Showing papers on "Antibody published in 1968"

Surface IgM-kappa Specificity on a Burkitt Lymphoma Cell In Vivo and in Derived Culture Lines

Abstract: Summary An exceptional Burkitt lymphoma patient, a 16-year-old boy, yielded tumor biopsy cells and derived tissue culture lines that displayed a strong surface accumulation of IgM heavy and kappa light chain specificities judged by direct membrane fluorescence and cytotoxicity tests. This property was maintained unchanged in the course of more than 5 months of serial passage in vitro . A fourth biopsy, obtained from the patient after massive necrosis had been induced in the tumor by cytosine arabinoside chemotherapy, did not show this property at either the biopsy stage or in the derived cell line. The possibility that the neoplastic transformation of lymphoid cells may have afflicted a cell specialized to carry immunoglobulin on its surface may be considered. The phenomenon has to be distinguished from immunoglobulin coating in vivo seen with certain biopsy samples from this and other patients. The latter type of coating can be of IgM, IgG, or IgA nature and disappears rapidly on cultivation in vitro .

Regulatory effect of antibody on the immune response.

Abstract: Publisher Summary This chapter deals with the regulatory effect of antibody on antibody formation. It is possible to analyze those factors that influence the process of antibody synthesis. Certainly antibody, the end product of the process, is among the most potent and specific of inhibitors of antibody synthesis. That this inhibition results from the interaction of antibody with antigen neutralizing the immunogenicity of the latter seems likely, and the evidence for this is critically presented. The potential use of this mechanism is suggested by its effectiveness in the enhancement of tissue grafts, its use in the therapeutic prevention of anti-D antibody responses in mothers of Rh-incompatible fetuses, and its possible role in the induction of some types of immunological tolerance. The immune response represents a predictable series of events, characterized by the sequential appearance of several classes of γ-globulin antibody molecules and the expression of various cell-mediated immune reactions. One mechanism is described for regulating the concentration of immunoglobulin (IgG) in the circulation. The mechanism operates by increasing the catabolic rate of IgG when the serum concentration is abnormally increased as, for example, in multiple myeloma. Two mechanisms are described both of which regulate the immune response. These are alteration of antigenic stimulation and suppression of the immune response by passive transfer of specific antibodies prior to or shortly after administration of antigen.

Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles.

Abstract: This paper describes the trapping of antigen in lymphoid follicles of rat popliteal lymph nodes as revealed by electron microscopic radioautographs following injection of (125)I-labeled Salmonella adelaide flagella and other materials. The antigen was taken up vigorously, and to an approximately equal extent, by both primary and secondary follicles. The rate of uptake was faster in preimmunized than in virgin adult rats. The bulk of the antigen in follicles was extracellular, and persisted in this location for at least 3 wk. Label was most frequently found at or near the surface of fine cell processes. Many of these were branches of dendritic follicular reticular cells. Such processes interdigitated with equally fine processes of lymphocytes, creating an elaborate meshwork. In some cases, antigen was found between lymphocytes which appeared to be in close apposition. Occasionally, a few grains appeared over lymphocyte nuclei and study of serial sections suggested that this probably represented true entry of small amounts of antigen into lymphocytes. The characteristic "tingible body" macrophages (TBM) of germinal centers appeared to play only a secondary role in follicular antigen retention. They showed degrees of labeling over their phagocytic inclusions varying from negligible to moderately heavy. Moreover, follicles lacking or poor in TBM retained antigen just as effectively as those containing numerous TBM. The hypothesis is advanced that TBM may be derived from monocytes that migrate down from the circular sinus. Follicular localization of three other materials was also studied, though not in such detail. These were (125)I-HSA complexed to anti-HSA: (125)I-labeled autologous IgG; and (125)I-monomeric flagellin. All of these showed the basic features of intercellular, membrane-associated deposition noted with (125)I-flagella. The role of follicular antigen depots in immune induction is discussed. The tentative conclusion is reached that follicular antigen in a primary follicle encounters natural antibody on the surface of certain antigen-reactive lymphocytes. The resultant reaction causes blast cell transformation and eventually the genesis of a germinal center.

Human Monocytes: Distinct Receptor Sites for the Third Component of Complement and for Immunoglobulin G

Abstract: Human monocytes contain two distinct receptor sites, one specific for the third component of complement (C'3), the other for immunoglobulin G(gammaG). The two receptors may function either independently or cooperatively in the induction of phagocytosis. Ingestion of erythrocytes coated with immunoglobulin M antibody requires a relatively large number of bound C'3 molecules per cell. Ingestion of erythrocytes sensitized with gammaG antibody is independent of complement; however, the reaction is inhibited by concentrations of gammaG far below those in normal serum. Inhibition by gammaG-globulin is overcome by a relatively small number of bound C'3 molecules per cell. The two monocyte receptors exert a cooperative effect on ingestion by monocytes of erythrocytes coated with gammaG antibody in the presence of inhibitory amounts of free gammaG.

Studies on human antibodies : vi. selective variations in subgroup composition and genetic markers

Abstract: The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major γG1-type However, a high preponderance of molecules of the minor γG2-subgroup was found for antibodies to dextran, levan, and teichoic acid These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of γG2-heavy chains and kappa light chains By these criteria as well as others, it closely resembled myeloma proteins

Immunoglobulin response in serum and secretions after immunization with live and inactivated poliovaccine and natural infection.

Abstract: The responses of the major immunoglobulins (gamma G, gamma M and gamma A) in serum and nasal and duodenal secretions were studied in infants and children after immunization with live and inactivated poliovaccines and after natural poliomyelitis infection. The serum immunoglobulin responses to these procedures resembled each other although higher levels followed the natural infection. After immunization with live attenuated vaccine, antibody activity was found regularly in nasal and duodenal secretory gamma A immunoglobulin, but not after immunization with inactivated vaccine. To explain the alimentary immunity that follows infection with attenuated or wild poliovirus, it is proposed that orally administered live virus, which implants and replicates in the pharynx and intestinal tract, stimulates local lymphoid cells, leading to the production of immunoglobulins predominantly of the gamma A class.

Particles associated with Australia Antigen in the Sera of Patients with Leukaemia, Down's Syndrome and Hepatitis

Abstract: AUSTRALIA antigen was first identified using an antiserum produced in a transfused patient1,2. The antiserum gave a clear precipitin line in a double diffusion experiment when placed adjacent to the serum from an Australian aborigine. Pending further identification of the antigen, the geographic name “Australian antigen” was given to the reacting material found in the aborigine's serum. Specific antisera against this antigen can be produced by immunizing rabbits with serum containing Australia antigen, and subsequent absorption with serum which does not contain Australia antigen3. The precipitin band which forms between the haemophilia antiserum and the serum containing Australia antigen stains faintly with sudan black, indicating that the antigen contains lipid. It has a specific gravity of less than 1.21 and appears in the first peak in ‘Sephadex G-200’ column chromatography (indicating a high molecular weight)4.

Deoxyribonucleic Acid Antibody: A Method to Detect Its Primary Interaction with Deoxyribonucleic Acid

Abstract: Antibody to DNA in human serums can be detected by the ammonium sulfate method. This sensitive and specific technique, which measures the primary interaction between DNA and antibody to DNA, is based on the observation that free DNA is soluble in 50-percent saturated ammonium sulfate whereas antibody-bound DNA is insoluble.

Competition of 19s and 7s antigen receptors in the regulation of the primary immune response

Abstract: Prior to sheep red cells (SRC) mice were given 7S or 19S anti-SRC antibodies or mixtures of both. All 7S preparations suppressed the immune response. All 19S preparations enhanced the primary response, as measured by an up to 15-fold increase in the number of PFC per spleen. Results obtained with mixtures showed that 7S and 19S antibodies are competitive in their effect. The kinetics of the appearance of PFC in the mouse spleen after injection of SRC suggest that the depressive effect of 7S antibody simulates a reduction in SRC dose, whereas the enhancing effect of 19S antibody appears as a temporary increase in the rate at which PFC appear. Antibodies from one animal species are quite effective in another species.

Antigenic modulation loss of tl antigen from cells exposed to tl antibody. study of the phenomenon in vitro

Abstract: Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro An ascites leukemia, phenotype TL1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C Thus modulation apparently is an active cellular process Antigens TL 1,2, and 3 are all modulated by anti-TL1,3 serum and by anti-TL3 serum This modulation affects all three TL components together, even when antibody to one or two of them is lacking aAnti-TL2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions

A new class of immunoglobulin in human serum.

Abstract: A new class of normal immunoglobulin corresponding to a myeloma protein (myeloma-IgND), which fails to react with specific antisera to IgA, D, G and M (Johansson and Bennich, 1967) was detected in serum from sixty-two blood donors using a radio-immunosorbent technique (Wide and Porath, 1966). IgND in normal sera corresponds to myeloma-IgND in Ouchterlony gel diffusion analysis. Isolated IgND gave a reaction of identity with myeloma-IgND in Ouchterlony gel diffusion analysis. The concentrations of IgND in 93·5 per cent of the samples was within the range of 100–700 ng/ml. Normal levels of IgND were found in four samples apparently lacking IgA and/or IgD as determined by single radial immunodiffusion. Elevated levels of IgND were found in four samples one of which was from a subject with previously undiagnosed extrinsic asthma. It is concluded that myeloma-IgND represents a new class of human immunoglobulin.

Protective Effects of Specific Immunity to Viral Neuraminidase on Influenza Virus Infection of Mice

Abstract: Antibody specific for viral neuraminidase can be demonstrated in mice following (i) pulmonary infection with influenza virus, (ii) immunization with ultraviolet-in-activated influenza virus, (iii) immunization with isolated neuraminidase of influenza A(2) virus, and (iv) passive immunization with sera of rabbits immunized with isolated A(2) neuraminidase. Neuraminidase antibody produced by any of these methods exerts a profound inhibiting effect on virus replication in the lungs of mice challenged with strains of virus having homologous neuraminidase protein, even in the absence of hemagglutinating inhibiting antibody to the challenge virus, and results in markedly decreased pulmonary virus titers and diminished lung lesions. These observations suggest that antineuraminidase immunity may play a significant role in the protection against influenza virus challenge observed in mice after infection or artificial immunization.

Alpha-chain disease: a new immunoglobulin abnormality.

Abstract: A new type of pathological immunoglobulin was found in the serum, urine, and saliva of a young Arab patient with abdominal lymphoma and diffuse lymphoplasmacytic infiltration of the small intestine. This protein is devoid of light chains and is closely related to the alpha polypeptide chains of the gamma(A1) (Le) subclass of immunoglobulin A. It is characterized by electrophoretic heterogeneity, tendency toward polymerization, and a high carbohydrate content. No intracellular synthesis of light chain was detected.

Lymphocyte in vitro cytotoxicity: mechanisms of immune and non-immune small lymphocyte mediated target L cell destruction.

Abstract: Mutual in vitro cell destruction resulted when nonimmune or immune mouse or rat small lymphocytes were attached to genetically dissimilar target cells with phytohemagglutinin or xenogeneic antibody The ability to induce this reaction resided only with viable cells of lymphoid origin The step(s) leading to aggressor-target cell destruction observed in these studies is suggested by the following sequence: a) attachment of the aggressor cell to the target cell, b) membrane site(s) interaction between the lymphocyte and target cell which serves as a recognition step and if the target cell is not recognized as “self,” d) a “triggering” of aggressor lymphocyte activity which results in enlargement of the lymphocyte and release of a soluble toxic factor termed “lymphocyte cytotoxic factor” (LCF) LCF may be the agent responsible for the death of both cells

Ultrastructural localization of antibody in differentiating plasma cells

Abstract: Antibody was localized by electron microscopy within differentiating and mature plasma cells of the spleens of hyperimmunized rabbits. Horseradish peroxidase was used as antigen. Intracellular antibody to peroxidase was revealed in glutaraldehyde-fixed tissue by coupling it with its antigen and then revealing the sites of peroxidase activity cytochemically. Antibody first appears in the perinuclear space of hemocytoblasts where it persists through differentiation into immature plasma cells, but it disappears from this site in mature plasma cells. Concomitant with the development of the ergastoplasm, antibody accumulates in many but not all of its cisternae. Antibody is present in the lamellar portion of the Golgi apparatus in all phases of plasmacytic differentiation. Mature plasma cells exhibit two types of antibody distribution, a concentration into large spherical intracisternal granules or an overflowing into all parts of the cytoplasm.

Observations on Australia antigen in Japanese.

Abstract: Summary. Frequency of Australia antigen in blood donors of the Tokyo area was estimated nearly 1%. A higher frequency in male donors was observed. The antigen was not an invariable serum antigen in patients who received blood transfusion and in patients with viral hepatitis. The antigen was found often only in the early phase of viral hepatitis. The appearance of Australia antigen did not always accompany clinical nor biochemical hepatitis. The antibodies against Australia antigen were found not only in the recipients of Australia antigen positive but also of Australia antigen negative blood. The nature of the antigen and its significance in blood transfusion were discussed.

Genetic control of the antibody response in inbred mice transfer of response by spleen cells and linkage to the major histocompatibility (h-2) locus

Abstract: The transfer of spleen cells from (C3H x C57Bl/6) F(1) mice, capable of responding to (T,G)-A--L, into irradiated C3H parental recipients, normally incapable of responding to (T,G)-A--L, transfers the ability to make either a primary or secondary immune response to this synthetic polypeptide antigen. This localizes the genetic control of the ability to respond to the spleen cell population and indicates that the genetic control is exerted upon a process directly related to antibody formation. Studies with congenic strains of mice and linkage studies in segregating backcross populations show that the ability to respond to (T,G)-A--L and (H,G)-A--L is linked to the H-2 locus and can thus be localized to the IXth mouse linkage group. Note Added in Proof: Of the three possible recombinant animals noted in Tables IV and V, two were infertile. The third animal was not a recombinant, since progeny testing and reimmunization showed that this animal was an H-2(2)/H-2(k) heterozygote capable of responding well to (T,G)-A--L.

Adsorption of Mycoplasma pneumoniae to Neuraminic Acid Receptors of Various Cells and Possible Role in Virulence

Abstract: Monkey, rat, and chicken tracheal epithelial cells, as well as monkey, rat, guinea pig, and chicken erythrocytes, adsorbed firmly to colonies of Mycoplasma pneumoniae and M. gallisepticum. Colonies of M. pulmonis also adsorbed erythrocytes but with less avidity than M. pneumoniae or M. gallisepticum; unlike the latter organisms, M. pulmonis did not adsorb tracheal epithelial cells. Colonies of M. orale type 1 and M. orale type 3 adsorbed only chicken red cells. Other mycoplasma species tested, including four of human origin and one of animal origin, did not adsorb red cells or epithelial cells. M. pneumoniae and M. gallisepticum appeared to attach to erythrocytes or tracheal epithelial cells by neuraminic acid receptors on these cells, whereas M. orale types 1 and 3 and M. pulmonis seemed to utilize another type or other types of receptors. Pretreatment of red cells or tracheal epithelial cells with receptor-destroying enzyme, neuraminidase, or influenza B virus removed the adsorption receptors for M. pneumoniae. Similarly, pretreatment of M. pneumoniae colonies with neuraminic acid-containing materials prevented adsorption of erythrocytes or respiratory tract cells. The adsorption sites on M. pneumoniae were specifically blocked by homologous but not heterologous antisera. This property made it possible to study the nature of the mycoplasma adsorption sites by testing the capacity of different fractions of the organism to block the action of adsorption-inhibiting antibodies. Such studies suggested that the mycoplasma binding sites were probably lipid or lipoprotein in nature. The glycerophospholipid hapten was implicated as one such site, since this serologically active hapten blocked the action of hemadsorption-inhibiting antibodies in M. pneumoniae rabbit antiserum. The affinity of M. pneumoniae for respiratory tract epithelium, unique among the mycoplasmas that infect man, may play a role in virulence, since this type of attachment provides an unusual opportunity for peroxide, secreted by the organism, to attack the tissue cell membrane without being rapidly destroyed by catalase or peroxidase present in extracellular body fluids.

A Modification of the Hemolytic Plaque Assay for Use with Protein Antigens

Abstract: Summary A method is presented which allows the in vitro enumeration of cells producing antibody against a variety of protein antigens. The proteins are covalently linked to red blood cells by means of a carbodiimide reagent. The concentrations of protein required for the plaque assay are greater than those required for passive agglutination. The method is simple and sensitive and the results mimic the kinetics of the response that is seen in in vivo assays of serum antibody. Both direct (probably 19 S) and indirect (probably 7 S) plaque-producing cells are detected.

A quantitative in vitro study of the chromatographic distribution and immunoglobulin characteristics of human blocking antibody.

Abstract: This report describes the immunoglobulin and chromatographic characteristics of human blocking antibody. Studies were carried out on a pool of serum from 20 allergic donors who had been immunized with ragweed antigen E as a form of therapy for ragweed hay fever. The serum and serum fractions were subjected to chromatography on DEAE-Sephadex, CM-cellulose, DEAE-cellulose and Sephadex G 200. Blocking activity was assayed by an in vitro technique: the inhibition of antigen E induced histamine release from isolated human leukocytes. This technique is more than 10 times as precise as the usual skin assay. Immunoglobulins were determined qualitatively by immunodiffusion against specific antisera and quantitatively by the Preer technique. Recovery of blocking activity was about 70%. In each fractionation procedure blocking antibody and IgG eluted together. Purified IgA had less than 1% the activity of IgG preparations and IgM antibody contributed less than 1% to the activity of the whole serum. Absorption of the serum with anti-IgA and treatment with 2-mercaptoethanol did not decrease its blocking titer, while absorption with anti-IgG caused a decrement of more than 97%. Circulating reaginic antibody appeared to account for less than 1% of the total serum activity. It was concluded that blocking activity is essentially a function of IgG molecules.

Cell to cell interaction in the immune response iii. chromosomal marker analysis of single antibody-forming cells in reconstituted, irradiated, or thymectomized mice

Abstract: Two new methods are described for making chromosomal spreads of single antibody-forming cells. The first depends on the controlled rupture of cells in small microdroplets through the use of a mild detergent and application of a mechanical stress on the cell. The second is a microadaptation of the conventional Ford technique. Both methods have a success rate of over 50%, though the quality of chromosomal spreads obtained is generally not as good as with conventional methods. These techniques have been applied to an analysis of cell to cell interaction in adoptive immune responses, using the full syngeneic transfer system provided by the use of CBA and CBA/T6T6 donor-recipient combinations. When neonatally thymectomized mice were restored to adequate immune responsiveness to sheep erythrocytes by injections of either thymus cells or thoracic duct lymphocytes, it was shown that all the actual dividing antibody-forming cells were not of donor but of host origin. When lethally irradiated mice were injected with chromosomally marked but syngeneic mixtures of thymus and bone marrow cells, a rather feeble adoptive immune response ensued; all the antibody-forming cells identified were of bone marrow origin. When mixtures of bone marrow cells and thoracic duct lymphocytes were used, immune restoration was much more effective, and over three-quarters of the antibody-forming mitotic figures carried the bone marrow donor chromosomal marker. The results were deemed to be consistent with the conclusions derived in the previous paper of this series, namely that thymus contains some, but a small number only of antigen-reactive cells (ARC), bone marrow contains antibody-forming cell precursors (AFCP) but no ARC, and thoracic duct lymph contains both ARC and AFCP with a probable predominance of the former. A vigorous immune response to sheep erythrocytes probably requires a collaboration between the two cell lineages, involving proliferation first of the ARC and then of the AFCP. The results stressed that the use of large numbers of pure thoracic duct lymphocytes in adoptive transfer work could lead to good adoptive immune responses, but that such results should not be construed as evidence against cell collaboration hypotheses. Some possible further uses of single cell chromosome techniques were briefly discussed.

Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism.

Abstract: The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 µg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with γ-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated.

Rubella: a method for rapid diagnosis of a recent infection by demonstration of the IgM antibodies.

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