Subpopulations of human T lymphocytes. IV. Quantitation and distribution in patients with mycosis fungoides and Sézary syndrome.

T cell subpopulations (Tμ and Tγ cells) were examined in the peripheral blood from fourteen patients with mycosis fungoides and Sézary syndrome. One patient with Sézary syndrome having low lymphocyte count had higher proportions of Tγ cells when compared to controls while the other with high lymphocyte count (75% Sézary cells) lacked Tγ cells and had normal proportions of Tμ cells. T cells from a third patient with Sézary syndrome having high lymphocyte count (95% Sézary cells) lacked almost completely both Tμ and Tγ cells. Three of eleven patients with mycosis fungoides had a high proportion of Tγ cells and one had a high proportion of Tμ cells. Study of T cells in the peripheral blood, lymph nodes, and bone marrow from two patients with mycosis fungoides demonstrated that the quantitative abnormality of tμ and Tγ cells is shared by the peripheral blood and bone marrow and not by the lymph nodes. Heterogeneity of T cells subsets in mycosis fungoides appears to be in non-malignant T cells. However, in Sézary syndrome malignant Sézary T cells demonstrate heterogeneity with regard to receptors for IgM (Tμ) and IgG (Tγ).     

Malignant and nonmalignant T cell lines from human T cell lymphotropic virus type I-negative patients with Sézary syndrome.

The establishment of an in vitro model for cutaneous T cell lymphomas and Sézary syndrome has been difficult since T cells from individuals with these diseases do not proliferate in response to T cell mitogens. We found that conditioned media, collected from mitogen-activated PBMC from Sézary patients, contain an IL-2 receptor inducing factor. Despite their ostensible proliferative disorder, using a combination Sézary cell-conditioned media and rIL-2, we established IL-2 responsive, human T cell lymphotropic virus type I negative T cell lines from 23 patients, nine of which contain cells with the structural and/or genetic characteristics of neoplastic Sézary T cells.     

SC5 mAb represents a unique tool for the detection of extracellular vimentin as a specific marker of Sezary cells

Circulating malignant Sézary lymphocytes result from a clonal proliferation of memory/activated CD4(+)CD45RO(+) T lymphocytes primarily involving the skin. Recently, the CD158k/KIR3DL2 cell surface receptor has been identified to phenotypically characterize these cells. We previously described a mAb termed SC5 that identifies an unknown early activation cell membrane molecule. It is expressed selectively by T lymphocytes isolated from healthy individuals upon activation, and by circulating Sézary syndrome lymphocytes. In addition, we found that SC5 mAb was reactive with all resting T lymphocytes once permeabilized, indicating that SC5 mAb-reactive molecule might present distinct cellular localization according to the T cell activation status. In this study, we show for the first time that SC5 mAb recognizes the intermediate filament protein vimentin when exported to the extracellular side of the plasma membrane of viable Sézary malignant cells. We demonstrate that SC5 mAb is unique as it reacts with both viable malignant lymphocytes and apoptotic T cells. As vimentin is also detected rapidly at the cell membrane surface after normal T lymphocyte activation, it suggests that its extracellular detection on Sézary cells could be a consequence of their constitutive activation status. Finally, as a probable outcome of vimentin cell surface expression, autoantibodies against vimentin were found in the sera of Sézary syndrome patients.     

Ultrastructure of adult T-cell leukemia/lymphoma

Eighteen cases of adult T-cell leukemia/lymphoma (ATLL) in Japan were analyzed by electron microscopy and compared with 5 cases of B-lymphoma and well-established groups of T-lymphomas (4 cases of T-lymphoblastic lymphoma and 2 cases of Sézary syndrome). Five hundred cells in each case, categorized ultrastructurally as to the cellular size and nuclear shape, showed an essentially pleomorphic cellular distribution in ATLL in remarkable contrast with the monomorphism of B-"histiocytic", B-well-differentiated lymphocytic, and T-lymphoblastic lymphomas. Some B-lymphomas and Sézary syndrome also showed pleomorphism. Cases of ATLL were classified according to the predominant cells and degree of nuclear irregularity, which delineated a spectrum of node-based, peripheral T-cells neoplasms probably encompassing T-immunoblastic sarcoma, T-zone lymphoma, as well as multilobated T-cell lymphoma. The characteristic fine structure of ATLL, in comparison with that of B-lymphomas, included slight to marked nuclear irregularity with convoluted-shape predominance, a specked chromatin pattern of the large cells, prominent lysosomes, and glycogen accumulation in addition to the difference in cellular distribution. Although T-lymphoblastic lymphoma and Sézary syndrome shared some of these features, the ultrastructural differentiation of ATLL from them seems to be possible.     

Can peripheral T-cell lymphomas be morphologically subclassified? A morphometric approach to 21 cases

Morphometric analysis of nuclear sizes and shapes was carried out on semithin sections of lymph node for 21 patients suffering from non-Hodgkin's peripheral T-cell malignant lymphoma (ML) (excluding mycosis and Sézary syndrome). Twenty cases of B-cell ML and three cases of Sézary syndrome with massive lymph node infiltration were also studied as references. Wright and Isaacson's recent proposals were applied to classify the peripheral T-cell MLs into monomorphic medium-cell ML (eight cases), pleomorphic ML (nine cases), and monomorphic large-cell ML (four cases). These three classes were readily distinguishable by morphometric analysis of nuclear sizes. Nuclear areas and their coefficients of variation were higher in pleomorphic MLs than in monomorphic medium-cell MLs (p less than 0.01). Large-cell monomorphic MLs were set apart by the histograms of their nuclear sizes. The mitoses were evaluated on histological sections and found to be more numerous in pleomorphic ML than in monomorphic medium-cell ML (p less than 0.05). Nuclear irregularity in the 21 cases of peripheral T-cell ML was lower than in Sézary cells. Morphometry clearly demonstrates the morphological distinctiveness of the subclasses of peripheral T-cell ML. Their biological significance has yet to be determined.     

Interdigitating reticulum cells in lymph nodes of Sézary syndrome. Freeze-fracture and ultrathin-section morphology

Lymph nodes with extensive leukemic infiltration from three patients with the Sézary syndrome were examined in ultrathin sections and in freeze-fracture replicas. Sézary cells (SC) and interdigitating reticulum cells (IDC) were the predominant cell types in the lymph nodes. Both were closely connected with each other by apparently interdigitating cytoplasmic processes. The projections between these cells were, in the main, processes from the IDC. In freeze-fracture replicas these cellular processes did not appear as interdigitations but were more bubble-like, and for this reason these cells are imprecisely described by the term "interdigitating." The SC were seen to possess only short cytoplasmic processes. The frequent polar grouping of cell organelles in SC in the region of the contact zone with IDC and the high organelle content of IDC ('activated IDC') could be the morphologic expression of intense interaction between IDC and SC. IDC displayed three features in freeze-fracture which are not specific to the Sézary syndrome, but should be applicable to IDC in general: (1) they exhibited an approximately equal density of intramembrane particles in both the E-face and the P-face, (2) some of the intramembrane particles in the P-face were assembled in clusters and (3) the surface showed bubble-like formations of the cytoplasmic processes. On the basis of these properties it was possible to distinguish IDC from macrophages and lymphocytes in freeze-fracture replicas.     

A unique antigen (sigma) on sézary cells

Summary Lymphapheresis was performed on a patient with Sézary syndrome. The Sézary cells were purified by removing E-rosette-forming and Fc receptor-bearing cells. Antiserum against these purified Sézary cells was raised in rabbits. This antiserum had cytotoxicity against Sézary cells as well as against normal peripheral blood lymphocytes. Absorption was carried out with chronic lymphocytic leukemia (CLL) and normal lymphocytes. The absorbed antiserum maintained cytotoxicity against Sézary cells but lost cytotoxicity against CLL and normal peripheral blood lymphocytes.Indirect immunofluorescence assay showed that the antiserum reacted against purified Sézary cells and a high percentage (66%) of peripheral blood mononuclear cells from five patients with Sézary syndrome. It also reacted against 5.7% of normal lymphocytes, 8% of CLL cells, 5% of the lymphocytes from a patient who had undergone splenectomy, 2% of lymphocytes from a patient with multiple myeloma, 5% of lymphocytes from a hairy cell leukemia patient, and 1% of acute lymphocytic leukemia cells (T cell). The antiserum did not react against thymocytes but reacted against 34.6% of the bone marrow lymphocytes. This unique marker was designated as sigma () antigen. It was suggested that Sézary syndrome may represent proliferation or malignant transformation of normally present antigen-positive lymphocytes.     

A condition resembling pagetoid reticulosis in a laboratory mouse.

A raised, hairless cutaneous nodule was found incidentally at necropsy of a 24-month-old CD1 mouse. Histologically there was infiltration of the epidermis by a monomorphic population of moderate to large lymphocytoid cells. Many large cells had bizarre convolutions of the nuclear membrane and resembled the so-called Sézary or mycosis cells seen in epidermotropic T-cell proliferative disorders. The pattern of cutaneous involvement and the presence of the large cells with convoluted nuclei is characteristic of pagetoid reticulosis. No previous reports of such cutaneous lymphoid neoplasms in mice were found in an extensive literature search.     

Membrane phenotype and response to deoxycoformycin in mature T cell malignancies.

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.     

Better than CD: Eugénie Cotton (1881-1967)

Aimé Cotton is known for his invention of circular dichroism spectroscopy. In 1913, he married Eugénie Feytis, a scientist who studied physics with Marie Curie. Following the Second World War, Eugénie Cotton was determined to advance the rights and standing of women, sure in the belief that doing so was necessary not only because it was just but also because a world with women in the forefront would be more secure and less susceptible to the catastrophe worldwide military conflict. She was a cofounder of the Women's International Democratic Federation and served as its first president. In 1951, she was awarded the Stalin Peace Prize, and in 1961, the gold medal from the World Peace Council. The extraordinary life of Eugénie Cotton is reconstructed in a new biography by Loukia Efthymiou, Eugénie Cotton (1881-1967) (Éditions Universitaires Européennes, 2019) that is reviewed here. Among the contributions of Eugénie Cotton of particular interest to the Chirality readership is the biography she wrote of her husband, Aimé Cotton, l'optique et magneto-optique (Éditions Seghers, 1967), the most complete source of information on the founder of the science of circular dichroism. This biography is also discussed here, thereby building two reviews of books, one new and one old, one about Eugénie Cotton and one by her, into a single essay.     

Analysis of clonality in cytologic material using the polymerase chain reaction (PCR)

Analysis of clonality in cytologic material using the polymerase chain reaction (PCR) Immunoglobulin heavy chain (IgH) gene rearrangement analysis was performed on 27 fine needle aspiration (FNA) specimens (13 reactive hyperplasia, 11 B cell non-Hodgkin's lymphoma (B-NHL), one Hodgkin's disease and two suspicious of non-Hodgkin's lymphoma). Satisfactory amplification was achieved in 23/27 cases. A polyclonal pattern was seen in 14 cases (11 reactive hyperplasia, one B-NHL, one suspicious of lymphoma, one Hodgkin's disease). A monoclonal band was seen in nine cases (eight B-NHL, one reactive hyperplasia). Amplification was unsuccessful in four cases. Clonal analysis by PCR-based IgH gene rearrangement analysis can be successfully applied to FNA material and can be useful in diagnosis, but the results must be interpreted in conjunction with morphology and other ancillary information. Analyse de la clonalité en utilisant la PCR sur matériel cytologique L'analyse des réarrangements géniques des chaînes lourdes des immunoglobulines (IgH) a été réalisée sur 27 produits de ponction à l'aiguille fine (13 cas d'hyperplasie réactionnelle, 11 cas de lymphome non hodgkinien de type B (LNH-B), un cas de maladie de Hodgkin et deux cas suspects de lymphome malin non hodgkinien. Une amplification satisfaisante a été obtenue dans 23 cas sur 27. Un aspect polychonal a été observé dans 14 cas (11 hyperplasies réactionnelles, 1 lymphome malin non hodgkinien de type B, 1 cas suspect de lymphome, 1 cas de maladie de Hodgkin). Une bande monoclonale a été observée dans 9 cas (8 LNH-B, 1 hyperplasie réactionnelle). L'amplification n'a pas réussi dans quatre cas. L'analyse de la clonalité par analyse des réarrangements géniques par PCR peut être appliquée avec succès au matériel cytologique qui est obtenu par ponction à l'aiguille fine et elle peut être utile au plan diagnostique, mais les résultats doivent étre interprétés en intégrant les informations morphologiques et les autres données complémentaires. Polymerase Chain Reaction an zytologischem Material Die Analyse schwerer Immunglobulinketten (IgH) wurde an 27 FNP (13 reaktive Hyperplasien, 11 B-NHL, 1 Hodgkin und und zwie verdächtige Fälle) analysiert. Eine ausreichende Amplifikation wurde in 23/27 Fällen erzielt. Ein polyklonales Muster wurde in 14 Fällen beobachtet (11 reaktive Hyperplasien, 1 B-NHL, 1 Hodgkin sowie 1 verdächtiger Fall). Ein monoklonales Band wurde 9 mal gefunden (8 B-NHL, 1 reaktive Hyperplasie). Die Amplifikation war ungenügend in 4 Fällen. Die PCR-Analyse kann für die Diagnostik von Nutzen sein muss jedoch zusammen mit der Morphologie und anderen Informationen interpretiert werden.     

Conception et suites de la Paléontologie française d’Alcide d’Orbigny

The whole formed by his Paléontologie française, his Prodrome, and his Cours élémentaire, which are closely linked, constitutes one of the major parts of Alcide d’Orbigny’s scientific production, in which he exposed his concept of Palaeontology as a science closely related with Zoology and as an indispensable tool for Stratigraphy. The result was a remarkable impulsion for palaeontological and stratigraphical research, which from that time developed on new scientific foundations. Two annexes complete this communication, the first concerning the ‘Comité de la Paléontologie française’ (1860–1893), the second specifying the publication dates of four volumes of the Paléontologie française.     

Paul Bert, scientist and politician

Paul Bert worked with Claude Bernard, one of the leading physiologists of the 19th century. In his laboratory at the Collège de France in Paris, Paul Bert carried out fascinating experiments in particular on respiratory processes, leading him to publish "La pression barométrique" in 1878. In this book are recalled his discovery of oxygen pressure decrease with altitude, divers diseases, the improved safety protocols in hyperbaric conditions, and the first development of gas anaesthetics for surgery. He was the third President of the Société de Biologie. Paul Bert was also a politician with strong convictions. Minister of Education under Gambetta's short term government, he initiated the fight for social equality and secular education and became one of the most prestigious figures of the developing socialist party. He received many distinctions and was given a state funeral.     

Influence des facteurs abiotiques sur la physiologie alimentaire des larves de la coccinelle aphidiphage,Semiadalia undecimnotata [Col.: Coccinellidae] — I. Action de la température

Résumé L'élevage de la coccinelleSemiadalia undecimnotata Schn. dans différentes conditions thermiques nous a permis de préciser l'action de la température sur la physiologie des stades préimaginaux. Les relations linéaires entre la consommation alimentaire exprimée sous forme cumulée et le poids des individus, qui avaient été mises en évidence dans un travail antérieur ne sont pas modifiées par les variations de ce facteur physique du milieu. I1 en résulte qu'à l'égard de la température, la méthode d'estimation de la consommation alimentaire qui a été proposée dans une publication antérieure peut être utilisée pour estimer la prédation dans le milieu naturel.

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Summary The larvae of the lady beetleSemiadalia undecimnotata Schneider have been reared under various thermic conditions (constant and alternate temperatures). We showed for every instar or only for the last one, that the length of the stage, the length of the feeding period, the daily or the total food consumption (in mg.), the gain of weight, and the top weight are depending on temperature. But the food consumption expressed in a cumulative form and the corresponding weight of the larvae show a constant ratio which is equal to the slope of the linear relations set up in a previous work. With respect to temperature, the method of estimation of larval food consumption which have been described in a former work, can be used to estimate the predatory efficiency of this species in natural conditions.

     

Single unit analysis of odour quality coding by the olfactory antennal receptor system of the Colorado beetle

Peripheral events underlying plant odour quality discrimination in the Colorado beetle were investigated. Responses to saturated and unsaturated C-6 alcohols and aldehydes (“green leaf” volatiles) and to other plant compounds were recorded extracellularly. The olfactory receptors could respond by inhibition and/or excitation; inhibition was especially observed at the higher stimulus intensities. Variations in the response patterns were analyzed for a number of receptors constituting a representative sample, as indicated by rank correlation between mean spike responses and electroantennogram amplitudes for each odour stimulus. Application of cluster analysis showed that the olfactory receptors may be divided into two main groups, one reacting differentially to the complex of “green leaf” volatiles and their isomers, and another group showing a selective sensitivity to the aromatic compound methylsalicylate. Evidence is provided suggesting that individual olfactory sensilla can be innervated by more than one functional type of receptor unit. Responses to natural plant odours support the conclusion that plant odour quality is encoded by response patterning across a limited number of olfactory receptor types. The findings are discussed in relation to concepts of chemosensory coding and to the behaviour of the Colorado beetle.

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Analyse Cellulaire du Codage de la Qualité des Odeurs par le Système de Récepteurs Antennaires Olfactifs Chez le Doryphore

Résumé On a étudié la capacité de distinguer la qualité des odeurs végétales chez le doryphore. On a enregistré extracellulairement les réactions de cellules de récepteur olfactif séparées à des C-6 alcools et des aldéhydes saturés et insaturés (substances volatiles de la “feuille verte”) et à d'autres composés végétaux. Les récepteurs olfactifs pouvaient réagir par inhibition et/ou par excitation; on a particulièrement observé l'inhibition aux intensités élevées de stimulus. Les variations des types de réactions ont été analysées pour un certain nombre de récepteurs, qui constituent un échantillon représentatif, sur la base de la corrélation de rang entre les réactions de pointe moyennes et les amplitudes de l'électroantennogramme pour chaque odeur-stimulus. L'application d'une analyse en grappe a montré que les récepteurs olfactifs peuvent être divisés en deux groupes principaux, un groupe qui réagit de fa?on différentielle au complexe des substances volatiles de la “feuille verte” et de leurs isomères et un autre groupe qui a une sensibilité sélective à l'égard du composé aromatique méthylsalicylate. Le premier groupe a été subdivisé en différents types de récepteurs avec des réactions qui se chevauchent. Il semble que les sensilles olfactives individuelles peuvent être innervées par plus d'un type fonctionnel de cellule réceptrice. Les réactions aux odeurs végétales naturelles enregistrées appuient la conclusion que la qualité d'une odeur végétale est codée par un modèle de réaction pour un nombre limité de types de récepteurs olfactifs. On discute les résultats par rapport aux concepts du codage chimiosensoriel et par rapport au comportement du doryphore.

     

Association of the melanocortin 4 receptor with feed intake and daily gain in F2 Mangalitsa x Piétrain pigs

The melanocortin 4 receptor (MC4R) is a key factor in the regulation of energy balance and body weight. Hence it is a candidate for feed intake and energy homeostasis-related traits. Studies in humans and swine have revealed several sequence variants in the gene that are associated with some of these traits. In pigs the coding non-synonymous missense variant Asp298Asn in MC4R has been associated with feed intake, fatness and growth. Here we confirm the association of this Piétrain-derived polymorphism with feed intake and daily gain in the F2 generation of a Mangalitsa x Piétrain cross. In one Piétrain founder animal, we detected an additional non-synonymous missense variant Arg236His. Thus, the MC4R gene could be a useful marker for increased growth in the relatively slow-growing Piétrain breed.     

Réflexion sur l'utilisation des auxiliaires entomophages contreDiprion pini [Hym. Diprionidae]

Résumé Le problème de la lutte biologique en forêt, par utilisation d'entomophages indigènes, est discuté dans le cas d'un hyménoptère, le diprion du pin,Diprion pini L. Des études de dynamique des populations montrent que le schéma de progression spatiale des populations de cet insecte dans le sud du Bassin Parisien semble se renouveler à chaque pullulation. De plus les parasites représentent un véritable “facteur clé”. Leur incidence varie notamment de génération en génération: en faible nombre au début d'une gradation, ils ne peuvent alors en empêcher le développement; mais ensuite leur multiplication assure une régression brutale du ravageur. Dans ces conditions, des interventions assez peu onéreuses et faciles à réaliser, comme de simples transports de matériel parasité pourraient être efficaces; elles supposent toutefois le développement d'un foyer initial d'infestation. En revanche l'élevage d'espèces régulatrices commeAchrysocharella ruforum Krausse etPleolophus basizonus Grav. permettrait d'assurer la préservation permanente des massifs forestiers.

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Summary The spatial pattern of insect populations progression in southern “Bassin Parisien”, showed by population dynamics studies, seems to happen again for every outbreak. Parasites are moreover a true “key-factor”. Their effect is quite different from one generation to another one; scarce at the beginning of an outbreak, they cannot stop its evolution; but then, their increase allows a brutal collape of the pest. In such a case, cheap and easily achieved operations as simple carryings of parasited insects may be efficient, but they need the development of a first infestation focus. In return breeding of regulating species asAchrysocharella ruforum Krausse andPleolophus basizonus Grav. would be able to sure forest stands permanently.

     

Trypanosoma congolense: lack of correlation between the resistance of cattle subjected to experimental cyclic infection or to field challenge

Twelve male cattle of the Baoulé breed were exposed to natural trypanosome challenge in an area of high Glossina density, to characterize them as trypanoresistant or trypanosensitive. Weekly blood samples were taken for the determination of parasitemia and packed cell volume, as a measure of anemia. Seven Zebu cattle were also exposed to challenge at the same time. The Zebu proved to be trypanosensitive with high parasitemia, pronounced anemia and died or were drug treated in extremis. Five Baoulé were as sensitive as the Zebu while 7 others were trypanoresistant since they showed little or no patent parasitemia, only mild transient anemia and survived in good condition. The 12 Baoulé were allowed to recover from challenge in the field and along with 7 Zebu were subjected to experimental fly challenge in fly-proof accommodation. Glossina morsitans submorsitans infected with a clone of Trypanosoma congolense derived from the stock Serengeti/71/STIB/212 were allowed to engorge on the shaven flanks of tranquilized animals. All animals showed persistent parasitemia for at least 7 weeks, including all the Baoulé resistant to natural challenge. Two Baoulé, one resistant and one sensitive to natural challenge, and 4/7 Zebu appeared unable to control parasitemia, had severe anemia, and were drug treated in extremis. The remaining Baoulé, 6 resistant and 4 sensitive, appeared to be undergoing spontaneous cure by Week 9-10, as did 3/7 Zebu. In Zebu, anemia was as pronounced as under natural challenge. Three resistant Baoulé maintained packed cell volume above 30 as under field challenge but the others showed marked anemia. On the contrary, 4 sensitive Baoulé showed only slight anemia after artificial fly challenge.(ABSTRACT TRUNCATED AT 250 WORDS)