Sponge secondary metabolites: biochemical and ultrastructural localization of the antimitotic agent avarol in Dysidea avara.

The secondary metabolite avarol, a potent cytostatic and antibacterial sesquiterpenoid hydroquinone, is present in large amounts only in the sponge Dysidea avara (2.7 g avarol/1 kg of fresh material). The present study was designed to determine the storage site of this compound within the organism. Light and transmission electron microscopic studies revealed that avarol is probably stored only in spherular cells. The compound is compartmented in intracellular cytoplasmic vesicles in a paracrystalline form, and therefore can have no inhibitory effect on the sponge cells. Quantitative analysis utilizing high-pressure liquid chromatography revealed that avarol is present at a concentration of 3.2 micrograms/10(6) spherular cells. It appears that avarol is released from the cells into the extracellular space in a merocrine manner. We suggest that it is involved in regulating the bacteria with which the sponge is symbiotically associated.

Influence of the antileukemic and anti-human immunodeficiency virus agent avarol on selected immune responses in vitro and in vivo.

The effect of the antileukemic and anti-HIV agent avarol on the lymphoid system was studied both in vitro and in vivo. Radioactively labelled avarol ([3H]-dihydroavarol) was found to accumulate in vitro in the cytoplasmic compartment primarily of T-lymphocytes and not of B-lymphocytes. Avarol increased significantly the IgG and IgM production by cultures of human lymphoid cells (unseparated) in vitro and slightly the number of plaque forming cells in vivo in spleen of mice. Moreover, a pretreatment of mice with avarol resulted in a higher [3H]-dThd incorporation rate in both macrophage-containing and macrophage-depleted lymphocyte cultures in vitro. The stimulatory influence of avarol on humoral immune responses is not accompanied by a change of the antibody-mediated hypersensitivity reaction, as measured by the Arthus reaction. No significant influence of avarol on the cellular immune system in vivo (rats or mice) was found, as taken from studies on delayed-type hypersensitivity reactions to sheep red blood cells and to oxazolone. The in vitro and animal data indicate that avarol combines useful properties (anti-HIV efficiency in vitro and augmentation of humoral immune responses) to consider it as a potential anti-AIDS agent.

Quantification of procedures and resuscitations in an emergency medicine residency.

Currently, there are no data that govern the number of procedures that are necessary to promote competence during emergency medicine (EM) training. Nonetheless, the Residency Review Committee requires each program to report the average number of procedures and resuscitations performed by its residents. For 7 years, we have used a computer database to track resuscitation and procedure experience for 42 residents. We have documented resident experience both in our 36,000-visit Level I Trauma Center emergency department and during off-service rotations in our 400-bed university teaching hospital. We report data from four graduating classes (n = 24). We estimate that residents have recorded 60% of the actual procedures performed. The 24 residents documented 11,947 procedures, averaging 498 per resident (range 264-1055), and participated in 3432 resuscitations, or 143 per resident (range 64-379). Mean and standard deviations are reported for 20 specific EM procedures and 4 types of resuscitations. EM residents perform a large number of procedures, but there is wide inter-resident variability. There is no documentation that some residents perform even one of some rare but critical procedures. This tracking system suggests, then, that procedure simulations, or cadaver and animal models, must be developed and used to enhance experience. This program can be modified to track resident experience in any specialty, as well as to document supervision by faculty and support credentialling inquiries.

[Renal aspergilloma: first manifestation of an occult sarcomatoid carcinoma]. / Aspergillom der Niere : Erstmanifestation eines okkulten sarkomatoiden Karzinoms.

A patient with b-symtoms and a sonographically detected kidney tumor entered hospital for a nephrectomy. An aspergillosis had been histologically accounted for. Up to that point, there was no indication of an immunodeficiency or invasive aspergillosis. Three months later, the patient was readmitted to hospital due to an indefinite retroperitoneal and hepatic mass on the right side. A punch biopsy ascertained a remanifestation of an aspergillosis at both localizations. The mass increased during systemic and antimycotic therapy, indicating the surgical resection of hepatic and retroperitoneal findings. The histological report yielded the diagnosis of a poorly differentiated sarcomatous carcinoma. Thus, an aspergillosis was the initial manifestation of what had up to that point been an occult sarcomatous carcinoma.

Biphasic and differential effects of the cytostatic agents avarone and avarol on DNA metabolism of human and murine T and B lymphocytes.

The two novel antimitotic and potent antileukemic agents avarone and avarol were determined to inhibit the [3H]-dThd incorporation rates of both murine spleen and human peripheral blood lymphocytes within the concentration range of 2-6 microM. The mitogens concanavalin A (ConA; for T lymphocytes), lipopolysaccharide (LPS; for murine B lymphocytes) and pokeweed mitogen (PWM; for human T and B lymphocytes) were used to stimulate DNA synthesis in the lymphocyte fractions. The ED50 concentrations, causing a 50% reduction of [3H]-dThd incorporation, were significantly lower in the experiments with avarone than in those with avarol. Moreover it was established that the DNA synthesis of ConA-activated lymphocytes was more sensitively inhibited by the compounds than that of LPS or PWM-activated cells, or non-activated cells. In addition it was elucidated that at low concentrations (1-2 microM) avarone and avarol caused a stimulation of dThd incorporation only in LPS or PWM-activated lymphocytes. Based on these results it is assumed that both antileukemic agents also affect differentially the different hematologic neoplasms.