Control of neuroblastoma cell proliferation and differentiation by human bone marrow.

BACKGROUND: Neuroblastoma (NB) is one of the few tumors known to undergo spontaneous regression. Its progression, however, often leads to bone marrow (BM) metastasis. Proliferation and differentiation of human NB cells may be regulated in vitro by a variety of biologic agents, some of which are released by low-density BM and peripheral blood (PB) cells. Little is known regarding BM cell-derived control of NB cell growth and differentiation. METHODS: The proliferative and differentiative responses of NB cells, to BM cell-, and to PB cell-derived conditioned medium (CM) were evaluated in comparison to cytokine-induced responses. RESULTS: CM from unstimulated cultures of low density BM and PB cells, from healthy donors, from newborn infants, and from NB patients, significantly and reproducibly stimulate NB cell growth in vitro. The intensity of CM-induced stimulation was not attained by recombinant human tumor necrosis factor (rhTNF), interferon (rhIFN), or granulocyte-monocyte colony stimulating factor (rhGM-CSF); and although epidermal growth factor (rhEGF) and transforming growth factor alpha (rhTGF alpha) were strongly stimulatory, neutralizing antibodies against each of these agents did not affect CM-derived activity. In contrast to growth stimulation, differentiation of CM-treated NB cells, was reproducibly suppressed, as reflected in abrogation of neuronal cell morphology as well as of neurofilament and neuron specific enolase expression. CONCLUSIONS: Spontaneous regression of NB tumors, on one hand and BM metastasis on the other may be associated with the extent and nature of the NB cell response to regulatory activity released by BM and PB cells.

Imbalance of immune responses in patients with chronic and widespread fungal skin infection.

Fungal infections of the skin are caused by dermatophyte fungi. Infections can be acute and inflammatory or chronic and non-inflammatory; it is believed that cell-mediated immunity is the cornerstone of host defence and is instrumental in the eradication of the infection. We describe here parameters of the immune response of a group of patients who although not immunocompromised, suffered from widespread and chronic infections. All patients lacked a specific delayed-type hypersensitivity (DTH) response; however, their in vitro lymphocyte proliferation in response to Trichophyton rubrum extract and to other fungal antigens was normal. The patients were not atopic by clinical history, and yet had high levels of non-specific IgE and of T. rubrum-specific IgG4. Taken together, the results of this study suggest that the group of patients studied suffered from an immune imbalance which has characteristics of a Th2-type response.

Carcinoma of the clitoris: a histologic study with cytokeratin profile.

A carcinoma of the clitoris showed a variety of histologic features not usually encountered in squamous cell carcinoma of the vulva. In addition to poorly differentiated nonkeratinizing squamous cell carcinoma, there were large areas showing a transitional cell carcinoma pattern, as well as foci of spindle and anaplastic cells. The clitoral neoplasm also differed in its cytokeratin (CK) profile from that described in invasive squamous cell carcinoma of the vulva, especially with regard to the widespread staining for CK 18 and 19 in the former. Thus, our study suggests that some carcinomas of the clitoris differ from those of ordinary squamous cell carcinomas of the vulva. More cases should be studied using immunohistochemical methods in order to establish the full histopathologic and CK range of the former.

The effect of the ArF excimer laser on Candida albicans in vitro.

Candida albicans colonies in Sabouraud agar plates were irradiated with the excimer laser as follows: (a) at 10 Hz, power densities of 115-300 mJ/cm2 and 200-3000 pulses, and (b) power density of 115 mJ/cm2 and 200 pulses at 10-50 Hz. Additional colonies were irradiated with a power density of 200 mJ/cm2 at 10 Hz and 500 pulses. Each colony was cultured and the visible colony forming units were counted after 24 h. The cultures remained sterile at: 115 mJ/cm2, 1500 or 3000 pulses; 200 mJ/cm2, 400 or 500 pulses; and 300 mJ/cm2, 300 or 400 pulses. They decreased significantly in other groups. Photoablation with a power density of 115 mJ/cm2 and 200 pulses significantly decreased the number of yeast colonies in the culture plates at 30 Hz (p < 0.029) and 50 Hz (p < 0.02). Photoablation did not affect the counts in colonies located 1 or 2 mm from the treated colonies. Various energies of the excimer laser may significantly reduce or eliminate yeast in vitro.

Synthesis and antifungal activity of medicagenic acid saponins on plant pathogens: modification of the saccharide moiety and the 23 alpha substitution.

The study of structure-antifungal activity relationships of medicagenic acid saponins was widened to include synthetic glycosides of mannose, galactose, cellobiose, and lactose as well as a 23 alpha-hydroxymethyl analog of medicagenic acid, namely, methyl 2 beta,3 beta-dihydroxy-23 alpha-hydroxymethyl-delta (12)-oleanene-28 beta-carboxylate, against Sclerotium rolfsii, Rhizoctonia solani, Trichoderma viride, Aspergillus niger, and Fusarium oxysporum. The native glucose-containing saponin was a more effective antifungal agent than the aforementioned saponins, except in the case of the cellobiose-containing derivative and F. oxysporum. A carboxyl substituent at the 23 alpha position of the sapogenin brought about higher fungistatic activity than a methyl carboxylate which, in turn, was more effective than an hydroxymethyl group at the same position.

Mode of action of the antimycotic agent G2 isolated from alfalfa roots.

The mode of action of the antimycotic alfalfa root saponin, medicagenic acid 3-O-beta-D-glucopyranoside (compound G2), which possesses a pronounced antifungal activity against medically important yeasts and dermatophytes, was studied in Saccharomyces cerevisiae. Compound G2 caused lethal leakage of ions out of the yeast cells. Exposure of S. cerevisiae to compound G2 resulted in a disappearance of the main sterol, ergosterol, from the cell membranes, suggesting that compound G2 was highly specific for ergosterol. Independently, chemical data indicated that compound G2 forms stable complexes with both ergosterol and cholesterol. Addition of cholesterol or ergosterol protected the cells of S. cerevisiae and several pathogenic yeasts from the inhibitory activity of compound G2 by producing a higher ratio of sterols (mainly ergosterol) to phospholipids in the membranes. The fact that an amphotericin B-resistant Candida tropicalis was susceptible to G2 suggested that its mode of action was different from that described for polyene antibiotics. This was also confirmed by the finding that 0.2 M KCl did not protect S. cerevisiae cells against ion leakage with G2, but did so with amphotericin B.

Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection.

Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P less than 0.01).

[T-cell lymphoma].

8 patients with lymphoproliferative disorders of T-cell origin were diagnosed during the years 1985-1987. They included 2 cases of so-called Lennert's lymphoma, 1 case of T-cell lymphoma simulating malignant histiocytosis and 1 case of T-cell lymphatic lymphoma with splenic T-cell lymphoma which survived 10 years. The other cases presented with peripheral T-cell lymphomas. Immunologic typing of malignant lymphomas with cell suspensions is of diagnostic value.

Activities of compound G2 isolated from alfalfa roots against dermatophytes.

An antimycotic agent, compound G2, isolated from alfalfa roots exhibited considerable activity against the six most common dermatophytes. MICs in agar and broth dilutions ranged from 10 to 30 micrograms/ml and from 2 to 10 micrograms/ml, respectively. G2 was fungicidal at 5 to 22 micrograms/ml. Structure and toxicity relations are discussed.

Activity of compound G2 isolated from alfalfa roots against medically important yeasts.

An antimycotic agent was isolated from roots of alfalfa and further purified to yield a nonhemolytic, homogeneous compound (G2). This compound contained considerable activity against 10 medically important yeasts. MICs obtained by both agar and broth dilution methods ranged from 3 to 15 micrograms/ml. Compound G2 was fungicidal at a relatively low concentration for nine different species of yeasts tested (minimum fungicidal concentrations ranged between 6 and 24 micrograms/ml). The considerable stability of compound G2 and its strong inhibitory and fungicidal activity against a broad range of yeasts suggest that after further development it might be useful as an active agent in the treatment of mycotic infections.

The susceptibility of Cryptococcus neoformans to an antimycotic agent (G2) from alfalfa.

Compound G2, 2-beta-hydroxy-3-beta-O-(beta-D-glucopyranosyl)-delta 12-oleanene-23,28-dionic acid, isolated from alfalfa roots, demonstrated considerable activity against Cryptococcus neoformans (MIC value of 2 micrograms/ml). Compound G2 exhibited rapid killing of this fungus (MFC value of 4 micrograms/ml) suggesting that it might be a useful active agent in the treatment of cryptococcosis.

Epidemiological trends of dermatophytoses and dermatophytes in Jerusalem between 1954 and 1981.

Data for dermatophyte infections analysed for five 3-year periods between 1954 to 1981 led to the following conclusions: Tinea pedis, tinea cruris and tinea manuum showed an increase in the 50's and 60's and declined in the 70's; Tinea unguium and tinea corporis showed an increase during the whole period; At all these sites, the percentage of Trichophyton rubrum, the main etiologic agent, increased steadily over the periods while the percentage of Trichophyton mentagrophytes, the secondary etiological agent, decreased. Epidermophyton floccosum, the third etiological agent in these sites, showed no sharp fluctuations; These three dermatophytes which show similar microclimatic requirements and favour the same microecological niches, were called 'glabrohydrophilic'. In tinea corporis they form a definite subset, their percentage being similar to that at other glabrous sites; Tinea capitis was at its peak in the 50's, decreased sharply until the second half of the 70's, its main etiological agent being Trichophyton violaceum. Since 1979, an increase of tinea capitis occurred due to the newly introduced Microsporum canis; Dermatophytes favouring scalp hair were called 'trichophilic'. In tinea corporis they form a definite subset, their percentage being similar to that of tinea capitis; A comparison with other studies from this country shows that macroclimate (i.e. humid warm coastal climate compared with dry cooler inland-mountain climate) is not an important factor in the etiology of tinea.

Demonstration of the polysaccharides in the cell wall of Candida albicans blastospores, using silver methenamine staining and a sequence of extraction procedures.

Blastospores of Candida albicans were subjected to a series of extractions of increasing severity to remove polysaccharides from the wall. The procedure was observed by electron microscopy, using silver methenamine staining to localize the polysaccharides.

In vitro phagocytosis of Candida albicans by peritoneal mouse macrophages.

The ability of sensitized mouse peritoneal macrophages to phagocytose and inhibit Candida albicans was studied in an in vitro system. Mice were sensitized to C. albicans by intraperitoneal infection with viable organisms or by intracutaneous injection of heat-inactivated cells in Freund complete adjuvant. Development of delayed hypersensitivity to C. albicans was evaluated by footpad tests with cytoplasmic and cell wall antigens as well as by macrophage migration inhibition by these antigens and by whole heat-inactivated cells. Inhibition of macrophage migration by heat-inactivated cells was significantly greater when the mice were sensitized by viable organisms. The macrophages from these mice were also larger and showed a greaer ability to inhibit germ tube production by phagocytosed yeasts. This suggests that macrophages may play a protective role in infection by C. albicans.