Critical Casimir forces for O(n) systems with long-range interaction in the spherical limit.

We present exact results on the behavior of the thermodynamic Casimir force and the excess free energy in the framework of the d -dimensional spherical model with a power law long-ranged interaction decaying at large distances r as r(-d-sigma) , where sigma T(c) and T< T(c) . The universal finite-size scaling function governing the behavior of the force in the critical region is derived and its asymptotics are investigated. While in the critical and subcritical region the force is of the order of L(-d) , for T> T(c) it decays as L(-d-sigma) , where L is the thickness of the film. We consider both the case of a finite system that has no phase transition of its own, when d-1sigma , when one observes a dimensional crossover from d to a d-1 dimensional critical behavior. The behavior of the force along the phase coexistence line for a magnetic field H=0 and T< T(c) is also derived. We have proven analytically that the excess free energy is always negative and monotonically increasing function of T and H . For the Casimir force we have demonstrated that for any sigma > or =1 it is everywhere negative, i.e., an attraction between the surfaces bounding the system is to be observed. At T= T(c) the force is an increasing function of T for sigma>1 and a decreasing one for sigma<1 . For any d and sigma the minimum of the force at T= T(c) is always achieved at some H unequal to 0 .

Correlated ultrastructural and immunological findings in CD8+ and CD4+ peripheral T-cell lymphomas.

Ultrastructural features of CD8+ and CD4+ peripheral T-cell lymphomas were studied and the results revealed distinct traits correlated with phenotype. CD8+ peripheral T-cell lymphomas were characterized by a rich organular pattern with a well-developed Golgi apparatus, dense granules, numerous and atypical giant mitochondria. CD4+ peripheral T-cell lymphomas were characterized by wide cytoplasmic areas devoid of organelles. Since similar ultrastructural features differentiated normal and pathological CD8+ and CD4+ peripheral T-lymphocytes, we conclude that under both normal and pathological conditions the expression on the part of the peripheral T-lymphocytes of CD8+ and CD4+ phenotypes is associated to morphological features which distinguish the two subsets.

Human thymocyte differentiation: an ultrastructural study using monoclonal antibodies and immunogold staining method.

The ultrastructural features of normal human thymocytes were analyzed at various stages of immunologic differentiation as defined by a panel of OKT monoclonal antibodies visualized by colloidal gold labelled antimouse IgG. The study shows that first stage thymocytes (OKT10+, OKT9+) have a typical morphology not found in more mature stages and describes the critical ultrastructural change which they undergo in becoming second stage thymocytes (OKT10+, OKT6+, OKT8+, OKT4+). No change in thymocyte fine morphology has been found in the progression from second to third stage (OKT10+, OKT3+, OKT8+ or OKT10+, OKT3+, OKT4+). Cells with ultrastructural features intermediate between those of the first and second stage have been found to react with monoclonal antibodies characterizing the first and the second stage. Ultrastructural similarity and homogeneity found in OKT8+ and OKT4+ thymic subpopulations suggests the acquisition by T lymphocytes of morphologic structures correlate with immunologic features previously found in peripheral blood T cell subpopulations to be a post-thymic process.

T lymphocytic subpopulations of normal human peripheral blood defined by monoclonal antibodies: an ultrastructural study using immunogold staining method.

Submicroscopic findings of T lymphocytic subpopulations of normal human peripheral blood defined by OKT monoclonal antibodies were studied using ultrastructural immunocytochemistry (immunogold staining). The results show that OKT4-and OKT8-positive lymphocytic subpopulations have a distinct morphological pattern, although some variations in the ultrastructural details of cells in each subset are evident. The most representative features of OKT8-positive cells are regular or slightly indented nucleus with condensed chromatin, abundant cytoplasm, prominent Golgi apparatus, several granules frequently localized in the Golgi area, and numerous mitochondria, often in cluster disposition. OKT4-positive cells show generally less condensed chromatin, scanty cytoplasm and poor organule pattern. Furthermore, positive lymphocytes with prominent nuclear irregularities are found in both lymphocytic subpopulations. Ultrastructural similarities between the T cell subsets phenotypically characterized by monoclonal antibodies and other immunological criteria are also discussed.

Ultrastructural appearance of malignant non-Hodgkin's lymphomas and lymphoid leukemias.

In this report the authors show the main ultrastructural features of malignant non-Hodgkin's lymphomas and lymphoid leukemias, trying to outline the more important findings useful to diagnostic purpose. Since, from an immunologic point of view, lymphoid malignancies reflect the main steps of normal B and T ontogenesis, the various tumours are progressively presented in relation to their stage of phenotypic differentiation. An exact knowledge of the potential information from electron microscopy and its intrinsic limitations, including the high cost and the time expense, permit a correct use of this investigation in diagnostic procedure in lymphoid malignancies.

Comparative microscopic study of cardiotoxicity and skin toxicity of anthracycline analogs.

Golden hamsters were submitted, three times a week during 4 weeks, to i.p. administration of an antracenedione, mitoxantrone (MTX), and 12 different anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (e-ADM), rubidazone (RBZ), aclacinomycin (ACM), N-trifluoroacetyladriamycin-14-valerate (AD-32), tetrahydropyranyl-adriamycin (THP-ADM), N-L-leucyl-daunorubicin (l-DNR), carminomycin (CAM), rubicyclamin (RBC) and N-trifluoroacetyl-adriamycin-14-9-hemiadipate (AD-143), at doses equivalent to 3/4 those which are optimally oncostatic on murine L1210 leukemia. The electron microscopic (EM) study of the myocardium showed that all studied drugs are cardiotoxic, but with different degree of cardiotoxicity. The histopathological study of the skin detect degenerative lesions with different degree of alopecia. According to the degree of their cardiotoxicity, skin toxicity, and general toxicity or mortality, all drugs studied are classified into 3 groups: 1st group, ADM, DNR, 1-DNR and RBZ, causing very severe cardiac alterations and alopecia (grade 2-3), and very high mortality, 2nd group, e-ADM, DTR, CAM RBC and MTX, with less severe cardiac alterations, and alopecia (grade 1-2), and always high mortality, and 3rd group, ACM, THP-ADM, AD-32 and AD-143, causing less severe myocardial alterations (grade 1-2), without alopecia (grade 0), and extremely low mortality and general toxicity.

Immunoelectron microscopy with immunogold staining method and monoclonal antibodies. A promising tool in ultrastructural study of lymphatic subpopulations.

The immunogold staining method has been recently introduced and proved to be of interest in immunoelectron microscopy as a tracer for detection of cell surface antigens defined by monoclonal antibodies in leukocytes. As variations in sample manipulations and different distribution patterns of gold particles in positive cells are reported, the authors described the experimental conditions which permit them to obtain a good and well interpretable labelling in peripheral blood lymphatic cells. In order to verify the sensitivity and the specificity of this labelling and the interpretation of positivity, a comparison between the percentages of positive cells obtained in electron microscopy and immunofluorescence has been reported. The correlation is acceptable and since the ultrastructural details are also well preserved, this method seems promising for the comparison of molecular phenotypic characteristics and submicroscopic appearance of lymphatic cells.

Ultrastructural study of the cardiotoxicity and light-microscopic findings of the skin after treatment of golden hamsters with seven different anthracyclines.

Golden hamsters were administered seven anthracyclines: adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), rubidazone (RBZ), aclacinomycin (ACM), and N-trifluoroacetyladriamycin-14-valerate (AD-32), three times a week during 4 weeks, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. We examined their myocardia by electron microscopy (EM) and their skin by light microscopy (LM), and report here the findings of these two examinations. The mortality was very high for the groups of hamsters treated with ADM, DTR, DRB, eADM, and RBZ (all treated hamsters died before the end of the fourth week) and very low for those treated with ACM and AD-32 (for each drug, only one of the 21 treated animals died after 4 weeks of treatment). After the first week of treatment and chiefly after the second week, all treated hamsters, except those treated with ACM, showed very severe EM alterations of their myocardia. EM detected almost no early myocardial lesions in ACM-treated hamsters but, after 4 weeks of treatment, severe cardiac lesions also appeared which, like those after AD-32, were nonlethal and reversible. LM of the skin detected degenerative lesions with atrophy of all epidermic layers and a loss of the hair (alopecia) in all treated hamsters except those treated with ACM and AD-32; the skin in these two groups preserved its normal histologic structure. These observations agree with phase I-II clinical ACM studies in which the rate of ECG abnormalities was 4.5% and the rate of alopecia 0%, and with an early AD-32 clinical study conducted by Blum [3].

Histopathologic sequence of events in adult mice undergoing lethal graft-versus-host reaction developed across H-2 and/or non-H-2 histocompatibility barriers.

The sequence of histologic events in graft-versus-host reaction (GVHR) caused by major and/or minor histoincompatibilities was studied. It was discovered that GVHR may manifest itself in the form of two distinct multiphasic disease entities, depending on whether the donor cells are incompatible with the host for both major and minor histocompatibility antigens ("major GVHR") or for minor histocompatibility antigens alone ("minor GVHR"). The acute or major GVHR has four phases: 1) a transient phase of aplasia, 2) a repopulation phase, 3) a proliferative phase involving lymphoid, presumably immunocompetent, cells, and 4) a phase of acute organ rejection (terminal). The chronic or minor GVHR is characterized by six phases, namely: 1) a transient phase of aplasia, 2) a repopulation phase, 3) a phase of proliferation and tissue infiltration by lymphoid, presumably immunocompetent cells, 4) a phase of major immunologic injuries, 5) a phase of repair, and 6)a terminal phase with advanced sclerosis and proliferative glomerulonephritis. In acute or major GVHR the disease was manifested by the tissue reactions characteristic of acute organ rejection. Lesions were seen in the kidney, liver, bone marrow, lymph nodes, spleen, thymus, intestine, and skin. In the chronic or minor GVHR, tissue injuries were more widespread, affecting the collagen, vessel walls, adipose tissue, renal glomeruli, heart muscle, fascias of skeletal muscles, lymph nodes, spleen, thymus, bone marrow, intestine, skin, esophageal mucosa, and urinary tract. A pronounced plasma cell proliferation was a striking feature in the minor GVHR. Its evolution coincided with advanced thymic epithelial atrophy. It is suggested that the destruction of thymic epithelium resulted in depletion of suppressor T cells and, consequently, in an unopposed proliferation of plasma cells.

Electron microscopic studies of the heart and light microscopic studies of the skin after treatment of golden hamsters with adriamycin, detorubicin, AD-32, and aclacinomycin.

Golden hamsters received Adriamycin (ADR), detorubicin (DTR), AD-32, or aclacinomycin (ACM) three times weekly at doses extrapolated from optimal doses in L1210 leukemia. Minimal early lesions of the myocardium were detected by electron microscopy in ACM-treated animals. These lesions were aggravated after several weeks of treatment but remained reversible. Lesions in AD-32-treated hamsters were slightly more marked than those seen in ACM-treated animals but were much less severe than those observed in ADR- or DTR-treated animals. Similarly, light microscopy revealed pathologic changes in the skin following ADR or DTR administration. These changes were not seen in animals receiving AD-32 or ACM.

[Ultrastructural study of cardiotoxicity and skin alterations in the golden hamster after treatment with 8 different anthracyclines]. / Etude ultrastructurale de la cardiotoxicité et des altérations de la peau chez le hamster doré après traitement avec huit différentes anthracyclines.

Golden hamsters were submitted to i.p. administration during 4 weeks of 8 anthracyclines, adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), adriamycin hydrochloride (ADMh), rubidazon (RBZ), aclacinomycin (ACM) and AD32, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. The comparative study of the mortality, the electron microscopic (EM) alterations of the myocardium, and the light microscopic (EM) alterations of the myocardium, and the light microscopic (LM) lesions of the skin, show that ACM and AD32 are the least toxic drugs. EM detected almost no early lesions of myocardium in ACM treated animals, but, after 4 week's treatment, severe cardiac alterations appeared which, like those after AD32 treatment, are non lethal and reversible. Similarly. LM revealed no histologic changes in the skin following ACM and AD32 administrations, but pathologic alterations, atrophy and alopecia, were observed in animals receiving all other drugs.

Preliminary results of a phase II trial of aclacinomycin in acute leukaemia and lymphosarcoma. An oncostatic anthracyclin that is rarely cardiotoxic and induces no alopecia.

A phase II trial of which preliminary results are available for 22 patients indicates that aclacinomycin applied in a continuous modality induced complete and partial remission in four of nine patients with acute lymphoid leukaemia that was resistant to all previously available drugs, and in four of eight patients with stage V lymphosarcoma (leukaemic). Bone-marrow toxicity was the major side-effect. Only one patient of 20 suffered from cardiac toxicity; no one had alopoecia. This very low incidence of myocardial lesions and the absence of hair loss had been predicted, respectively, by our electron microscope study of the myocardium and the light electron microscope study of the skin of golden hamsters [7], a test that detects frequent severe myocardium and skin toxicities for adriamycin and some anthracyclin analogues such as detorubicin, which was found to be toxic in a high percentage of patients in a clinical trial conducted by the E.O.R.T.C. Clinical Screening Group [8].