Smyth Line Research Articles

Alopecia areata and universalis in the Smyth chicken model for spontaneous autoimmune vitiligo.

The Smyth line (SL) chicken model for spontaneous, postnatal expression of vitiligo may also show varying incidences and degrees of severity ranging from alopecia areata-like to universalis-like integumental changes. Although human vitiligo patients are known to have a four times greater chance of having alopecia areata than do people without vitiligo, in the SL model, feather loss is limited to birds that show some degree of amelanosis of feather and skin tissue. Both the vitiligo and the alopecia have an autoimmune component, as shown by histologic and immunologic studies, including the correctional influences of corticosterone and cyclosporine-A. The major histocompatibility haplotype (MHC) has a major effect on the incidence and expression of the vitiligo, as well as the alopecia that occurs within vitiliginous birds. Three different MHC haplotypes were identified in the original line that was selected for vitiligo, and from these, three sublines were developed, each homozygous for a different haplotype. Of the three sublines (SL101, SL102, and SL103) the vitiligo has a significantly earlier onset and severity in the SL101 than in the other two lines. The incidence of alopecia, however, is significantly lower in the SL101 subline than in the other two. Inheritance of the vitiligo is polygenic with an additional genetic component for the alopecia trait. It is hypothesized, but as yet unproven, that a feather development defect interacts with the SL melanization and immunologic defects to initiate the partial (areata) and complete (universalis) alopecias. The alopecia universalis is rarely seen until adulthood and is characterized by short (<0.5 cm), undeveloped feathers. If feather growth resumes in these birds, the feathers dry up, cease to grow, and often break off.

The Delayed Entry of Thoracic Neural Crest Cells into the Dorsolateral Path Is a Consequence of the Late Emigration of Melanogenic Neural Crest Cells from the Neural Tube

Neural crest cells migrate along two pathways in the trunk: the ventral path, between the neural tube and somite, and the dorsolateral path, between the somite and overlying ectoderm. In avian embryos, ventral migration precedes dorsolateral migration by nearly 24 h, and the onset of dorsolateral migration coincides with the cessation of ventral migration. Neural crest cells in the ventral path differentiate predominantly as neurons and glial cells of the peripheral nervous system, whereas those in the dorsolateral path give rise to the melanocytes of the skin. Thus, early- and late-migrating neural crest cells exhibit unique morphogenetic behaviors and give rise to different subsets of neural crest derivatives. Here we present evidence that these differences reflect the appearance of specified melanocyte precursors, or melanoblasts, from late- but not early-migrating neural crest cells. We demonstrate that serum from Smyth line (SL) chickens specifically immunolabels melanocyte precursors, or melanoblasts. Using SL serum as a marker, we first detect melanoblasts immediately dorsal and lateral to the neural tube beginning at stage 18, which is prior to the onset of dorsolateral migration. At later stages every neural crest cell in the dorsolateral path is SL-positive, demonstrating that only melanoblasts migrate dorsolaterally. Thus, melanoblast specification precedes dorsolateral migration, and only melanoblasts migrate dorsolaterally at the thoracic level. Together with previous work (Erickson, C. A., and Goins, T. L.,Development121, 915–924, 1995), these data argue that specification as a melanoblast is a prerequisite for dorsolateral migration. This conclusion suggested that the delay in dorsolateral migration (relative to ventral migration) may reflect a delay in the emigration of melanogenic neural crest cells from the neural tube. Several experiments support this hypothesis. There are no melanoblasts in the ventral path, as revealed by the absence of SL-positive cells in the ventral path, and neural crest cells isolated from the ventral path do not give rise to melanocytes when explanted in culture, suggesting that early, ventrally migrating neural crest cells are limited in their ability to differentiate as melanocytes. Similarly, neural crest cells that emigrate from the neural tubein vitroduring the first 6 h fail to give rise to any melanocytes or SL-positive melanoblasts, whereas neural crest cells that emigrate at progressively later times show a dramatic increase in melanogenesis under identical culture conditions. Thus, the timing of dorsolateral migration at the thoracic level is ultimately controlled by the late emigration of melanogenic neural crest cells from the neural tube.

Lymphocyte populations in dermal lymphoid aggregates of vitiliginous Smyth line and normally pigmented Light Brown Leghorn chickens

Smyth line (SL) chickens develop a spontaneous, autoimmune loss of melanocytes (vitiligo) from the feather. To determine whether lymphocyte infiltration into two-week-old regenerating feathers of vitiliginous chickens was accompanied by lymphocyte infiltration into the skin, skin biopsies were conducted in SL chickens at two-week intervals throughout the development of vitiligo (SLV) when the chicks were 6 to 14 weeks of age. Control skin samples were obtained from age-matched, normally-pigmented Light Brown Leghorn (LBL) chickens. Frozen skin sections were labelled with a panel of mouse mAb to identify various lymphocyte populations. There was no lymphocyte infiltration into the skin of SL or control chickens. However, in both lines of chickens, dermal lymphoid aggregates (DLA), consisting primarily of T cells, were observed. In the DLA of SL chickens, the ratio between CD4 + and CD8 + T cells was lower ( P = 0.005) and the percentage of γδ T cells higher ( P = 0.027) than in the controls. Additionally, in SL chickens the lymphocyte populations in the DLA varied depending on the developmental stage of vitiligo. These data suggest a relationship between the DLA and autoimmune vitiligo in the SL model.

Profiles of Pulp Infiltrating Lymphocytes at Various Times Throughout Feather Regeneration in Smyth Line Chickens with Vitiligo

Smyth line (SL) chickens develop a spontaneous, autoimmune, posthatch loss of pigment cells (vitiligo) in regenerating feather tissue. Smyth line vitiligo (SLV) is associated with lymphocyte infiltrations prior to and throughout the development of the disorder. It was the purpose of this study to determine the type, relative amounts, and proportions of pulp-infiltrating lymphocytes at various times throughout the growth of regenerating feathers. Feathers were plucked from 8-week-old chickens with and without SLV. Feather pulp cell suspensions were prepared when the regenerating feathers were 2, 3, 4, and 6 weeks of age. Cells were fluorescently labeled using a panel of mouse monoclonal antibodies specific for chicken lymphocytes. Both T and B cells infiltrated the feather pulp of chickens with SLV. T cell levels remained elevated throughout the 6 weeks of feather growth, while B cell levels steadily declined to control levels over the same time. The pulp-infiltrating cells were primarily T cells with an αβ T cell receptor expressing the Vβ1 gene (TCR2+). The ratio between CD4+ and CD8+ cells was 1.42 and 0.75 in 2- and 6-week-old regenerating feathers from chickens with autoimmune SLV, respectively. In non-vitiliginous chickens this ratio was always near 1. These data suggest that TCR2+ T cells play an important role in SLV. CD4+ cells may play a recruiting/activating role, whereas CD8+ cells may have cytotoxic activity specifically directed against melanocytes. Additionally, this is the first report demonstrating the infiltration of B cells into the feather pulp of vitiliginous chickens. These B cells may directly/indirectly contribute to melanocyte destruction in SLV.

5-Azacytidine Treatment Induces Autoimmune Vitiligo in Parental Control Strains of the Smyth Line Chicken Model for Autoimmune Vitiligo

The effect of 5-Azacytidine (5-AzaC) on melanization was examined in two sublines of the Smyth line (SL) chicken model for autoimmune vitiligo, in two MHC-matched vitiligo-susceptible but normally pigmented controls (BL), and in nonsusceptible controls (LBL). 5-AzaC was administered ip every 3 days from day of hatch to 18 weeks at levels of 1 or 3 mg/kg body wt. Both treatments increased (P< 0.01) the incidence of autoimmune vitiligo in BL controls. In contrast, treatment significantly depressed (P< 0.01) the expected high incidence of vitiligo in one SL subline, but not in the other. There were no apparent pigmentation changes in 5-AzaC-treated LBL controls. 5-AzaC had dose-dependent depressing effects (P< 0.01) on body and lymphoid organ weights. Histological and mitogen assay data suggest negative effects on lymphocyte number and function. The data show that 5-AzaC can initiate autoimmune disease in genetically susceptible but phenotypically normal individuals.

Alterations in Blood Leukocyte Populations in Smyth Line Chickens with Autoimmune Vitiligo

Smyth line (SL) chickens spontaneously develop a posthatch autoimmune loss of pigment cells (vitiligo) in the feather. Concurrent with the development of Smyth line vitiligo (SLV), mononuclear cell infiltration and altered T cell profiles can be observed in the pulp of developing feathers.To determine whether the development of SLV is preceded by or associated with alterations in blood lymphocyte and leukocyte populations, blood leukocyte profiles were established at various times prior to and throughout the spontaneous development of SLV. The proportions among various blood leukocyte populations (percentage of lymphocytes, monocytes, heterophils, eosinophils, and basophils) were determined by differential leukocyte counts. The proportions among blood lymphocyte populations were examined by immunofluorescence and flow cytometric analyses. Lymphocyte markers included fluorescence-conjugated monoclonal antibodies to identify T cells (CD3), T helper cells (CD4), cytotoxic T cells (CD8), and B cells (IgM).The proportions among blood lymphocyte populations examined did not differ between SL and MHC-matched parental Brown line (BL) control chickens prior to and throughout the development of SLV. Compared to BL controls, SL chickens had, however, increased proportions of inflammatory leukocytes in the blood, particularly at the time when most hatchmates developed SLV. Examination of leukocyte alterations with respect to first observation of SLV revealed that inflammatory leukocyte levels were elevated early in SLV.Although altered leukocyte profiles in the blood were observed during the development of SLV, blood from SL chickens did not reflect alterations in lymphocyte populations known to occur at the site of melanocyte destruction. The role of inflammatory blood leukocytes in the development of SLV needs to be further investigated.

T Cells in Regenerating Feathers of Smyth Line Chickens with Vitiligo

Smyth line (SL) chickens exhibit a spontaneous, autoimmune, depigmentation (SL vitiligo, SLV) in regenerating feather tissue due to the death of pigment cells (melanocytes). It was the purpose of this study to characterize mononuclear leukocytes which infiltrate the feather as SLV develops. Frozen sections of regenerating feathers from SL and control chickens were labeled with a panel of mAbs specific for chicken mononuclear leukocytes. SL chickens were found to have significantly greater numbers of T cells in the feather pulp prior to, and throughout, the development of SLV. Initially, both SL and control chickens had a CD4/CD8 ratio near 1.0 in their feather pulp. Following the onset of SLV, the CD4/CD8 ratio in SL chickens dropped below 0.4. Throughout the development of SLV, SL chickens had greater proportions of T cells with α/β T cell receptors than controls. Histological evidence strongly supports an important role for T cells in the pathology of SLV.

Immune Response to Sheep Red Blood Cells in Two Smyth Line Populations Homozygous for Different Major Histocompatibility Complex Haplotypes

The Smyth line (SL) chicken is characterized by a high incidence of spontaneous, posthatch, selective destruction of melanocytes, caused by an autoimmune phenomenon. It has been shown that the MHC is associated with the development and severity of the disease. To clarify further the role of MHC haplotypes and other factors leading to an autoimmune response, mean antibody titers to SRBC were determined for 37-wk-old females from 2 SL sublines (SL101 and SL102), each homozygous for a different MHC haplotype, their MHC-matched parental control sublines (BL101 and BL102), and a normally pigmented control, LBL. Although total incidence of amelanosis is approximately the same for both SL sublines, amelanosis occurs earlier and is more severe in SL101 birds. Within sublines, chickens were further classified as to the extent of the feather amelanosis. Neither SL MHC subline had a mean SRBC titer that differed significantly from unrelated LBL controls. Although the secondary response of the two sublines differed from each other (P < .05), neither differed from its MHC-matched parental control; therefore, the differences in immune response appear to be largely MHC-related and not closely related to melanocyte destruction. When SRBC titers were related to amelanotic severity, no differences were found within the SL101 subline, although, SL102 birds that became amelanotic at a later age had a lower primary response to SRBC (P < .05) than the more severely affected group. Birds simultaneously producing both pigmented and amelanotic feather tissue had higher (P < .05) primary and secondary anti-SRBC titers than did the complete amelanotics.

Avian Models of Autoimmune Disease: Lessons from the Birds

Many important lessons have been learned from studies of autoimmune diseases in chicken models. It is now quite clear that both cellular and humoral immune responses are important in developing the final picture of autoimmune disease. In the case of the amelanosis of Smyth line (SL) chickens, antibody appears to play the primary role, whereas the sclerosis of University of California/Davis line-200 (UCD-200) birds is mainly mediated by T cells. Chronic thyroiditis of the OS chicken is due to both humoral and cellular effector mechanisms. The Obese strain (OS) chicken is particularly valuable for studies of genetics. Multiple genetic factors converge in producing maximal susceptibility to the development of autoimmune thyroiditis. They include MHC genes responsible for immune recognition; genes affecting thymus development, critical for regulation of the immune response; and genes that control thyroid function, influencing the vulnerability of the target organ to autoimmune attack. The importance of environmental factors, such as dietary iodine, is also strongly supported by studies in the OS chicken. Thus, the birds have provided valuable clues to our understanding of human autoimmune disorders in the past and are expected to do so in the future.

Smyth Chicken Melanocyte Autoantibodies: Cross‐Species Recognition, In Vivo Binding, and Plasma Membrane Reactivity of the Antiserum

Smyth line (SL) chickens, which develop a depigmenting disorder similar to human vitiligo, produce circulating anti-melanocyte antibodies (Austin, L.M. et al., (1992) The detection of melanocyte autoantibodies in the Smyth chicken model for vitiligo. Clin. Immunol. Immunopathol., 64:112-120). In order to characterize these autoantibodies, we studied the reactivity of cultured chicken, mouse, and human melanocytes, as well as frozen sections of chicken feather follicles and embryonic eyes, against SL serum, employing indirect immunofluorescence. Light Brown Leghorn (LBL) serum was used as a negative control. Chicken (SL and LBL), mouse, and human melanocytes exhibited greater fluorescence with SL serum than with LBL serum (up to a 1:60,000 dilution). The fluorescent pattern was predominant along the perimeter of the cells, suggesting plasma membrane staining. Fluorescence-activated flow cytometry analysis and immunocytochemical localization at the ultrastructural level using intact chicken cells supported this hypothesis. Melanocytes were readily stained in cryosections of regenerating feather follicles and embryonic eyes incubated with SL, but not LBL, serum. In addition, amelanotic melanocytes in albino chicken feathers reacted with SL serum. SL serum also preferentially stained cells emigrating from cultured avian neural tubes and within the dermis of the proliferative germ of regenerating feather follicles suggesting that melanoblasts express the antigens. We conclude that Smyth line serum contains melanocyte autoantibodies that cross-react with mouse and human melanocytes, are able to bind to pigment cells within tissues, and recognize antigens expressed in the cytoplasm and on the surface of melanocytes and melanoblasts.

The detection of melanocyte autoantibodies in the Smyth chicken model for vitiligo

Smyth line (SL) chickens are phenotypically characterized by a posthatch depigmentation (vitiligo) of the feathers. The destruction of melanocytes in the feather follicle as well as in other tissues such as the choroid is genetically determined. Previous studies have shown that bursectomy or treatment with immunosuppressive agents decreases the incidence and severity of SL depigmentation (1). These observations implicate a role for the immune system, specifically the humoral component, in melanocyte destruction. In this study we show that there are circulating melanocyte-specific autoantibodies in the sera of depigmented SL chicks which are not present in sera from Light Brown Leghorn (LBL) control chicks. By immunoblots and by immunoprecipitation of radiolabeled melanocyte proteins, SL autoantibodies were shown to bind to multiple melanocyte proteins between 65 and 80 kDa. These proteins are not detected in SL fibroblasts. By immunoblotting, the incidence of autoantibodies for these 65- to 80-kDa proteins was determined to be 95% in deigmented SL chicks ( n = 20), 0% in normally pigmented SL chicks ( n = 8), and 5% in LBL chicks ( n = 20). Melanocyte autoantibodies are detectable in the sera of affected chicks at or several weeks prior to the expression of depigmentation. This information, plus previously published data, implicate melanocyte autoantibodies in the depigmentary phenomenon of vitiligo observed in Smyth line chickens.

Extensive Antigenic Mimicry by Retrovirus Capsid Proteins

AIDS Research and Human RetrovirusesVol. 6, No. 12 Extensive Antigenic Mimicry by Retrovirus Capsid ProteinsRobert F. GarryRobert F. GarrySearch for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1990.6.1361AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Extensive Antigenic Mimicry by Retrovirus Capsid Proteins." , 6(12), pp. 1361–1362FiguresReferencesRelatedDetailsCited byApoptotic Effect of Macrophages against Mycobacterium tuberculosisJournal of Bacteriology and Virology, Vol. 46, No. 4References30 April 2014Epitope mapping of ribonucleoprotein antigens: answers without questions?28 June 2008 | Clinical and Experimental Immunology, Vol. 94, No. 2Antibodies to EYRKK vesicular stomatitis virus-related peptide account only for a minority of anti-Ro60kD antibodies28 June 2008 | Clinical and Experimental Immunology, Vol. 98, No. 3Retroviruses and autoimmune rheumatic diseases28 June 2008 | Clinical and Experimental Immunology, Vol. 98, No. 1Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic DiseaseMicrobiology and Molecular Biology Reviews, Vol. 72, No. 1Involvement of human intracisternal A-type retroviral particles in autoimmunity1 January 2005 | Microscopy Research and Technique, Vol. 68, No. 3-4Direkte Gelenkinfektionen bei anderen infektiösen und parasitären Erkrankungen (M 01)Analysis of the Effect of Endogenous Viral Genes in the Smyth Line Chicken Model for Autoimmune VitiligoThe American Journal of Pathology, Vol. 156, No. 3Urine Antibody Tests: New Insights into the Dynamics of HIV-1 Infection1 September 1999 | Clinical Chemistry, Vol. 45, No. 9Antiretroviral antibodies: implications for schizophrenia, schizophrenia spectrum disorders, and bipolar disorderBiological Psychiatry, Vol. 45, No. 6Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteinsArthritis & Rheumatism, Vol. 42, No. 2Sjögren’s Syndrome: The Significance of Epithelial CellsHIV INFECTION–ASSOCIATED INFLAMMATORY MUSCULOSKELETAL DISORDERSRheumatic Disease Clinics of North America, Vol. 24, No. 2Reactivity of Sera from Systemic Lupus Erythematosus and Sjögren’s Syndrome Patients with Peptides Derived from Human Immunodeficiency Virus p24 Capsid AntigenClinical Diagnostic Laboratory Immunology, Vol. 5, No. 2Antiribonucleoprotein Antibodies in Children with HIV Infection: A Comparative Study with Childhood-Onset Systemic Lupus Erythematosus CARLOS M. GONZÁLEZ, FRANCISCO J. LÓPEZ-LONGO, JOHANNE SAMSON, INDALECIO MONTEAGUDO, RAQUEL GRAU, MARGARITA RODRÍGUEZ-MAHOU, CLAIRE ST-CYR, NORMAND LAPOINTE, and LUIS CARREÑO25 June 2009 | AIDS Patient Care and STDs, Vol. 12, No. 1The HIV/AIDS epidemic: its evolutionary implications for human ecology with special reference to the immune systemScience of The Total Environment, Vol. 191, No. 3The Potential Roles of Endogenous Retroviruses in AutoimmunityImmunological Reviews, Vol. 152, No. 1HIV and ComplementCharacterization of an Antigen Shared by Human Thymic Epithelium and Human T Cell Leukemia Virus p19 Gag ProteinJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 11, No. 1Immunopathogenesis and Therapy of Systemic Lupus Erythematosus3 November 2012 | Clinical Immunotherapeutics, Vol. 4, No. 6The etiopathogenesis of Sjögren's syndromeSeminars in Arthritis and Rheumatism, Vol. 25, No. 2Anti-human immunodeficiency virus type 1 antibodies of noninfected subjects are not related to autoantibodies occurring in systemic diseasesClinical Diagnostic Laboratory Immunology, Vol. 2, No. 4Retroviruses and Their Roles in Chronic Inflammatory Diseases and AutoimmunityHTLV-I Associated Myelopathy: A Case of Viral-Induced Auto-Immunity7 July 2009 | Autoimmunity, Vol. 21, No. 3New evidence for involvement of retroviruses in sjögren's syndrome and other autoimmune diseasesArthritis & Rheumatism, Vol. 37, No. 4Sequence Similarities between Retroviral Proteins and Components of the Spliceosome Scott A. Tenenbaum, Thomas G. Voss, Robert F. Garry, and William R. Gallaher16 March 2009 | AIDS Research and Human Retroviruses, Vol. 10, No. 5Endogenous Human RetrovirusesPathogenesis of human immunodeficiency virus infectionMicrobiological Reviews, Vol. 57, No. 1Human T cell Leukemia Virus Type I Infection and Chronic MyelopathyBrain Pathology, Vol. 3, No. 1Molecular mimicry and autoantigens in connective tissue diseasesMolecular Biology Reports, Vol. 16, No. 3Evidence for polyclonal B cell activation as the mechanism for LCMV-induced autoimmune hemolytic anemiaImmunology Letters, Vol. 31, No. 3 Volume 6Issue 12Dec 1990 To cite this article:Robert F. Garry.Extensive Antigenic Mimicry by Retrovirus Capsid Proteins.AIDS Research and Human Retroviruses.Dec 1990.1361-1362.http://doi.org/10.1089/aid.1990.6.1361Published in Volume: 6 Issue 12: March 16, 2009PDF download

Effect of Eumelanic Phenotypes on the Expression of Amelanosis in the Smyth Chicken

The Smyth line is characterized by an autoimmune loss of melanin in the feather and eye in association with a hypermelanizing melanocyte, which presumably triggers immune system intervention. Inheritance appears to be multigenic. The present study was designed to determine if eumelanin-enhancing modifiers influence the incidence and severity of the line-associated amelanosis.Smyth chicks with dark brown (eb) down had a higher incidence of amelanosis (P<.01) than did their hatchmates with light brown down. Furthermore, parents with dark down at hatch produced a higher incidence of amelanotic progeny than parents with light down. Reciprocal crosses of the Smyth line to a highly eumelanized (eb/eb) Recessive Black (RB) line produced F1 amelanosis. However, sires from the Smyth line produced significantly more amelanotics than did RB males (P<.01). The influence of dark down on amelanotic development was also apparent in the Smyth-RB F1. The use of amelanotic F1 parents produced a significantly higher incidence of affected F2 offspring than did the use of unaffected parents. A backcross to the Smyth line produced an incidence of 67.6% amelanosis, whereas only one chick (2.04%) developed amelanosis from an F1 × RB mating. The finding that dark-downed Smyth chicks exhibit, and subsequently produce, a significantly higher incidence of amelanosis supports ultrastructural observations that associate the Smyth line amelanosis with a hyperactive melanocyte. The unusually high expression of amelanosis (22.7%) in the Smyth-RB F1 suggests that the two lines share one or more common eumelanogenic genetic factors.

Delayed-Amelanotic (DAM or Smyth) Chicken: Melanocyte Dysfunction In Vivo and In Vitro

Chickens of the autoimmune delayed-amelanotic (DAM or Smyth) line develop postnatal feather amelanosis and severe visual defects, both of which are presumed to be due to a dysfunction of melanocytes and a subsequent autoimmune response that eliminates pigment cells. In this report we elucidate further the melanocytic defect. We present a morphologic analysis of the mildly affected erratic (eDAM) group of Smyth chicken whose partial depigmentation and lack of visual impairment resemble human vitiligo more so than do the complete amelanosis and blindness in the classical Smyth line. Histologically, the sequential events leading to amelanosis in the young Smyth chicken occur simultaneously in the feathers of adult eDAM Smyth chickens, and the infiltration of the feather pulp with mononuclear leukocytes correlates with the extent of local pigmentary abnormality. Cytochemical localizations of dopa-oxidase and acid-phosphatase activities in eDAM feather melanocytes suggest that melanogenesis and autophagocytosis of melanosomes occur in tandem and that the rates of both are higher in these cells than in melanocytes of normally pigmented control chickens. Assays for tyrosinase activity in feather follicles indicate a hypermelanization in eDAM feathers and in the pigmented feathers of young Smyth chicks prior to the onset of depigmentation. Finally, we report on the establishment of pure, proliferative cultures of neural crest-derived melanocytes from control and Smyth chicken embryos. The degenerative events in Smyth chicken melanocyte cultures mimic in part those of the cells in vivo and are therefore indicative of a genetic defect that is independent of the immune system.

Extraordinary Atmospheric Phenomenon

I INCLOSE a paragraph from the Glasgow Evening Citizen of this date relating to that peculiar form of lightning known as fire-balls. The explanation of the explosion in the funnel is, I think, erroneous, it having been caused by the explosion of the fire-ball, thus driving out the smoke by the fire-doors. The aurora was very bright here on Wednesday evening, showing Piazzi Smyth's line with a small direct vision spectroscope. Before the eye became sufficiently sensitive for measurement, clouds cut off the bright part. The aurora was a general bright northern glow without streamers, and was observed brightest a little after eight (p.m.). These notes may be of use to you in connection with those of other observers.