Experimental investigation of the effects of ionic micelles on colloidal stability.

The effects of ionic micelles (tetradecyltrimethylammonium bromide (C14TAB) and sodium dodecylsulfate (SDS)) on the stability of a dispersion of highly charged silica particles was investigated both visually and using UV-vis absorption. As the surfactant concentration increased from 0 to 30 cmc, a clear critical flocculation concentration was observed with both surfactants. For SDS, restabilization was observed at 20 cmc. These stability results were compared to energy profiles that were calculated using measured force profiles between a single silica sphere and plate obtained with colloid-probe atomic force microscopy. It was found that flocculation would occur once the energy well formed by depletion attraction exceeded 3 k(B)T, while restabilization occurred once the long range structural energy barrier exceeded 8 k(B)T. These values are consistent with the energy levels needed for flocculation and restabilization predicted by other researchers.

Total synthesis of (-)-ulapualide A, a novel tris-oxazole macrolide from marine nudibranchs, based on some biosynthesis speculation.

A new, second generation, total synthesis of ulapualide A (1), whose stereochemistry was recently determined from X-ray analysis of its complex with the protein actin, is described. The synthesis is designed and based on some speculation of the biosynthetic origin of the contiguous tris-oxazole unit in ulapualide A, alongside that of the related co-metabolites that contain only two oxazole rings, e.g. 6 and 7. The mono-oxazole carboxylic acid 67b and the mono-oxazole secondary 55b alcohol which, together, contain all of the 10 asymmetric centres in the natural metabolite, were first elaborated using a combination of contemporary asymmetric synthesis protocols. Esterification of 67b with 55b under Yamaguchi conditions gave the ester 77 which was then converted into the omega-amino acid 18a following simultaneous deprotection of the t-butyl ester and the N-Boc protecting groups. Macrolactamisation of 18a, using HATU, now gave the key intermediate macrolactam 17, containing two of the three oxazole rings in ulapualide A (1). A number of procedures were used to introduce the third oxazole ring in ulapualide A from 17, including: a) cyclodehydration to the oxazoline 78a followed by oxidation using nickel peroxide leading to 76; b) dehydration to the enamide 79, followed by conversion into the methoxyoxazoline 78b, via 80, and elimination of methanol from 78b using camphorsulfonic acid. The tris-oxazole macrolide 76 was next converted into the aldehyde 82b in four straightforward steps, which was then reacted with N-methylformamide, leading to the E-alkenylformamide 83. Removal of the TBDPS protection at C3 in 83 finally gave (-)-ulapualide A, whose 1H and 13C NMR spectroscopic data were indistinguishable from those obtained for naturally derived material. It is likely that the tris-oxazole unit in ulapualide A (1) is derived in nature from a cascade of cyclodehydrations from an acylated tris-serine precursor, e.g.9, followed by oxidation of the resulting tris-oxazoline intermediate, i.e.10. It is also plausible to speculate that the biosynthesis of metabolites related to ulapualide A, e.g. the bis-oxazole 6 and the imide 7, involve cyclisations of just two of the serine units in 9. These speculations were given some credence by carrying out pertinent interconversions involving the bis-oxazole amide 24, the enamide 25, the imide 26, the oxazoline 27 and the tris-oxazole 30 as model compounds. An alternative strategy to the tris-oxazole macrolide intermediate 76 was also examined, involving preliminary synthesis of the aldehyde 73, containing a shortened (C25-C34) side chain from 67b and 47b. A Wadsworth-Emmons olefination reaction between 73 and the phosphonate ester 74 led smoothly to the E-alkene 75, but we were not able to reduce selectively the conjugated enone group in 75 to 76 without simultaneous reduction of the oxazole alkene bond, using a variety of reagents and reaction conditions.

Inverted Meckel's diverticulum: an entity simulating an ileal polyp.

A case of inverted Meckel's diverticulum is described. This presented as an ileal polyp in an individual with chronic unexplained iron deficiency anemia. Most prolapsed Meckel's diverticula occur acutely as intussusceptions with bowel obstruction and characteristically develop in childhood. This case therefore represents an unusual surgical problem in an older individual in which the diagnosis was clinically unexpected.

Clinicopathological analysis of follicular lymphoma with a polyploid karyotype.

The prognostic significance of specific cytogenetic abnormalities in follicular lymphoma (FL) is an area of ongoing research. A small percentage of FL are characterized by a polyploid karyotype. Several studies have analyzed ploidy level to determine its role as an independent prognostic factor in non-Hodgkins lymphoma, with equivocal results, mostly using DNA flow cytometry to ascertain ploidy status. We have performed cytogenetic analyses on 180 cases of FL with a t(14;18) diagnosed between 1980 and 1995. Cases were divided into a polyploid group (20 cases) and a non-polyploid group (160 cases), polyploidy defined as a modal chromosome number of 58 or greater. Each group included examples of the 3 subtypes of FL, [Working Formulation]: 1) follicular small cleaved cell (FSC), 2) follicular mixed, small and large cell (FM), and 3) follicular large cell (FLC). The median follow-up time was 38.5 months. The histological subclassification of the polyploid group revealed much less FSC (30% vs 66%, p < 0.004) and much more FLC (25% vs 4%, p < 0.003) than the non-polyploid group, implying histological progression may occur in parallel with the development of polyploidy. Recognized clinical prognostic factors were evenly distributed between the two groups and no survival difference was detected. We show that polyploidy as determined by classical cytogenetics is present in different frequencies across the subtypes of FL with a t(14;18), but is not an independent prognostic factor for survival in FL.

Salivary duct carcinoma secreting prostate-specific antigen.

Prostate-specific antigen (PSA) is a 30 kDa glycoprotein serine protease that shows high tissue specificity for prostatic tissue, both benign and malignant. However, recent reports have shown that a variety of normal and neoplastic tissue types express PSA immunohistochemically. In addition, rare instances of the secretion of PSA by nonprostatic cancers have been reported in the literature. The authors present a case of salivary duct carcinoma associated with elevated serum levels of PSA. Both the primary tumor and metastases stained positively with anti-PSA monoclonal antibodies, but were negative with antibodies directed against prostate-specific acid phosphatase. Elevated serum PSA levels were confirmed with three different immunoassay methods. A peak serum level of 140 micrograms/L was measured and this correlates with levels of PSA associated with metastatic prostatic carcinoma. High performance liquid chromatography with a molecular sieve column characterized the serum PSA into both free protein (approximately 20%) and protein bound to alpha-1-antichymotrypsin (PSA-ACT)(approximately 80%). Molecular weights of the free PSA and PSA-ACT subfractions were 27-31 kDa and 100-110 kDa, respectively.

Karyotypic analysis of two related cervical carcinoma cell lines that contain human papillomavirus type 18 DNA and express divergent differentiation.

The cell lines C-4I and C-4II were established in culture from a nonkeratinizing squamous carcinoma of the uterine cervix. Both lines contain human papillomavirus (HPV) type 18 DNA (Brandt et al., Cold Spring Harbor Laboratories, 5:179, 1987) and both are hypodiploid with similar, but not identical, karyotypes. Each line expresses multiple characteristics of ectocervical epithelial differentiation, but the characteristics differ between the lines. In the present study, G banding of the lines showed that cells of both lines have two normal chromosomes 1-5, 8-10, 13, 16, and 17, one normal chromosome 12 and 14, and no normal chromosomes 15 and 18. The lines share three abnormal chromosomes, der(8)t(8q;12q), der(18)t(18q;?), and i(5p). There are specific differences between the lines. C-4I has two normal chromosomes 6, while C-4II has one; C-4II has two chromosomes 11 and der(18)t(18q;?), while C-4I lacks both chromosomes 11 and has one der(18)t(18q;?). Each line has unique markers that include del(11)(p11), del(22)(q12), and del(21)(q21) in C-4I and i(15q), der(X)t(Xq;9p), der(6)t(6p;14q), and del(4)(q21) in C-4II. The results show that these phenotypically distinct lines are derived from the same clone and that the 8q arm (the site of HPV 18 integration) is present in three copies in both lines. They also define several chromosome rearrangements that are compatible with the expression of specific differentiation markers.

Simple ultraviolet calibration source with reference spectra and its use with the Galileo orbiter ultraviolet spectrometer.

We have developed a simple compact electron impact laboratory source of UV radiation whose relative intensity as a function of wavelength has an accuracy traceable to the fundamental physical constants (transitions probabilities and excitation cross sections) for an atomic or molecular system. Using this laboratory source, calibrated optically thin vacuum ultraviolet (VUV) spectra have been obtained and synthetic spectral models developed for important molecular band systems of H(2) and N(2) and the n(1)P(0) Itydberg series of He. The model spectrum from H(2) represents an extension of the molecular branching ratio technique to include spectral line intensities from more than one electronic upper state. The accuracy of the model fit to the VUV spectra of H(2) and N(2) is sufficient to predict the relative spectral intensity of the electron impact source and to serve as a primary calibration standard for VUV instrumentation in the 80-230-nm wavelength range. The model is applicable to VUV instrumentation with full width at half-maximum >/= 0.4 nm. The present accuracy is 10% in the far ultraviolet (120-230 nm), 10% in the extreme ultraviolet (EUV) (90-120 nm), and 20% in the EUV (80-90 nm). The n(1)P(0) Rydberg series of He has been modeled to 10% accuracy and can be considered a primary calibration standard in the EUV (52.2-58.4 nm). A calibrated optically thin spectrum of Ar has been obtained at 0.5-nm resolution and 200-eV electron impact energy to 35% accuracy without benefit of models over the EUV spectral range of 50-95 nm. The Ar spectrum expands the ultimate range of the VUV relative calibration using this source with the four gases, He, Ar, H(2), and N(2), to 50-230 nm. The calibration of the Galileo orbiter ultraviolet spectrometer for the upcoming Jupiter mission has been demonstrated and compared to results from other methods.