Aplidiasterols A and B, two new cytotoxic 9,11-secosterols from the Mediterranean ascidian Aplidium conicum

Two novel 9,11-secosterols, aplidiasterols A (3β,6β,11-trihydroxy-9,11-seco-5α-cholest-7-en-9-one, 1) and B (3β,5α,6β,11-tetrahydroxy-9,11-secocholest-7-en-9-one, 2), along with the known secosterols 3 and 4, were isolated from the Mediterranean ascidian Aplidium conicum and their structures were determined by spectroscopic data. Aplidiasterols A and B were found to be cytotoxic against rat glioma (C6) and murine monocyte/macrophage (J774) tumor cells in vitro. Compounds 1-4 represent the first example of secosterols isolated from tunicates.     

Heat shock cognate protein 70 is involved in rotavirus cell entry

In this work, we have identified the heat shock cognate protein (hsc70) as a receptor candidate for rotaviruses. hsc70 was shown to be present on the surface of MA104 cells, and antibodies to this protein blocked rotavirus infectivity, while not affecting the infectivity of reovirus and poliovirus. Preincubation of the hsc70 protein with the viruses also inhibited their infectivity. Triple-layered particles (mature virions), but not double-layered particles, bound hsc70 in a solid-phase assay, and this interaction was blocked by monoclonal antibodies to the virus surface proteins VP4 and VP7. Rotaviruses were shown to interact with hsc70 at a postattachment step, since antibodies to hsc70 and the protein itself did not inhibit the virus attachment to cells. We propose that the functional rotavirus receptor is a complex of several cell surface molecules that include, among others, hsc70.     

Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2

We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III–IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m² cisplatin i.v. on day 1 plus 1000 mg m⁻² day⁻¹ 5-FU on days 1–5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8–12 and 15–19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients (20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients (13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus, there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were 2 toxic deaths (6.7%), 1 from hematological causes in group A and 1 from cardiac causes in group B. Myelosuppression and gastrointestinal toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable that a clinically significant difference between the two treatment groups will be observed even if the calculated patient sample size is achieved. Received: 9 April 1998 / Accepted: 30 June 1998     

New triterpene oligoglycosides from the Caribbean sponge Erylus formosus

Seven new triterpene glycosides, erylosides R₁ (1), T₁ (3), T₂ (4), T₃ (5), T₄ (6), T₅ (7), and T₆ (8) along with the known formoside (2) were isolated from the sponge Erylus formosus collected along the Caribbean coast of Mexico. Glycoside 1 was determined as a trisaccharide, glycoside 2 as a tetrasaccharide while glycosides 3–8 were hexasaccharide. Their carbohydrate chains were unprecedented and have never been found in oligosaccharides from other biological sources, except Erylus spp. Three carbohydrate chains in the glycosides 3 and 6, 4 and 7, 5 and 8 correspondingly are new. The glycosides 1–5 have penasterol as aglycone while glycosides 6–8 proved to be glycoconjugates of 24-methylene-14-carboxy-lanost-8(9)-en-3β-ol.     

Mycoflora and Potential for Mycotoxin Production of Freshly Harvested Black Bean from the Argentinean Main Production Area

A mycological survey was carried out, for the first time, on black bean samples from the northwestern Argentinean province of Salta in the 1999 harvest season. Ten varieties of black beans were evaluated at three locations. Species of the genus Alternaria were the most prevalent component of the black bean mycoflora. Species of Fusarium, Sclerotinia, Rhizoctonia and Acremonium were also recorded. The predominant species of the genera isolated were Alternaria alternata, Sclerotinia sclerotiorum, Rhizoctonia solani, Fusarium semitectum and Acremonium strictum. An analysis of variance was applied to determine possible differences between black bean varieties. Variety FT88/519 was the most susceptible to Sclerotinia sclerotinia infection, while the variety DOR 604 was the least susceptible. As toxigenic species were recovered, Alternaria toxins, zearalenone and trichothecenes may pose a contamination risk for black bean.     

A codon window in mRNA downstream of the initiation codon where NGG codons give strongly reduced gene expression in Escherichia coli

The influences on gene expression by codons at positions +2, +3, +5 and +7 downstream of the initiation codon have been compared. Most of the +2 codons that are known to give low gene expression are associated with a higher expression if placed at the later positions. The NGG codons AGG, CGG, UGG and GGG, but not GGN or GNG (where N is non-G), are unique since they are associated with a very low gene expression also if located at positions +2, +3 and +5. All codons, including NGG, give a normal gene expression if placed at positions +7. The negative effect by the NGG codons is true for both the lacZ and 3A′ model genes. The low expression is suggested to originate at the translational level, although it is not the result of mRNA secondary structure or a lowered intracellular mRNA pool.     

Recent trends on the molecular biology of pneumococcal capsules, lytic enzymes, and bacteriophage

Streptococcus pneumoniae has re-emerged as a major cause of morbidity and mortality throughout the world and its continuous increase in antimicrobial resistance is rapidly becoming a leading cause of concern for public health. This review is focussed on the analysis of recent insights on the study of capsular polysaccharide biosynthesis, and cell wall (murein) hydrolases, two fundamental pneumococcal virulence factors. Besides, we have also re-evaluated the molecular biology of the pneumococcal phage, their possible role in pathogenicity and in the shaping of natural populations of S. pneumoniae. Precise knowledge of the topics reviewed here should facilitate the rationale to move towards the design of alternative ways to combat pneumococcal disease.     

Role of endothelins in animal models of hypertension: focus on cardiovascular protection

Investigation of the regulation of vascular function by endothelium-derived factors has been a prominent topic of research in the field of hypertension during the last decade. Of the different endothelial factors, endothelins, which play an important role in vasodilatation-vasoconstriction balance, have been the subject of great interest and an impressive number of publications. This peptide, a very potent vasoconstrictor, triggers as well events involved in growth, proliferation, matrix production and local inflammation. In parallel, its role in hypertension has evolved from a simple vasoconstrictor to a central local regulator of vascular homeostasis contributing not only to the elevation of blood pressure, but also to the complications of hypertension. This review summarizes research on endothelins and its receptor antagonists in experimental hypertension, with special emphasis on vascular remodeling and target-organ protection.