Studies on the increase of antibodies in nasal secretions of human beings after intracutaneous vaccination with influenza virus,with the aid of the haemagglutination inhibition technique

Summary With the aid of the haemagglutination inhibition test in nasal secretions of human beings it is possible to demonstrate an increase of antibodies against influenza virus after pararespiratory vaccination, provided the non-specific inhibition of the secretions is climinated by means of enzymes ofVibrio cholerae. The antititre of the nasal secretions fluctuated greatly. After intracutancous vaccination of 0.3 ml in the skin of the back with concentrated vaccine it amounted on an average to 3% of that of the blood titre. The possible importance of this simplified technique for further investigations is pointed out. Financial support was provided by the Institute of Preventive Medicine, Leyden; N. V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Cura?ao Fund for Preventive Medicine.     

The influence of treating ferret influenza antisera with enzymes of crude filtrate ofVibrio cholerae on the titre of the antibodies

Summary After treating influenza antisera from ferrets with enzymes of a crude filtrate ofVibrio cholerac (pH 7.6) for the purpose of eliminating the non-specific inhibitors it is not possible to detect a significant fall in the titre of the antibodies with the aid of the egg protection test. Financial support was provided by the Institute for Preventive Medicine, Leyden; N. V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Cura?ao Fund the Preventive Medicine.     

Studies on the antigenic behaviour of egg- and egg-mouse-egg-lines of strains of influenza virus,with the aid of the haemagglutination-inhibition test

Summary Egg- and egg-mouse-egg-lines of strains of influenza virus were compared with the aid of the haemagglutination inhibition test. In most experiments it was found that the crossing of an antiserum of an egg-mouse-egg-line against the homologous egg-line or against a heterologous egg-line of a strain belonging to the same subgroup yields a low or very low antititre. We are indebted to DrG. K. Hirst (New York) and DrJ. Y. Sugg (New York) for sending us the strains of influenza virus Ala and Cam. Financial support was provided by the Institute for Preventive Medicine, Leyden; N. V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Cura?ao Fund for Preventive Medicine.     

Studies on the elimination of non-specific inhibitors in sera against influenza viruses with the aid of filtrates ofVibrio cholerae

Summary In the sera of humans and various animals there are two different non-specific inhibitors (α-and β-inhibitors) which may be specifically abolished by two substances (α-and β-“enzymes”) both present in filtrates ofV. cholerae. This neutralization is necessary for the rapid classifying of influenza virus strains with the aid of the haemagglutination inhibition test. The egg line strains of the A- and A′-groups are only sensitive to β-inhibitor, while the mouse line strains of the same groups are only sensitive to the α-inhibitor. This does not apply to strains of the B group, where mouse as well as egg lines are sensitive to both inhibitors. With the aid of isolated β-inhibitor (easily to be prepared from cattle serum), it is possible to decide in a quick manner whether or not a strain from the A- or A′-group has previously been adapted to the mouse. With the technical assistance of Miss I.de Nooyer and with the financial support provided by the Institute for Preventive Medicine, Leyden; N.V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Curacao Fund for Preventive Medicine.     

Co-localisation of autoimmune antibodies specific for double stranded DNA with procorticotrophin-releasing hormone within the nucleus of stably transfected CHO-K1 cells

Human autoantibodies and corticotrophin-releasing hormone (CRH)-specific antibodies have been used in a double-labelling immunofluorescence technique to demonstrate that immunoreactive CRH structures are co-localised with immunostaining produced by double stranded DNA-specific human autoantibodies within the nucleus of cultured ovarian cells of Chinese hamsters (CHO-K1). This co-localisation was confirmed using confocal microscopy. A metabolic labelling technique was used to investigate the role of the cytoskeleton in mediating nuclear translocation of proCRH within stably transfected CHO-K1 cells and showed that microtubule and actin disrupting agents had no effect upon the nuclear translocation of proCRH. These results, therefore, suggest that nuclear translocation of proCRH is not affected by drugs which disrupt the cytoskeleton and, consequently, modify the diameter of the nuclear pores.This work was supported by proproject grants from the BBSRC to M.G.C. and P.R.L., and an MRC (UK) grant to M.G.C. M.G.C. and P.R.L. would also like to acknowledge the support received from the, The Wellcome Trust, Welsh Scheme for the Development of Health and Social Research, Sir Halley Stewart Trust, The Royal Society, and the Department of Physiology, UWCC. P.R.L. is a Research Fellow from the Lister Institute of Preventive Medicine.     

Application of protein-A indirect ELISA (PAI-ELISA) for the detection of anti-Smith antibodies in systemic lupus erythematosus patients

An indirect form of protein-A ELISA (PAI-ELISA) was optimized and, when used to detect anti-Smith antibodies in sera of 31 systemic lupus erythematosus (SLE) patients, gave results comparable with those using a commercial immunodiffusion kit. The number of sera found to be positive for anti-Smith antibodies by ELISA was seven, four of which were also found positive by immunodiffusion.B.O. Siti-Rohana is with the Universiti Kebangsaan Malaysia (UKM), Faculty of Medicine, Kuala Lumpur, Malaysia. I.B. Ahmad is with the Department of Microbiology, Faculty of Life Sciences, Universiti Kebangsaan Malaysia, Bangi, 43600 UKM, Malaysia; B.A. Nasaruddin is with the Institute for Medical Research, Malaysia.     

The interrelationships of disease and culture in a primitive New Guinea community

This article explores links between disease and social standing in a primitive New Guinea community. Social and cultural events have modified the incidence of certain diseases. Furthermore, the changing patterns of disease may have influenced the development and form of social distinctions.This work is based on data collected as a predoctoral fellow in the Department of Anthropology at Columbia University. Fieldwork in New Guinea was done with NIH support under Training Grant 1 T01-MH11775-01 (related to 2 F1 MH301640-02), with Dr. Margaret Mead as the sponsor. Additional funding for analysis of data was obtained from the Harvard School of Public Health, the Department of Preventive Medicine of the Harvard Medical School, and the Institute for Transcultural Studies in New York.     

Evaluation of dose equivalent using a tissue-equivalent ionization chamber and a Geiger-Müller dosimeter

Summary When detailed neutron energy spectrum data are lacking for a mixed field of neutrons and photons, it is permissible when estimating the dose equivalent to assume that the quality factor for the neutrons is 10. With this assumption, it is shown that the responses of a tissue-equivalent ionization chamber and a Geiger-Müller dosimeter can be used to obtain an acceptable approximation of the dose equivalent in the mixed field without requiring precise knowledge of the relative neutron sensitivity of the Geiger-Müller dosimeter.This investigation was supported by Contract EP-78-S-02-4733 from the Department of Energy to the Radiological Research Laboratory/Department of Radiology and by Grant No. CA13696 to the Cancer Center/Institute of Cancer Research, awarded by National Cancer Institute, DHEW     

Some aspects of the adaptation of influenza virus onto mice

Summary The author describes the adaptation onto mice of an influenza A strain, isolated byMulder from the tracheal mucosa of a man, who died from an acute fulminant staphylococcal-pneumonia and discusses the nature of the adaptation phenomenon.Communication of the Workteam of Acute Respiratory Diseases of the Institute for Preventive Medicine.     

Highlights of the 3rd international BCG symposium: 100th anniversary of the first administration of BCG

2021 was the year of the 100th anniversary of the first administration of the Bacillus Calmette-Guérin (BCG) to a human being. It was the start of a long journey of the world's most widely used vaccine and the oldest vaccine still in use. More than 4 billion children have been vaccinated with BCG for protection against tuberculosis. However, over the years it became apparent that BCG also has beneficial non-specific effects. As such, it provides protection against various heterologous infectious and non-infectious diseases and is used to treat non-muscle-invasive bladder cancer. As BCG was developed at the Institut Pasteur de Lille by Albert Calmette and Camille Guérin, the Institute has celebrated this important anniversary with an international scientific symposium on all aspects of BCG, held from November 17 to 19, 2021 at the Institut Pasteur de Lille. It covered BCG against tuberculosis and described novel vaccine approaches, the effect of BCG against heterologous infections, including BCG and COVID-19, the effect of BCG against cancer, and BCG against auto-immune and inflammatory diseases. To discuss these areas, the symposium gathered close to 200 participants from all five continents, 2/3 on-line. This article presents the highlights of this 3rd International Symposium on BCG.     

A Conversation About Health Care Reform

Professor Victor R. Fuchs is the Henry J. Kaiser Jr Professor at Stanford (California) University, where he applies economic analysis to social problems of national concern, with special emphasis on health and medical care. He holds joint appointments in the Economics Department and the School of Medicine''s Department of Health Research and Policy. Professor Fuchs is a Distinguished Fellow of the American Economic Association and a member of the American Philosophical Society, the American Academy of Arts and Sciences, and the Institute of Medicine of the National Academy of Sciences. He was the first economist to receive the Distinguished Investigator Award of the Association for Health Services Research and has also received the Baxter Foundation Health Services Research Prize. Professor Fuchs is president-elect of the American Economic Association. His latest book, The Future of Health Policy, was published by Harvard University Press in 1993.The following edited conversation between Professor Fuchs and Linda Hawes Clever, MD, Editor of the journal, took place on April 8, 1994.     

The ontogenesis of calcium-binding protein in fetal rat kidney

Summary The presence of calcium-binding protein (CaBP) in the nucleus and cytoplasm of epithelial cells of renal tubules varies with the physiologic state. As part of a study to determine whether or not intranuclear CaBP precedes intracytoplasmic CaBP in the same cell, we used peroxidase-labeled antibody against human renal CaBP to localize CaBP in fetal rat kidney tubules. This paper reports examination of kidneys from rats on each day of gestation from the 10th to term (21 days) and on each of the first seven postnatal days. CaBP was first detected in fetal rat kidneys on the 19th gestational day. The histochemical staining reaction that revealed the CaBP was less intense than that produced in kidneys from adult animals, but its distribution was like that in adults, with some cells having no CaBP, others having it in the cytoplasm only, in the nucleus only, or in both. By the seventh postnatal day the staining reaction was similar to the adult patterns in all respects. Send offprint request to:commander,Department of Comparative Medicine, Letterman Army Institute of Research, Attn. : Research Librarian, Presidio of San Francisco, CA 94129, USAIn conducting the research described in this report, the investigators adhered to the Guide for Laboratory Animal Facilities and Care, as promulgated by the Committee on the Guide for Laboratory Animal Resources, National Academy of Sciences-National Research CouncilThe opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense     

Effects of anti-cholinoceptor antibodies on the frog heart]

Research on isolated hearts of Rana temporaria has shown that upon treating them with anti-cholinoreceptor antibodies, there occurs a considerable reduction of inhibition effect on cardiac activity of acetylcholine or carbacholine. A reduction of inhibition effect was noticed after incubation of frog's heart with antibodies against cholinoreceptors obtained from motor-denervated muscles of frogs as well as from muscles of mice Balb/c. Cholinoreceptor protein was obtained and purified by A. Sobel's method. Control tests were made with serum of non-immunized rabbits and rabbits immunized with material obtained from non-denervated muscles of frogs. It was concluded that acetylcholinoreceptor antibodies are capable of provoking atropine-like effect on frog's heart. According to our data, anti-cholinoreceptor antibodies as well as cholinoreceptors are relatively non-specific to species.     

Antibodies to the N-terminus of human Gastrin-34 react with material in rat and ferret brain

Antibodies specific for the N-terminus of human big gastrin, or NT G34, reveal in immunohistochemistry extensive systems of nerve cell bodies and fibres in the rat and ferret brain. However, when the same antibodies were used in radioimmunoassay of rat and ferret brain tissue extracts they failed to reveal immunoreactive material. At least one of the antibodies used for radioimmunoassay could be shown to react with NT G34 in rat pyloric antral extracts. Antibodies specific for other peptides derived from progastrin failed to reveal the systems demonstrated with the N-terminal G34 antibodies. It is concluded that expression of the gastrin gene is unlikely to account for the present observations. Instead we suggest that a novel peptide with low affinity for NT G34 specific antibodies is found in rat and ferret central neurones.     

Lack of expression on cultured human T-lymphocytes of a T-cell antigen shared by the molt-4 cell line and normal human thymocytes

Summary Four hematopoietic cell lines (CCRF-CEM, HSB-2, MOLT-4, and RPMI-8402), derived from acute lymphoblastic leukemia and expressing T-cell surface markers (T-HCL), were studied with two specific anti-T-cell sera. The sera were raised in rabbits against human thymocytes (anti-HTY) and against T-cells cultured in the presence of conditioned medium derived from lymphocytes stimulated with PHA (anti-CTC). Both sera were absorbed to obtain a T-cell specific pattern of reaction and were further absorbed with normal peripheral blood lymphocytes or with each of the four T-HCL. The anti-HTY sera absorbed with CEM, 8402, and HSB-2 still reacted with MOLT-4. A similar pattern of reactivity was found only with the anti-CTC absorbed with 8402, whereas, after absorptions with the other cell lines, this antiserum was unreactive against MOLT-4. After absorption with normal peripheral blood lymphocytes, anti-HTY still reacted with thymocytes and MOLT-4 but was negative on CTC. In contrast, anti-CTC absorbed with peripheral blood lymphocytes (PBL) was negative on thymocytes and MOLT-4 but still reacted against CTC. Our data confirm the existence of a T-cell antigen (probably an early T-cell differentiation antigen) shared between thymus and MOLT-4. This antigen is not expressed on CTC, although these cells express an antigenic pattern more complex than PBL. Antisera to CTC represents a source of anti-T-cell sera free of contamination with antibodies to early thymus-related antigens but containing other T-cell-related specificities. Supported in part by Naval Medical Research and Development Command, Research Task No. ZF51.524.013.1025, and National Cancer Institute Contract No. Y01-CB-00319. The opinions and assertions contained herein are the private ones of the writers and are not to be construed as official or reflecting the views of the Navy Department or the naval service at large. The experiments reported herein were conducted according to the principles set forth in the current edition of the “Guide for the Care and Use of Laboratory Animals,” Institute of Laboratory Animal Resources, National Research Council.     

Antibody toEscherichia coli 0127 in human colostrum

The maternal contribution to infant antibacterial immunity via colostrum has been examined. It was shown that human colostrum can be a rich source of antibody against a typical Gram-negative pathogen,Escherichia coli 0127. However in newborn infants, possessing little or no serum bactericidal antibody against this pathogenic serotype, the feeding of such colostrum ad lib. did not result in augmented serum antibody levels. The portion of this study conducted in the Department of Microbiology, University of Puerto Rico School of Medicine received financial aid from the NIH in the form of General Support Grant No. FR-05419-01 and Research Grant No. E-2371.     

Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses

Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.     

Variability of the lytic susceptibility of Neisseria gonorrhoeae to human sera.

The bactericidal activity of human sera for Neisseria gonorhoeae was studied. Sera were obtained from a group of patients with gonococcal infections who had acute urethritis, acute pelvic inflammatory disease, disseminated gonococcal infection, or who were asymptomatic carriers. The homologous and heterologous strains were tested with these sera. The development of serum bactericidal antibodies was not a universal event. With few exceptions, the susceptibility of a particular strain to human antibody and complement appeared to be largely independent of the particular person from whom the serum was obtained and was due instead to antigenic properties intrinsic to each individual strain. Lipopolysaccharide appeared to be the predominant antigen against which bactericidal antibodies were directed. The principal bactericidal antibody class was IgM. Blocking antibodies were not found to account for the lack of lytic activity. A correlation of bactericidal antibodies with protection from developing gonococcal infection could not be demonstrated in three pateints.     

Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge

A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the extreme variability of the virus. We identified human monoclonal antibodies (mAbs) that neutralize genetically diverse HCV isolates and protect against heterologous HCV quasispecies challenge in a human liver-chimeric mouse model. The results provide evidence that broadly neutralizing antibodies to HCV protect against heterologous viral infection and suggest that a prophylactic vaccine against HCV may be achievable.     

H1 and H2 histamine actions on lung vessels; their relevance to hypoxic vasoconstriction.

Pulmonary vasomotor actions of histamine and the possible relationship of histamine to hypoxic pulmonary vasconstriction were studied in anaesthetized cats with one lobe of lung perfused at constant flow and in isolated perfused rat and ferret lungs. In the cat histamine caused dilatation, biphasic responses and constriction with increasing doses. Histamine induced dilatation was better demonstrated during hypoxic vasoconstriction and was reduced by an H2 histamine antagonist; constriction with histamine was abolished by an H1 antagonist. Histamine also caused both vasodilatation and vasoconstriction in ferret lungs. A mast cell stabilizing agent had no effect on hypoxic pulmonary vasoconstriction in cats or rats. This response was unaffected in cats but greatly reduced in rats and ferrets by cyproheptadine, a combined histamine and 5-hydroxy-tryptamine inhibitor. It was unaffected in cats but abolished in ferrets an H1 histamine inhibitor. It was again unaffected in cats but greatly reduced in rats and ferrets by an H2 histamine inhibitor. These species differences may reflect differences in mechanism but more probably reflect non-specific effects of the inhibitors in certain circumstances. However, when drugs nearly abolished hypoxic vasoconstriction, ATP still caused vasoconstriction.