[Macrophage-lymphocyte contact in peripheral blood smears. Brief report]. In the brief report the contact of macrophagues and lymphocytes which up till now was only observed in the bone-marrow, spleen, lymph nodes and in lymphocyte cultures as an expression of a beginning immunoreaction was also demonstrated photographically for the peripheral blood and in vivo.


[Complex genesis of anemia in chronic liver diseases]. 36% of a total of chronic liver patients suffered from anaemia and 50.5% of patients affected with liver cirrhosis. In most cases the anaemias were normochrome and hypochrome or hyperchrome only in some cases. In analyzing possible single factors the reductions of vitamin B12 absorption could be made probable by means of the Schilling test and sometimes a folic acid deficiency in macrocyte anaemia with normal vitamin B12 absorption by determining the folic acid content in the serum and by successes of test treatment 82% of patients with liver cirrhosis showed a latent or manifest haemolysis. However, it was only in 1/3 of the patients with liver cirrhosis that the spleen turned out to be the place of an increased degradation of erythrocytes. In some cases an increased erythrocytoclasia into the liver could be identified. Predominantly, however, an increased degradation of erythrocytes in the total RHS had to be assumed. Twice an ineffective erythropoiesis could be found by ferrokinetic examinations. As a whole ferrokinetic examinations cannot be interpreted easily, because their static and dynamic values of iron transport in the plasma volume of liver patients will undergo considerable changes. Patients with disturbances of haematopoiesis and with haemolysis remaining in the latent stage may develop a manifest anaemia because of the influence of additional factors, such as increase of the plasma volume at lowered haematocrit value or microbleedings. The cause of anaemia cannot be concluded with sufficient probability from the type of anaemia; in a single case all pathogenetic factors will rather have to be analyzed. Therapeutic possibilities for hepatogenous anaemia of complex genesis are discussed.


[Animal experimental studies of hemolysis following extracorporeal blood irradiation]. In experimental studies on animals, extracorporal blood irradiation was performed in 3 sheeps and 1 goat by means of 500 Ci 137 cesium source. The sheep died of the sequelae of narcosis, with anaemia being only moderately marked. In the goat a transit dosis of 466566 rad could be applied before the animal died of the sequelae of haemolytic anaemia.


Some aspects of haematology of a common Indian field rat, Rattus rattus arborious (Linn.) in relation to sex and size. In the present investigation the studies on erythrocyte and leucocyte counts, haemoglobin concentration, haematocrit values, blood biochemistry of protein, glucose and cholesterol, erythrocyte sedimentation rate, pH value, diameter of erythrocyte and clotting time were made in different sex and size (weight group) of an Indian field rat, Rattus rattus arborious. The number of erythrocyte, haemoglobin concentration, haematocrit values were found to be higher in females than the males, while the number of leucocyte was lower in females in comparison to males. In the biochemical estimation the value of protein in females was high while that of the glucose and cholesterol were lower than that of the males. All the above values showed an increasing tendency with the increase in body weight. pH value, diameter of erythrocyte and clotting time were found to be almost constant in rats of different weight groups and different sex.


[State and development of liquid conservation of thrombocytes]. In the present investigation the storage effect of AcD-AG and CPD-AG-stabilizers on thrombocytes was tested. The platelets were stored in platelet-rich plasma (PRP) at 4 degrees C or room temperature for 3 days. The concentrates gained by it were marked with Na251CrO4 and reinjected. The thrombocytokinetic parameters were evaluated. The results show that storage with the help of the mentioned stabilizers can be made to a certain extent only. Platelets stored in AcD-AG stabilizerhad a survival time of 2.7 +/- 1.1 days towards 9.0 +/- 1.0 days of fresh whole blood concentrates. The survival time of CPD-AG thrombocytes stored at 4 degrees C for 3 days amounted to 2.0 +/- 0.5 days. Storage of CPD-AG platelets at room temperature showed favourable results. Their survival time amounted to 6.2 +/- 0.6 days. Measurements of surface activity above the spleen and the liver indicate that degradation of stored platelets is mainly performed in the spleen. Problems of liquids storing in view of the significance of therapeutic thrombocyte substitution for hospitals are referred to.


[Studies of thrombocyte function in CPD blood]. The CPD stabilizer according to Gibson with an addition of 1.25 mMol adeninesulfate and 2.50 mMol guanosine is used in blood storage for better preserving 2.3-bis-phosphoglycerate of erythrocytes. Here platelet-rich CPD plasma was investigated before and during a 3 days storage at 4 degrees C or room temperature with regard to preserving the global thrombocyte function. The latter consists in the ability to seal blood vessels and is tested by means of pressure registration in combined thrombocyte-aggregation-adhesion (DKTA method) as an ability to close the pores of a sieve by adding 10(-5) mM/l of ADP. At room temperature this thrombocyte function is approximately 0 following 3 days of storage in CPD plasma excess without shaking. When stored at 4 degrees C it is preserved to a slight degree. Loss of thrombocyte function will depend on pH, thus being particularly evident at room temperature.


[Postoperative changes of the thrombocyte number and function]. In 30 patients the number of thrombocytes was determined 24-48 hours after surgical interventions and compared with the normal range. The function of thrombocytes was determined by the method of pressure registration in combined thrombocyte-aggregation-adhesion (DKTA method). In spite of the occurring thrombocytosis there is a tendency towards a decrease of response in most cases and thus of haemostatic function of blood platelets. The influence of the thrombocyte function caused by fibrinolytic split products or by a change of prostaglandine metabolism is discussed.


[An inhibitor in the Willebrand-Jürgens syndrome and its effect on the factor VIII molecule properties]. In a patient with a clinically serious Willebrand-Jürgen's syndrome an inhibitor appeared at the age of  1 1/2 years, which, contrary to inhibitors in haemophilia A, was directed against all properties of factor VIII molecule. In a quantitative test the height of the inhibitor level to factor VIIIag was determined. Administrations of plasma concentrate resulted in a titre increase which could not be suppressed even by an immunosuppressive therapy with cyclophosphamide. After a long break in the substitution a severe bleeding could be successfully treated and the substitution effect for factor VIIIc, factor VIIIag and Ristocetin co-factor could be identified for several days.


Incidence of ABO(H) blood group variants among the Bulgarian population. The result of a screening of ABO (Hh) variants after investigating the blood group of 106,980 persons are presented. The Ax variant is registered most frequently among the Bulgarian population. As a whole the frequencies of ABO blood group variants Ax, Ael, A3, Aend and Am among the Bulgarian population are similar to that established by other authors among the French population and nearly twice as high as among the population of Bombay. The group of H-deficient phenotypes includes AA1Xh, AHm, OHm variants. Their frequency is significantly lower when compared with the frequency of AHm and OHm variants among the population of Thailand. Variants A1 and Aint with unusually high H-content are classified as A1H, A1Hint, Aint H and integrated as a category of H-excess phenotypes. Their incidence among the Bulgarian population is significantly lower than that registered among Maharastrian, South African Bantu and Indian.


Cytological analyses of 14p+ variant by means of N-banding and combinations of silver staining and chromosome bandings. An inherited human karyological variant (14p+) has been studied with a number of cytochemical techniques. The short arm of this variant chromosome 14 is nearly as long as the long arm, giving the chromosome a submetacentric to metacentric appearance. In conventionally Giemsa-stained preparations, maximum of three secondary constrictions can be observed the marker arm. The secondary constrictions are silver-positive in Ag-NOR preparations. However, the entire arm stains deeply in N-banded preparations. The 14p+ arm is also Q-negative, C-negative, G-negative, and R-positive with an almost homogeneous texture. The difference between N-banding and silver staining is interpreted as the result of gene activities of the ribosomal cistrons.


[Hydroxyethyl starch (HAS 450/0.7) in human plasma and liver. Course of concentration and histological changes]. In 12 patients 1,000 ml hydroxyethyl starch (Mw 450,000, degree of substitution 0.7) was infused intravenously. A liver biopsy was performed in 10 patients undergoing abdominal surgery 30 minutes to 28 days after the infusion. The liver tissue was investigated by light and electron microscopy. The plasma level of hydroxyethyl starch decreased to 4.8% of the initial concentration 28 days after the infusion (Anthron method). Single intracellular vacuoles were shown by electron microscopy 30 minutes after the end of infusion in Kupffer's cells only. However, 6 to 28 days after infusion intracellular vacuoles were demonstrated in parenchymal liver cells, Kupffer's cells, interstitial histiocytes and to a lesser degree in the cells of the small bile ducts. The pathogenic importance of the portracted elimination from the plasma and the liver storage is unknown.


[Mathematical decription of the human intravascular elimination of HAS after repeated infusions]. Serum concentrations of high molecular weight-hydroxyethyl starch (HMW-HES, Mw 450,000 d, Mn 71,000 d, Mw/Mn = 6.3, MS = 0.7) were determined in normovolemic subjects dosed with three consecutive daily 500 ml infusions, to mathematically calculate the influence of the two-variable (Mw and MS) HES drug design system, on elimination of this material from the intravascular space under controlled conditions. Following the initial 500 ml (6% solution) infusion, the intravascular clearance up to 24-hours post-injection, was well predicted by the exponential equation: y = 3.94 + 3.34e-0.15x. On days two and three, the clearances up to 24-hours post-injection, were described by the equations: y = 6.32 + 3.75e-0.15x and y = 9.39 + 5.41e-0.15x, respectively. From these mathematical models, it appears that up to 24-hours post-injection on each of the three infusion days, HMW-HES is cleared from the bloodstream in a similar manner. HMW-HES clearance from the blood on day three, however, exhibited a slightly faster rate of decline, as seen by the larger coefficient attributed to the exponential component. The serum concentration of HMW-HES, 480 hours (2.9 weeks) following the third and final infusion, was 2.3 +/- 0.3 (SD) mg ml-1. Thus, in the 480-hour interval following the third and final injection, the serum concentration of HMW-HES measured at 10 minutes after injection 3, had been reduced by 85%. This decline in serum concentration following the infusion of HMW-HES, appears to be greater than previously reported by other investigators.


Human beta-endorphin. Immunoreactivity of synthetic analogs with various chain lengths. Immunoreactivity of synthetic human beta-endorphin analogs with various chain lengths has been examined using a specific radioimmunoassay. It was found that beta-endorphin-(1--21) and analogs of shortened chain exhibit no immunoreactivity, whereas beta-endorphin-(1--15) possesses significant in vitro opiate activity. It appears that immunoreactivity of beta-endorphin resides in the COOH-terminal segment of residues (22--31). The data also show the lack of correlation between opiate and immunological activities of beta-endorphin.


Axoplasmic and nonaxoplasmic transport along the optic pathway of albino rabbits; a theoretical pattern of distribution. Distribution of nonaxoplasmically transported material along the optic pathway of the rabbit was studied after blockage of the axonal flow by vinblastine, and a clear pattern of distribution of the axoplasmic transport was deduced by subtraction from the pattern seen in nontreated animals. Vascular participation in the nonaxoplasmic transport was certified by autoradiographic studies. The theoretical pattern of distribution of axoplasmic transport in the optic system under ideal conditions was calculated from an idealized model system. From the comparison of theoretical and experimental patterns, partial obstruction of the axonal flow likely occurs at the optic foramen and chiasma.


Immunoelectrophoretic identification and purification of herpes simplex virus antigens released from infected cells in tissue culture. Proteins released from herpes simplex virus type 1 (HSV-1)-and type 2 (HSV-2)-infected HEp-2 cells have been characterized by the crossed immunoelectrophoretic technique. Both HSV type-common and type-specific antigens were found in the tissue culture medium 24 h after infection. Antigen Ag-6, an HSV-1-specific antigen, was found in high concentration in the medium as compared to other HSV antigens released from HSV-1-infected cells. The HSV-2-specific antigens, Ag-4 and Ag-1, were released in molecular modifications with altered electrophoretic mobility as compared to their cellular counterparts. Purification of HSV antigens was performed by ion-exchange chromatography, and an HSV type-common antigen, Ag-11, and an HSV-2-specific antigen, Ag-4A, were isolated.


Isolation of Dhori virus from Hyalomma marginatum ticks in Portugal. An agent pathogenic for mice was isolated from Hyalomma m. marginatum ticks collected from cattle in southern Portugal. Serologically, the agent was indistinguishable from Dhori virus, an antigenically ungrouped virus isolated in India.


Cellular immune response to human cytomegalovirus. I. Lymphocyte transformation studies in the rabbit. The lymphocyte transformation assay was used to monitor the cellular immune response of rabbits sensitized to cytomegalovirus (CMV). Peripheral blood lymphocytes from animals inoculated with purified virus were specifically stimulated by crude or twice-banded CMV. Blood cells from rabbits immunized to herpes simplex virus type 1 (HSV-1) responded to that antigen but not to CMV. Viable or heated CMV preparations stimulated unwashed blood cells as efficiently as washed cells. Furthermore, preincubation of stimulating antigen with anti-CMV serum did not prevent lymphocyte activation. Lymphoid cells readily stimulated by virus antigen were not stimulated by cells transformed by CMV or HSV-1.


Effect of azacytidine in SV40-infected BSC-1 cells. 5-Azacytidine (5-AzaCR) reduced significantly the levels of ribosomal 28S and 18S RNAs in the cytoplasm of uninfected and simian virus 40 (SV40)-infected BSC-1 cells. The percent inhibition of ribosomal RNAs was correlated to both the dose of AzaCR and the time of exposure. In SV40-infected cultures treated with 200 microgram/ml AzaCR, a portion of the total cytoplasmic radioactivity was observed to sediment as 19S and 16S by sucrose gradient analysis. The 19S and 16S peaks represented in part the viral-specific RNA species. This result was due to the drastic reduction (70--75%) of ribosomal RNAs in the cytoplasm of infected cultures.


Correlation of individual skeletal muscle fibres from "semithin" sections stained with p-phenylene-diamine and histochemical sections incubated for myofibrillar ATP-ase. Muscle fibres in transverse "semithin" sections of osmium-fixed and plastic embedded muscle tissue stained with p-phenylene-diamine has been classified into three types (M, INT and H) and correlated to the same fibres in neighboring sequential preincubated myofibrillar ATP-ase sections. A close correlation, but no equality was found between the fibre types classified according to the ATP-ase and the p-phenylene-diamine methods. On the average, the content of mitochondria and fat droplets was highest in the ATP-ase classified type I fibres (dominated by M fibres), and higher in the endurance trained than in the untrained subjects.


Cytological and histochemical studies on the mechanism of the selective silver staining of nucleolus organizer regions (NORs). A new silver staining method is presented (Ag-II staining) providing a rapid and reproducible way to selective silver staining of nucleolus organizer regions (NORs). In comparison with other techniques, such as the Ag-AS method and the Ag-I method, factors influencing silver stainability are discussed. Histochemical studies on the nature of the NOR-specific silver precipitate were performed either by employing various pretreatments or by inhibiting the participation ("blocking") of the various proteins or protein compounds in the staining reaction. The results would seem to indicate that the interactions of silver-ions with the carboxyl groups of acidic proteins which are involved in the rRNA-transcription process are mainly responsible for the selective silver staining of NORs.


Two-dimensional electrophoresis of plasma proteins without denaturing agents. A technique of two-dimensional polyacrylamide gel electrophoresis for the separation of plasma proteins is described. Human plasma proteins were separated by isoelectric focusing followed by electrophoresis in a 4 to 21% linear gradient gel slab. No denaturing agent was used throughout the procedure, so that the analysis of native proteins is possible. Two-dimensional patterns obtained from normal human plasma samples were recorded as "staining density maps," which are similar to contour line maps, and more than 230 protein spots were counted reproducibly on each "staining density map." This technique permits the simultaneous estimation of pI's and approximate molecular weights of native proteins on the slab gel. Applications of this technique to an IgA myeloma plasma sample and a porcine serum sample are described.


The one admissible alternative to bloody pictures. This paper presents guidelines for preparing non-inflammatory visuals for use in the courtroom and emphasizes the need for attestable accuracy in artwork submitted as evidence.


Audiovisuals and non-print learning resources in a health sciences library. The MD undergraduate program at McMaster University, based entirely on self-instruction, requires the provision of all kinds of learning resources. How these are assembled and made available is described. Emphasis is placed on the practical library problems of cataloging, shelving, maintenance, and distribution of audiovisual materials including pathology specimens and 'problem boxes' as well as the more usual films, videotapes and slide/tape sets. Evaluation is discussed briefly.


Serological analysis of species specificity in the high mobility group chromosomal proteins. The non-histone chromosomal protein of the high mobility group (HMG-1) present in mouse liver was purified to homogeneity. Antibodies against this protein as well as pure HMG-1 derived from calf thymus and HMG-E purified from duck erythrocytes were elicited in rabbits. The interaction between the antibodies and the immunogens was measured by passive hemoagglutination and by quantitative microcomplement fixation. Quantitative microcomplement fixation assays revealed that the immunological distance between HMG-1 from calf thymus and HMG-1 from mouse liver and duck erythrocytes was 15. This corresponds to 3% sequence differences. It was estimated that amino acid substitution occurred at about seven positions in the polypeptide chain. Thus, HMG-1 proteins display remarkable evolutionary conservation in their primary sequence, similar to that displayed by histones H4 and H3, suggesting that their biological function is dependent on stringent structural requirements. HMG-E protein is significantly different from both HMG-1 and HMG-2 derived from calf thymus. As such, it is a protein unique to avian erythrocytes.


Immunoglobulin carbohydrate requirement for formation of an IgG-IgG complex. In addition to their Fc oligosaccharides, some immunoglobulin molecules have oligosaccharides linked to variable segments of H or L chains. These Fab oligosaccharides are potential determinants of antibody specificity. This possibility was considered in a study of the IgG antiglobulin from a patient with IgG-IgG complexes. F(ab')2 fragments of the antiglobulin retained the ability to form complexes with normal IgG as detected by analytical ultracentrifugation. Removal of F(ab')2 sialic acids by neuraminidase abolished complex formation. Recombination experiments further localized antiglobulin activity to the L chains. Antiglobulin activity of the recombinant molecules was shown by analytical ultracentrifugation and by column chromatography with molecules containing 125I-labeled L chains. L chains from the subject's IgG were enriched in sialic acids. Thus, a sialic acid-containing oligosaccharide on the L chain of this antiglobulin is required for its binding action.


[Serum alpha 1-fetoprotein and extrahepatic digestive cancers. Apropos of 4 further cases]. The authors report four new cases of primary digestive carcinoma other than hepatoma with alpha 1 feto-protein in the serum (greater than 200 ng/ml). Two were carcinoma of the colon without liver metastases. The remaining two were also colonic carcinoma but with liver metastases. In the first cases, alpha 1 feto-protein disappear after surgical procedure. In spite of the rareness of primary digestive carcinoma with presence of alpha 1 feto-protein noted until now, these cases require reconsideration of the idea that AFP is specific for hepatoma.


Influenza viruses in birds: rapid identification by counterimmunoelectrophoresis. Counterimmunoelectrophoresis with an antiserum raised in rabbits against the M protein of the avian N virus proved to be particularly useful for large-scale identification of influenza A virus isolates. Of a total of 231 hemagglutinating agents isolated from 1,656 rectal swabs collected from shore and open-country birds, 158 could be identified as influenza A viruses by counterimmunoelectrophoresis, and 75 were serologically related to Newcastle disease virus by hemagglutination inhibition with an antiserum to Newcastle disease virus. Two isolates contained a mixture of influenza A virus and Newcastle disease virus; although the Newcastle disease virus virus particles outnumbered the influenza A virus particles in a ratio of 1,000:1, as seen by electron microscopy, the latter could be readily detected by counterimmunoelectrophoresis. This type of assay appears to be of potential use for epidemiological surveillance of influenza virus isolated from humans and animals. It combines specificity, sensitivity, and simplicity.


Thermonuclease seroinhibition test for distinguishing Staphylococcus aureus from other coagulase-positive staphylococci. Since coagulase-positive staphylococci from animals are heterogeneous, another test is necessary to distinguish Staphylococcus aureus from them. Staphylococcal thermonucleases appear to be heterogeneous; antisera raised against S. aureus isolated from humans inhibit thermonuclease activity as demonstrated by the metachromatic well-agar diffusion method. The serological specificity of the thermonuclease elaborated by S. aureus of human origin was demonstrated using three antisera and 407 strains of staphylococci from diverse human and animal sources.


The effects of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation. The effect of the antigen-induced, immunoglobulin (Ig)E-dependent release of mediators from human lung tissue was analyzed for coincident changes in the tissue levels of cyclic nucleotides. Simultaneously with the appearance of mediators, lung cyclic guanosine 3',5'-monophosphate (GMP) increased from 0.9+/-0.2 to 12.63+/-4.5 pmol/mg protein and cyclic AMP increased threefold from the initial levels of 5.1+/-1.4 pmol/mg protein. The release of histamine and prostaglandin (PG)F(2alpha), as well as the associated increases in cyclic nucleotides, peaked within 10 min of anaphylaxis. Antagonists of histamine's H-1 receptor prevented anaphylaxis-associated increases in cyclic GMP, whereas H-2 antagonists prevented the cyclic AMP response. Neither of these antagonists influenced the pattern or quantity of histamine or slow-reacting substance of anaphylaxis release. Prevention of PGF(2alpha) synthesis with acetylsalicylic acid failed to influence histamine or slow-reacting substance of anaphylaxis release or the concomitant increases in cyclic nucleotides. Histamine, added exogenously, produced a prompt increase in the cyclic AMP and cyclic GMP levels of human lung. As was seen after anaphylaxis, H-1 anatagonists prevented the cyclic GMP response to histamine, whereas H-2 antagonists prevented the cyclic AMP response.H-1 antagonists prevented 50% of the PGF(2alpha) synthesis accompanying anaphylaxis; H-2 antagonists had no effect. Exogenous histamine induced PGF(2alpha) synthesis; this synthesis was prevented by H-1 but not H-2 antagonists, and was reproduced by 2-methylhistamine (H-1 agonist) but not by dimaprit (H-2 agonist). Arachidonic acid generation of PGF(2alpha) was not influenced by antihistamines. Therefore, histamine interactions with human lung result in the synthesis of both PGF(2alpha) and cyclic GMP in response to H-1 stimulation, and of cyclic AMP through H-2 stimulation.


Tissue distribution of human alpha1-microglobulin. Human alpha(1)-microglobulin was isolated from the urine of patients with tubular proteinuria, and its molecular weight was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at 33,000 daltons. The carbohydrate content was 21.7%. Anti-alpha(1)-microglobulin serum was prepared and observed to react monospecifically in gel diffusion to purified alpha(1)-microglobulin, as well as to normal human serum and urine. Sera from the domestic chicken, mouse, rat, rabbit, dog, calf, cow, goat, sheep, and horse, however, did not react to anti-alpha(1)-microglobulin serum in immunodiffusion. The lymphocyte culture supernate was found to contain alpha(1)-microglobulin. Both thymus-derived(T)- and bone marrow-derived(B)-lymphocyte culture media clearly displayed a specific precipitin line against anti-alpha(1)-microglobulin serum when tested with the Ouchterlony immunodiffusion method. The tissue distribution of alpha(1)-microglobulin was studied under immunofluorescence, and a positive staining was recognized on the lymphocyte surface. Identical staining patterns were noted on both T and B lymphocytes, though B lymphocytes took a more intense stain. It would thus seem quite possible that lymphocytes are the primary source of alpha(1)-microglobulin and that this is filtered through the glomerular basement membrane and partly reabsorbed by the renal tubules. This, then, would suggest the possibility that alpha(1)-microglobulin shares some immunological role in vivo with lymphocytes and(or) is one of the membrane proteins of lymphocytes.


Comparison of counter-current immunoelectrophoresis, latex agglutination, and radioimmunoassay in detection of soluble capsular polysaccharide antigens of Haemophilus influenzae type b and Neisseria meningitidis of groups A or C. Three serological methods, radioimmunoassay (RIA), latex agglutination (LX), and counter-current immunoelectrophoresis (CIEP), for sensitivity in the detection of the capsular polysaccharide antigen of Haemophilus influenzae type b or Neisseria meningitidis groups A and C were compared. RIA was consistently the most sensitive, LX the next, and CIEP the least sensitive. When RIA and LX were used to test cerebrospinal fluid (CSF) samples of patients with meningitis, they gave very similar results. In only two out of 47 samples, in which RIA detected one of the three antigens, was the amount of the specific polysaccharide too low to be detected by LX. By the serological methods we could detect evidence of specific pathogen in 49 samples, including nine from patients who had received intensive antimicrobial treatment for up to three days and from whom specimens yielded no bacteria on culture. The reactions were specific in all cases except two out of 47 tests positive by LX. From these two CSF samples N. meningitidis group B could be cultivated, whereas the LX was recorded positive for N. meningitidis of group A in one case, and of group C in the other. The nonspecific reactions could be due to antibodies to bacterial components other than the capsular polysaccharide.


Meningococcal infection and proteolytic control. Cascade enzyme inhibitors (C1-esterase inhibitor, C3b inactivator, antithrombin III) and other major proteolytic enzyme inhibitors (alpha 1 trypsin inhibitor, alpha 1 chymotrypsin inhibitor, inter-alpha-trypsin inhibitor, alpha 2 macroglobulin) as well as C3 and alpha 1 acid glycoprotein, have been examined in the sera of Nigerian patients suffering from meningococcal infection of varied severity. Patients with meningococcaemia had lower serum concentrations of important inhibitors than did patients with localised meningitic infection. Within the coccaemic group, those who died had the lowest values, notably of antithrombin III and alpha 2 macroglobulin (and also of C3). The clinical end-result of meningococcal infection may be related to the degree of disequilibrium of the linked system of proteolytic control induced by the meningococcal endotoxin.


The escape of cyclic AMP from human diploid fibroblasts: general properties. A variety of human diploid fibroblasts released large amounts of cAMP to the medium in a time-dependent fashion concomitant with stimulation of the cells by agonists of the adenylate cyclase. In WI-38 cells increased medium cAMP levels were detectable as quickly as increased cellular levels. Escape was not secondary to serum deprivation nor cell injury. It occurred in defined media, and was pH and temperature dependent. Elevated rates of escape were maintained for up to 24 hours after stimulation. A variety of PDE inhibitors reduced the rate of escape. A rough proportionality existed between the potencies of the compounds as potentiators of PGE1 increased cellular cAMP levels on the one hand and as inhibitors of escape on the other. In the case of IBMX, the inhibition of escape was transient, the most pronounced effect being during the first 5 minutes of incubation. In addition, a variety of compounds without significant acute effects on cellular cAMP levels inhibited escape.


Effects of phosphodiesterase inhibitors, imidazole and phosphate on cyclic CMP phosphodiesterase are different from those on cyclic AMP and cyclic GMP phosphodiesterases. The effects of various agents on the newly identified cyclic CMP phosphodiesterase (C-PDE) in crude extracts of a number of rat tissues and on the enzyme partially purified from the rat liver were examined. Papaverine and 1-methyl-3-isobutylxanthine were without effects on C-PDE at concentrations that inhibited up to 90% of cyclic AMP phosphodiesterase (A-PDE) and cyclic GMP phosphodiesterase (G-PDE) activities. When assayed using 1 micron substrates, theophylline inhibited C-PDE to a lesser extent than A-PDE and G-PDE. 2'-Deoxy cyclic AMP (specific A-PDE inhibitor) and 2'-deoxy cyclic GMP (specific G-PDE inhibitor) were relatively poor and non-specific inhibitors for C-PDE. Imidazole, while augmenting the high Km A-PDE and G-PDE from the liver but not from the heart, was without effect on the liver C-PDE but stimulated the heart C-PDE. Potassium phosphate was more specific in inhibiting C-PDE than A-PDE and G-PDE. The present findings suggest that C-PDE represents a potential site of specific pharmacological regulations, and that C-PDE may be a separate enzyme distinguishable from the purine cyclic nucleotide class of phosphodiesterases.


A possible role for cyclic GMP in mediating the effect of luteinizing hormone releasing hormone on gonadotropin release in dispersed pituitary cells of the female rat. In continuing studies on cyclic nucleotide involvement in the regulation of gonadotropin release, we have measured the cyclic nucleotide content and rate of LH and FSH release during stimulation by LHRH of dispersed overnight cultured cells from the pituitaries of adult female rats. The minimal effective concentration of LHRH was 0.1 nM and half maximal stimulation of gonadotropin release was observed in the presence of 1.0 nM LHRH. Significant release of both LH and FSH was detectable after only 10 min in the presence of 5 nM LHRH. The presence of fetal calf serum (FCS) in the overnight culture medium increased basal cGMP levels significantly, whereas horse serum (HS) had no effect, therefore all experiments were conducted on cells cultured in the presence of HS. Treatment of the cultured cells with the phosphodiesterase inhibitors theophylline (TH) or isobutyl-methyl-xanthine (MIX) revealed a preferential stimulatory effect of TH on basal cAMP levels and of MIX on cGMP levels. Throughout these experiments, LHRH had no effect on cAMP levels. In the presence of MIX, concentrations of the releasing hormone as low as 1 nM induced a significant rise in the level of cGMP whereas in its absence, cGMP levels appeared to be unchanged by LHRH. The increase was detectable after 10 min of incubation. MIX alone slightly increased LH and FSH release and significantly potentiated the response of the cells to increasing doses of LHRH up to, but not beyond, 10 nM. The data support the possibility that cGMP may be involved in the mechanism of action of LHRH.


The audio-visual revolution: do we really need it? In the United Kingdom, The audio-visual revolution has steadily gained converts in the nursing profession. Nurse tutor courses now contain information on the techniques of educational technology and schools of nursing increasingly own (or wish to own) many of the sophisticated electronic aids to teaching that abound. This is taking place at a time of hitherto inexperienced crisis and change. Funds have been or are being made available to buy audio-visual equipment. But its purchase and use relies on satisfying personal whim, prejudice or educational fashion, not on considerations of educational efficiency. In the rush of enthusiasm, the overwhelmed teacher (everywhere; the phenomenon is not confined to nursing) forgets to ask the searching, critical questions: 'Why should we use this aid?','How effective is it?','And, at what?'. Influential writers in this profession have repeatedly called for a more responsible attitude towards published research work of other fields. In an attempt to discover what is known about the answers to this group of questions, an eclectic look at media research is taken and the widespread dissatisfaction existing amongst international educational technologists is noted. The paper isolates out of the literature several causative factors responsible for the present state of affairs. Findings from the field of educational television are cited as representative of an aid which has had a considerable amount of time and research directed at it. The concluding part of the paper shows the decisions to be taken in using or not using educational media as being more complicated than might at first appear.


Development of allergy in children. I. Association with virus infections. Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process.


Anaphylactic reactions to muscle relaxants under general anesthesia. Eleven patients who suffered a reaction to the administration of muscle relaxants during induction of general anesthesia were explored using skin tests, leukocyte histamine release, lymphocyte transformation test, and the Prausnitz-Küstner test (P-K). Fifteen normal subjects served as controls. Patients who suffered a reaction showed considerable cutaneous hypersensitivity to muscle relaxants. Leukocyte histamine release was positive in three cases and the P-K test was positive in one case. These findings suggest possible specific serum IgE antibodies to muscle relaxants. However, reliable discrimination between immunological and idiosyncratic pharmacological mechanism is difficult to obtain.


Haemagglutination-inhibiting (HI) antibodies against four prototype strains of influenza A virus in different age groups. Sera of 197 apparently well persons were tested for residual haemagglutination-inhibiting antibodies against live Hong Kong/68, A/FM/47 and A/PR/34 strains. Sera of 62 well persons, regularly exposed to contacts with swine, were tested against an inactivated A/New Jersey/76 antigen. Those born some time before and during a certain influenza era showed a significantly greater proportion of homologous residual titres against the subtype prevailing in that influenza era, than those born after the termination of the same era. In each of the seven age groups tested both the percentage of positives and the geometric mean titres were usually highest against the Hong Kong strain (representing the most recent era); the next highest were those against the FM1 strain and the lowest were those against the PR8 strain (representing the most distant of these three influenza eras). The serological involvement of donors exposed to regular contacts with swine was relatively stronger against the New Jersey antigen than the response of other serum donors shown against the other three, more recent, prototypes of influenza virus A. The oldest age groups showed significantly lower antibody response against the PR8, FM1 and Hong Kong strains (but not against the New Jersey antigen) than the next one or two of the younger age groups.


Experimental infection with Ancylostoma caninum larvae in mice. V. Serum protein pattern during infection with various doses. Serum protein patterns of Swiss albino mice during Ancylostoma caninum infection with varying dose levels were studied electrophoretically. There was a significant decrease in albumin associated with a corresponding increase in beta globulin in all the infected groups. Gamma globulin decreased significantly in all groups except the one infected with a challenge dose of 4000 larvae. Maximum changes occurred on day 31, 15, 9, 15 and 6 when mice were infected with 250, 500, 1000, 2000 and 4000 larvae, respectively. There was a significant negative correlation between albumin and the infective doses and a positive correlation between beta globulin and the infective doses and among the changes caused by different infective doses.


Coupling of acid labile Salmonella specific oligosaccharides to macromolecular carriers. A coupling method for covalent attachment of acid labile oligosaccharides isolated from S. typhimurium O-polysaccharide to macromolecular carriers is described. Arylamine groups were introduced into the terminal reducing end of oligosaccharides by reacting them with 2-(4-aminophenyl)-ethylamine. After subsequent conversion to the corresponding saccharide-phenylisothiocyanato derivatives saccharides were covalently linked to free epsilon-lysylamine groups of different carrier proteins. The resulting conjugates were highly immunogenic and elicited in rabbits both anti-harptenic and anti-carrier protein specific antibodies. Some of the advantages of this coupling procedure are: (i) it can be used with oligosaccharides containing highly acid or alkali labile structures and/or glycosidic linkages, (ii) it produces conjugates with high degrees of substitution at low saccharide/protein molar input ratios, (iii) it does not grossly affect the immunogenic specificities of the carrier protein, and (iv) it is suitable for preparation of highly substituted affinity columns, e.g., coupling to a polyacrylamide matrix.


Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP antibodies bearing 460 idiotype. An idiotype of the dinitrophenyl-binding myeloma protein MOPC 460 was expressed on a small but significant proportion of anti-TNP antibodies which appeared after in vivo or in vitro immunization of BALB/c mice with three T-independent TNP antigens. In vitro experiments show that the depletion of T cells before culture increased significantly the number of plaques secreting anti-TNP antibodies bearing MOPC 460 idiotype (460Id). T cells from BALB/c mice, but not from C.B20 mice, exhibit this suppressor activity. Plate-binding experiments indicate that the suppressive action of the T-lymphocyte population depends on a cell which can bind to MOPC 460 myeloma protein. The possible role of these normally occurring, idiotype-specific T cells on expression of 460Id in the anti-TNP antibody response of BALB/c mice is discussed.


Cell-surface antigens associated with recombinant mink cell focus-inducing murine leukemia viruses. Distinct type-specific antigens were detected on cells infected with cloned mink cell focus-inducing (MCF) murine leukemia viruses by means of cell surface immunofluorescence absorption assays with rabbit antisera raised against naturally-occurring AKR MCF viruses. The MCF type-specific antibodies were present in high titer and not absorbable by cells infected with ecotropic, xenotropic, or wild mouse amphotropic murine leukemia viruses, or combinations of ecotropic and xenotropic viruses. Three MCF subtype-specific reactions were identified. One subspecificity (operationally designated MCFA-1) defined antigenic determinant(s) distributed among MCF viruses in general. Another (MCFA-2) specified determinant(s) induced by all naturally occurring MCF isolates not of Friend or Moloney origin. A third subspecificity (MCFA-3) was induced by some MCF isolates, and not by others; the presence of this antigen did not correlate with the source of any presently known biological property of the viruses. In addition, type-specific antigenic determinants of ecotropic and xenotropic murine leukemia viruses were expressed on MCF virus-infected cells. The serological profile of MCF viruses thus supports the contention that they are env gene recombinants between ecotropic and xenotropic murine leukemia  viruses. However, new, distinct MCF-specific determinants are also generated, and these could be useful markers in studying MCF viruses.


The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells. A mouse model of cell-mediated immunity (CMI) and tolerance to protein antigens horse gamma globulin (HoGG) and cytochrome (Cyt C) was investigated. A reliable CMI response as measured in vivo by ear swelling or by an in vitro T-cell proliferation assay could be induced by one of two methods: (a) sensitization by antigen-complete Freund's adjuvant in the base of the tail, or (b) sensitization by s.c. injection of antigen coupled to syngeneic lymphoid cells. The in vivo response exhibited characteristic CMI parameters, delayed kinetics, and transfer by viable T cells. Prior i.v. injection of HoGG-modified lymphoid cells (HoGG-LC) or Cyt C-LC before sensitization resulted in a rapidly induced, dose-dependent, antigen-specific suppression of both in vivo and in vitro manifestations of the CMI response. In addition, tolerance in this system was transferrable by an antigen-specific suppressor T cell (Ts). The Ts were found to diminish the in vivo ear swelling reaction in recipient animals, but had no effect on the in vitro T-cell proliferative response of the recipients. In contrast to the rapid development of tolerance in donor mice (phenotypic tolerance), transferrable Ts were first demonstrable 4--7 d posttolerization. This latter result indicates that at least two mechanisms of tolerance are operative in this system: the rapid induction of clone inhibition of reactive T cells and the slower induction of Ts. These results indicate again that the mode of antigen presentation is crucial in determining the immunologic outcome. In these experiments, cell-bound proteins injected subcutaneously led to delayed hypersensitivity while the same antigens injected intravenously led to tolerance. These results are considered in the light of recent experiments which show that T cells recognize antigens on cells in association with major histocompatibility complex products. We believe the following pathways are involved. In sensitization via subcutaneous injection of HoGG-LC, antigen reaches the lymph node via lymphatic pathways which lead to immunogenic macrophage-associated presentation and the activation of delayed hypersensitivity T cells (TDH). In tolerization via intravenous injection of HoGG-LC, antigen (a) reaches the lymph node via the blood, probably directly meeting the TDH, preventing its subsequent activation by immunogenic  HoGG (clone inhibition) and (b) reaches the spleen, also via the blood, activating suppressor T cells.


Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. The antibody response of BALB/c mice to trinitrophenyl (TNP)-levan or TNP-Nocardia water-soluble mitogen (NWSM) includes a small but significant fraction of antibodies which share idiotypes (Id) with the dinitrophenyl (DNP)- and TNP-binding myeloma protein MOPC-460. Active immunization of BALB/c mice with MOPC-460 or passive administration of anti-460-Id antibodies suppresses the 460-Id+ component of the anti-TNP response. By contrast, active immunization of BALB/c with anti-460-Id antibodies or passive administration of BALB/c anti-[anti-460-Id] antibodies leads to an enhanced 460-Id+ component in the anti-TNP antibodies produced in response to TNP-levan or TNP-NWSM. This enhanced 460-Id+ response appears to be a result of the elimination of suppressor T lymphocytes specific for the 460-Id as T lymphocytes from such mice are unable to suppress the in vitro 460-Id+ response to TNP-NWSM whereas normal T cells are suppressive. These results indicate that suppressor cells specific for 460-Id normally regulate the activation of precursors of cells capable of secreting 460-Id+ anti-TNP antibodies.


Idiotypic determinants on T-cell subpopulations. Killer T cells with specificity for major histocompatibility antigens have been shown in mice and rats to display idiotypic receptors allowing the lysis of such cells at the effector phase by anti-idiotypic antibodies and complement. A comparison was made between idiotypes displayed by Lyt-1-2+3+ and Lyt-1+2-3- T blasts, generated in the same mixed leucocyte culture (MLC), across an entire H-2 locus barrier. This was done by absorption of anti-idiotypic antibodies with respective T blasts, followed by estimation of the ability of the absorbed antiserum to inhibit MLC or killer T-cell function. Further, the capacity of Lyt-purified, MLC-generated T blasts to provoke specific unresponsiveness via anti-idiotypic immunity in syngeneic recipients was analyzed. Taken together, the results demonstrate that Lyt-1+2-3- T blasts responsible for the major part of MLC proliferation have distincly different idiotypes from those on the Lyt 1-2+3+ killer T cells. That the idiotypes on the killer T-cell presursors can serve as triggering sites for induction of effector T-cell function was then suggested by experiments with Lyt-1-2+3+-purified, normal T cells as precursor cells in vitro. The fact that autoanti-idiotypic antibodies may circumvent the need for helper Lyt-1+2-3- T cells in the generation of allospecific killer T cells indicates that the former cells may normally function partly via such anti-idiotypic reactions.


Distinct functions of monoclonal IgG antibody depend on antigen-site specificities. Intraveneous hyperimmunization of selectivity bred rabbits with streptococcal group A-variant vaccines elicits antibody responses of restricted heterogeneity at high antibody levels. All antisera contain two functionally distinct antibody populations, which can be isolated in single-band purity upon analytical isoelectric focusing. Typical examples of these two kinds of single-band antibodies were investigated in great detail for several parameters by a variety of methods. 85--99% of the streptococcal group A-variant polysaccharide (Av-CHO)-specific antibody in the antisera does not precipitate the isolated 5,000 daltons poly-L-rhamnose antigen, neither agglutinates nor lyses in the presence of complement Av-CHO-coated sheep erythrocytes (SRBC), binds the radio-labeled Av-CHO with an association constant in the ragne of 10(5)--10(6) M-1, and is of terminal specificity (nonreducing end) for the linear Av-CHO. In contrast, the minor fraction of Av-CHO-specific antibody (1--15%) does precipitate the linear Av-CHO, both agglutinates and lyses Av-CHO-coated SRBC in the presence of complement, has an affinity range of 10(8)--10(9) M-1, and is of internal specificity for the Av-CHO. The antigenic determinants of the Av-CHO for the antibodies are nonoverlapping, only one Fab of the low affinity antibody can be bound whereas four Fab of the high affinity antibody are accommodated. Hence, the determinant specificity explains the functional differences observed, for there is no indication of subclass differences. A mechanistic model of the A-variant carbohydrate presentation on the vaccine appears to account best for the unbalanced levels of low and high affinity antibody.


On the serological specificity of the Escherichia coli O8 and O9 antigens. The O8 and O9-specific lipopolysaccharides of Escherichia coli lost their serological activity during liberation of the polysaccharide moieties (alpha-mannans) by mild acid hydrolysis, as tested by passive haemagglutination and haemagglutination inhibition. The serological activities and specificities were restored by substitution of the polysaccharides with 1 to 2 stearoyl groups per polysaccharide chain. The mannans obtained by biosynthesis in vitro were serologically active only when bound to the membrane-associated hydrophobic carrier molecule. Liberation of the polysaccharides from the carrier by treatment with aqueous phenol resulted in loss of the serological activity. The O8- and O9-specific mannans of E. coli are thus serologically active when they are part of an amphiphilic molecule and not as free polysaccharides.


Effect of interferon on murine leukaemia virus infection. IV. Formation of non-infectious virus in chronically infected cells. Interferon (150 units/ml) was used to treat SC-1 and AKR-2B cells which were chronically infected with murine leukaemia virus (MuLV). This led to a 100-fold decrease in the amount of infectious virus released into the medium and a 10-fold decrease in the number of virus particles measured by the virion-associated reverse transcriptase assay. However, there was little change in the amount of cell-associated infectious virus, though nearly twice as many cell-associated virions were counted in electron micrographs. With both types of cells, interferon blocked MuLV replication at the post-budding stage, but it did not change the morphology of the particles produced or their content of virion 70S RNA. Infectious virus assembled on the cell membranes of interferon-treated cells was less stable at 37 degrees C than that grown in the absence of interferon. Release of infectious virus from interferon-treated cells was not inhibited by actinomycin D or cycloheximide, though both agents inhibited virus production in controls. These results show that interferon inhibits MuLV replication through effects on virion assembly; these lead both to the formation of non-infectious particles and of fewer virions. Kinetic analysis further shows that interferon affects MuLV assembly rapidly and induction of an antiviral protein may not be required.


Demonstration of an unusual DNA polymerase activity associated with the L cell virion. Purified preparations of L cell virions (LCV) were found to possess an associated DNA polymerase activity. This enzyme was active with poly(C).oligo(dG) and poly(Cm).oligo(dG) and was able to transcribe poly(A).oligo(dT). Endogenous DNA synthesis was also demonstrable in disrupted virion preparations but this reaction was enhanced, rather than inhibited, by RNase pre-treatment. The effects of variations in a number of the assay parameters on these activities were examined in an attempt to determine the class of DNA polymerase involved.


Association of hepatitis B e-antigen (HBeAg) determinants with the core of Dane particles. Immunoprecipitates obtained by reacting Dane particle cores with human antibodies to hepatitis B core antigen (HBcAg) were chromatographed on columns of Sepharose 4B CL using 3 M-NaSCN as eluant. An antigen having the size and immunological specificity of monomeric e-antigen (HBeAg) was separated from HBcAg by this method. Antisera from animals immunized with HBcAg or HBeAg reacted not only with the antigen used for immunization but also with HBeAg and HBcAg, respectively. This indicates that HBeAg determinants are associated with the core of Dane particles.


Tectopontine pathway in the cat: laminar distribution of cells of origin and visual properties of target cells in dorsolateral pontine nucleus. 1. The superior colliculus projects to the dorsolateral nucleus of the pons. Retrograde transport of horseradish peroxidase (HRP) revealed that cells in the superior colliculus, which send their axons to the pons, lie in both superficial (III) and deep (IV--VII) layers. Superficial cells outnumbered deep cells. The inferior colliculus also projects heavily to the dorsolateral pontine nucleus. 2. Dorsolateral pontine visual cells were activated only by visual stimulation. Cells responsive to somatic or auditory stimulation were also found in the dorsolateral nucleus, and they too responded to only one sense modality. 3. Of the dorsolateral pontine visual cells, 69% were directionally selective. 4. Dorsolateral pontine visual cells were responsive to moving targets over a wide range of stimulus velocities. Velocities between 25 and 100 degrees/s were the most effective. No cells responded to a stationary stimulus. 5. Single-spot targets were the most effective stimuli. Stimulus size was a more important parameter than stimulus configuration. Many cells had inhibitory regions outside of their excitatory fields. 6. The excitatory receptive fields of dorsolateral pontine cells were very large (median, 1,100 deg2). 7. Nearly all receptive fields were centered in the contralateral visual hemifield, and 91% of the dorsolateral visual cells were activated from either eye. 8. We conclude that the visual cells in the dorsolateral nucleus have receptive-field properties that are similar to those of cells in the superior colliculus. The preference of dorsolateral cells for single-spot targets contrasts strongly with the multiple-spot preference of medial pontine cells, which receive their input from visual cortex.


Nocodazole action on tubulin assembly, axonal ultrastructure and fast axoplasmic transport. The action of a synthetic antitubulin agent, nocodazole, on tubulin self-assembly, preformed microtubules, fast axoplasmic transport and axonal ultrastructure was studied. Nocodazole completely blocks the self-assembly of tubulin containing or lacking associated proteins. This inhibition is readily reversible. At similar concentrations, nocodazole also depolymerizes preformed microtubules in vitro. Fast axoplasmic transport in cat vagus nerve is disrupted by bathing the nerve fivers in a medium containing 10 micrometer nocodazole for periods of 2.5 hr or longer. A 4-hr exposure results in extensive inhibition. The nocodazole action on fast axoplasmic transport appears to be reversible but with a high degree of variability. After 2.5 hr of exposure to 10 micrometers nocodazole, there is a slight decrease in axonal microtubules and an increase in 10 nm neurofilaments. A 4 hr exposure results in a marked reduction in microtubules. These results suggest that nocodazole has a mode of action similar to other antimicrotubule agents.


Comparison of the temperature-dependence of rapid axonal transport and microtubules in nerves of the rabbit and bullfrog. 1. The average velocity of transport of dopamine-beta-hydroxylase, an enzyme confined to unmyelinated adrenergic nerves, was measured in rabbit and bullfrog sciatic nerves or branches incubated in vitro at various temperatures. In parallel experiments, the number and density of microtubules were measured in cross-sections of randomly selected unmyelinated axons from another set of nerves incubated under the same conditions. 2. Average transport velocity was exponentially related to temperature over a wide range, but it fell abruptly towards zero at temperatures below 13 degrees C in the case of rabbit nerves and 10 degrees C in the case of frog nerves. 3. The number of microtubules per unmyelinated axon had declined considerably before the transport of dopamine-beta-hydroxylase was impaired. At 13 degrees C, axons in rabbit nerves lost 30% of their microtubules. Axons in bullfrog nerves were, if anything, more sensitive to cold, losing 35% of their microtubules at 15 degrees C and 65% of them at 10 degrees C. 4. Since the temperature-dependence of the axonal transport of dopamine-beta-hydroxylase is probably typical of rapid axonal transport in general, it was concluded that transport in unmyelinated axons can continue unaffected when a substantial fraction of the microtubular population has been lost. 5. Although these results could imply that microtubules are not essential for transport, they are equally compatible with the view that these organelles determine the capacity of the transport system and are normally present in excess.


Drug-induced modifications of the immune response. 1. Substituted 1-phenylisoquinolines. A series of 1-phenylisoquinolines and related compounds was prepared and tested for potential antiallergic activity. Several compounds of this series inhibited the antigen-induced wheal formation in rat passive cutaneous anaphylaxis (PCA) assay, a commonly used test for antiallergic activity. Many of these compounds also inhibited the antigen-induced histamine release from passively sensitized guinea pig lung slices. Furthermore, almost all of these derivatives inhibited the cyclic nucleotide phosphodiesterase, suggesting this as one of several possible mechanisms of action.


Microscopical image analysis: problems and approaches. This article reviews some of the problems which have been encountered in the application of automatic image analysis to problems in biology. Some of the questions involved in the actual formulation of such a problem for this approach are considered as well as the difficulties in the analysis due to lack of specific constrast in the image and to its complexity. Various practical methods which have been successful in overcoming these problems are outlined, and the question of the desirability of an opto-manual or semi-automatic system as opposed to a fully automatic version is considered.


Differential and staining of cobalt-and nickel-filled neurones using rubeanic acid. A staining procedure is described with differentiates with distinct colours, cobalt and nickel ions introduced into neurones. Densely coloured precipitates are produced with these ions when rubeanic acid, a spot-test reagent, is added. Formation of the coloured complexes takes place within a few minutes, and may be followed under the dissecting microscope. This technique permits observation of the relative positions, within ganglia, of somata related to two emergent nerves following multiple axonal-backfilling. It also appears to be of value in tracing neurone branching after the intracellular injection of ions.


Lead and uranium stain artefacts in electron microscopy: a technique for minimizing their occurrence. A new technique is presented which significantly reduced the occurrence of artefacts by eliminating the air-stain interface when staining thin sections of biological material. It is designed for simultaneous treatment of large numbers of samples. The experiment described deals mainly with the specific staining problems encountered when using grids coated with Formvar.


Thiacetazone toxicity in the treatment of tuberculosis patients in Nigeria. In a series of 1,212 tuberculosis patients treated on a regime of streptomycin/isoniazid/thiacetazone (S/INH/thiacetazone) over a period of 10 years in Nigeria there were 171 cases considered to have toxic reactions to thiacetazone (14%). 134 of these (11%) were sufficient to require a change of treatment. Giddiness and rashes were the commonest effects, the former occurring mainly in association with streptomycin, and considered to be largely due to potentiation of streptomycin toxicity by thiacetazone. The advantages of the S/INH/thiacetazone regime in Nigeria are considered to outweigh the disadvantages, so long as necessary precautions are taken to keep the effects of toxicity to a minimum.


In vitro synthesis of infectious transforming DNA by the avian sarcoma virus reverse transcriptase. Infectious DNA molecules, capable of transforming chicken embryo fibroblasts, can be synthesized by the Rous sarcoma virus-associated reverse transcriptase in vitro. The optimal enzymatic conditions employed for infectious DNA synthesis also facilitate maximum synthesis of genome length DNA. Analysis of the DNA product synthesized by detergent-disrupted Rous sarcoma virus under these conditions indicates that DNA complementary to viral RNA (minus-strand DNA) is genome length in size, whereas DNA complementary to genome length minus-strand DNA (plus-strand DNA) appears as subgenomic-length molecules ranging between 300 and 3,500 nucleotides in length. These features of the DNA product synthesized by the Rous sarcoma virus reverse transcriptase in vitro are similar to those identified in the cytoplasm of cells shortly after infection and lend credence to studies of the mechanism of reverse transcription in vitro and their significance to proviral DNA synthesis in vivo.


Isolation of a nucleocapsid polypeptide of herpes simplex virus types 1 and 2 possessing immunologically type-specific and cross-reactive determinants. A polypeptide (p40) of approximately 40,000 molecular weight was isolated from herpes simplex virus type 1 and 2 nucleocapsids by gel filtration and ion exchange chromatography. This protein appears to be the same as protein 22a described previously (Gibson and Roizman, J. Virol. 10:1044--1052, 1972). Competition immunoassays were developed by using purified p40 and antisera prepared in guinea pigs. The assays indicated that the p40's from herpes simplex virus types 1 and 2 possess both type-specific and cross-reactive antigenic determinants. Antibodies to the p40 cross-reactive determinant reacted with antigens in simian herpes virus SA8-infected cells, but not with antigens induced by pseudorabies virus. Preliminary results indicated that a radioimmunoprecipitation test can be used to detect type-specific herpes simplex virus p40 antibodies in human sera.


Reverse transcriptase from avian myeloblastosis virus. From lots of 20 to 30 g of avian myeloblastosis virus RNA-dependent DNA polymerase was obtained in preparations of purity greater than 95% by using a two-step column chromatographic procedure employing DEAE (DE 52) and carboxymethylcellulose (CM 52.). Yields of RNA-dependent DNA polymerase varied from approximately 20,000 to 35,000 U/g of virus. Specific activity of the enzyme was about 35,000 to 60,000 U/mg of protein. Free of detectable RNase activity, the product exhibited a molecular weight of about 160,000, an isoelectric point of 6.5, and approximately 2 mol of fatty acid per mol of enzyme.


Serological definition of the lentivirus group of retroviruses. The major polypeptides of visna viruses and other lentiviruses have been isolated and shown to be closely related if not identical in radioimmunoassays. By this criterion the lentiviruses form a distinct group of retroviruses unrelated to spuma viruses, mammalian and avian retroviruses that cause tumors, and unclassified retroviruses of cattle and horses. Two sera obtained from goats immunized with Mason-Pfizer monkey virus or squirrel monkey virus reacted with visna p30. Additional data suggest that this reaction represents infection of goats with a lentivirus or a new retrovirus closely related to the lentiviruses.


Simian virus 40 T- and U-antigens: immunological characterization and localization in different nuclear subfractions of simian virus 40-transformed cells. Simian virus 40 (SV40)-transformed cells and cells infected by the nondefective adenovirus 2(Ad2)-SV40 hybrid viruses Ad2+ND1 and Ad2+ND2 were analyzed for SV40 T- and U-antigens, respectively, using individual hamster SV40 tumor sera or serum for which U-antibodies were removd by absorption. These studies showed that (i) T- and U-antigens can be defined by separate classes of antigenic determinants and (ii) the U-antigenic determinants in SV40-transformed cells and in hybrid virus-infected cells are similar. The apparent discrepancy in the subcellular location of U-antigen in SV40-transformed cells (nuclear location) and in hybrid virus-infected cells (perinuclear location) as determined by immunofluorescence staining of methanol/acetone-fixed cells could be resolved by treating hybrid virus-infected cells with a hypotonic KCl solution before fixation. Upon this treatment hybrid virus-infected cells also showed nuclear U-antigen staining. The possibility of an association of T- and U-antigens with different nuclear subfractions in SV40-transformed cells was investigated. Detergent-cleaned nuclei of SV40-transformed cells were fractionated into nuclear matrices and a DNase-treated, high-salt nuclear extract. Analysis of the nuclear matrices by immunofluorescence microscopy with T+U+ and T+U- hamster SV40 tumor serum revealed that U-antigen remained associated with the nuclear matrices, whereas T-antigen could not be detected in this nuclear subfraction. T-antigen, however, could be immunoprecipitated from nuclear extracts of the SV40-transformed cells.


Antigenic determinants specific to the envelope glycoprotein of exogenous avian tumor viruses. Antibody in the sera of 15B X 7(2) chickens was measured for reactivity to determinants of the envelope glycoprotein of endogenous and exogenous avian tumor viruses. The pattern of reactivity of animals infected with exogenous sarcoma virus served to operationally define a class of determinants present on the envelope glycoprotein of exogenous viruses and absent from that of the endogenous virus Rous-associated virus-0.


Rosettes from Friend leukemia virus envelope: preparation and physicochemical and partial biological characterization. Rosette-shaped particles mainly containing gp85 were isolated from Friend leukemia virus. The isolation procedure comprised lysis of the virion by Triton X-100, affinity chromatography on concanavalin A-Sepharose, and velocity sedimentation. The rosettes displayed a mean sedimentation constant of 32S and a buoyant density of 1.21 g/ml. They contained 1% Triton X-100 and about 2% phospholipid. gp85 was identified by polyacrylamide electrophoresis, staining with periodic acid-Schiff reagent, and immunoprecipitation with antisera against Friend leukemia virus gp71 and p15(E). Rosettes completely blocked the cytotoxicity of the gp71 antiserum. The ability to hemagglutinate was inhibited by antibodies to gp71.


Analysis of specific proteins in prostatic fluid for detecting prostatic malignancy. In an attempt to identify an indicator(s) specifically associated with prostatic cancer prostatic fluid was collected by rectal massage from patients with prostatic cancer, prostatitis, benign prostatic hyperplasia and from those without recognized prostatic lesions in order to measure various immunoproteins. The proteins examined were IgG, IgA, IgM, complements C3 and C4, and transferrin. Prostatic fluid samples were subjected first to immunoelectrophoresis. Distinct differences in C3, C4 and transferrin concentrations were noted between patients with prostatic cancer and other patients. These proteins were stained heavily in the electrophoresis gels of fluid from cancer patients but were either missing or lightly stained in all other groups. These qualitative determinations were replaced subsequently by a quantitative measurement using the radial immunodiffusion technique. Results of the latter study confirmed the aforementioned observations and indicated that the levels of C3, C4 and transferrin in the prostatic fluid of cancer patients were elevated significantly when compared to all other patient groups. These observations indicate that the measurement of complements C3 and C4, and transferrin in the prostatic fluid may assist in the identification of patients with a high risk of prostatic cancer.


Immunological studies on CS-1170, a new semisynthetic cephamycin antibiotic. The antigencity of CS-1170, a newly developed semi-synthetic cephamycin, and it's cross-reactivity with beta-lactam antibiotics were studied. The antigencity was confirmed by the following tests: 1)the passive hemagglutination test with anti-CS-1170 antisera of guinea pigs immunized with CS-1170 plus Freund complete adjuvant, 2)lymphocyte proliferation response in vitro stimulated with this drug in the guinea pigs, 3) the PCA test using mice immunized with CS-1170-protein conjugates. The antibody to CS-1170 appears to be directed to the acyl side chain because cyanomethylthioacetylglycine, an univalent acyl side chain of the CS-1170, can significantly cross-react with the antibody. A methoxy group on the C-7 alpha-position of the antibiotic plays no important part for the antigenic specificity of the molecule. The cross-reactivity of CS-1170 with cefazolin, cephalothin, benzylpenicillin and ampicillin was only to a minimal extent in the passive hemagglutination test. The cross-reactivity of CS-1170 and the related antibiotics was not observed among them in the PCA system with IgE anti-CS-1170. These findings support a conclusion that CS-1170 is one of beta-lactam antibiotic with an immunologically minimal cross-reactivity to the related antibiotics.


A method for the identification and detection of alpha-fetoprotein. This paper describes the detection and identification of alpha-fetoprotein (AFP) using a simple, economical, time saving and sensitive method. Twelve serum samples can be evaluated at the same time. Antigens are precipitated within 45--60 minutes on a cellulose acetate membrane by counter-immunoelectrophoresis. This method was used with great success for the testing of 14,240 serum samples.


Dissociation of alpha-macrofetoprotein and alpha-fetoprotein production during experimental injury. The concentrations of two major fetal serum proteins of the rat, alpha-macrofetoprotein (AMF) and alpha-fetoprotein (AFP) are measured following administration of croton oil, carbon tetrachloride, galactosamine or ethionine, and after partial hepatectomy. Greatly elevated serum concentrations of AMF are found after croton oil injection, following oral administration of CCl4, and after partial hepatectomy, but not after ethionine or galactosamine. Elevations of AFP occur after administration of hepatotoxic agents during the stage of restitutive proliferation and after exposure to the hepatocarcinogen ethionine, but not after croton oil. Therefore, elevations of AMF and AFP are clearly dissociated under certain conditions. In situations such as partial hepatectomy, after which elevations in both AMF and AFP occur, AMF appears before AFP. Therefore, the production of AMF and AFP appear to be under completely independent regulation in the adult.


Inhibition by protease inhibitors of binding of adrenal and sex steroid hormones. Binding of steroid hormones is inhibited by protease inhibitors and substrates. The protease inhibitors phenylmethyl sulphonylfluoride, tosyl-lysine chloromethyl ketone, and tosylamide-phenylethyl-chloromethyl ketone and the protease substrates tosyl arginine methyl ester and tryptophan methyl ester eliminate specific binding of aldosterone, dexamethasone, dihydrotestosterone, estrogen, and progesterone to their respective receptors. These protease inhibitors and substrates also inhibit binding of progesterone to the 20,000 molecular weight mero-receptor formed from the progesterone receptor in chick oviduct. The binding of estradiol to rat alpha-fetoprotein is inhibited by the protease inhibitors and substrates but not by tryptophan or tryptophan amide, indicating the importance of an ester structure in the inhibition of steroid binding. Our results suggest that all steroid hormone receptors have a site with both common structural features and a role in the regulation of steroid hormone binding.


Gut-hormone profile in coeliac disease.

Gut-hormone profile in coeliac disease. Patients with coeliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.


Intravenous aminoacids and intravenous hyperalimentation as protein-sparing therapy after major surgery. A controlled clinical trial. A solution of aminoacids without a calorie source was infused postoperatively in ten patients undergoing proctocolectomy or rectal excision and the results were compared with those in ten matched controls and ten patients who received intravenous hyperalimentation. Aminoacid infusion prevented the nitrogen and potassium loss that occurred in the untreated group but no clinical advantage could be seen. Nitrogen and potassium loss was also prevented in the patients treated with intravenous hyperalimentation but these patients had significantly fewer postoperative complications than either the controls or those given aminoacid infusion. It is suggested that aminoacid infusion is of very little benefit after major surgery. On the other hand the skilled administration of intravenous hyperalimentation to patients after major surgery can be of real benefit.


Bedside rebreathing technique for measuring carbon-monoxide uptake by the lung. The uptake of carbon monoxide can be measured at the bedside by a rebreathing technique using an anaesthetic bag. A good correlation was found between this method and the standard single-breath measurement in normal subjects and in patients with interstitial lung disease. The rebreathing technique was as sensitive as the single-breath method in detecting lung haemorrhage in a patient with Goodpasture's syndrome, and was able to monitor its resolution as quickly.


Effect of sera from cystic fibrosis homozygotes and heterozygotes on glucose metabolism in Vero cells. The effect on intracellular production of carbon dioxide from glucose of sera from cystic fibrosis (C.F.) homozygotes and heterozygotes was determined in an established cell line (Vero cell) by a double-blind assay. CO2 production was reduced when cells were incubated with an ammonium-sulphate-precipitated fraction of sera from C.F. homozygotes and heterozygotes but not by a similar fraction from sera of healthy donors.


Circadian variation of blood-pressure.

Circadian variation of blood-pressure. Continuous intra-arterial blood-pressure and electrocardiogram recordings were obtained in twenty hypertensive and five normotensive ambulant patients. Blood-pressure was highest mid-morning and then fell progressively throughout the remainder of the day. Blood-pressure was lowest at 3 A.M. and began to rise again during the early hours of the morning before waking. These findings may have important consequences with regard to the therapeutic management of hypertension.


Epstein-Barr virus infections in the X-linked recessive lymphoproliferative syndrome. Prospective studies demonstrated variable phenotypic expression of the X-linked recessive lymphoproliferative syndrome (X.L.R.L.S.) in three brothers: (1) hypogammaglobulinaemia and subclinical Epstein-Barr-virus (E.B.V.) infection with antibody response to E.B.V.; (2) E.B.V. infection with defective immune response to E.B.V., fatal infectious mononucleosis (I.M.), and immunoblastic lymphoma; and (3) histiocytic lymphoma. Hypogammaglobulinaemia and measles pneumonitis had preceded infection with E.B.V. The diverse phenotypic expressions probably resulted from the varied immune response to E.B.V. Recombination of X chromosomes was documented by Xg-blood-group studies in a survivor. E.B.V. can induce fatal I.M. and malignant lymphoma in X.L.R.L.S., but an immune response to E.B.V. can be protective.


Treatment of renovascular hypertension with percutaneous transluminal dilatation of a renal-artery stenosis. Percutaneous transluminal dilatation of a left-sided renal-artery stenosis was done in a 61-year-old patient with hypertension. Shortly after dilatation blood-pressure fell to normal and renal plasma flow increased. Dilatation might be an alternative to renal vascular surgery in severe renal hypertension.


Aetiology of antimicrobial-agent-associated colitis. Clostridium difficile was isolated from the faeces of a patient with clindamycin-associated pseudomembranous colitis (P.M.C.). The presence of a preformed faecal toxin and the toxigenicity of both the faecal isolate of C. difficile and a reference strain of C. difficile were demonstrated by tissue-culture assay. The toxin of both strains of C. difficile and that in the patient's faeces were neutralised by heating and by incubation with antitoxin to C. sordellii, but not by incubation with antitoxin to C. histolyticum, C. oedematiens (novyi), C. welchii (C. perfringens) or C. septicum. These data implicate the toxin of C. difficile as a major, and perhaps the sole, cause of antimicrobial-agent-associated P.M.C. of man and suggest that the neutralisation of the faecal toxin of P.M.C. by C. sordellii antitoxin, as described by other investigators, may be a non-specific phenomenon.


Provision of medicines in a developing country. In many developing countries the money spent on drugs could often be used more effectively to prevent disease. A large proportion of the drug budget of one developing country is spent on expensive proprietary preparations for use mainly in the larger hospitals, draining resources from health care in rural areas. A major factor in determining the country's expenditure on drugs is the promotional activities of pharmaceutical companies; the number of drug company representatives in the country is proportionately five times that in Britain. Many drugs are promoted for diseases for which they are not indicated and in which their use may be hazardous, and information on side-effects and contraindications is inadequate. Information supplied by drug firms to health workers in different countries must be standardised and the purchase and use of drugs in Third-World countries made more appropriate to their needs.


Is it ethical to conduct volunteer studies within the pharmaceutical industry? There is a case for appropriately selected drug studies within the pharmaceutical industry in which employee volunteers are used. Provided the organisation and conduct of such studies are approached in an ethical manner, with attention to safe-guarding the volunteer and recognising the limitations, this work can be done expeditiously, cheaply, and safely. Some details are given of the arrangements made for volunteer studies within a company.


1, 25-dihydroxycholecalciferol in the pathogenesis of the hypercalcaemia of sarcoidosis. A 36-year-old man with sarcoidosis had four episodes of hypercalcaemia in seven years, all of them during the summer months. Measurement over three years showed that hypercalcaemia was associated with small seasonal increases in serum-25-hydroxycholecalciferol within the normal range. These changes could be mimicked by the administration of 3000 units of vitamin D3 daily. Serum 1, 25-dihydroxycholecalciferol concentrations ranged between 26--62 pg/ml when serum calcium was normal, but were strikingly high, up to 137 pg/ml, when the patient was hypercalcaemic. These studies show for the first time that hypercalcaemia in sarcoidosis is associated with abnormally high circulating concentrations of 1, 25-dihydroxycholecalciferol, probably as a result of overproduction of this, the hormonal form of vitamin D.


Adrenal suppression after short-term corticosteroid therapy. Adrenal function was evaluated in fourteen cancer patients receiving chemotherapy which included short-term high-dose courses of prednisone. 90 min corticotropin stimulation tests were performed before therapy and 1, 2, 4, and 7 days after steroids were discontinued. Responses were evaluated by standard criteria of adrenal function and by measurement of the intergrated cortisol response to corticotropin over 90 min. Thirteen of fourteen patients had suppressed adrenal function for at least 24 h. Although in most patients adrenal function had returned to normal between day 2 and 4, in five patients it remained suppressed for 7 days or more. Suppression did not correlate with either steroid dose or duration of therapy. Four of five patients receiving only 5 days' therapy showed evidence of adrenal suppression. Although overt clinical adrenal insufficiency after steroid administration is rare, these results indicate that adrenal function is suppressed more regularly after short-term high-dose steroid therapy than has been appreciated.


Screening for pancreatic disease: A comparison of grey-scale ultrasonography and isotope scanning. The efficiency of ultrasound in the diagnosis of pancreatic disease was compared prospectively with that of selenomethionine isotope scanning in 46 patients presenting with abdominal pain or weight-loss or with jaundice. Of 14 patients who later proved to have pancreatic carcinoma, all had an abnormal isotope scan and 13 had an abnormal ultrasound scan. Of 10 patients with chronic pancreatitis, all had an abnormal isotope scan and 9 had an abnormal ultrasound scan. The small advantage of selenomethionine was, however, offset by a higher false-positive rate: of 22 patients who proved not to have pancreatic disease, 13 had abnormal isotope scans compared with only 3 with ultrasound. Review of earlier experience with the two techniques yielded similar results: in pancreatic carcinoma and chronic pancreatitis, isotope scanning gave slightly fewer false-negative results than ultrasound but many more false-positives. Because of its lower false-positive rate, because it avoids ionising radiation, and because it can usually distinguish carcinoma from pancreatitis, ultrasound is the procedure of choice for initial investigation of patients with suspected pancreatic disease.


Effect of gel fibre on gastric emptying and absorption of glucose and paracetamol. To determine the part played by altered gastric emptying in the modification of glucose absorption by gel fibres, glucose tolerance tests were done in seven healthy volunteers with and without the addition of pectin to the ingested glucose solution and after pharmacological inhibition of gastric emptying with propantheline. Compared with the controls, pectin significantly reduced blood-glucose. Propantheline had a similar but more pronounced effect. Pectin and guar gum did not substantially alter glucose tolerance in a patient who had had total gastrectomy. In a further investigation, gastric emptying and paracetamol absorption were studied simultaneously in fourteen subjects. In eight of these the study was repeated after addition of guar gum and pectin to the ingested paracetamol. Both gastric emptying and paracetamol absorption were slower after gel fibre but the total absorption of the drug, reflected in urinary recovery, was not significantly reduced. The results suggest that the effects of guar gum and pectin on glucose tolerance and paracetamol absorption could be due simply to alteration in the rate of gastric emptying.


Raised total thyroxine and free thyroxine index but normal free thyroxine. A serum abnormality due to inherited increased affinity of iodothyronines for serum binding protein. 2 people from different families had high levels of serum-thyroxine (T4) and a high free T4 (FT4) index but a normal serum triiodothyronine (T3) and serum-reverse-T3 (rT3). The abnormal serum thyroid hormone profile appeared to be inherited in an autosomal dominant manner. Serum-FT4 in affected relatives was normal. The increases in serum-T4 and FT4 index are explained on the basis of an observed increase in affinity of T4 for thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin. The FT4 index did not reflect the true concentration of circulating free T4 in these cases. Thyroid function in the propositi was normal and the results of T4, T3, and rT3 kinetic studies accorded with increased binding of T4 by serum proteins and normal binding of the other iodo-thyronines. This "euthyroid high total T4, normal T3 syndrome" should be kept in mind during diagnostic evaluation of thyroid function.


Visual disability and home lighting.

Visual disability and home lighting. 13 men and 43 women (average age 76) attending a low-vision clinic with visual acuity of 6/18 (Snellen) or less had acuity measurements made under standard (measured) hospital conditions, under normal home conditions, and under home conditions with augmented lighting. Median levels of ambient lighting in the home were 1/10 of those in hospital, while levels for reading were 1/7. Augmented lighting at home (a 60 watt bulb in a small adjustable lamp) improved visual acuity in 82% of subjects, restoring all but 11% to the levels achieved in hospital or above. Improvement was unrelated to disease. General levels of lighting are often so poor in the homes of elderly people that the number of people functioning as "blind" is twice what it need be. Simple improvements to lighting would reduce the prevalence of "visual disability" (less than 6/18 Snellen) from 520/100,000 home-based adults to about 300.


Splanchnic production of discoidal plasma high-density lipoprotein in man. The morphology of human plasma high-density lipoprotein (H.D.L.) subfractions in arterial and hepatic venous blood from seven human subjects was investigated by electron microscopy. The H.D.L.3 subclass from both sources and the H.D.L.2 subclass from arterial blood were composed of spherical particles, identical with normal human peripheral venous H.D.L. In contrast, H.D.L.2 isolated from hepatic venous blood was composed of a mixture of spherical and discoidal particles. The latter tended to form rouleaux, and had a diameter similar to that of nascent H.D.L. particles obtained from the peripheral venous blood of a patient with lecithin: cholesterol acyltransferase deficiency. This supports the view that nascent H.D.L. is secreted into the splanchnic bed in man.


Epidemic of chancroid in Greenland 1977-78. In Greenland there has been a rapid increase in the incidence of gonorrhoea and syphilis during past decades. In 1977 there was an epidemic of chancroid along the west coast of Greenland, with 975 cases reported from some 32,500 adults. The number of reported cases increased until October, 1977, and subsequently decreased. 186 patients were studied. Many of these had previously had gonorrhoea and syphilis. Male patients were both Eskimoan and Danish but female patients were solely Eskimoan. The sex ratio (M/F) was 1.6/1. The incubation period was 4 days in men and 13 days in women. Symptom-free female carriers did not seem to be an important reservoir of infection. 15% of the patients were admitted to hospital with buboes or extensive lesions. The clinical course was uncomplicated in most cases. Ulcers healed within a week of treatment with sulphonamide. Chancroid can be expected to disappear in Greenland within a short time.


Test of a novel method for analysis of the efficacy of antihypertensive drugs. Diastolic blood-pressure data from 42 published studies, representing 23 anti-hypertensive drug regimens and 971 patients, were used to test the hypothesis that there is a linear relation between pretreatment diastolic pressure (P.T.D.P.) and the drug-induced fall in pressure (deltaD.P.), such that the "ideal-response line" relating these variables has a slope=1.0 and intercepts the P.T.D.P. axis at 90 mm Hg. Most of the regimens failed to show ideal behaviour; slopes of the regression lines were usually less than 1.0, and the intercepts were generally not at 90 mm Hg. Low coefficients of determination (r2) and broad 95% confidence intervals for the slopes and intercepts of the regression lines were common. Only 2 of the 23 regimens examined yielded r2 greater than 0.7, whereas 8 of the regimens exhibited r2 less than 0.25. These findings suggest a large interpatient variation in response to a given regimen. The data reported here show that what is thought to be an ideal-response relation for antihypertensive drug regimens is not observed in practice. However, the manner of presenting the data in order to test the hypothesis provides a useful method for assessing the effectiveness and variability of patient-responses to treatment.


Amniotic-fluid acetylcholinesterase as a possible diagnostic test for neural-tube defects in early pregnancy. Raised levels (greater than or equal to 4.5 munits/ml) of acetylcholinesterase (AChE) activity in amniotic fluid at 14--23 weeks of pregnancy were significantly associated with open fetal neural-tube defects. Out of 72 pregnancies correctly classified by the amniotic-fluid alpha-fetoprotein (A.F.P.) test, 2 of 56 without neural-tube defects and all 16 with open neural-tube defects (8 with anencephaly and 8awith open spina bifida) had raised levels of AChE. Out of 5 pregnancies misclassified by the A.F.P. test (4 without neural-tube defects and 1 with open spina bifida), only 1 was misclassified by the AChE test--namely, one of those without a neural-tube defect. Thus, only 3 of the 77 pregnancies tested were misclassified by the quantitative AChE test. A qualitative test for an isoenzyme of AChE found in cerebrospinal fluid correctly classified these 3 pregnancies. These findings suggest that the analysis of AChE in amniotic fluid may be a useful test in the diagnosis of open neural-tube defects.


Acetylcholinesterase in human amniotic fluid: An index of fetal neural development? Acetylcholinesterase (AChE) activity was detected in amniotic fluid either sampled by amniocentesis at 14--23 weeks gestation or collected at normal parturition. Activity ranged from 0.2 to 8.9 u/l in the earlier samples and from 0.2 to 4.2 u/l in the later samples. Since the fetal but not the maternal serum contained AChE activity, we suggest that the AChE in the amniotic fluid is derived from the fetus. AChE is released from both neural and nonneural tissues, and the release of the enzyme from both sources may diminish as the nervous system matures. The amount of AChE found in amniotic fluid may be affected by abnormalities of the nervous system. Amniotic fluid from two fetuses with spina bifida contained AChE activity: one, with a gestational age of 21 weeks, was in the upper levels of the normal range (4.5 u/l), whereas the other, at 36 weeks, contained 1.9 times more activity than the next highest sample. In a 20-week fetus with anencephaly, the AChE activity in the amniotic fluid was increased 2.8-fold over the activity of the highest "normal" sample.


Inhibition of pentagastrin-stimulated and nocturnal gastric secretion by ranitidine. A new H2-receptor antagonist. Ranitidine hydrochloride (an H2-receptor-blocking drug which does not contain the imidazole nucleus of histamine) powerfully inhibited nocturnal and pentagastrin-stimulated gastric secretion in fifteen patients with duodenal ulceration. The drug is satisfactorily absorbed and therefore warrants clinical trial.


Carrier detection in Duchenne muscular dystrophy: Assessment of the effect of age on detection-rate with serum-creatine-kinase-activity. In 40 known carriers of the gene for Duchenne muscular dystrophy (mean age 38 years) the detection-rate with a standard assay of serum-creatine-kinase was 53%. In 52 daughters of known carriers (mean age 16 years) the detection-rate was 45% after correction of age. This implies a much higher detection-rate (about 90%) in young carriers and suggests that discrimination between carriers and noncarriers may best be achieved by testing in childhood.


Lateralisation of tumours of the nasal cavity and paranasal sinuses and its relationship to aetiology. Lateralisation was studied in 601 cases of carcinoma of the nasal cavity and paranasal sinuses. Squamous and anaplastic carcinomata and adenocarcinoma had a pronounced left-sided predominance in the ethmoid and to a much lesser extent in the nose. The results of a study of 298 cases of septal defection are invoked in support of the hypothesis that squamous and anaplastic carcinomata, as well as adenocarcinoma, are caused by exogenous factors.


Biochemical and haematological changes induced by tienilic acid combined with propranolol in essential hypertension. Sixteen patients with moderate essential hypertension completed a double-blind crossover trial with four treatment periods each of 6 weeks. They received in random order: placebo; tienilic acid 250 mg/day; propranolol 80 mg twice daily; and tienilic acid 250 mg/day combined with propranolol 80 mg twice daily. Average blood-pressure in the lying position was 22.6/13.1 kPa (169/98 mm Hg) on placebo; 21.0/12.5 (157/94) on tienilic aicd; 21.2/12.0 (159/90) on propranolol, and 18.9/11.5 (142/86) on tienilic acid combined with propranolol. The effects of tienilic acid and propranolol on blood-pressure were additive and there were no statistically significant interactions. Tienilic acid significantly reduced serum-urate from 0.33 to 0.18 mmol/l and induced hypokalaemia which was corrected by propranolol. Basophil count and haemoglobin were lower after tienilic acid treatment than they had been at the start of the study.


Serological response of patients with non-gonococcal urethritis to causative organism of contagious equine metritis 1977. The presence of allugtinins to the causative organism of contagious equine metritis (C.E.M.) in human serum has been confirmed. Agglutinins were found in the serum of 84 (37.6%) of 223 patients with non-gonococcal urethritis (N.G.U.), and in 12.5% of these patients there was a four-fold or greater rise in titre during the course of their illness. There was no evidence that these agglutinins were the result of infection by chlamydiae or ureaplasmas. Certain patients with these agglutinins seemed to respond better to therapy with antibiotics to which the C.E.M. bacterium is susceptible in vitro than did patients in whom these agglutinins were not found. The findings suggest that the C.E.M. bacterium or a microorganism related to it may be aetiologically involved in a proportion of patients with N.G.U. A search for such an organism in these patients is in progress.


Is trachoma an ocular component of a more generalised chlamydial infection? In industrialised countries, inclusion conjunctivitis of the newborn is now known to be just one manifestation of a more generalised infection with Chlamydia trachomatis. Pneumonia and enteric infection can develop in perinatally infected infants. It is possible that trachoma in developing countries may reflect extraocular infection that may contribute to the high frequency of pneumonia and diarrhoea in infants in these countries. If true, this would explain the short-term effects of topical treatment, since children could reinfect their eyes by autoinoculation from other sites. Thus systemic treatment with macrolides would result in benefits beyond the temporary suppression of eye disease.


Prevention of group-B beta-haemolytic streptococcal septicaemia in low-birth-weight neonates by penicillin administered within two hours of birth. Between January, 1969, and May, 1974, 11 of 1208 low-birth-weight infants had early onset group-B streptococcal septicaemia. All 11 infants were of less than 35 weeks gestational age and 9 presented with the clinical and radiological signs of idiopathic respiratory distress syndrome. 10 died. Antibotics were given to 3 infants only, but not before the age of 12 h. From June, 1974, infants less than 35 weeks gestational age, and from January, 1977, infants less than 2500 g, received systemic penicillin by 2 h of age after throat, ear, umbilical, rectal, and blood cultures. Penicillin was continued for 10 days if group-B streptococci were isolated but was stopped at 48 h of age if all cultures were negative. Between June, 1974, and November, 1977, there was 1 case of septicaemia and no death from group-B streptococal infection in the 983 low-birth-weight infants born during this period. These data suggest that systemic penicillin from birth prevents low-birth-weight infants from dying of group-B streptococcal infection.