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Biomedical subjects

E Mullen

Publications and source records attributed to E Mullen.

13 recordsLinked to original sources

[Multifocal biliary papillomatosis: an indication for liver transplantation].

Biliary papillomatosis is a uncommon disease. Because of the high rate of recurrence and the possibility of malignant transformation, liver resection or transplantation was recommended. A case of diffuse bilobar biliary papillomatosis, in a 60 years old patient, responsible for cholangitis, cholestasis and for high portal pressure (esophageal varices grade I and II and hypersplenisme) is reported. The patient had had an external biliary drainage leading to an great loss of hydroelectrolytic component important. Opacification and biopsies under endoscopic control assert the right diagnosis. He was treated by a orthotopic liver transplantation. Post operative course was simple. In the 9th month, it was asymptomatic with a completely satisfactory evolution. The other therapeutic modalities was discussed, as well as the review of the literature.

Biliary Tract Neoplasms↗

A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin.

We performed a pilot clinical trial with safingol (L-threo-dihydrosphingosine), a protein kinase C-specific inhibitor that potentiates the effect of doxorubicin (DOX) in tumor-bearing animals. Safingol was initially administered as a 1-h infusion at escalating doses. Fourteen days later, patients received the same dose of safingol in combination with a fixed dose of DOX. The combination was repeated at 3-week intervals. Safingol dose levels ranged from 15 to 120 mg/m2. The plasma levels achieved at the final dose level were comparable to those associated with potentiation of DOX in animals. The mean Cmax and area under the curve for safingol at the 120 mg/m2 dose level were 1040 +/- 196 ng/ml and 1251 +/- 317 mg x h/ml, respectively. The mean plasma half-life for safingol was 3.97 +/- 2.51 h, the mean estimated clearance was 3140 +/- 765 ml/min, and the mean volume of distribution was of 995 +/- 421 liters. Coadministration of a fixed dose of DOX did not significantly change the pharmacokinetics of safingol, nor did increasing doses of safingol significantly affect the pharmacokinetics of DOX. Minor responses were observed in three patients with pancreatic cancer and one patient with angiosarcoma of the scalp. This pilot Phase I study indicates that the protein kinase C inhibitor safingol can be given safely with 45 mg/m2 of DOX at a dose that is potentially pharmacologically active without dose-limiting toxicity.

Adult↗

Fibrinoid and trophoblastic necrosis with massive chronic intervillositis: an extreme variant of villitis of unknown etiology.

A placental lesion, characterized by fibrinoid and trophoblastic necrosis with massive infiltration of the intervillous space by mononuclear cells (massive chronic intervillositis, MCI), was observed in six cases, five with intrauterine growth retardation (IUGR) and one with sudden intrauterine fetal death. Four out of six had chronic villitis of unknown etiology (CVUE) associated with this lesion, and five had lesions of anchoring villitis. In three cases, acute atherosislike lesions in spiral arteries of parietal and/or basal decidua were observed. Massive deposits of IgM, a smaller amount of C3 and Clq, and slight deposits of IgG and IgA were found in these vessels. Neither mothers nor infants had any clinical or serological evidence of infection. Cases with MCI were compared with those having CVUE without intervillositis. Patients with MCI showed lower values of infant weight, infant length, and ponderal index than controls. However, cases with MCI group showed a higher incidence of IUGR. Placentas from the MCI group had a greater number of acute atherosislike lesions than controls. Massive chronic intervillositis may represent an extreme variant of villitis of unknown etiology. A maternal immunological aggression toward fetal tissues is proposed as pathophysiological mechanism, although a nondetermined placental infection cannot be excluded.

Adult↗

Structural studies on membrane-bound bovine rhodopsin.

Our previous work has shown that the treatment of bovine rhodopsin with the proteolytic enzyme papain gives rise to a cleaved, but fully functional, complex consisting of three fragments, H, M and L (heavy, medium and light), held together by strong non-covalent forces. By using some of the chemical and physical differences between the three fragments, a protocol for the preparative isolation of each fragment was devised. Purified M-fragment, which had been radiochemically labelled at the retinal-binding site was treated with CNBr and the mixture subjected to a multi-step separation to furnish a retinyl peptide. The sequence analysis of the latter showed that the retinal-binding lysine residue was located at position 296 from the N-terminal of rhodopsin (or residue 53 from the C-terminal). In order to ascertain the position of the cytoplasmic loop which exists between the M- and L-fragments, radiochemically labelled L-fragment was isolated from the cleaved complex. The purified L-fragment was shown to consist of two populations of peptides which were produced by the action of papain on the bonds between Lys-311 and Gln-312 and between Gln-312 and Phe-313.

Amino Acid Sequence↗

The incorporation of tritiated retinyl moiety into the active-site lysine residue of bacteriorhodopsin.

Purple membranes were isolated from Halobacterium halobium bleached and regenerated with all-trans-[15-3H]retinal. The incorporation of label was 1.2 mol of retinal/mol of bacterio-opsin. The [3H]retinyl-bacterio-opsin obtained from regeneration was hydrolysed to give tritiated retinyl-lysine, which, on hydrogenation to N-epsilon-perhydro[3H]retinyl-lysine and reaction with 1-fluoro-2,4-dinitrobenzene, gave bis-(2,4-dinitrophenyl)-N-epsilon-perhydro[3H]retinyl-lysine. This result confirmed that the retinyl moiety of the chromophore is attached to an epsilon-amino group of lysine.

Bacteriorhodopsins↗