine release of the copper and cobalt lidocaine complexes was observed in concentration of 10(-4) M. Histamine release by ionophores A23187 and X537A was also affected by zinc lidocaine complexes. However, coordination complex had more potent action on histamine release than the ionic one.


Synthetic antigens. Rabbit antibodies against interpolymer of styrene and maleic acid (PSM). Rabbit antibodies against interpolymer of styrene and maleic acid (PSM) are described. Rabbits immunized with PSM (mol. weight 292,000) produced precipitating and non-precipitating antibodies of IgG class. Interaction of rabbit antibodies with PSM was mainly of electrostatic character. It was found that various low molecular weight compounds resembling structural unit of the polymer inhibited reaction of PSM with antibodies. The reaction was also inhibited by picric acid and epsilon-TNP-aminocaproic acid. It suggested a multifunctional character of antibodies studied. The apparent affinity constant was 2 x 10(5) M-1 for interaction of PSM with the rabbit antibodies. Spectral studies suggested the presence of tyrosine in the combining site of anti-PSM antibodies. Specifically purified antibodies showed no restriction of heterogeneity, in comparison with rabbit IgG containing anti-PSM antibodies.


Serological abnormalities in families of patients with rheumatoid arthritis: eight to twelve years follow-up study. Serum gammaglobulin level, the presence of rheumatoid factor and of anti-nuclear antibodies were re-examined after 8 to 12 years in families of 21 seropositive rheumatoid arthritis patients. In the time 8 members of the families developed rheumatoid arthritis and the number of persons with elevated serum gammaglobulins increased. Rheumatoid tests yielded variable results. No relationship could be demonstrated between development of disease symptoms and the earlier presence of rheumatoid factor.


Investigation of biological activity of antigen--immunosuppressive drugs conjugates. The influence of conjugate 6MP with bovine gamma-globulin on some cellular immunologic reactions was investigated. The animals were immunized with the protein carrier and then conjugate or its components, in not coupled form, were introduced. Selective, but not strong, suppression of the immunological answer was observed in the migration inhibition of the mice splenocytes and the foot pad test. Conjugate was not changing the activity of the factor increasing vascular permeability. It was also confirmed, that conjugates of the nonsteroidal antiinflammatory drugs, except for conjugate of phenylbutazone with HSA, were not different in its influence (in the hyperaemic and oedema tests) from the individual components in not coupled form.


The effect of uremia and dialysis on cell-mediated immunity. Delayed-type hypersensitivity to PPD, two types T rosettes as well as lymphokine production were studied in patients with end-stage renal failure maintained on hemodialysis. A significant impairment of skin reactivity and the lowering of the number of T cells were found, while no definite changes of lymphokine production were detected. No conclusive data are obtained as to the role of hemodialysis in reversing of immunologic deficits noted in uremia.


Peritoneovenous shunting in the management of malignant ascites. The incapacitating, malignant ascites of 37 patients were treated with peritoneovenous shunt using the LeVeen valve. Palliation of ascites was achieved in 27 of 37 patients until they died of their underlying diseases. In ten of the 37 patients, no long-term palliation was accomplished. Complications relating to the shunt procedure were noted in six patients. No evidence of abnormal malignant dissemination was noted. We concluded that the peritoneovenous shunt can be used with relative safety to manage progressive malignant ascites.


The isolated human cortex. A Golgi analysis of Krabbe's disease. The clinical course of a child with Krabbe's leukodystrophy was characterized by clinical seizures, startle myoclonus, and paroxysmal activity recorded by EEG. At autopsy in the fourth year, myelinated subcortical axons were destroyed, virtually completely. Despite isolation from major subcortical and interhemispheric connections, the cell and fiber pattern of the cortex appeared remarkably normal in routine histologic preparations. The normal range of pyramidal and stellate interneurons were also present in rapid Golgi impregnations. The dendritic arbors of pyramidal neurons appeared to be normally formed and were richly invested with spinous postsynaptic specializations. The near-normal morphology of neurons isolated in the neocortex by the myelinoclastic process illustrates the sustaining influence of local intracortical synaptic connections. Alterations of cortical neuronal circuits resulting from synaptic remodeling of local interneuronal connections may account for cortical hyperexcitability as seen in cases of leukodystrophy.


The immunological basis of immediate hypersensitivity. IgE is a homocytotropic antibody which binds to the surface of the mast cell. Antigen with affinity for IgE triggers conformational change at the cell surface, resulting in the release of chemical mediators from the mast cell granules. The mediators histamine, slow reacting substance of anaphylaxis and eosinophil chemotactic factor cause smooth muscle contraction, increased capillary permeability, eosinophil attraction and increased glandular secretions. The release of mediators from the mast cell granules is controlled by intracellular levels of cyclic nucleotides. In particular, elevated cyclic AMP inhibits mediator release. Adrenergic, cholinergic and prostaglandin receptors all influence mediator release. The characteristic immunopathology of immediate hypersensitivity reactions is a result of local or systemic mediator release. Such reactions include anaphylaxis, asthma, allergic rhinitis, urticaria and angioedema. Similar immunopathology may sometimes result from mechanisms not involving IgE or histamine mediators. Routine investigation of patients with immediate hypersensitivity should include eosinophil counts and IgE levels in blood and secretions, and immediate hypersensitivity skin tests. RAST testing is not routine. Therapeutic principles of these reactions include restoration of inhibitory levels of cyclic nucleotides, antagonism of mediator effects and immunological manipulation of the IgE mediated allergic reaction.


Low dose lithium-carbimazole in the treatment of thyrotoxicosis. Fifteen patients with thyrotoxicosis were treated with low dose sustained release lithium carbonate 400 mg, combined with carbimazole 40 mg daily, and the therapeutic response was followed over a two week period. This response was compared with that obtained in a similar group of patient treated with carbimazole alone. Li-carbimazole treatment brought about a fall in the mean total serum T4 of 57.4% compared with a drop of 32.8% in patients treated with carbimazole alone. The mean serum T3 fell by 69.4% in the Li-carbimazole group compared with 47.3% in the group treated with carbimazole only. No lithium adverse effects were encountered.


Whipple's disease involving the pericardium: Pathological confirmation during life. Cardiac involvement in Whipple's disease has been a frequent autopsy finding but is rarely recognized clinically. We report here a patient, a 63-year-old man, in whom Whipple's disease was diagnosed in 1974, based on a seven-year history of arthralgia, one-year history of weight loss and steatorrhea, and diagnostic small bowel biopsy. Despite complete regression of all joint and bowel symptoms following a prolonged course of tetracycline therapy, the patient developed incapacitating congestive heart failure and signs of constrictive pericarditis, for which a thoracotomy and pericardectomy was performed. Histologic examination revealed fibrous pericarditis with mononuclear infiltrates, including PAS-positive histiocytes. The characteristic bacilliform bodies were identified by electron microscopy in the resected pericardium. This to our knowledge is the first such demonstration during life of Whipple's disease involving the heart.


Unresectable malignant obstruction of the bile ducts. Over a 13-year period we encountered 135 patients with malignant obstruction of the bile ducts, and in 81 of these patients only palliative surgery was possible. The type of operation was largely determined by the site and nature of the obstruction and the condition of the patient. The operative mortality of palliative operation was 37%. Relief of jaundice or pruritus was obtained in 68%, and this figure included a number of patients who died in the first 30 days. The majority of survivors lived for between three and four months after operation, although occasional patients have lived for more than one year.


The treatment of carcinoma of the stomach. A personal series of 200 patients with carcinoma of the stomach have been reviewed. Approximately 30% were regarded as suitable for curative resection; approximately 30% of the patients who underwent curative excision, survived five years; and approximately 30% surviving five years died of the disease before the 10th year. There were no early endoscopically diagnosed tumours in this series.


The identification of distinctive forms of human alpha 2-macroglobulin by using the numerical relationship between trypsin binding in alpha- and beta-modes. Interactions between the serine proteinase trypsin and the protein proteinase inhibitors in human blood were expressed in terms of a coupled set of non-linear differential equations, which has been solved for each of 110 samples of serum obtained from colleagues and from a variety of hospital sources. Optimization of nine unknown theoretical parameters and 21 experimental rate measurements of the hydrolytic activity of trypsin in free and bound states after admixture with various amounts of a given serum was achieved by an iterative procedure using initial estimates of the parameters derived from the "four-straight-line" model described in the preceding paper [Topping & Seilman (1979) Biochem. J. 177, 493--499.] Such a procedure yielded the following information for each sample of serum examined: (a) the concentrations of alpha 1-antitrypsin and alpha 2-macroglobulin; (b) the unequivocal assignment of alpha 2-macroglobulin into one of seven categories on the basis of trypsin binding in two kinetically differentiated modes (alpha and beta); (c) the hydrolytic activities of trypsin (versus Bz-Arg-OEt) when bound to alpha 1-antitrypsin, and to alpha 2-macroglobulin in the alpha- and beta-modes. Molecular interpretations of the binding of trypsin to alpha 2-macroglobulin are discussed and the potential clinical value of recognizing the nature of such binding is reported.


Estrogens in carcinoma of the prostate. Effects on enzymes and polypeptide hormones. Patients with benign hyperplasia of the prostate and with anaplastic carcinoma have similar activities in their cells in staining for acid phosphatase. After therapy with estrogens the acid phosphatase is significantly inhibited, leucin amino peptidase and succinate dehydrogenase appear to be reactivated in the cells of anaplastic carcinoma. Serum TSH is decreased distinctly, serum levels of LH and prolactin are significantly elevated especially in patients with anaplastic carcinoma of the prostate in comparison to that of patients with treated benign hyperplasia.


Sodium binding sites of gramicidin A: sodium-23 nuclear magnetic resonance study. In ethanol-water mixtures (90:10), the gramicidin dimer binds Na+ cations at well-defined sites, with a binding constant K = 4 M-1. Partial desolvation of Na+ occurs upon binding, as judged from the magnitude of the quadrupolar coupling constant (1.7 MHz) for bound sodium. The binding sites are identified with the outer sites flanking the channel entrances. The rate constants for binding and release are k+ less than or equal to 2.2 X 10(9) M-1 s-1 and k- less than or equal to 5.5 X 10(8) s-1, respectively.


Modification of membrane lipids. Phenethyl alcohol-induced alteration of lipid composition in Tetrahymena membranes. Tetrahymena pyriformis NT-I cells in the early-logarithmic phase were incubated with phenethyl alcohol (2-phenylethanol) and effects on the lipid composition were examined in various membranes. 1. There was a marked modification in phospholipid head, as well as fatty acyl group composition in pellicles, mitochondria and microsomes of the phenethyl alcohol-treated cells. Compared with membranes of the control cells, the membranes from phenethyl alcohol-treated cells were found to contain a higher level of phosphatidylcholine content with the compensating decrease in phosphatidylethanolamine, while 2-aminoethylphosphonolipid showed only a slight decrease in these membranes. The acyl group profile of membrane phospholipids in the presence of phenethyl alcohol was also modified so that a profound elevation of the content of polyunsaturated fatty acids, linoleic and gamma-linolenic acids. The major monounsaturate, palmitoleate decreased. Such lipid alteration is a reversible process, and therefore upon removal of phenethyl alcohol the modified lipid composition returned to normal. 2. By freeze-fracture electron microscopy in combination with temperature quenching, the outer alveolar membrane of the phenethyl alcohol-treated cell was observed to reveal less aggregation of intercalated-membrane particles, as compared with the control membrane. The quantitative analysis of the thermotropic lateral movement of membrane particles provided evidence that the membrane in the phenethyl alcohol-treated cell became more fluid. Such fluidizing effects may result from an increase in the acyl group unsaturation and also in the phosphatidylcholine content. 3. With regard to the mechanism responsible for the marked decrease in palmitoleate in membrane phospholipids, there was found a depressed conversion of the palmitate to palmitoleate in the phenethyl alcohol-treated cells. It was further suggested that the drug may have an inhibitory effect on the synthesis of palmitoyl-CoA desaturase involving the (16 : 0 leads to 16 : 1) conversion. Also, it was demonstrated that the increase in a precursor-product fashion of phosphatidylcholine with the corresponding decrease in phosphatidylethanolamine was not due to transformation of phosphatidylethanolamine to phosphatidylcholine through stepwise methylation.


Analysis of the genetic complexity and abundance classes of messenger RNA in human liver and leukemic cells. In an effort to determine the number of genes expressed as messenger RNA in disparate human tissues we have analyzed the genetic complexity of the polyribosome-associated poly(A)-containing RNA population obtained from liver and lymphoblastic leukemic cells. This was accomplished by measuring the kinetics of hybridization of mRNA to a complementary DNA probe synthesized by avian myeloblastosis virus reverse transcriptase in vitro. The results obtained from such an analysis revealed the presence of two major abundance classes of mRNA with a total genetic complexity of approximately 10,000 diverse mRNA species in both of these cell types. Diversity of mRNA species in these unrelated human cells was studied by heterologous hybridization reactions between the cDNA of one cell type and a vast excess of poly(A)-containing mRNA from another. These types of studies indicated that extensive homology (more than 80%) exists in the mRNA sequences of disparate human cell types and suggest that the vast majority of genetic information expressed as mRNA is required for the maintenance of cellular functions common to functionally different human tissues.


The structure of the O-antigenic side chain of the lipopolysaccharide of Vibrio cholerae 569B (Inaba). Mineral acid hydrolysis of the lipopolysaccharide from Vibrio cholerae 569B (Inaba) gives an oligosaccharide fraction which was shown, by use of 13C NMR and chemical methods, to be a regular alpha-(1 leads to 2) linked chain of D-perosamine (4-amino-4,6-dideoxy-D-mannose) units. This chain represents the O-antigen of the lipopolysaccharide, in which the amino functions are acylated with 3-hydroxypropionyl groups. The chromatographic properties of some hydroxamic acids are described and used to characterize these acyl groups.


The role of cell-fixed calcium in histamine release by compound 48/80. 1. Histamine release by compound 48/80 was substantially reduced in a time-dependent manner (maximum at 30 min) by pre-incubating mast cells in calcium-free medium at 37 degrees C but not at 2 degrees C. This effect was optimal at pH 7.0 to 7.5. 2. The re-introduction of calcium (0.1 to 3 mmol/l) restored histamine release to the control value; this effect was independent of temperature. 3. Strontium (1 to 30 mmol/l) partially reversed the effect of calcium deprivation but the same concentrations of barium and magnesium depressed histamine release even further. Magnesium (3 to 15 mmol/l) antagonized the effect of calcium replacement. 4. Results suggest that the level of cell-fixed calcium involved in compound 48/80-induced histamine release may be controlled by the combination of rapid passive influx and slow active efflux.


Inhibition of neuronal firing by opiates: evidence against the involvement of cyclic nucleotides. 1. Extracellular recordings were made in vitro from single neurones of the myenteric plexus of the guinea-pig ileum. 2. Neuronal firing was inhibited by morphine and normorphine (10 nM to 1 micrometer). Cyclic adenosine 3',5'-monophosphate (cyclic AMP) (100 micrometer to 1 mM) also inhibited the firing of the majority of the neurones. Prostaglandin E2 usually caused a short-lasting excitation of myenteric neurones and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was usually without effect on firing rate. 3. The inhibition of neuronal firing by normorphine was unaffected by prior and/or concurrent administration of cyclic AMP, dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E2 or 3-isobutyl-1-methylxanthine. As these four treatments might be expected to elevate intracellular levels of cyclic AMP, the results lend no support to the notion that a reduction in intracellular cyclic AMP is essential to the inhibition of firing produced by morphine.


[Myocardial parameters controlling vulnerability. Analysis of mathematical models]. Vulnerability induced by application of a properly timed premature stimulus was studied on mathematical models. Two mechanisms of vulnerability 1) reentry, 2) focal reexcitation were analysed. Tissue with a region of increased refractory period Rmax was simulated on Wiener's type model. The influence of high refractoriness region dimensions and tissue parameters on the duration of vulnarable period was studied. Reentry was shown to appear on the border of high refractoriness region, which minimal length lmin being the shorter, the greater was tau (maximal latency of response) and epsilon (epsilon = deltaR/R--degree of heterogeneity). The dependence of vulnerable period duration on current strength was computed for Nobel's model. The dip-phenomenon was found in this model, the vulnerable zone was located above the minimal value of threshold.


Health problems of anaesthetists and their families in the West Midlands. A survey of all anaesthetists in the West Midlands region--that is, 10% of all the anaesthetists in England and Wales--showed that one in 10 of their children had been referred to a consultant because of a congenital or nonacquired anomaly. Abortions among anaesthetists' families were also common but more so when the mother was an anaesthetist. The anomalies were concentrated particularly in the central nervous system and musculoskeletal system, and girls were worst affected. The mean birth weights were below normal, more so when the mothers were anaesthetists. Girls with anomalies were particularly underweight. Other effects observed were unexpected infertility, cancer both in the adults and in the children, and, possibly, impaired intellectual development in the children. Many anaesthetising areas were inadequately ventilated, and scavenging devices despite their inefficiency are recommended as a stopgap measure. The results of the study closely resemble those of other studies with similar high response rates to requests for information.


Some experience in an area health authority child health clinic. Three years' experience as a doctor taking two clinics a week in an area health authority child health clinic was reviewed. A wide range of clinical conditions was seen, including: problems associated with feeding in breast- and bottle-fed infants; minor developmental abnormalities (mental, behavioural, and physical); surgical and orthopaedic conditions requiring treatment; medical conditions, mainly respiratory and alimentary infections, skin conditions, and problems of over-treatment for minor ailments; and minor genetic abnormalities. Mothers asked for advice on a wide range of topics, risks and benefits of immunisation being the most common. The clinic doctor needs a wide experience in paediatrics to deal with such problems. It is suggested that all lecturers in child health and paediatric and senior registrars should take one clinic a week for six months, and all medical students should attend some clinics as part of their paediatric training. Health visitors have an important role in helping the clinic doctor, but their training should be more realistic and appropriate facilities should be provided to keep them up to date in their work.


Reactivity of amniotic fluid alpha-fetoprotein with concanavallin A in diagnosis of neural tube defects. Alpha-fetoprotein (AFP) concanavallin-A-affinity molecular variant patterns were determined in amniotic fluid samples from 10 pregnancies complicated by anencephaly (6), spina bifida (1), Turner's syndrome (1), osteogenesis imperfecta congenita (1), and fetal death (1) and 20 normal pregnancies between 14.6 and 25.5 weeks of gestation. With the exception of one anencephalic pregnancy, the AFP concentrations in samples from women with a fetal abnormality were more than 5 SD above normal for gestational age. In every case, however, the proportion of total amniotic fluid AFP that was not reactive with concanavallin A was significantly smaller in the presence of a fetal abnormality (mean 2%) than when the fetus was normal (mean 20%). The results suggest that measuring the amount of concanavallin-A-non-reactive amniotic fluid AFP will be a valuable test for diagnosing fetal abnormality, especially when an increase in total amniotic fluid AFP concentration is equivocal or gestational age is uncertain.


Precision in estimating gestational age and its influence on sensitivity of alphafetoprotein screening. The interpretation of maternal serum alpha-fetoprotein (AFP) concentrations in relation to fetal neural tube defects depends on accurate assessment of the gestational age. In a quadruple-blind study three antenatal methods of assessment--namely, menstrual dates, clinical examination, and ultrasound scanning--were correlated with postnatal assessment using the Dubowitz scoring system. The best agreement to +/- 1 week was obtained using menstrual dates and ultrasound in combination, such agreement being found in 91 (77%) of the 118 women studied. Since serum AFP concentrations vary with gestational age, precise gestational dating is necessary. In many cases, particularly in women who are unsure of their dates or have irregular menstrual cycles, ultrasound examination is needed to supplement clinical findings.


Autoradiographic study of the development of the neostriatum in the rabbit. Autoradiographic labelling has been employed to analyze the morphogenesis of the neostriatum. Pregnant rabbits received a single intraperitoneal injection of tritiated thymidine at different stages of gestation. Careful microscopical observation of the autoradiographs shows that cellular components of the neostriatum originate between days 15 and 18 of the intrauterine life from a layer of proliferating matrix cells that lies on the floor of the anterior part of the lateral ventrical (ganglionic eminence). From this proliferating layer, precursor cells migrate outwards to reach the developing neostriatum in a sequential fashion according to two gradients of histogenesis. Thus, it was found that neurons formed at early stages occupy a ventromedial position in the neostriatum, while those formed at later stages occupy a dorsolateral position (ventromedial to dorsolateral gradient). Furthermore, the present study indicates that the rostral regions of the neostriatum arise somewhat later than the caudal ones, demonstrating the existence of a caudocephalic gradient of cytogenesis.


Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra. Selective, highly efficient uptake of [125I]NGF by nerve terminals followed by retrograde axonal transport, and specific induction of tyrosine hydroxylase by NGF are well known phenomena in peripheral adrenergic neurons of adult rats. In the present study these parameters were used in order to detect possible interactions of NGF with central catecholaminergic neurons. No selective retrograde transport of [125I]NGF could be detected by light microscopic autoradiography from the caudate nucleus to the dopaminergic neurons in the substantia nigra or from the hippocampus to the noradrenergic nerve cells of the locus coeruleus. Biochemically, no change in tyrosine hydroxylase activity could be observed for up to 3 days after injection of either NGF, anti-NGF antibodies, or control proteins close to the nerve cell bodies in the substantia nigra or the locus coeruleus. These data suggest a fundamental difference between central and peripheral adrenergic neurons with regard to their responsiveness of NGF.


Midbrain projections to the trigeminal, facial and hypoglossal nuclei in the opossum. A study using axonal transport techniques. It has been proposed (see Berntson and Micco for review) that circuits intrinsic to the midbrain play an important role in the elaboration and control of behaviors involving the motor nuclei of the trigeminal, facial and hypoglossal nerves (e.g. defense, threat, attack); but because of technical problems, it has been difficult to analyze their organization. Using the horseradish peroxidase technique we have localized those midbrain neurons which project to each of the above nuclei and by using the autoradiographic method we have plotted the intranuclear distribution of their axons. Using both techniques, we have seen that mesencephalic projections to oral-facial motor nuclei strongly favor the nucleus of the facial nerve. Cells ventral to the cerebral aqueduct, including the ventral periaqueductal gray, the interstitial nucleus of Cajal, the nucleus of Darkshchewitsch and the rostral oculomotor nucleus provide major midbrain-facial projections in the opossum. Their axons terminate densely and bilaterally within areas innervating auricular muscles and to a lesser extent, the platysma sheet. The projection to the caudal auricular area of the facial complex is particularly dense. Neurons within and dorsal to the red nucleus project to regions of the contralateral facial nucleus reported to supply buccolabial, zygomatic and cervical musculature. There is also a minor tectal projection to the facial nucleus. Direct projections to the hypoglossal nuclei also arise within the periaqueductal gray and interstitial nucleus, but if such regions influence the motor trigeminal nucleus, it is mainly by way of dendrites that extend outside the nucleus or by at least one synaptic delay. The mesencephalic nucleus of the trigeminal nerve, however, projects strongly to the motor trigeminal nucleus. These data are discussed in light of their possible functional significance.


Double-stranded protamine cDNA: synthesis and characterization. Double-stranded protamine complementary DNA (cDNA) was synthesized from a protamine mRNA template via the single-stranded cDNA intermediate using avian myeloblastosis virus reverse transcriptase. Synthesis at 37 and 46 degrees C resulted in similar overall yields (greater than or equal to 18%), although the initial rate of synthesis was higher at 46 degrees C than at 37 degrees C. The DNA of the second strand of the double-stranded cDNA product was 84% resistant to prolonged digestion with excess S1 nuclease. The S1 nuclease resistant material ranged in size from 235 to 100 base pairs (bp) with an average length of 185 bp. Analysis of the products released from double-stranded protamine cDNA by depurination indicated that there were a number of cytosine-rich oligopyrimidine tracts in protamine mRNA, namely C4, C4U1, C5U1, C6U1, C6U4, and C7U1. On the basis of the amino acid sequences for rainbow trout protamines, C5U1, C6U1 and C7U1 must be located within the noncoding regions. Double-stranded protamine cDNA was cleaved at least once by the restriction endonucleases HaeIII and HhaI and in several places by HpaII. These restriction endonucleases cleave at sequences which have a high probability of occurring within the coding region of protamine mRNA, again based on the known amino acid sequences of the rainbow trout protamines.


Antenatal diagnosis of neural tube defects in Canada: extension of a collaborative study. Experience with the diagnosis of neural tube defects from alpha1-fetoprotein (AFP) concentrations in amniotic fluid is reported from a prospective study of five laboratories testing for 13 Canadian genetic centres. The results of the study indicate that antenatal diagnosis of open neural tube defects is being carried out effectively in Canada (in 99.2% of cases the AFP measurements were interpreted correctly). Amniocentesis should be recommended to women at high risk for having a child with a neural tube defect (i.e., those who have a child, a parent or a sibling with a neural tube defect). The rate of neural tube defects in 182 high-risk pregnancies was 2.2% for an open defect and 1.1% for a closed defect, whereas the rate in 673 pregnancies in which amniocentesis was being performed for other reasons was 0.3%. This suggests that the AFP concentration should be measured in any sample of amniotic fluid collected for other reasons (usually fetal karyotyping). There were three instances of false-negative results, for a rate of 0.4%. Two closed neural tube defects were not detected; this limitation of the test has also been found by others. One of the six fetuses with an open neural tube defect, who died in utero, had a large myelocele in the neck that was not recognized. There were also four instances of false-positive results, for a rate of 0.5%. The findings suggest that AFP values that are more than 2 but less than 7 standard deviations (SDs) above the mean may indicate a neural tube defect, and that values 7 or more SDs above the mean very likely indicate such a defect, although other reasons for such high values (e.g., fetal erythrocytes in the amniotic fluid, intrauterine death and mistaken gestational age) must be ruled out by other methods.


Antenatal genetic diagnosis: current status and future prospects. The current status of antenatal genetic diagnosis is reviewed and the limitations of present techniques are discussed. It is suggested that multidisciplinary clinics are the most efficient means of providing this aspect of health care. Advances in cell culture techniques, in ultrasonography and in fetoscopy will extend the services available, and the impact of this will be felt by the community. Education of the medical profession and the public in this area is necessary so that informed decision-making can take place.


Evidence for the presence of an antitumor factor in serum of normal animals. We have previously reported finding a factor with antitumor activity (TNF, tumor necrosis factor) in extracts of serum from normal mice. The possibility that TNF exists in the blood of normal animals of other species was explored. Horse, mouse, dog, human, sheep, calf, rat and shark serums were fractionated with (NH4)2SO4 and filtered through S-200 sephacryl gel. Proteins of molecular weight 90,000 to 180,000 were pooled, concentrated and dialyzed. TNF, determined by L-cell assay in vitro and Meth A assay in vivo found in fractions from mouse, dog and human serum. Agarose electrophoresis of the TNF from mouse and human serum indicated the principle components were alpha 1-alpha 2 globulins. Preparative PAGE indicated that mouse TNF migrated slowly and was made up of at least 4 components while human TNF was a faster moving, monomeric protein.


[Hepatic tumors in childhood (author's transl)]. The results of Treatment of Liver malignant primary tumors are analyzed. 16 Tumors have been treated in 15 years. The best method appeared to be radical Hepatic resection. The post operative level of A.F.P. is the first sign of Tumor recurrence and permits an Intensive Chemotherapy.


New natural products of interest under development at the National Cancer Institute. Fourteen new agents of natural products origin which are under development as antitumor agents at the National Cancer Institute are discussed with reference to their sources, structures, antitumor activity, current status, and future prospects as clinically effective agents.


Determination of pregnancy zone protein in serum using an automated immunoprecipitin reaction method. Determination of pregnancy zone protein in serum by means of an automated immunoprecipitin reaction method and pretreatment with polyethylene glycol for reducing the serum blanks is described. Using this procedure the sensitivity of the method was greatly improved, from originally 100 mg/l to 1 mg/l. The precision "between days" was 9.9%. A positive and significant correlation to electroimmuno assay is demonstrated. In apparently healthy controls the median serum pregnancy zone protein in females was 38 mg/l (2--91 mg/l) and in males 2 mg/l (0--20 mg/l). No correlation between serum pregnancy zone protein and age could be demonstrated. In malignant diseases our results seem to confirm a relationship between increased pregnancy zone protein and spreading of the tumours. Serum pregnancy zone protein in disseminated malignancies are increased significantly compared to controls. In males 75% with disseminated tumours have elevated serum pregnancy zone protein.


Radioimmunoassay of serum myelin basic protein and its application to patients with cerebrovascular accident. Myelin basic protein-like immunoactivity was measured in the serum of patients after cerebrovascular accident (CVA) using a double antibody radioimmunoassay for myelin basic protein with a detection limit of 3 ng/ml serum. For up to 6 days after ictus, serum myelin basic protein levels in patients with severe CVA and patients who died as a result of CVA were significantly greater than those in control patients, patients with moderate CVA and patients surviving CVA. All patients with serum myelin basic protein levels greater than the range found in control subjects subsequently died. Serial dilutions of positive sera suggested that the immunoactivity differs from authentic myelin basic protein and may represent breakdown products of the protein. Serum from some patients with a previous history of moderate CVA had myelin basic protein binding activity consistent with the presence of antibodies to the protein.


Tryptic and elastolytic inhibitory capacities of serum from various Pi phenotypes. Alpha-1-antitrypsin deficiency is responsible for emphysema in adults. The genetic polymorphism of this protein (Pi system) is used to detect these deficiencies. The relationship between the serum protease inhibitory capacities and M, MZ and Z Pi phenotypes was investigated. 120 sera including 31 M, 33 MZ and 56 Z were studied. The alpha-1-antitrypsin concentration varied according to the Pi phenotype, the sex and the health of the subject. The alpha-2-macroglobulin level did not depend on the Pi phenotype. The trypsin inhibitory capacity fluctuated with the age and the health of the subject, but did not faithfully represent the Pi phenotype. In contrast, the elastase inhibitory capacity depended only on the Pi phenotype. The relationship between alpha-1-antitrypsin levels and the serum elastase inhibitory capacities was linear. Canonical analysis was employed to determine the relative contributions of each antiprotease to the two inhibitory capacities. It appeared that the elastase inhibitory capacity was influenced more by the alpha-1-antitrypsin level while the trypsin inhibitory capacity was more sensitive to alpha-2-macroglobulin.


Prenatal diagnosis of severe congenital malformations associated with elevated amniotic fluid alpha-feto protein. Two cases of severely malformed infants with abnormal fetal images on B-scan sonography and markedly elevated amniotic fluid AFP are presented. There was no evidence of neural tube anomalies. The importance of an amniocentesis and AFP in pregnancies with an abnormal fetal image on B-scan sonography is emphasized, taking into consideration that most pregnancies with elevated fluid AFP have serious fetal anomalies.


Prevention of tolerance in differentiating B lymphocytes by T cells. Normal, but not tolerant, adult thymocytes prevented particulate antigen inducing tolerance in differentiating B lymphocytes. This was demonstrated by measuring the emergence of responsive B cells (identified by their allotype) developing from a foetal liver innoculum in irradiated hosts with or without the addition of antigen, thymocytes or tolerant thymocytes. The relevance of these findings to the recruitment of B lymphocytes in adult animals and to the development of those autoreactive B cells found in normal animals is discussed.


Cerebrospinal fluid lymphocytes in experimental allergic encephalomyelitis. We report characteristics of the cerebrospinal fluid (CSF) pleocytosis (616+/-148 cells/microliter) that occurred in guinea-pigs with definite clinical experimental allergic encephalomyelitis developing 12 to 16 days after sensitization with homologous myelin basic protein. This pleocytosis was not present in the cerebrospinal fluid of a group of animals studied when still healthy, 9 or 10 days after similar sensitization. Eighty-nine per cent of cells in the CSF pleocytosis were small lymphocytes, 8% were larger lymphocytes and the remainder mostly monocytes. Of the lymphocytes, most were E-rosetting or null cells. B-cell markers were uncommon. The cellular patterns in this CSF pleocytosis appear to be similar to those seen in some delayed hypersensitivity responses.


Excretion of chlordecone by the gastrointestinal tract: evidence for a nonbiliary mechanism. Workers exposed to chlordecone (Kepone), a toxic organochlorine pesticide, excreted larger amounts of chlordecone in bile than in stool, suggesting that it may undergo enterohepatic recirculation. We found in a single subject that equal amounts of chlordecone and of its reduced metabolite, chlordecone alcohol, were excreted in bile at a rate four times as great as in stool. When biliary contents were diverted from the intestine through a T tube, fecal excretion of chlordecone alcohol was abolished, presumably due to interruption of its passage via bile to intestine. This change was not accompanied by disappearance of chlordecone from the stool. The amount of chlordecone in stool when bile was diverted was increased six- to tenfold over that when diverted bile was continuously infused into the duodenum. Analogous experiments with [14C]-chlordecone-treated rats in which bile flow was exteriorized through a plastic cannula showed that the excretion of radioactivity in feces was in the same range when bile was reinfused in the duodenum or was totally diverted. Moreover, in rats with bile diverted, cholestyramine, an anion-exchange resin which binds chlordecone in vitro, doubled the excretion of radioactivity in stool. A similar effect was observed in intact animals. We conclude that chlordecone enters the intestinal lumen from a nonbiliary source, probably the gut, and that net excretion of chlordecone from this source can be augmented by cholestyramine.


Estracyt in advanced carcinoma of the breast: a phase II study. Estracyt, a conjugate of an alkylating agent with an oestrogenic sterol, was given in a dose of 420 mg daily to a group of 44 postmenopausal patients with very advanced breast carcinoma. Thirty-eight of these were in relapse following chemotherapy and 32 had evidence of distant metastases. Seventeen patients had an objective response and marked or complete alleviation of symptoms, four others had a useful symptomatic response but no beneficial effect was observed in the remainder. Three who had shown no response to previous oestrogen therapy also failed to respond to Estracyt as did all nine patients with hepatic metastases. Oestrogen receptor status and age within the postmenopausal group seemed to have no bearing on the result. Side-effects were minimal with nausea in 18 patients but in only two did this necessitate withdrawal of the drug. Bone marrow depression did not occur. Changes in acute-phase reactant proteins suggested that part of the Estracyt was de-esterified in the liver liberating oestrone but the low incidence of vaginal haemorrhage and the recalcification of bony metastases suggested that on the whole Estracyt behaves as an anti-oestrogen as well as an antimitotic.


HLA serum screening based on an heuristic solution of the set cover problem. A computer program initially written by the Milwaukee Blood Bank has been modified to use a new algorithm for the assignment of HLA specificities to antisera. The assignment is based on the reactions of cells with known specificities. Specificities which are present only on cells which do not react are first ruled out. This step is followed by one or more steps in which the 'least reactive' specificities are ruled out. The rationale for the algorithm is discussed and an example is presented.


[Means for motivation].

[Means for motivation]. The possibilities of and devices for motivating good oral hygiene in patients with periodontal disease were discussed briefly. Recognition of the first signs of periodontal disease appears to be particularly important. Even if treatment for periodontal disease is successful, the chance of it developing again is high if the patient is not motivated to maintain good oral hygiene. According to the author, only a small portion of the motivation provided by the dentist can be replaced by audiovisual aids.


Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls. Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O1, O2, Oz, C3 and C4 to combined ear reference (A1--A2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman--Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.


Evaluation of event-related desynchronization (ERD) preceding and following voluntary self-paced movement. A method of accurate storage and on-line preprocessing of an EEG signal, preceding and following a trigger signal, elicited by button pressing, is described. The method was used to study the changes occurring in the power of the rhythmic activity within the alpha band in central areas, during voluntary, self-paced movement in 10 normal humans. A short-lasting decrease or phasic event-related desynchronization (ERD) of alpha power, representing mu activity, was observed in all 10 subjects. During the 2 sec period preceding movement the phasic ERD was mostly bilateral, but larger prior to right than to left thumb movement. At onset and during the first second of execution of movement, the phasic ERD was mostly bilateral but predominant in ipsilateral areas. Preceding or during movement, maximum ERD was observed in most cases in central-vertex regions.


Electroencephalographic quantification by time domain analysis in normal 7--15-year-old children. Automatic EEG analysis was performed on 239 apparently healthy school age children. The children were classed in 3 age groups: (1) average age of 7; (2) average age of 11; (3) average age of 15. A time analysis method, comparable to classical visual analysis, permitted quantification of the records. The mean amplitude, frequency and percentage time for alpha and theta rhythms were determined for each subject for fronto-central and centro-occipital derivations bilaterally. Records were performed during periods of rest with eyes open and eyes closed. During hyperventilation, records were taken with eyes closed. The normal ranges of parameters were determined by calculating their means and standard deviations, for each age group under each recording condition. Delta and beta rhythm values were not calculated, because of their rarity in this apparently normal sample. The precision obtained by automatic analysis could not have been obtained by means of classical visual analysis. The present findings suggest that the statistical analysis of well-defined groups of normal and pathological children could be of significant value.


Topography and intracranial sources of somatosensory evoked potentials in the monkey. I. Early components. Averaged somatosensory evoked potentials (SEP) were recorded in the monkey from arrays of surface electrodes overlying the brain, cervical cord and peripheral nerve; from epidural electrodes over the cerebral convexity; and from movable intracerebral electrodes. The initial cortically generated responses peak at mean latencies of 10 and 12 msec following stimulation of the median nerve at the wrist. Preceding these potentials 5 small positive wavelets were identified in scalp and epidural recordings. The sources of the latter three of these waves have been identified, based in part on the observation of amplitude maxima in depth recordings within cerebrum and brain stem. P7.2 is primarily generated within the thalamocortical radiations, whereas P5.3 and P6.2 reflect bursts of highly synchronized action potentials travelling along the medial lemniscus. Recordings of multiple unit activity within these tracts confirmed the source identifications made on the basis of potential distribution. Continuing activity within the more caudal portions of the somatosensory pathways produces potentials that sum with those generated more rostrally. This circumstance precludes the identification of the intracranial source of a surface recorded potential by demonstrating a concurrent wave form at a single location within the brain. It is necessary to examine the intracranial potential distribution and trace the potential from the surface to its maximum in order to identify its source with confidence. P3.1 and P3.8 were identified only as farfield potentials in intracranial recordings from the pons and more rostral regions. They were ascribed to activity of primary somatosensory neurons ascending in the dorsal columns on the basis of their timing, surface distribution and amplitude vs. interstimulus interval functions. The early SEP components recorded in the monkey closely resembled in configuration and topography those recorded from human subjects, although the latter were longer in latency, reflecting differences in length of the somatosensory pathways in the two species.


The activity of cerebellar neurones during epileptiform activity induced by penicillin in the cerebral cortex of the rat. In urethane anaesthetized rats an epileptiform focus was made in one cerebral cortex with penicillin (25 U). The relationship between epileptiform spikes in the cerebral cortex and the activity of cerebellar cortical and nuclear neurones have been investigated by means of extracellular recording techniques and computation of peri-event histograms and 'CUSUMs' (cumulative sums of differences from the mean). In the cerebellar cortex two distinct patterns of evoked activity were recorded: (a) In units showing little or no spontaneous activity, a brief evoked discharge followed the epileptiform spike. (b) In units showing steady spontaneous activity, a period of evoked inhibition followed the epileptiform spike. These included Purkinje cells and probably inhibitory interneurones. In the intracerebellar nuclei, cells with marked spontaneous activity showed a prolonged period of increased discharge following the epileptiform spike. It is concluded that the output of the intracerebellar nuclei is increased by epileptiform activity in the cerebral cortex. The significance of these results is discussed.


Alpha increase in puerperium.

Alpha increase in puerperium. Significant increases of both alpha peak amplitude and power were found in the EEG after delivery as compared to those observed at the 32nd week of pregnancy. Controls failed to display the same gain in the alpha rhythm. The frequency was unaffected. Beside these quantitative changes no particular EEG pattern occurred. Neither the methodology nor habituation were considered responsible for these increases, which are also independent of the prolactin levels, because they were observable after blockage by bromocryptine, a drug which also fails to modify the EEG. Significant reduction of anxiety, tension and irritability was scored in the Hamiltonian test for depression. It is likely that both aspects depend on a common humoral process. The role of the progesterone drop is discussed.


Computer analysis of the EEG as an aid in the evaluation of dietetic treatment in phenylketonuria. The effect on the EEG of the reintroduction of phenylalanine in the diet of 6 patients with PKU on treatment was studied. Patients received daily loads of 100 or 150 mg L-phenylalanine/kg, equally divided over the meals, and computerized spectral EEG analysis was performed. The following EEG changes were seen: (1) occurrence of activity in the low frequency band (2--5 c/sec), (2) change of frequency of dominant rhythms; (3) change in the degree of synchrony between identical frequencies, occurring in different derivations. EEG changes increased quantitatively parallel to increasing blood phenylalanine and reversed after stopping the phenylalanine administration, suggesting that the EEG abnormalities are a measure for the degree of intoxication caused by phenylalanine or its metabolites. It is suggested that the EEG data may be useful deciding to terminate the diet in PKU.


Sleep induced by low doses of apomorphine in rats. The effect of apomorphine on the EEG of freely moving rats was studied. Apomorphine at the dose of 1 mg/kg caused stereotypy and a marked reduction of total sleep. On the contrary, acute subcutaneous administration of apomorphine at the dose of 100 microgram/kg, or less, markedly increased the amount of total sleep (corresponding mostly to synchronized sleep). Moreover, the infusion of apomorphine (80 microgram/kg/h) for 4 h doubled the duration of slow and REM sleep. The hypnotic effect of apomorphine was prevented by neuroleptics, such as pimozide, benzperidol and L-sulpiride, at doses which, per se, did not modify the EEG of the animals. These results suggest the existence in the CNS of DA receptors mediating sleep.


Isolating low frequency activity EEG spectrum analysis. A method for isolating and removing very slow activity from EEG records prior to spectrum computation is presented. This is accomplished by an autoregressive filter whose frequency transfer characteristic can be easily controlled. Examples of spectra computed for various filter parameter values are shown.


Automatic analysis of interictal epileptic activity related to its morphological aspects. The objectives of this paper are to describe: (i) an algorithm, conventionally called TD (transient discriminator) which allows morphological discrimination among different EEG transients, and (ii) an automated methodology, based upon the proposed algorithm. The completely automated analysis performed by this method can indicate the temporal distribution of a 'family' of spikes, a family being defined by the morphology of a sample spike. Temporal relationships among the detected spikes of the family and other possible epileptic potentials arising from different cerebral zones are automatically defined by an averaging technique. The reliability of the proposed algorithm was investigated comparing the computer detection with the identification performed by 3 electroencephalographers.


Automatic EEG analysis: a segmentation procedure based on the autocorrelation function. A new automatic procedure for EEG segmentation is presented. Based on the autocorrelation function, it is simple to implement and gives good segmentation and clustering results.


Effects of ouabain on insulin release, adenosine 3',5'-monophosphate and guanine 3',5'-monophosphate in pancreatic islets. Isolated pancreatic islets of noninbred ob/ob mice were used to test the hypothesis that adenylate cyclase responds to changes of the transmembrane milieu or electric field in intact beta-cells. In the presence of a phosphodiesterase inhibitor, ouabainstimulated both the release of insulin and the islet content of cAMP. Ouabain had no noticeable effect on the islet content of cGMP. These results support the hypothesis at test. However, because ouabain also had some stimulatory effect on cAMP in islet homogenates, a direct action of ouabain on adenylate cyclase cannot be ruled out.


The effect of cortisol on the adenosine 3',5'-monophosphate response to parathyroid hormone of bone in vitro. Newborn rat calvariae, cultured for 24 h in the presence of cortisol (10(-6) M) have a cAMP response to parathyroid hormone (PTH) about twice as high as calvariae cultured in a control medium. This effect of cortisol is dose related; a maximal effect is evident at 10(-6) M, while none is detectable at 10(-9) M or less. With 10(-6) M estradiol, progesterone, or cholesterol, no effect on cAMP responsiveness is observed. This indicates that the effect observed with cortisol is specific. The effect of cortisol is more pronounced when isobutyl-methylxanthine (10(-4) M) is present during the subsequent incubation with PTH. Preincubation of the tissue with cortisol for 30 min before the addition of PTH has no effect. Similarly, when cortisol is added in conjunction with PTH, no effect is found. In no case did cortisol (10(-6) M) alter the time course of the PTH-induced cAMP effect when compared to the response of fresh calvariae. The results indicate that corticosteroids have an important function in maintaining cAMP responsiveness of bone to PTH in vitro.


Diethylstilbestrol and estradiol binding to serum albumin and pregnancy plasma of rat and human. The equilibrium binding of diethylstilbestrol (DES) and 17 beta-estradiol (E2) to plasma proteins has been characterized. DES exhibits a 10- to 20-fold greater binding affinity index for bovine serum albumin and rat plasma than E2. As expected, E2 gave high values for binding to plasma from pregnant mice or rats, reflecting the presence of alpha-fetoprotein. DES bound to these samples as it did to bovine albumin and rat plasma. These results suggested that DES ineracts weakly with alpha-fetoprotein. This was verified by Scatchard plots of DES and E2 binding to rat and human pregnancy plasma. High affinity, low capacity binding was demonstrated with E2 but not with DES. The significantly lower binding of DES suggests that increased delivery of DES to the fetus may be at least partially responsible for the transplacental toxicity and carcinogenicity of DES.


Production of anti-glucagon sera with a C-terminal fragment of pancreatic glucagon. The C-terminal region-sepcific anti-glucagon sera were raised in rabbits using as immunogen, and conjugate of BSA and a C-terminal fragment of pancreatic glucagon. The hapten was prepared by trypsin digestion of the glucagon, which was proved to be a 1:3 mixture of glucagon (18--29) and (19--29). Six rabbits were immunized by subcutaneous injection of an emulsion of the conjugate with complete Freund's adjuvant and five of the rabbits produced antibodies to the glucagon (GC-1, GC-2, GC-3, GC-5 and GC-6). For comparison, rabbit antisera were also produced against glucagon polymer (GA-10) and syrupy glucagon fibrils (PGA-2). All these antisera as well as the pancreatic glucagon-specific antiserum 30 K were characterized with dog gut-extract (gut-GLI) and glucagon-related peptide fragments in the radioimmunoassay systems. The assay systems utilized 125 I-monosubstituted pancreatic glucagon as tracer and human mono-component glucagon as standard. All sera of the GC-series crossreacted with the dog gut-extract very weakly and antisera GC-5 and GC-6 exhibited the lowest crossreactivities with the extract, which were shown to be as low as that of 30k. Characterization of the antiserum GC-5 with purified glucagon related fragments indicated that the major antigenic determinant located exactly in the C-terminal region of glucagon. The present results clearly showed high efficiency of the use of the glucagon C-terminal fragment as hepatenic immunogen in obtaining the C-terminal region-specific, i.e., pancreatic glucagon-specific antisera.


Effects of antiprostatic agents on 5alpha-dihydrotestosterone binding to rat hypophyseal and hypothalamic cytosol macromolecules. The binding of 5alpha-dihydrotestosterone to the hypophyseal and hypothalamic cytosol macromolecules prepared from castrated male rats was observed. The effects of antiprostatic agents on 5alpha-dihydrotestosterone binding to both hypophyseal and hypothalamic cytosol macromolecules was examined. Cyproterone acetate and chlormadionone acetate showed the significant inhibiting effects on 5alpha-dihydrotestosterone binding to 7-8 S macromolecules of cytosol from both hypophysis and hypothalamus. SCH 13521 and AA 560 did also affect 5alpha-dihydrotestosterone binding to 7-8 S macromolecules of cytosol from both tissues.


270-MHz nuclear-magnetic-resonance study on linear gramicidin A in dimethylsulfoxide. A new interpretation. On the basis of the finding of two sets of coupling constants (8.8 Hz and 6.7 Hz) in the 270-MHz proton magnetic resonance spectra of linear Gramicidin in dimethylsulfoxide and the comparison of its infrared spectrum with those of known conformations of alternating poly(gamma-benzyl-D-glutamate--gamma-benzyl-L-glutamate), it is proposed that the antibiotic has an LD-ribbon structure.


Effect of gammaglobulin injection on circulating immune complexes in various diseases. Immune complexes (ICs) participate in the pathogenesis of various diseases and can be shown in 18% of all hospitalized patients (excluding those with infectious diseases) by means of a sensitive method such as the Raji-cell radioimmune assay. However, before this test can be applied to quantify disease activity in renal, connective tissue and neoplastic diseases, it must be recognized that febrile infections of the upper respiratory tract also induce ICs in 86% of all patients. The immune complexes containing microbial antigens can be reduced or removed by a single injection of human immunoglobulin. This is a simple method to distinguish between the immune complexes of different specifities. The resulting removal of some immune complexes may be the explanation for the claimed therapeutic effect of gammaglobulin injection in normogammaglobulinemic patients.


Gammaglobulin level and soy-protein intake in early infancy. 39  normal full term infants were fed during the first four months of life with three different diets based on the same formula of heated soy-flour fortified with DL-methionine. Each diet supplied 100 kcal/kg/day and gave about 2.5 (11 infants), 4.0 (19 infants) or 5.5 (9 infants) g/kg/day or soy-protein. After four months, growth was slightly lower in infants fed 2.5 g/kg/day of protein but was similar in the other two groups. Haematological parameters were in the normal range in all three groups. Serum gammaglobulin and immunoglobulin levels increased with the increase of dietary protein. The highest levels of gammaglobulin (0.51 +/- 0.16 mg/100 ml) and IgG (463.13 +/- 210.17 mg/100 ml) were observed in infants fed 5.5 g/kg/day of soy-protein and were similar to those previously observed in infants fed 2.5 g/kg/day of cows-milk protein. Morbidity was reduced with the increase of serum gammaglobulin and immunoglobulins.


Free amino acids and ninhydrin-reacting compounds of median and lateral lobes in human benign prostatic hypertrophy. The levels of free amino acids and ninhydrin-reacting substances were determined in median and lateral lobes of human benign prostatic hypertrophy. Student's paired t test showed only a statistical difference for the hypotaurine concentration. This compound is present at higher levels in the lateral lobes. The different hypotheses formulated in the literature about the presence and possible metabolic role of hypotaurine in the male reproductive tract are examined.


The clonal analysis of cytotoxic lymphocytes against 2,4,6-trinitrophenyl (TNP)-modified cells. The frequency and specificity of clones of cytotoxic lymphocytes (CL) produced when (CBA X C57BL)F1 spleen cell populations were cultured with 2,4,6-trinitrophenyl (TNP)-modified syngeneic F1 cells, was examined. The frequency of clones which lysed F1-TNP targets was 1/3.3 X 10(4) spleen cells, and the frequency of clones which lysed the modified parental cells, CBA-TNP and C57BL-TNP was 1/6.7 X 10(4) and 1/2.9 X 10(5) spleen cells, respectively. Using a clonal analysis of the specificity of the CL, it was shown that the majority of the clones of CL which lysed the two modified parental tarets, were specific for one or the other of the targets. Activity against modified allogeneic DBA/2-TNP targets was also detected. The activity against DBA/2-TNP targets was due mainly to clones of CL which were specific for DBA/2-TNP targets. Only a minor part of the activity was due to clones which were cross-reactive for both F1-TNP and DBA/2-TNP target cells.


Differences in the expression of histocompatibility antigens on mouse lymphocytes and tumor cells: immunochemical studies. Immunochemical studies have shown that labeled, detergent-solubilized extracts of SL2 (H-2d) lymphoma cells contain components reactive with several anti-H-2 alloantisera of restricted specificity. Anti-H-2k and anti-H-2ja as well as anti-H-2d sera precipitated labeled polypeptides of a molecular weight similar to that of H-2 heavy chains. In addition, all antisera tested precipitated a component of 70000 daltons molecular weight, which is antigenically related to gp 69/71 of Friend murine leukemia virus. Reactions with antisera directed against haplotypes other than H-2d could be blocked by addition of unlabeled, detergent-solubilized extracts of H-2d lymphocytes, or by H-2 antigens against which the antiserum was directed. Sequential immunoprecipitations initially using antisera against the K, D, or L region gene products to remove individual known H-2d antigens have made possible the identification of some molecules responsible for these reactions. The results show that antisera against haplotypes other than H-2d which react with SL2 cells, cross-react with normal H-2d antigens. Quantitative absortion of these antisera with intact or solubilized cells has shown that lymphocytes and tumor cells differ in their expression of some H-2 determinants. The antibodies bind only weakly to intact H-2d lymphocytes, but strongly to the corresponding detergent-solubilized antigens. These results do not, therefore, support the derepression hypothesis put forward earlier.


Normal immunosuppressive protein inhibition of human and murine lymphoblastoid cell line proliferation. Normal immunosuppressive protein, prepared from human plasma by DEAE-cellulose chromatography, inhibits DNA synthesis in human cell lines of lymphocytes of both T and B origin. It also inhibits [3H]thymidine incorporation in mouse cell lines. Normal immunosuppressive protein was able to inhibit the proliferation of these cells, although they were already transformed and had a high rate of DNA synthesis. On the other hand, it does not inhibit myeloid cells or fibroblasts.