Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types.

Transient transfection of pLB2CAT constructs bearing short synthetic oligonucleotides derived either from the tyrosine hydroxylase (TH) promoter or other sources was used to examine functional cAMP regulatory element (CRE) activity in a variety of cell lines. The region containing only the putative TH CRE was found to be as or more effective in conferring cAMP responsiveness onto pLB2CAT (which employs the TK promoter) than the immediate 272 bp region of the TH promoter. Increases in CAT activity of 10- to 20-fold were observed in JEG-3 cells with a single insert of the TH CRE region (-31 to -54) in pLB2CAT, and the presence of a second insert generated only a modest further increase. This construct also responded to cAMP in 4 other cell lines tested but the degree of increase was less dramatic. Inserts containing the consensus 8 bp CRE motif embedded in other natural or artificial contexts served generally as weak functional CREs in all cell lines tested. In vitro analysis revealed that a specific protein-DNA complex apparently containing a single protein with a MW of 45-50 kDa was formed equally well with JEG-3 cell nuclear extract and CRE-bearing-TH and other fragments which produced dramatically different cAMP effects in vivo. These results suggest specificity in the effects of cAMP on different CREs which are dictated by contextual differences.     

Cytologic criteria for the formation of a risk group in Barrett esophagus]

Oncologic screenings of the populations in the areas with increased incidence of esophageal cancer have revealed Barrett's ulcer in 1 percent of the examinees. Endoscopic and cytologic characteristics of this condition are presented. Precancer changes--severe dysplasia--are most frequent in male Kazakhs (14.1 percent) aged 50 to 59 (14.7 percent). Subjects with Barrett's ulcer developing severe dysplasia, as evidenced by cytograms, should be included in the group of subjects at risk for carcinoma of the lower third of the esophagus and cardia.     

Enucleation combined with orbital implants for malignant melanoma of the uvea

Advanced malignant melanomas of the uvea unsuited for an eye salvaging approach require enucleation of the tumor containing eye. A series of 68 patients is reported who underwent enucleation combined with insertion of a spherical dura-encased implant after 30 Gray pre-irridiation therapy of the orbit. Postoperative results with special attention to cosmetic outcome and motility of the prosthesis suggest that the insertion of an orbital implant should be preferred to the enucleation with no implant.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

A structurally oriented approach to the repair of cicatricial entropion

A modified technique for the repair of moderate to severe cicatricial entropion has been developed. This method is unique, as it involves the creation of a bipedicled tarsoconjunctival advancement flap. The technique avoids the causes of surgical failure seen with standard tarsal fracturing procedures.     

Smoking and stroke.

The purpose of this review is to evaluate literature published since 1978 on the association between smoking and stroke. Two cohort studies found a dose-response relationship between the amount of cigarettes smoked per day and the relative risk of stroke. Also, two of the cohort studies found that when smoking ceased, the risk of stroke lessened (p less than 0.001). Nine case-control studies found a significant association between smoking and stroke for men and women. The biological association between smoking and stroke is plausible and several epidemiologic studies are supportive of this thesis. Additional, well-designed epidemiologic studies with a sufficient sample size to detect reasonably small odds ratios or relative risks (thus providing adequate statistical power) are warranted.     

Articular ossification after malignant neurolepsis. A case of schizophrenia treated with phenothiazines

Following administration of phenothiazines for schizophrenia, a 25-year-old patient developed a malignant neuroleptic syndrome followed by bilateral periarticular ossification of the knees, with severely limited motion. Two years later, the patient regained useful motion after bilateral excision of the ossified tissue and intensive physiotherapy. No recurrence of ossification was observed 3 years after operation, and the patient has maintained almost normal motion.