[Osseous metastasis of bladder cancer. Apropos of 15 cases].
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Adult↗
Biomedical subjects
G Kaplan
Publications and source records attributed to G Kaplan.
The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin.
Our knowledge of the induction of new molecules by IFN-gamma has led to the characterization of IP-10 and the preparation of a monospecific, polyclonal antibody. Using this reagent we have now examined inflammatory states occurring in human skin and used immunocytochemical staining for the expression of both Ia and IP-10 determinants. After evoking a delayed-type response to purified protein derivative of tuberculin (PPD), we noted the presence of IP-10 in dermal macrophages and endothelial cells. Intense staining of the basal layer of epidermal keratinocytes was prominent at 41 h, and by 1 wk the entire epidermis was staining. The comparison of the amount of IP-10 secreted by keratinocytes vs. macrophages, fibroblasts, and endothelial cells revealed that keratinocytes were by far the major producers of this molecule. The expression of Ia occurred in conjunction with IP-10. The injection of rIFN-gamma mimicked many of the features of the PPD response, including the expression of both Ia and IP-10 by epidermal keratinocytes. Coexpression was also found in the natural lesions of tuberculoid leprosy and cutaneous Leishmaniasis. However, it was absent in lepromatous leprosy, a state where activated T lymphocytes are not present. We suggest that the local production of IFN-gamma by T cells of the dermal infiltrate induces IP-10 formation in both the dermis and epidermis. IP-10 and Ia then serve as specific markers of immune IFN and its possible influence on effector cells of the cell mediated immune response.
Animals↗
Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro.
The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens.
Antigens, Bacterial↗
[Spontaneous fissures and fractures of the legs in patients with osteoporosis treated with sodium fluoride].
Thirteen cases of spontaneous fissure or fracture of the lower limbs observed in 8 patients under treatment with sodium fluoride are reported; 7 of these patients were being treated for osteoporosis. The fissures occurred after 20 months of treatment on average and were revealed by pain in the metaphysis with early high radionuclide uptake. Three to 4 weeks later, X-ray films showed a linear bone condensation area, involving in most cases, the tibial metaphysis, the femoral neck and the calcaneum. The prognosis was usually favourable, but 2 patients required surgery for fissure of the femoral neck with rupture of the cortex. Fluor seems to be responsible for the fissures which cannot be avoided by calcium and/or vitamin D intake. The main pathogenic hypotheses are excessive bone resorption, large amounts of poorly mineralized osteoid tissue and architectural abnormalities of the trabeculae. When such fissures occur, fluoride therapy must be discontinued and the limb put at rest, but since this side-effect is rare and usually benign the principle of a treatment that is beneficial in many cases of osteoporosis need not be revised.
Aged↗
Distribution and turnover of Langerhans cells during delayed immune responses in human skin.
The changes in distribution and turnover of T6+ Langerhans cells (LC) in the skin during delayed immune responses to tuberculin, and in the lesions of tuberculoid leprosy and cutaneous Leishmaniasis were investigated. In each situation, there was a dermal accumulation of monocytes and T cells and epidermal thickening with keratinocyte Ia expression. In the tuberculin response a dramatic change in the distribution of LC was observed. By 41 h, T6+ LC were displaced to the upper zone of the thickening epidermis followed by an almost complete loss of LC from the epidermis by approximately 72 h. After 7 d, T6+ cells started to reappear in the epidermis, which regained almost normal numbers of T6+ LC by 14 d. After antigen administration and initiation of the delayed immune response, enhanced numbers of T6+ cells appeared in association with the mononuclear cell infiltrate of the upper dermal lesions. Their numbers peaked by 72 h, were reduced at 7 d, and again enhanced by 14 d, when the epidermis was being repopulated. Similar numbers of T6+ cells were found in the chronic lesions of tuberculoid leprosy and cutaneous Leishmaniasis but not lepromatous leprosy. The cells of the dermis were identified as typical LC by the presence of Birbeck granules and surface T6 antigen at the electron microscope level. These cells were closely associated with lymphocytes. We have quantified the number of LC, evaluated their directional flux into the epidermis and dermis, determined nearest neighbors, and made predictions as to their fate.
Cell Count↗
Cutaneous leishmaniasis. The defect in T cell influx in BALB/c mice.
Local cellular responses to cutaneous infection with Leishmania mexicana amazonensis were examined in susceptible (BALB/c) and resistant (C57BL/6) mouse strains by immunocytochemical and electron microscopic studies. Infection during the first 8 wk in both animal strains was characterized by progressively enlarging lesions, epidermal thickening and ulceration, and accumulation of eosinophils and Ia+ infected macrophages. Healing of C57BL/6 mouse lesions began after 12 wk of infection and was associated with local influx of both Th (L3T4+) and T cytotoxic/suppressor (Lyt-2+) cells into the dermis, and Ia antigen expression on epidermal keratinocytes. T lymphocyte infiltration was marked and intracellular parasites were scarce by 21 wk of C57BL/6 infection. Similarly, granulomas in C57BL/6 livers contained L3T4+ and Lyt-2+ T lymphocytes and no visible intracellular parasites by 21 wk of infection. In contrast, BALB/c mouse lesions continued to enlarge and never healed. Throughout the entire course of infection, T lymphocyte influx into the heavily infected dermis was minimal. Keratinocyte Ia expression was absent in BALB/c lesions. BALB/c livers were heavily infected by 18 wk of cutaneous infection, with few demonstrable T lymphocytes. A systemic absence of T cells could not be demonstrated in BALB/c mice. Both L3T4+ and Lyt-2+ T cells were found in the peripheral blood in normal numbers in both mouse strains. Our results support the role of T cells as important local effector cells in the healing response of murine cutaneous leishmaniasis. We suggest that local T lymphocyte infiltration may provide lymphokines, particularly IFN-gamma, that can activate infected macrophages to destroy the intracellular parasites. Alternatively, T cells may play a cytotoxic role, killing infected macrophages and allowing local humoral factors to destroy released extracellular parasites.
Animals↗
[Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases].
The authors report the data collected by a national investigation organized by the French Society of Rheumatology, concerning the osteo-articular manifestations of severe acne, palmo-plantar pustulosis and primary thoracic and peripheral hyperostosis. This investigation collected 85 case-reports including 13 severe acne, 44 PPP and 28 hyperostosis without the dermatitis mentioned above. From this investigation, it appears that dermatological and osseous pictures described under various denominations, present common characteristics and transition forms justifying their common study under the acronym SAPHO (Syndrome Acne-Pustulosis-Hyperostosis-Osteitis). The bony involvement, especially anterior thoracic, but also vertebral and even peripheral seems to be the common denominator between these diseases. It realizes a true rheumatoid inflammatory osteitis, osseous counterpart of synovial and cartilagenous affections in inflammatory rheumatoid diseases. This group has rather loose connections with common psoriasis and slightly more definite relationships with primary ankylosing spondylarthritis. These clinical and immunogenetic connections occur also through bony involvement.
Acne Vulgaris↗
Cellular responses to the intradermal injection of recombinant human gamma-interferon in lepromatous leprosy patients.
The local response to a single intradermal injection of 10 micrograms recombinant gamma-interferon (rIFN gamma) has been studied in 17 patients with lepromatous leprosy. Of these, 2 patients additionally received two intradermal injections of 10 micrograms rIFN gamma at another site. The results were compared with those of 3 patients who received three injections of the same dose at a single site in an earlier study. One to 7 days after lymphokine administration 4-mm punch biopsies were obtained and examined for cellular alterations in the dermis and epidermis. This allowed a kinetic analysis of mononuclear cell infiltration, keratinocyte proliferation and differentiation, and Langerhans cell redistribution. At 24 hours, the migration of large numbers of helper T cells and monocytes was already prominent and associated with induration. Mononuclear cell accumulation peaked at 72 hours but then persisted for 5-7 days. Only small numbers (one-third or less of total T cells) of suppressor/cytotoxic T cells were present at any time, and granulocytes were absent. Two daily injections of rIFN gamma led to a more intense accumulation of cells. Ten micrograms of rIFN gamma resulted in enhanced keratinocyte proliferation, Ia expression, and thickening of the epidermis. At 24-48 hours major histocompatibility Class II (Ia) antigen was first noted on the dividing cells of the basal layer. By 72-96 hours the entire epidermis exhibited strong expression of Ia antigen on cell surfaces. Repeated doses of lymphokine accentuated these changes and resulted in a more prompt keratinization and sloughing of this layer. Whereas a single dose of rIFN gamma resulted in the upward movement of T6+ Langerhans cells (LCs) in the epidermis, two injections led to a 50% reduction in their numbers and three doses were associated with an almost total loss of detectable T6+ LCs from the epidermis. These are probably sloughed along with keratinocytes. In contrast to the situation with a delayed immune response in the skin (purified protein derivative), no LCs accumulated in the dermis in association with helper T cells.
Animals↗
[Sclerodermatomyositis. Apropos of 13 cases].
13 cases of sclero (dermato)myositis are reported with cutaneous signs specific of dermatomyositis in 6 cases. Scleroderma was rather benign, without any visceral involvement. In contrast, myositis was much more severe that usually encountered in systemic sclerosis, threatening the vital prognosis and requiring aggressive therapeutic measures to be controlled. In 6 cases, the axial musculature was involved. Occurrence of each component was not simultaneous. No case was paraneoplastic. Antinuclear antibodies were present in all cases. Antibodies against soluble nuclear antigens, specifically found by others in sclerodermatomyositis, were absent. The very peculiar clinical spectrum of this syndrome associated with immunologic abnormalities, elsewhere described, confirm the individualization of sclerodermatomyositis.
Adult↗
Effect of recombinant interferon-gamma on hydrogen peroxide-releasing capacity of monocyte-derived macrophages from patients with lepromatous leprosy.
Monocyte-derived macrophages from 14 patients with lepromatous leprosy respond to rIFN-gamma with an enhanced secretion of H2O2 in a fashion similar to that of cells obtained from normal donors. The activation is not dependent on the cutaneous bacterial index, the length of treatment, or the stage and activity of the disease. H2O2 release can be triggered in these cells both by phorbol myristate acetate and by intact irradiated Mycobacterium leprae. Uptake of M. leprae by both normal donors' and patients' macrophages is proportional to the number of bacilli added. Prior ingestion of M. leprae does not interfere with the ability of macrophages to respond to IFN-gamma by the production of oxygen intermediates. We conclude that the immune defect in lepromatous leprosy probably results from a lack of response to M. leprae by the patients' T cells rather than an inability of mononuclear phagocytes to respond to IFN-gamma.
Adolescent↗
Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy.
Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.
Adult↗
Biochemical characterization of a foot-and-mouth disease virus strain attenuated for cattle. Brief report.
Wild-type, virulent (A-24 Cruzeiro subtype) foot-and-mouth disease virus (FMDV), a related attenuated strain and revertants of the attenuated strain were examined by titration on primary bovine kidney (PBK) and baby hamster kidney (BHK-21) cells, as well as, by infection of unweaned mice. Wild type virus grew equally well in all three systems, whereas the attenuated strain had a titer 2-3 log lower in PBK cells than in the other 2 assays. Within 9 successive passages in BHK-21 cells the attenuated strain gave rise to revertants that had regained the growth properties of wild-type virus in PBK cells. After cloning of the attenuated strain by plaque isolations, the same revertant phenotype was obtained within 9 successive passages. Oligonucleotide mapping indicated that the attenuated strain differed from the wild-type and revertants by at least one additional oligonucleotide. Differences in poly(C) length were not found among any of the three strains of FMDV. These results correlate attenuation and virulence with point mutation(s) and not with deletions. Possible reversions in nature with this attenuated strain may be anticipated.
Animals↗
Influence of delayed immune reactions on human epidermal keratinocytes.
The epidermal changes that occur in human cutaneous immune responses have been investigated in the tuberculin reaction and in the lesions of tuberculoid and lepromatous leprosy and cutaneous leishmaniasis. In each situation, there was a dermal accumulation of monocytes and T cells, and the epidermis exhibited thickening. In the tuberculin response, the thickness of the epidermis sometimes doubled in 48-72 hr, and this was attributed to increases in both size and number of keratinocytes. In addition, the phenotype of the keratinocytes changed from Ia- to Ia+. Similar changes in keratinocyte Ia-antigen expression occurred in the epidermis overlying untreated tuberculoid leprosy and cutaneous leishmaniasis lesions, but not in lepromatous leprosy. We suggest that one or more epidermal growth factors may be generated in the course of a delayed immune reaction in the dermis.
Antigens, Bacterial↗
Mechanism of in vitro synthesis of covalently linked dimeric RNA molecules by the poliovirus replicase.
Four RNA fragments of approximately 1,000 to 1,200 nucleotides, representing both the 5' and 3' termini of poliovirus plus- and minus-strand RNAs, were generated by transcription of poliovirus cDNA by using bacteriophage SP6 RNA polymerase. The copying of these templates by the poliovirus replicase invariably produced RNA products approximately twice the size of the templates. In experiments with templates uniformly labeled with 32P it was shown that some of the apparently double-length products were generated by extension from an internal site of the template. Filter hybridization of the labeled in vitro-synthesized products with various unlabeled templates suggested a second mechanism by which double-length molecules could be synthesized; the results can be best explained by de novo synthesis of the first strand by copying of the template RNA, followed by snap-back of the newly synthesized RNA, generating a template-primer structure for the synthesis of the second strand. Highly purified poliovirus replicase was able to support the synthesis of double-length RNA products in response to these templates. These reactions did not require host factor. In contrast, synthesis of genome-length copies of poliovirion RNA by the same replicase was absolutely dependent on added host factor. The synthesis of double-length RNA products did not require either the 3'-terminal poly(A) of plus RNA or sequences within the 3' termini of both plus- and minus-strand RNAs.
Base Sequence↗
Regulation of cell-mediated immunity in lepromatous leprosy.
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Humans↗
[Comparative profile of antinuclear antibodies in Gougerot-Sjögren syndrome with and without diffuse interstitial pulmonary fibrosis].
Eleven patients with an isolated Gougerot-Sjögren syndrome and a diffuse interstitial fibrosis were compared with twenty patients with an isolated Gougerot-Sjögen without pulmonary involvement. Patients with pulmonary fibrosis are younger and the evolution of their dry syndrome is shorter (p less than 0.05) than in patients without fibrosis. The frequency of extra-articular clinical manifestations (except for the lung) is identical in both groups. Antinuclear antibodies are present in 100 p. cent of patients with pulmonary fibrosis. Specific antibodies of soluble nuclear antigens are detected in 64 p. cent of them. This frequency is 55 p. cent in the group without pulmonary fibrosis. The specificities of these antibodies are anti-U1-RNP (3 cases), anti-SS-B (La) (3 cases), anti-SS-A (Ro) (2 cases), non identified (1 case). There was no serum containing antibodies Jo1 or anti-Sm. This immunological profile is identical to the profile found in isolated Gougerot-Sjögren syndromes without pulmonary fibrosis. The search for specific antibodies of soluble nuclear antigens permits to differentiate pulmonary fibrosis secondary to an isolated Gougerot-Sjögren syndrome, from primary diffuse interstitial fibrosis and fibrosis associated to a polymyositis.
Adult↗
The immunobiology of leprosy.
Leprosy, a chronic infectious disease of man, is caused by the obligate intracellular bacterium M. leprae. Infection with M. leprae affects the peripheral nerves and the dermis, causing an accumulation of macrophages and other immune cells at the infected sites. Host resistance to the bacterium determines the extent of local inflammatory reactions and its resulting damage to the affected tissues. In lepromatous disease little if any cellular immunity develops. Bacterial multiplication is uncontrolled and M. leprae disseminate throughout most of the dermis. In tuberculoid disease, marked cellular immunity is observed and bacterial growth and dissemination are controlled. The depression of cellular immunity in lepromatous patients is not fully understood. Since M. leprae cannot be grown in vitro, and a suitable animal model has not yet been developed, the study of host immunity to the pathogen is limited primarily to investigations of the cutaneous lesions of patients and to in vitro responses of the peripheral blood leukocytes to M. leprae. While the blood monocytes of leprosy patients appear to be activated normally by lymphokines, T cell proliferation and production of lymphokines in response to M. leprae are impaired in lepromatous patients. Attempts to restore responsiveness in cells from these patients have been unsuccessful in our hands. The addition of exogenous IL-2 to leukocyte cultures does not appear to restore responsiveness to M. leprae in cells from nonresponsive patients. Rather, some enhancement, often not antigen specific, is observed in cells from patients with a preexisting response. Similarly, depletion of monocytes does not restore responsiveness to M. leprae in nonresponder patients, but a nonspecific enhancement of proliferation is observed in monocyte-free cultures from patients that do respond to M. leprae. Thus, the defect in lepromatous nonresponder patients does not result from a simple lack of IL-2 production or suppression by monocytes and/or their products. Possibly, there is a low level or lack of M. leprae-responsive T cells in the circulation of these patients. Attempts to overcome the defect in immunity of patients with lepromatous leprosy by immunoprophylaxis and immunotherapy are being investigated. This approach has become of major importance since the development of widespread drug resistance to Dapsone as well as to the other chemotherapeutic agents used to control leprosy.
Animals↗
[Villonodular synovitis of the wrist. Apropos of a case].
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Adult↗