Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Readily available fluorescein isothiocyanate-conjugated antibodies can be easily converted into targeted phototoxic agents for antibacterial, antiviral, and anticancer therapy.

Fluorescein-labeled antibodies have little, if any, photodynamic effect because energy acquired by light absorption is rapidly dissipated in fluorescence. However, they can be easily and efficiently converted to selective photodynamic sensitizers by iodination under mild conditions. We have outlined general experimental procedures that can be used to turn a fluorescein-labeled anti-Escherichia coli antibody into a photodynamic sensitizer that selectively kills E. coli while sparing closely related Salmonella typhimurium. These results demonstrate that iodination did not destroy the specificity or activity of the antibody. This technique should be applicable to the large number of fluoresceinated antibodies that are commercially available. Thus, this strategy provides a simple way to rapidly prepare a large number of targeted phototoxic agents that can be used for the selective destruction with light of nearly any type of tissue or organism.     

Myometrial invasion by endometrial carcinoma: sonographic assessment

The depth of myometrial invasion by endometrial carcinoma was evaluated using real-time sonography (US) in 20 patients with histologically proved adenocarcinoma of the endometrium. In 14 of 20 (70%) cases, US-based estimation of the depth of myometrial invasion was within 10% of the actual measurement in the gross specimen. The US-based estimation of tumor invasion was low in seven patients, high in four patients, and agreed with pathologic findings (+/- 5%) in nine patients. In four patients with polypoid intraluminal extension of tumor, a deeply invasive tumor was suspected on US but was not found on pathologic examination. In 12 superficially invasive tumors, the continuity of the demarcating subendometrial halo was intact in nine and incomplete in three. In six patients with deeply invasive tumors, this zone was partially disrupted in four, totally disrupted in one, and intact in one. Errors of estimation of the depth of myometrial invasion on US most frequently occurred when a tumor had a significant intraluminal polypoid extension. Demonstration of a subendometrial halo usually indicated superficial invasion, whereas the absence of a halo was frequently associated with deep invasion.     

Characterization of oligonucleotide transport into living cells.

Addition of antisense oligonucleotides to cell cultures has been used to specifically inhibit gene expression. We have investigated the mechanism by which oligonucleotides enter living cells. These compounds are taken up by cells in a saturable, size-dependent manner compatible with receptor-mediated endocytosis. Polynucleotides of any length are competitive inhibitors of oligomer transport, providing they possess a 5'-phosphate moiety. Using oligo(dT)-cellulose for affinity purification, we have identified an 80-kDa surface protein that may mediate transport. Knowledge of the oligonucleotide transport mechanism should facilitate the design of more effective synthetic antisense oligomers as potential clinical agents.     

Breast and axillary tissue MR imaging: correlation of signal intensities and relaxation times with pathologic findings

We tested a variety of inversion-recovery (IR) and spin-echo (SE) sequences by imaging the breast masses of 22 patients before surgery and 23 tissue specimens with magnetic resonance (MR) imaging at 0.6 T to determine the most effective pulse sequences to evaluate breast disease. An SE pulse sequence using a long repetition time (TR) of 1,600 msec and a long echo time (TE) of 90 msec was found to be the most sensitive in depicting carcinoma in the excised tissue specimens, with all of the carcinomas (n = 15) demonstrating irregular areas of higher signal intensity (SI) than that of the adjacent fat. However, only five of 11 breast carcinomas present in the preoperative patients produced a higher SI than that produced by fat on the same T2-weighted sequence. Five of the remaining six carcinomas in the preoperative patients appeared as localized distortions of fibroductular architecture on both T2-weighted SE and IR sequences. In axillary tissue specimens, both metastatic carcinoma and hyperplastic lymph nodes produced a high SI on T2-weighted SE sequences. However, metastatic carcinoma had a significantly longer T2 relaxation time than did hyperplastic lymph nodes.     

Cutaneous events during treatment of chronic inflammatory joint disorders with anti‐tumour necrosis factor alpha: a cross‐sectional study

Background Anti‐tumour necrosis factors (anti‐TNF) are more and more used, but the rate of skin adverse events is not known. Objective The aim was to assess the number of skin infections and other dermatoses in patients treated with anti‐TNFα. Patients and methods One hundred eighty‐seven patients suffering from rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam. Patients with anti‐TNF were compared with those without this treatment in a prospective transversal study. Results Among them, 59 patients were treated with anti‐TNFα and steroids were prescribed in 100 cases. There was no difference in the prevalence of skin infections or eczema or tumours. Skin drug reactions were observed in six patients. Infections by dermatophytes appear very frequent, approaching 70% in both groups. Conclusions This study shows that skin infections (or other skin diseases) are not more frequent in these patients. No differences were observed in infections (bacterial fungal, parasital or viral), tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a long‐term survey might be interesting, especially about skin tumours.