The fibulins are a family of proteins that are associated with basement membranes and elastic extracellular matrix fibres. This review summarizes findings from studies of animal models of fibulin deficiency, human fibulin gene mutations, human tumours and injury models that have advanced our understanding of the normal and pathological roles of members of this formerly obscure family.

TEN for acute pancreatitis is as safe and effective, but is significantly less costly than TPN. Compared with TPN, TEN may promote more rapid resolution of the toxicity and stress response to pancreatitis. TEN via jejunal feeding should be used preferentially in this disease setting.

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also

High gastric residual volumes (RVs) are a frequent cause for cessation of total enteral nutrition (TEN). This study was designed to determine the RV that indicates intolerance or inadequate gastric emptying and to compare the RV findings in a blinded fashion with those findings obtained on physical examination and radiography. Twenty healthy normal volunteers (HNV), 8 stable patients with gastrostomy tubes (GTP), and 10 critically ill patients (CIP) were evaluated prospectively for 8 hours while receiving TEN. No subjects were clearly intolerant (ie, vomiting, aspiration). Of the total RVs recorded, 13.1% were greater than or equal to 150 mL in the CIP group, whereas only 2.4% of the RVs were greater than or equal to 150 mL in the HNV group. None of the RVs in the GTP group were greater than or equal to 150 mL. Objective scores on physical examination failed to correlate with RV (p = .397), as did objective scores on radiography (p = .742). However, objective scores on physical examination were significantly related to scores on radiography (p = .016). Abnormal physical examination findings were found in 4 out of 11 patients (GTP + CIP) with RVs less than 100 mL and in 6 out of 7 with RVs greater than or equal to 100 mL. Abnormal radiographic results were found in 6 out of 11 patients with RVs less than 100 mL, in 7 out of 7 patients with RVs greater than or equal to 100 mL, and in 4 out of 20 HNVs. There was no difference in RVs obtained from the supine or right lateral decubitus positions.(ABSTRACT TRUNCATED AT 250 WORDS)

We have demonstrated previously that certain members of a series of novel pyrrolo-1,5-benzoxazepine (PBOX) compounds potently induce apoptosis in a variety of human chemotherapyresistant cancer cell lines and in primary ex vivo material derived from cancer patients. A better understanding of the molecular mechanisms underlying the apoptotic effects of these PBOX compounds is essential to their development as antineoplastic therapeutic agents. This study sought to test the hypothesis that proapoptotic PBOX compounds target the microtubules. We show that a representative proapoptotic PBOX compound, PBOX-6, induces apoptosis in both the MCF-7 and K562 cell lines. An accumulation of cells in G 2 /M precedes apoptosis in response to PBOX-6. PBOX-6 induces prometaphase arrest and causes an accumulation of cyclin B 1 levels and activation of cyclin B 1 /CDK1 kinase in a manner similar to that of two representative antimicrotubule agents, nocodazole and paclitaxel. Indirect immunofluorescence demonstrates that both PBOX-6 and another pro-apoptotic PBOX compound, PBOX-15, cause microtubule depolymerization in MCF-7 cells. They also inhibit the assembly of purified tubulin in vitro, whereas a nonapoptotic PBOX compound (PBOX-21) has no effect on either the cellular microtubule network or on the assembly of purified tubulin. This suggests that the molecular target of the pro-apoptotic PBOX compounds is tubulin. PBOX-6 does not bind to either the vinblastine or the colchicine binding site on tubulin, suggesting that it binds to an as-yetuncharacterised novel site on tubulin. The ability of PBOX-6 to bind tubulin and cause microtubule depolymerization confirms it as a novel candidate for antineoplastic therapy.Microtubules are highly dynamic cytoskeletal fibers that are composed of ␣/␤ tubulin and play an important role in many physiological processes, especially mitosis and cell division. Their importance in mitosis and cell division makes microtubules an important target for anticancer therapy (Jordan and Wilson, 2004). The well characterized antimitotic drugs that have proven clinical efficacy, such as the taxanes (paclitaxel, docetaxel) and the Vinca alkaloids (vincristine, vinblastine, etc.) bind to tubulin. Alternating ␣-and ␤-tubulin polymerize to microtubules that constitute the mitotic spindles. Microtubule inhibitors disrupt microtubule dynamics of tubulin polymerization and depolymerization, which results in the inhibition of chromosome segregation in mitosis and consequently the inhibition of cell division. The three major classes of agents that bind tubulin are the taxanes, which stabilize the microtubules by blocking disassembly, the Vinca alkaloids, and agents that bind to the colchicine site on tubulin. The latter two classes are microtubuledestabilizing agents that act by blocking assembly of tubulin heterodimers.In the field of antineoplastic chemotherapy, antimicrotubule agents constitute an important class of compounds, with broad activity both in solid tumors and in hematological This work was su...