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Biomedical subjects

G Kaplan

Publications and source records attributed to G Kaplan.

At least 271 records · Page 15Linked to original sources

Effect of treatment on the cellular composition of cutaneous lesions in leprosy patients.

We report on the cellular composition of the cutaneous lesions of 38 leprosy patients prior to and after 12-18 months of chemotherapy. All of the patients with tuberculoid (TT) disease had OKT4/OKT8 ratios that exceeded 1.0. In the indeterminate patients, the ratio varied depending upon the immune status of the individual. A low ratio of OKT4/OKT8 cells (0.25) was found in the LL patients as previously reported. The low ratio of OKT4/OKT8 in the lesions of lepromatous patients did not undergo significant changes after treatment in spite of a marked reduction in the number of intracellular bacilli.

Humans↗

[Spinal cord compression in malignant plasmacytic diseases. Apropos of 6 cases].

Myeloma may be complicated or revealed by spinal cord compression. Out of 105 cases of myeloma admitted to this Department, 6 cases of spinal cord compression were observed, with a favourable outcome after treatment by laminectomy combined with radiotherapy. In 5 cases out of 6, spinal cord compression was either the presenting sign or occurred within the first months after diagnosis. Compression occurred in the thoracic cord in 5 cases, and in the lumbar cord in 1 case. The interval between the first symptom and diagnosis varied greatly (from a few hours to 1 year), as did the degree of paraplegia, which ranged from paraparesis to flaccid paraplegia. A favourable outcome occurs in most other reported cases, in contrast with spinal cord compression from metastases. Treatment (laminectomy-radiotherapy or both) remains controversial.

Adult↗

Defective gamma interferon production in leprosy. Reversal with antigen and interleukin 2.

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.

Antigens, Bacterial↗

The cutaneous infiltrates of leprosy. A transmission electron microscopy study.

The dermal lesions of 18 patients with leprosy have been examined by transmission electron microscopy. The patients exhibited a spectrum of disease from polar lepromatous to polar tuberculoid with intermediate stages in various states of therapy and relapse. The nature and quantities of inflammatory cells and bacteria have been determined by electron microscopy to supplement previous light and fluorescence microscopy studies. Lepromatous leprosy was characterized by many parasitized foam cells containing large, multibacillary vacuoles with intact, osmiophilic Mycobacterium leprae: Bacteria were embedded in an electron-lucent matrix. No extracellular bacteria were evident. Only small numbers of scattered lymphocytes were found. As one approached the borderline state, smaller numbers of bacilli were present as singlets and doublets in small vacuoles of macrophages. The more reactive forms showed increasing bacillary fragmentation, larger numbers of lymphoid cells, and an occasional epithelioid cell. At the tuberculoid end of the spectrum, clear evidence of an exuberant lymphocyte response was evident. Large numbers of T cells with extremely long and complex filipodia were closely associated with epithelioid and multinucleated giant cells. Many of the mononuclear phagocytes appeared nonviable, and areas of necrosis were evident. Bacillary remnants were scarce and the cytoplasm of the epithelioid cells contained occasional dense bodies and many stacks of endoplasmic reticulum and mitochondria. These results suggest that Leu 3a/OKT4 helper cells may be capable of driving the effector function of mononuclear phagocytes. This would lead to a significant microbicidal effect on M. leprae, perhaps through the production of toxic oxygen intermediates.

Humans↗

Arachidonic acid metabolism by human monocytes. Studies with platelet-depleted cultures.

Purified human monocytes release and metabolize endogenous arachidonic acid (20:4) from phospholipid stores when challenged with particulate inflammatory stimuli or the calcium ionophore A23187. Using radiolabeled cultures, the percentage of total [3H]20:4 released was similar with each type of stimulus. However, the spectrum of 20:4 metabolites differed. With opsonized zymosan (OpZ) or Sephadex beads coated with IgG immune complexes (Ig-beads), the predominant product was thromboxane (25% of the total) together with smaller amounts of other cyclo-oxygenase products and lipoxygenase metabolites. Levels of thromboxane synthesis by monocytes were comparable to those by platelets, as measured by radioimmunoassay. In contrast, exposure to the nonspecific agent A23187 led to mainly lipoxygenase products (70% of the total). Monocytes isolated from mononuclear cell fractions of peripheral blood contain platelets specifically rosetted to their surfaces. These platelet contaminants were removed by sequential incubations of monocytes in serum and EDTA followed by adherence and detachment from tissue culture vessels. The presence of platelets in routinely isolated monocytes presented a major difficulty in the study of human monocyte 20:4 metabolism since platelets also synthesize thromboxane. Loss of 12-HETE synthesis (16-fold reduction relative to 5-HETE) in A23187-stimulated cultures provided a convenient measure of platelet depletion. This together with the response to monocyte-specific stimuli (OpZ and Ig-beads) allowed for the distinction between monocyte and platelet 20:4 metabolism.

Arachidonic Acid↗

In vitro differentiation of human monocytes. Monocytes cultured on glass are cytotoxic to tumor cells but monocytes cultured on collagen are not.

Cultivation of human blood monocytes on glass gives rise to cells nonspecifically cytotoxic to tumor cells. If the monocytes are cultured on collagen gels with no contact with glass, no such cytotoxic activity is induced. Killing appeared to be extracellular and probably contact dependent. The glass-induced cytotoxic activity was not related to protein content or cell viability. Rather, it appeared that the monocytes cultured on glass differentiated into cells resembling activated macrophages. On the other hand monocytes cultured on collagen differentiated into cells resembling resident tissue macrophages. These observations are compatible with numerous studies carried out in rodents, showing that activated macrophages, and not resident cells, are cytotoxic to tumor cells.

Adult↗

Tumour-activated macrophages as effector cells in a tumour neutralization assay in vivo.

Macrophages from C3D2 or C57B1/6 mice were activated in vitro by coculture with MC1M-AA sarcoma cells or by addition of cell free tumour ascites fluid from the same tumour. After 5-7 days of in vitro activation, macrophages were harvested, mixed with MC1M-AA or B-16 melanoma cells, and reinjected into C3D2 or C57B1/6 mice respectively. Mice were evaluated for tumour development, and the early histological appearance of the B16 melanomas was studied. Activated macrophages gave a significant delay and decrease in tumour take when mixed with B16 melanoma cells at a tumour cell: activated macrophage ratio of 1:20. When activated macrophages were mixed with MC1M-AA cells at a tumour cell: activated macrophage ratio of 1:50, a slight delay and a significant decrease in tumour take was observed. BCG-activated macrophages did exhibit a very weak effect on MC1M-AA tumour growth. When B16 melanoma cells were injected into mice together with activated macrophages, an acute inflammatory reaction was observed at the site of injection. The organization of the tumour was delayed, and necrotic tumour cells could be found. In some cases, small islands of tumour cells escaped killing, and gave rise to delayed tumour development.

Animals↗

[Antinuclear, anti-DNA and anti-lymphocyte antibodies in systemic scleroderma. 62 cases].

The authors describe a prospective study of serum immunological abnormalities in 62 cases of systemic sclerodermia. Antinuclear antibodies were found in 67 percent of the cases. Contrary to expectation, the homogenous type was the most common. Anticentromeric antibodies were found in 4 of the 10 CREST syndrome patients. Anti-RNP (2/62) and natural anti-DNA antibodies are rarely found in sclerodermia. Non-cytotoxic anti-lymphocytic antibodies were found in more than half of the serums studied. They were frequently found in the CREST cases and in cases associated with Gougerot-Sjögren syndrome. Their significance is unknown. Lastly, almost all of the cases of systemic sclerodermia showed an immunological serum abnormality.

Antibodies, Antinuclear↗

The cutaneous infiltrates of leprosy: cellular characteristics and the predominant T-cell phenotypes.

We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions.

Antibodies, Monoclonal↗

[Arthrosis of the hand].

The hand joints most commonly involved by the degenerative process are, in decreasing order of frequency, the distal interphalangeal joints, the trapezo-metacarpal joint, the metacarpo-phalangeal joint of the thumb, the carpal metacarpal joint of the second and third fingers, the metacarpo-phalangeal joints and the proximal interphalangeal joints. Erosive osteoarthrosis can be confused with arthropathy associated with psoriasis. Degenerative joint disease of the hand is more common in women. Even though some authors have suggested a genetical origin, the most commonly accepted etiology is recurrent microtrauma of the pinching mechanism. Treatment consists of anti-inflammatory drugs during episodes of acute pain, and physiotherapy. Surgery is rarely indicated.

Female↗

In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen.

We demonstrated that the in vitro differentiation of human peripheral blood monocytes to macrophages is dependent on the environment and conditions of monocyte culture. Cultivation of monocytes on glass or microexudate-coated glass gave rise to cells resembling foreign body granuloma macrophages. After an initial rise in Fc receptor- and C3 receptor-mediated phagocytosis, a progressive loss of Fc receptor expression and C3-mediated ingestion were observed. The monocyte surface antigens recognized by the anti-human monocyte monoclonal antibodies 1D5 and 63D3 were lost from the surface of the majority of cells cultured on glass and microexudates. A subpopulation of Fc receptor-positive cells that were 1D5 and 63D3 positive was retained in fully differentiated cell populations. In comparison, monocytes cultivated on collagen matrices gave rise to highly phagocytic cells resembling human resident tissue macrophages. Both Fc- and C3-mediated phagocytosis were enhanced and remained so during the entire length of culture. The surface antigens recognized by the 1D5 antibody, expressed on all freshly seeded monocytes, was maintained on the macrophages. The antigen recognized by the 63D3 antibody was not expressed on mature cells. The present evidence would indicate that variations in expression of phagocytic receptors and the surface antigens 1D5 and 63D3 can be ascribed to the stage of development of the macrophage or its stage of activation, rather than to independent subsets of mononuclear phagocytes.

Antibodies, Monoclonal↗

rRNA accumulation and protein synthetic patterns in growing mouse oocytes.

The rRNA contents of mouse primordial oocytes, three stages of growing oocytes, full-grown oocytes, and ovulated ova have been measured by hybridization of RNA samples to excess 3H-DNA complementary to rRNA. Since it was known from previous work that rRNA is stable, the results when plotted against days of oocyte growth indicated that rRNA was synthesized at a constant rate over the first 9 days of growth and about 1.5 times faster in the last 5 days. The maximum value of 0.3 ng per oocyte was attained by about 14 days of growth in oocytes 59 micrometers in diameter, well below the maximum diameter of 77 micrometers for full-grown oocytes. The stability of proteins synthesized in mid-growth phase oocytes was measured by labeling for 5 h with 35S-methionine and then following the decline of incorporated label during a 48h chase; 40% of the label decayed with a half-life of 11 h. and 60% was apparently stable. The two-dimensional electrophoretic patterns of labeled proteins synthesized by growing and full-grown oocytes were compared. The principal change was the appearance or great increase in intensity of several spots in full-grown oocytes as compared to growing oocytes. Egg proteins separated on a two-dimensional gel were visualized by silver staining. The cytoskeletal proteins actin, tubulin, and putative intermediate filament protein, as well as putative lactate dehydrogenase, were synthesized in growing and full-grown oocytes, and accumulated to form a significant portion of bulk egg protein.

Animals↗

Human dendritic cells. Enrichment and characterization from peripheral blood.

Previous studies demonstrated that lymphoid tissues of mice and rats contain small numbers (less than 1 percent of nucleated cells) of dendritic cells (DC) with special cytologic, surface, and functional properties. We show here that similar DC represent 0.1-0.5 percent of human peripheral blood mononuclear cells. DC can be enriched to 20-60 percent purity by a multistep procedure analogous to that used in mice. Adherent peripheral blood mononuclear cells are cultured overnight, and the released cells are depleted of monocytes and B cells by readherence to plastic, rosetting with erythrocytes coated with anti-human IgG, and centrifugation in dense albumin columns. Enriched DC have similar cytologic features to rodent DC by light and electron microscopy. DC express HLA, and HLA-DR and the leukocyte-common antigens. They lack phagocytic capacity, receptors for antibody-coated and neuraminidase-treated erythrocytes, surface and intracellular Ig, esterase, peroxidase, and azurophilic granules. DC do not react with several monoclonal antibodies directed to phagocytes (OKM 1, "mac-1," 63D3, and 61D3) and T cells (OKT 3, 6, 8). Unlike the mouse, human DC express complement receptors. When maintained in culture for 4 d, human DC did not give rise to either B cells or monocytes. Therefore, DC identified by cytologic criteria are distinct from other leukocytes. Enriched populations of DC have been compared to fractions enriched in monocytes, B cells, and T cells in three functional assays: stimulation of the primary allogeneic mixed leukocyte reaction, stimulation of the primary syngeneic MLR, and accessory function for the proliferation of periodate- modified T cells. In each case, the DC fraction was 10-fold or more active than other cell fractions. We conclude that DC circulate in man, and represent the principal cell type required for the initiation of several immune responses.

Animals↗