Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is -10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficUe colitis in man. (J.

Previous studies indicated that the peptide substance P (SP) causes Cl−-dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10−8 to 10−6 M) induced a rapid, monophasic concentration and Cl−-dependent, bumetanide-sensitive short-circuit current ( I sc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1(SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced I sc increase without impairing forskolin- and carbachol-mediated I sc increase. We conclude that SP stimulates Cl−-dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

The glycoproteins of herpesviruses and of HIV/SIV are made late in the replication cycle and are derived from transcripts that use an unusual codon usage that is quite different from that of the host cell. Here we show that the actions of natural transinducers from these two different families of persistent viruses (Rev of SIV and ORF57 of the rhesus monkey rhadinovirus) are dependent on the nature of the skewed codon usage. In fact, the transinducibility of expression of these glycoproteins by Rev and by ORF57 can be flipped simply by changing the nature of the codon usage. Even expression of a luciferase reporter could be made Rev dependent or ORF57 dependent by distinctive changes to its codon usage. Our findings point to a new general principle in which different families of persisting viruses use a poor codon usage that is skewed in a distinctive way to temporally regulate late expression of structural gene products.

Hypothesis: Endoscopic thoracic sympathetic block at T4 (ESB4) provides excellent results in patients with primary hyperhidrosis (HH) of the upper limb. Most patients have combined palmo-plantar or palmo-axillaryplantar HH. This study evaluates the clinical outcome of patients with upper limb HH with special emphasis on plantar sweating and patients' quality of life. Design: Review of a prospectively gathered database. Setting: Tertiary care university teaching hospital. Patients: The cohort included 73 patients (50 women and 23 men; mean age, 30.2 years). Twenty-six patients had palmar; 3, isolated axillary; and 44, combined HH. Sixty-six patients (90.4%) had concomitant plantar HH. Interventions: One hundred forty-five operations were performed by applying one 5-mm clip above and below the fourth sympathetic ganglion. Results: Of palms, 71.9% were completely and 28.1% were nearly dry. Corresponding percentages were 45.1% and 50.5% for armpits and 4.5% and 37.9% for the soles, respectively. Of soles, 42.4% remained unchanged and 15.2% became slightly worse. Compensatory sweating occurred in 19.4% of patients, with 2.8% having severe compensatory sweating. Feet were rarely affected by compensatory sweating (5.6%). Gustatory sweating was reported by 31.9% of patients but did not bother them. Quality of life improved significantly after ESB4. Most patients (87.5%) were completely satisfied with the outcome; 9.7% were partly satisfied. Conclusions: In the treatment of upper limb HH, ESB4 yields excellent success rates. Plantar sweating can be relieved in nearly half of patients, although exact neurophysiologic mechanisms remain unclear. Incidence of compensatory and gustatory sweating is low, contributing to a high patient satisfaction and improvement in quality of life.