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This prospective multicenter study aimed at investigating the safety and metabolic advantages of steroid withdrawal (SW) therapy in kidney transplant recipients with tacrolimus-mycophenolate mofetil-based immunosuppression.We analyzed 179 recipients who received kidney transplantation from March 2016 and September 2018. In 179 recipients, 114 patients maintained an immunosuppressive regimen including steroids (steroid continuation [SC] group). The remaining 65 patients were determined to withdraw steroid therapy after 6 months posttransplant (SW group). Metabolic parameters and graft functions of the two groups were evaluated.The estimated glomerular filtration rates at 12 months posttransplant were 67.29 ± 20.29 ml/min/1.73 mIn conclusion, a 6-month withdrawal of steroids in recipients with low immunological risk and stable graft function can be safely conducted and result in improvement of metabolic profiles. Stable recipients without biopsy-proven acute rejection and proteinuria can safely withdraw from steroids out of a maintenance immunosuppressive regimen 6-months posttransplant. A long-term follow-up study is needed to verify our results.

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The purpose of this study was to explore the clinical and pathogenic significance of vitamin D metabolites in primary Sjögren's syndrome (primary SS). We measured blood concentrations of 25-hydroxyvitamin D (25 OH D) and calcitriol (1,25(OH)2D)vc in 41 patients and correlated the results with blood levels of various immune activation products, as well as with patients' clinical status. Levels of 25 OH D were slightly decreased as compared to normal controls and the reduced levels of 25 OH D were stable over the observed period of 2 years. Levels of 25 OH D correlated inversely with levels of soluble interleukin-2 receptor, status indices for global disease, total exocrine disease, surface exocrine disease, internal organ exocrine disease, and mediator-induced disease. Levels of 1,25(OH)2D varied considerably and compared to normal control values. Levels of 1,25(OH)2D did not correlate with clinical/immunopathological status. In conclusion the inverse correlations found between levels of 25 OH D and measures of clinical and immunoinflammatory status support the notion that vitamin D metabolism may be involved in the pathogenesis of primary SS.

Summary An evaluation of atabrine suppression under field and combat conditions is attempted. The malaria rate in itself is of little value since the total amount of malaria to be suppressed is unknown. The percentage of men showing positive smears (very few parasites) when on good suppression (checked by atabrine levels) is assumed to be roughly indicative of the amount of malaria in this group of men. An index of 14% positive was obtained in a group of whom 80% relapsed with attacks of vivax malaria within two months after stopping atabrine. This relationship is true only if the smears are made on individuals who have had few or no previous attacks of clinical malaria. A combination of careful history taking, determination of atabrine levels, and examination of smears showed that at least 98% of the men in strenuous combat were protected by 1.0 gm. atabrine per week. This was usually taken in 2 doses of 0.5 gm. each. No data on 0.6 gm./wk. from troops during strenuous combat is available. Sample histories showing the difficulties of administration are given.

The synergistic effect of Hemophilus influenzae suis and swine influenza virus in the pig can be reproduced by the inoculation of these agents on the chorioallantoic membrane of 9 to 10 day old chick embryos. Two strains of human influenza virus that were studied failed to substitute for the swine virus in the synergistic reaction. No loss of synergistic effect was noted when the swine influenza virus was put through 11 chick embryo passages. Recently isolated and old stock strains of Hemophilus were equally able to enhance the effect of the virus. Heat-killed cultures of H. influenzae suis can be substituted for the bacterial component of the reaction. Infection of the embryo with swine influenza virus predisposes to infection with H. influenzae suis. The combination of H. influenzae suis and swine influenza virus causes a selective destruction of the embryo lungs, not produced by the individual components. This pneumonia exhibits the essential features of the natural disease.

In a serological laboratory with a routine service for determining autoantibodies to human neutrophils, antibodies giving a selective or preferential reaction with the nucleus or perinuclear area of neutrophils are not uncommon. The aim of this study was to look for clinical correlates with the presence of such neutrophil-reactive autoantibodies. The specificity of such antibodies for nuclear or cytoplasmic antigens was studied in 65 consecutive sera displaying nuclear/perinuclear reactivity at a titre of at least 80 using the indirect immunofluorescence technique (IIF) on ethanol-fixed leucocytes. The sera were also investigated by IIF on formalin-acetone fixed leucocytes and on HEp-2 cells. ELISA techniques were used to measure antibodies to azurophil granule constituents (ANCA), purified myeloperoxidase (MPO-ANCA), and lactoferrin (LF-ANCA). Furthermore a qualitative spot immunoassay was used for the detection of antibodies to α, β, and γ fractions, and the nuclear fraction of neutrophils, purified proteinase 3 (PR3), MPO, enolase, lysozyme, elastase, lactoferrin, and cathepsin G. The diagnoses linked to such GS-ANA/pANCA positivity were arthritides, vasculitides, inflammatory bowel disease and chronic hepatic conditions. MPO was the main antigen recognized in the vasculitis group, but apart from that, rather limited antigen reactivity was demonstrable by these techniques, lysozyme being the most frequently recognized autoantigen in patients with arthritides. Human lymphocytes served as a suitable control substrate when distinguishing between GS-ANA/pANCA and ANA, whereas HEp-2 cells usually could not be used if both classes of antibodies were present in a sample. Furthermore, formalin-acetone fixation is not recommended for routine use.

A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01).

In nature, the urn cell complexes which swim in the coelomic fluid of the marine invertebrate, Sipunculus nudus, produce "tails" of mucus in response to bacterial pathogens. Since they produce measurable tails of mucus in vitro, suspensions of urn cell complexes provide a bioassay for mucus-stimulating substances (MSS) in biological fluids, including several human body fluids. Heat-activated seawater dilutions of human serum contain MSS. Serum from 87 cystic fibrosis (CF) homozygotes, 60 obligate heterozygotes, and 45 controls were fractionated on a Sephadex G-200 gel filtration column. After subsequent heating for 4 min at 85 degrees C, the fractions of all normal sera showed two characteristic peaks of MSS activity. The pattern differed in heated serum fractions of CF patients, in that the second peak was lacking in 59% of individual tests. The pattern was intermediate in heterozygote sera. Of the 36 CF serum fractions which did have two peaks of activity, 89% had the predominant activity in peak 1. The frequency of single peaks of activity increased with patient age, from 33% in those under 10 years to 75% in those over 16. The molecular weight of peak 1 is about 75,000 daltons, of peak 2 about 30,000. One may speculate that the frequent lack of peak 2 serum components may be associated with the inability of most CF patients to produce normal mucus following respiratory infection.

The course of an infection apparently caused by a filterable virus of the blood of the shore crab. Carcinus maenas , has been experimentally studied in this host both at Roscoff, France. where it was originally found, and at Woods Hole, Mass., where the local species was also found susceptible. Although a portion of the infected animals die with the symptoms of inadequate blood clotting, recovery of this function occurred promptly in about two-thirds of the animals. Half of the animals that recovered this function did so within 4 to 6 days. Recovery was not accompanied by disappearance of the virus from the whole blood. In tests done as late as 40 days after recovery, virus was still present. Autointerference was demonstrated after acute infection. It was found in the serum of animals with manifest disease on all days tested and in whole blood of animals taken more than 2 days after the clotting defect appeared. It was not demonstrable within the whole blood within the first 2 days of disease. The role of this in the recovery phenomenon is discussed.

SummaryT and B lymphocyte rosetting values were obtained for 18 children with kwashiorkor, marasmus, or nutritional edema. T cell values were subnormal in all malnutrition classes, but were lowest in children with kwashiorkor. Four of five malnourished children who were sensitized with 2,4-dinitrochlorobenzene (DNCB) before refeeding failed to respond to repeated subsequent challenges; five of six children who were sensitized after refeeding responded strongly to the first challenge.

The adult seastar is an ideal model for study of phagocytosis and inflammation. The behavior of the circulating amebocytes responsible for phagocytosis and clumping can be directly observed in the coelomic fluid circulating in the transparent papulae of the limbs. Intracoelomic injection of an autologous amebocyte extract induces temporary, reversible, clumping and adherence of amebocytes. Injected, foreign, red-pigmented sea urchin amebocytes are phagocytosed by seastar amebocytes which then form clumps in the tips of the papulae and traverse to the external surface through penetrating lesions. Successive injections may cause acute inflammation and edema. During the acute inflammatory response, a substance(s) is released into the coelomic fluid which stimulates the urn cell complex of Sipunculus nudus to secrete mucus in vitro; the substance disappears from the fluid by 24 hours. A spontaneous ciliate infection of seastar testes causes failure of the infected animal's amebocytes to clump on glass or plas...

By pretreatment with concanavalin A (Con A) both in vivo and in vitro genetically susceptible mice and their cultured macrophages have been converted to animals and cells which are phenotypically resistant to mouse hepatitus virus (MHV). Con A at 1.0 mg/mouse decreased the mortality from 100% to less than 40% by inducing a prominent inflammatory response, increasing the number of macrophages in the virus inoculation site, and producing a population of macrophages not uniformly susceptible to the virus. In addition, mediators derived from Con A-treated spleen cells conferred resistance to normally susceptible syngeneic macrophages to 100 TCID50 of MHV.

Genetic resistance to mouse hepatitis, which resides largely in the macrophages of resistant C3H mice, may be altered by exposing the cells in vitro to fluid from allogeneic mixed lymphocytes. A 1,000-fold increase in susceptibility was produced in these genetically resistant cells by exposure to this fluid. This presumed lymphokine was effective without producing any change in host adaption of the virus.

Genetically resistant G3H mice routinely yielded macrophages that were resistant when grown in 90% horse serum. These mice also routinely yielded macrophages that were susceptible to the same virus, MHV (PRI), in vitro after the mice had been treated with three intraperitoneal doses, of hydrocortisone. Dexamethasone and prednisolone when similarly administered also increased the susceptibility of C3H macrophages taken from the treated animal, but progesterone and testosterone did not. In addition, spleen cells from mice treated with cortisone made the resistant C3H macrophages 100 times more susceptible in vitro. Increased in vitro susceptibility induced in this way by hydrocortisone was reversed by exposure to supernatant fluid removed from cultures of concanavalin A-treated spleen cells.

Circulating antibody appeared in the convalescing NDV-infected chicken concomitantly with the disappearance of virus from the tissues. The antigenic response to the CG 179 and B strains was demonstrated to be approximately equal. The neutralization test in the embryo and the hemagglutination inhibition technique yielded parallel results in the measurement of antibody early in convalescence, but late in convalescence the hemagglutination inhibition titers were relatively lower. This disparity indicates the possible duality of the antibodies. There was a wide ratio between the neutralizing antibody titers found in the brain and in the serum after an asymptomatic infection with NDV. The antibody level in the brain appeared to be related to the extent of virus growth and damage in the central nervous system. It appeared likely that a major factor in determining the virulence of the CG 179 strain was the more rapid attainment in the central nervous system of high virus concentration which outstripped the defense mechanisms of the host.

Infectious laryngotracheitis can be produced in chickens as an experimental model of severe nonfatal rhinitis and sinusitis. Inoculated intranasally into unanesthetized baby chicks it remains limited to the nasal fossa, produces acute desquamation of all nasal epithelia, results in functional recovery of the respiratory epithelium, but leaves important residual abnormalities. From the earliest recognizable lesions through 4½ months' convalescence, the principal changes are as follows: 1. Initial lesions, or small syncytia of intranuclear "inclusions", first identifiable in the mucociliated cells of the shallowest portion of the epithelium at about 21 hr postinoculum (the inner surface of the maxillary conchal scroll). 2. Acute sloughing, (about 3 to 7 days), marked by: (a) spread of lesions from cell to cell via multinucleated "giant cells" which progressively slough and desquamate respiratory, olfactory, and sinus epithelia, epithelial neural elements and blood vessels; (b) appearance of numbers of eosinophilic leukocytes along the basement membrane at the sites of lesions just previous to sloughing; intensive infiltration of the submucosa with small lymphocytes after sloughing begins; (c) histochemical change in the intracellular mucus of the cells which comprise the syncytia: this mucus stains with Alcian blue alone when stained with AB-PAS; and (d) all cartilages of the maxillary conchae become flaccid, and the cell nuclei and matrix lose both basophilic and Alcian blue staining properties, effects which recede by about the 8th day. 3. Repair (about 8 to 21 days), marked by rapid initial spread of a sheet of epithelial cells over the infiltrated subrmucosa, appearance of numbers of plasma cells circulating in the tissues, formation of encapsulated secondary nodules, and mucosal adhesions. 4. Convalescence (about 1 to 4½ months when experiments terminated), marked by functional restoration of the mucociliary lining of the nasal fossa. However, at 4½ months eight specimens all show complete metaplasia of the olfactory organ (end nerves, supporting cells, and glands of Bowman) to mucociliated epithelium, all show abnormal formation and alignment of mucous acini, and about 50% have severe persistent sinusitis.

The titration curve for the virus of Eastern equine encephalomyelitis inoculated into the 10 day old chick embryo shows that the maximum increase in virus content continues until shortly before the generalized destruction of the embryo is apparent. This is followed by a stationary phase. Histological studies of infected embryos fail to demonstrate selective tissue destruction, and titrations show the virus to be distributed throughout the egg, although concentrated in the embryo. The chorioallantoic membrane gradually becomes increasingly resistant with age to both the Eastern and Western viruses. Increased resistance with age is also apparent in the hatched chick. These findings are based on the use of the chick embryo itself as the test animal to determine the 50 per cent mortality end-point. The limits of accuracy of this method are defined.

Summary Studies on the efficacy of atabrine suppression of malaria in American and Australian troops in New Guinea and Australia from June 1943 to January 1945 are presented. The concentration of atabrine present in the plasma of those developing malaria despite supposed suppression is compared with data from adequately suppressed troops. This comparison shows that clinical malaria develops in the presence of inadequate amounts of atabrine. The concentration of atabrine present in “break-throughs” is the same in chronic relapses and “primary” attacks of malaria. It is possible that P. falciparum requires in the field a slightly greater amount of atabrine to be completely suppressed. Our data would support but not establish such a contention. The difference is not great enough to be of practical importance. The difficulty of obtaining any large number of cases of malaria who consistently claim to have regularly taken 0.1 gram or more of atabrine every day and who have nevertheless developed clear-cut malaria emphasizes the fact that atabrine suppression is mainly a problem of drug administration. However, the development of malaria in an individual can not be taken as definite proof that that individual has failed to take atabrine regularly even if his drug level is low. Variation of drug level obtained with a standard dose is so great that, granting concentration is related to protection, a small percentage would be unprotected by the standard dosage of 0.7 grm of atabrine per week. The evaluation of several different dosages of atabrine by studies of the concentration of atabrine in the plasma under different conditions and at different times fails to indicate any need for a dosage greater than 0.1 gram per day. Atabrine levels are adequate between doses when 0.4 gram or 0.5 gram is given twice a week. This dosage scheme must be judged on the realtive value of giving the drug fewer times during the week, the increased nausea produced by larger doses, and the greater hazard of more serious reactions when such amounts of atabrine are ingested over a long period.

Summary Earlier experiments had shown that injection of crab blood containing large numbers of a ciliate parasite, Anophrys magii, into a marine worm, Sipunculus nudus, was followed by the development of a lysin for the ciliate in the plasma. Lysis of the ciliate was first apparent in a slower rate of swimming, then erratic motion, cessation of forward motion, all within a minute. The ciliate then fell to the bottom of the fluid, the shape changed to a rounded balloon form with a swollen posterior vacuole, the cilia disappeared and the whole ciliate superficially resembled a cyst. Lysis continued and in strongly positive plasmas, the entire ciliate disintegrated within 15 min. The lysin was destroyed by heating to 45°C for 5 min, and was inactivated by ether. It was “used up” by repeated additions of Anophrys to the plasma. The presence of bacteria did not inhibit the test. The response, i.e., the development of the lysin, lasted 5 to 7 days in most cases, and was evoked repeatedly, but did not persist. A regular but briefer response was evoked by injection of fresh broth cultures of Vibrio sp. or large amounts of heat-killed bacteria. No response was evoked by injecting fresh or sterilized sea water or a preparation of endotoxin. The release of an apparently identical substance from the blood cells of Sipunculus was evoked in vivo within 15 min of injection of either Anophrys or bacteria. This released substance apparently persisted in the plasma only for a few hours after the injection, and then 1 or 2 days later the lysin reappeared and persisted for 5 to 7 days. The release of lysin was also evoked by in vitro addition of Anophrys to freshly drawn blood. The in vivo release of lysin from cells was regularly accompanied by the failure of blood to form irregular loose clots of several types of blood cells, by a number of changes in the cells, including a breakdown of innominate cells and a release of crystalline substance from these cells. However, in animals which had lysin again for several days after the injection, innominate cells with crystals were frequently found. A spontaneous disease, apparently caused by a flagellate which burrowed into surface ulcerations and papules, was accompanied by a high titer of lysin. All Sipunculus nudus were negative for lysin if tested within 1 to 2 days of capture, but about a third became positive 1 to 2 weeks after capture. By 14 days, laboratory-“adapted” (recovered?) worms were negative. Repeated bleedings of such negative laboratory-adapted animals did not provoke the appearance of the lysin.

The chick embryo responds to experimental infection with the virus of pseudorabies with a disease pattern simulating the natural infection. Virus lesions of the membrane are followed by infection of all tissues of the central nervous system. Fixed strains produce a hemorrhagic destruction of the central nervous system of the embryo, which is referable to destruction of blood vessel endothelium. Field strains lack the hemorrhagic tendency, but infect the brain when inoculated on the membrane. Neutralization of the virus by specific hyperimmune serum can be demonstrated by inoculation on the membrane. The reaction of the embryo to the virus varies with the age of the embryo. This is reflected both in the membranal lesion and in the subsequent encephalitis.

Chickens 3 wk old, inoculated intranasally with a mesogenic (moderately virulent) strain of Newcastle disease virus, developed necrotic lesions of the mucous acini, predominantly of the middle turbinates. The infection subsequently spread to involve much of the rest of the mucosa, including mucous and ciliated epithelial cells, and other acini. The early phase of adsorption of a virulent strain of the virus to the middle turbinates of chicks 5–21 days of age was studied by giving a standard inoculum intranasally to unanesthetized animals. Variation in amounts adsorbed by individual chickens was large, but was minimized by making measurements on pools of turbinates from three chicks at intervals of 1, 3, and 5 hr after exposure of the excised turbinates to antibody, by washing, and by trypsinization. The virus released from the cells into the trypsin was designated as adherent virus, and the infectious virus in the cells after destruction of the cells by water grinding, as cell virus. Paralysis of ciliary action by cocaine increased the number of infected cells in the turbinates about 10-fold at all three time intervals. Pilocarpine injection before virus inoculation caused a large increase in the amount of infected cells 1 hr after virus administration, but was followed by a sharp drop in infected cells by 3 or 5 hr. Pilocarpine given after the virus decreased the number of infected cells and changed the relationship of infected cells to adherent virus. Exposure of chicks to sustained or severe cold caused a similar but less marked effect. The drop in infected cells was restored to control values if chicks were returned to brooder temperatures. The marked drop of infected cells produced by pilocarpine and cold in living chicks, and in cultures of chicken trachea (previous study), is consonant with the idea that virus has been adsorbed on mucus granules in the mucous cells of the turbinates and then has been reexcreted, as unincorporated virus, into the moving mucous sheet. A series of accessory data support this interpretation.

1. It is likely that certain tailed and filamentous particles seen on electron microscope examination of partially purified saline suspensions of Newcastle virus are the individual virus particles because: (a) They have a highly characteristic shape not seen in other virus preparations. (b) They are present whenever the virus is present in high concentration. (c) Their size agrees with the size of the virus as calculated from light scattering and centrifuge data. (d) They are agglutinated by specific antisera. (e) Infection may be produced in the embryo by relatively few of these particles. 2. It is possible that these filamentous forms have been derived from spherical forms without loss of activity because: (a) Such filamentous forms are not found in the original allantoic fluid when this contains a comparable amount of virus. (b) Filamentous forms appeared in the original allantoic fluid when it was dialyzed against saline solution. (c) Filamentous forms were produced at certain hydrogen ion concentrations but not at others, in solutions maintaining the same infectivity for the embryo. (d) Spherical forms were obtained by suspending the partially purified virus in water instead of saline. In this the virus remained moderately stable. (e) These round forms could apparently be converted into tailed and filamentous forms by the addition of saline, again without loss of activity. (f) This "conversion" could be inhibited by partial inactivation of the water suspension of virus.

Summary The virus of fowl pox has been grown in roller tube cultures of chick fibroblasts in which it survived and multiplied through constant association in low titers with the same continuous cultures for a period of over a hundred days. The cells failed to show any inclusion or destruction. Epithelial cells in culture are killed by the virus, but without the formation of definite inclusion bodies. The refractile inclusion body of the chick chorio-allantoic membrane is osmophilic and can be partially extracted with ether. The residual inclusion is still resistant to purified desoxyribonuclease, ribonuclease and trypsin. The inclusion can be dissolved and elementary bodies liberated by treatment with sodium lauryl sulphate (Duponal C) but this in the concentrations used inactivates the virus. The individual elementary bodies as seen in the electron microscope have a central dark area and are brick shaped. This is brought out more clearly by acid peptic digestion. Smear preparations of the whole inclusion show an amorphous material, presumably fat, surrounding the individual bodies. Some inclusions have thin threads of material running through this matrix. Thin sections of infected membranes show an intracellular edema at the start of the infection, then swelling and destruction of the mitochondria. Few virus particles are present at the start. The number of virus particles and the amount of fat increase to form the final dense osmophilic inclusion.

Summary Three strains of NDV (CG179, B and vaccine), differing from each other in virulence for chickens and chicks, multiplied equally well in the allantoic sac of embryos and attained a maximum titer about 24 hours after allantoic inoculation. This was demonstrated both by repeated sampling of the same embryo and by titering pooled allantoic fluids from different eggs at different intervals. The results of the two methods were identical. The virulent strain (CG179) multiplied rapidly in all tissues of the embryo and produced an early viremia and a fulminating infection. The embryos died in less than 48 hours. In contrast, the vaccine strain gained entrance to the blood much later, and multiplied slowly in embryo tissues such as muscle, liver and brain. However the lungs of 16–17 day old embryos were particularly susceptible to this strain of virus. The severe pneumonia was accompanied by an accumulation of a large amount of virus in this tissue.

The conversion of chick embryonic epidermis to mucous epithelium by excess vitamin A in organ culture as reported by Fell and Mellanby (5) was shown to be accompanied by a corresponding change of susceptibility to influenza and vaccinia viruses. Untreated epidermis of 10- to 12-day chick embryos supported the growth of influenza (PR8) virus in organ cultures and a maximum infectivity (EID50) titer was reached 2 to 3 days after infection. At the same time) the epidermis showed squamous keratinization, beginning about the 4th day of cultivation. Addition of excess vitamin A (40 µg per ml) to the skin organ culture induced the following changes: (a) mucous metaplasia of the epidermis which was usually first evident after 4 to 5 days in the vitamin A medium, (b) increase in the daily and maximum yield of influenza virus, if the epidermis had been grown for 4 or more days in the vitamin A medium before infection took place, and (c) decrease in the production of vaccinia virus under similar conditions. The maximum yield of both viruses remained unchanged, however, if excess vitamin A was introduced to the organ culture at the time of virus inoculation. The magnitude of increase in the yield of influenza virus in this organ culture system was found to be proportionally related to the concentration of vitamin A added 4 or more days before inoculation of this virus. Increasing doses of vitamin A however, had no effect on the short-term growth of influenza virus in tissue cultures of chorio-allantoic membrane. Observation on the early period (2 to 12 hours) of influenza virus growth initiated in the 4-day organ cultures of chick embryonic skin showed no significant difference in virus production between the normal and the vitamin A medium groups. The change of virus specificity apparently is not due to the presence of excess vitamin A per se, but appears to be related to the change of differentiation produced in the organ culture system.

SummaryOne localized area of nasal mucous membrane in chickens was selectively susceptible to initial infection with a myxovirus (NDV) and a giant-cell-forming herpesvirus (LTV). The same quite extensive mucosal area shows earliest signs of incipient keratinizing metaplasia in vitamin A-deprived chickens, and complete conversion to keratinized epithelium following NDV infection. Specific questions of interplay of A-deficiency and respiratory infection are open to study in this whole-animal model.

Summary Neutralization of Newcastle virus by 3 different types of antisera (chicken, rabbit, and human) was studied in several ways. When embryos were inoculated with the mixture of virus and serum on the chorio-allantoic membrane, there was a direct, roughly 1:1 relationship between the amount of virus neutralized and the dilution of serum used. When the mixtures were inoculated into the allantoic sac, the loss of neutralizing activity by the diluted sera exceeded the amount of dilution, i.e., the slope was 2 or more. These results were obtained with all 3 sera. The steeper slope obtained with allantoic inoculation in the case of chicken and rabbit sera seemed to depend on a greater neutralization following allantoic inoculation with undiluted serum. This difference in effective neutralization brought about by different routes of inoculation was not apparent with diluted sera. Incubation of serum and virus for periods up to 2 hr at 35°C had no effect on the amount of virus neutralized by convalescent chicken sera but did increase the neutralization brought about by immune human sera. Incubation of serum and virus before adding red cells increased the amount of inhibition of red cell agglutination caused by all 3 types of sera. Chicken antisera delayed the death of embryos beyond the 6-day period during which embryos inoculated even with minimal infectious doses do not survive. This delay in virus effect was not produced by rabbit or human sera.

Cellular blood clotting in the crab which is initiated on contact with glass is rapidly accelerated in vitro by the addition of a crude amebocyte extract to the syringe and needle with which the blood is obtained. This accelerating action is destroyed by boiling, but is not destroyed by exposure to N -ethylmaleimide.

The domestic chicken was used as an experimental model in which to demonstrate morphological and functional relationships of nasal organ systems, principally of mucous systems. Mucous secretions of olfactory, respiratory, lacrimal, and accessory areas were found to have clear histochemical differences, yet were sufficiently miscible in normal circumstances to form an unbroken, synchronously moving sheet. Changes induced experimentally in host physiology did not all affect the mucous components of given areas in the same way or to the same degree. Mucosal changes were produced by the following methods: Topically administered cocaine 20%, in a single application, temporarily paralyzed the cilia, and the consequently reduced traction apparently held mucus in the acini and effected a temporary lag in mucus excretion. Three successive applications caused acute acinar depletion and ciliary paralysis. Hexylcaine chloride 5% immediately desquamated all intranasal epithelia, damaged the proximal portion of the acini, and induced acinar exhaustion and mucosal inflammation—effects not overcome within 5½ days. Internal dehydration produced progressively viscous mucus, severe acinar gaping with mucus anchored in the acini, a heavy surface sheet, and deceleration or arrest of mucociliary flow. Avitaminosis A induced reduction in the height (about 50%) of all mucosae and acini, especially the inner lining of the maxillary concha, caused an actual 50% reduction in the number of cells per acinus, and retarded the mucociliary flow rate about 50%. Pilocarpine induced initial hypersecretion, later exhaustion, and, still later, slow production of densely staining mucus in the acinar cells; also acinar gaping. Breeding in a germfree environment produced a greatly reduced mucosal depth throughout the nasal fossa, an extraordinary reduction in the number of cells per acinus, relative reduction in the number of acinar neck cells, and concomitant increase in ciliated cells in that region. Exposure to a temperature of –20°C for 1 hr caused blanching of all secretory cells, acinar gaping, and temporary reduction of mucosal depth.

A variant mouse hepatitis virus MHV(C3H) to which cultured peritoneal macrophages from both PRI and C3H mice were susceptible was isolated from stocks of the MHV(PRI) strain of mouse hepatitis virus. It was cloned on C3H macrophage monolayers and killed both adult PRI and C3H mice when injected intraperitoneally. This new variant was antigenically indistinguishable from the wild type virus. While the emergence of the variant virus was delayed in the course of infecting C3H macrophages with large inocula of MHV(PRI), the second passage grew to a high titer in both cell types without delay. Thus, adaptation to the new host was immediate. Interference, apparently not interferon-mediated, between the two variant viruses may have been the cause for the delay in the emergence of the variant virus. The delayed destruction of C3H-cultured macrophages by large inocula of MHV(PRI) uniformly resulted in the emergence of MHV(C3H). Whether the new variant emerged as a result of a selection of a pre-existing stable mutant or was conditioned by "growth" in the resistant host was not determined.

Adult or weanling C3H mice were found to be genetically resistant to a strain of mouse hepatitis virus. Infant C3H mice, however, developed infection and died from mouse hepatitis virus when minimal infectious doses of virus were given to them. There was a delay in the time of death compared to that of the genetically susceptible strain, and the virus recovered from these mice had increased pathogenicity for C3H mice. The ontogeny of resistance to hepatitis in the C3H mice thus progresses from delayed susceptibility to complete resistance as the age of the host increases. It is reflected in increased resistance of macrophages derived in vitro from liver cultures of infant mice of different ages. This increase in resistance with age was reduced by maintaining the cultures for a longer period of time before inoculation, or by increasing the number of explants in a given culture. Resistant cells were uniformly furnished by mice age 16 days, or more. It is concluded that a process of maturation of resistance of the cells takes place after the mice are born, but that this does not continue under in vitro conditions, and that it may be modified by the environment of the cells.

1. The reaction of the chick embryo to nine strains of gonococci was studied. Four of these were inoculated intra-amniotically in 14 to 15 day embryos. 2. Infection of the 10 day chorio-allantoic membrane was localized and accompanied by polymorphonuclear leucocytic phagocytosis. 3. Infection was either transitory or persisted until hatching. Several strains killed the 10 day embryo in 3 days. 4. Chicken immune sera placed on the infected membranes failed to affect phagocytosis. 5. Slight sinusitis, bronchitis, and infection of the pulmonary alveoli were common following intra-amniotic injection of 14 to 15 day embryos. Infection also extended to the pulmonary and abdominal air sacs. 6. Serial passage on the membrane so modified one strain that it killed a greater percentage of both 10 day and 14 day embryos. The infection after modification was also accompanied by bacteremia and meningitis in one embryo. 7. The ability of meningococci to invade tissue and produce septicemia is contrasted with the inability of gonococci to produce more than a superficial infection. 8. The infection of the embryo with gonococci reproduces all of the essential characteristics of the disease in man. 9. Gonococci were found within columnar epithelial cells in a case of acute human urethritis.

Respiratory virus transmission in children was studied comparatively in three ecologically different low-income communities in West Bengal: an isolated village, a suburban village, and a crowded urban community. Continued use of contaminated pond water for bathing, irrigation of nasal passages, post-defecation washing of the anus, and washing of food vessels was common to all, as was intense crowding of indoor sleeping quarters during cold and wet seasons. Intensity of infection was highest (26%) in the most crowded urban area, the variety of virus types least in the most isolated village. Sources of drinking water differed but seem unrelated to virus transmission. Toxigenic diphtheria organisms were found in non-specific skin lesions in children in each area.

In 3 separate experiments, cells derived from chick embryo muscle explants have been grown in either Waymouth's medium or Ling's (AN.54) medium with 20% human placental cord serum. Continuous transfer and new outgrowth from a succession of 2 × 2 mm fragments has continued for periods of 24 to 44 months. Continuous growth was achieved only on a collagen substrate, and no continuous growth was obtained when cells were transferred to glass. When incubator temperature was raised to 43 °C over a period of 1 month, new cell types developed and had the capacity to both survive and grow directly on glass for several months.

The hypothesis that homeostatic control mechanisms control mucociliary function in ciliated mucous membrane was tested. Nasal mucociliary transport rates were recorded in chickens in vivo at successive intervals during exposure to SO2 or after inoculation with Newcastle disease virus (NDV), or both. Either agent alone caused deceleration of the turbinate clearance. However, when SO2 exposure was limited to one nasal fossa and turbinate mucociliary rates were determined in the unexposed and infected side, the two acted antagonistically and yielded approximately normal rates. Exposure of the nasal mucosae to SO2 caused decreased rates of sinus clearance, while NDV infection of nasal membranes induced increased rates of sinus clearance. Exposure of nasal mucosae to both agents acted antagonistically to effect rates of sinus clearance in normal ranges. These data support the idea of homeostasis.

Recognition of self and non-self by invertebrates apparently varies from species to species and as yet there is no general understanding of this variation within the phylum. Injection of Arbacia (sea urchin) cells, about half of which are deeply pigmented, into Asterias (sea star) in vivo was followed by an abrupt drop in the number of circulating amebocytes of the host. The Arbacia cells adhered to and were phagocytosed by the host cells; the latter consistently clumped within the papulae and later ruptured to the exterior. The interaction of Asterias and Arbacia amebocytes was not prevented by either the treatment of the host Asterias , or by the treatment in vitro of Arbacia cells, wth N -ethyl maleimide (NEM). Injection of Asterias cells into Asterias did not elicite cell clumping, nor was it followed by a drop in the circulating amebocytes.

The problem of cell blockade or interference has been studied using Newcastle disease of chickens as a model. Embryos may be protected against the uniformly lethal effect of the virus by previous inoculation with ultraviolet-irradiated virus. It was necessary to use 0.5 to 1 mg. of partially purified washed virus in order to demonstrate this effect. Blockade by inactive virus in the embryo was not complete, since it could be overcome by inoculating increasing amounts of active virus or by injecting the active virus into the allantoic sac instead of placing it on the membrane. The lethal effects of small doses of Newcastle virus could also be blocked by previous infection of the embryo with either swine influenza virus or human influenza A. Again this blockade may be overcome by using larger doses of active Newcastle virus. Simultaneous injection of chickens with viruses of equine encephalomyelitis and a virulent strain of Newcastle disease virus merely delayed the incubation period of the Newcastle virus a day or so. Simultaneous inoculation of chickens with virulent and avirulent Newcastle strains caused complete blocking of the virulent strain. This blocking or interfering effect of the avirulent strain could be demonstrated 1 or 2 days after the inoculation of the virulent strain but was not effective after symptoms of the virulent disease had set in.