Adenocarcinoma cervicis uteri. An appraisal of treatment results for a period of 40 years

A retrospective study was done in 316 patients with primary cervical adenocarcinoma treated at the Research Institute for Clinical and Experimental Oncology in Brno over a period of 40 years (1939-1978). The treatment results were compared to those in 2571 patients with epidermoid carcinomas of the uterine cervix treated at the Institute over the same period. The 5-year survival rate was significantly lower in adenocarcinoma patients (in Stage I patients, 77.8% vs. 84.5%, and, in the whole group, 60.8% vs. 70.3%). The assessment of the treatment results of this study has clearly showed that in cervical adenocarcinomas, surgery combined with radiotherapy was much more effective than radical radiotherapy alone (77.4% vs. 64.7%). In contrast to this, in epidermoid carcinomas the treatment results were better after radical radiotherapy (86.5% vs. 81.3%). Thus, in the prognosis of cervical adenocarcinomas the mass of the tumor, the size of the uterus, as well as the grading play a role. That means that primary cervical adenocarcinomas at early stages can be successfully treated by a combination of radical surgery and radiotherapy, while radiotherapy of advanced stages of this tumor is less successful.     

Successful bridge to transplantation in a patient with Becker muscular dystrophy-associated cardiomyopathy.

A 28-year-old male patient diagnosed with Becker muscular dystrophy (BMD)-associated cardiomyopathy was successfully bridged to transplantation with the Cardiowest total artificial heart. Dramatic improvement of muscular functional status occurred following transplantation.     

Mutational analysis of HOXD13 and HOXA13 genes in the triphalangeal thumb-brachyectrodactyly syndrome.

The triphalangeal thumb-brachyectrodactyly syndrome is a very rare autosomal dominant disorder of unknown etiology characterized by an unusual pattern of limb malformations: triphalangeal thumbs and brachyectrodactyly in the hands, and ectrodactyly in the feet. In a previous report, we described the clinical and radiographical features of three related subjects with the disease and suggest that due to the unusual combination of limb defects and to its phenotypic similarity with the limb malformative pattern induced by disrupting the Hoxd13 gene in mouse, the triphalangeal thumb-brachyectrodactyly syndrome might be caused by mutations in a HOX gene. After sequencing the entire coding region of HOXD13 and the highly conserved homeodomain encoding region of HOXA13, we do not detect any deleterious mutation in any of the patients excluding that alterations at these sequences are responsible for the disease. Mutations in regulatory regions of these genes or in other genes involved in limb development might be responsible for the disease.     

Dexamethasone inhibits food intake suppression induced by low doses of interleukin-1 beta administered intracerebroventricularly.

Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1 beta (rhIL-1 beta, 0.125 to 2.0 ng/rat) dose-dependently suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. ICV infusion of bovine serum albumin (BSA), or heat-treated rhIL-1 beta had no effect on food intake. Pretreatment with dexamethasone (200 micrograms/rat, intraperitoneal) blocked the food intake suppression induced by low doses of rhIL-1 beta. This ability of dexamethasone, a synthetic corticosteroid, may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression.     

Effects of galanin on insulin and glucagon secretion in the rat

Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80 pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets was dose-dependently suppressed by galanin (10^-6-10^-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower dose levels, the peptide also inhibits basal glucagon release.     

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.     

The in vitro permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane

The permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane was studied using excised skin in a flow-through diffusion cell. The rate of resorption was determined by measuring the amount of substance found in the receptor fluid beneath the skin at steady-state. The rates of resorption (microgram X cm-2 X hr-1) were: benzene 99. ethylene glycol 118, formaldehyde from a concentrated solution of formalin 319, formaldehyde from a solution of 10% formalin in phosphate buffer 16.7, and n-hexane 0.83. The amount of substance in the skin at steady-state and after 0.5 hr of exposure was also determined. For all substances, the sum of the amount in the receptor medium and in the skin at steady-state, were larger than the amount obtained by multiplying the resorption rate by the time of exposure. For benzene, ethylene glycol and n-hexane the amount absorbed during the first half-hour of exposure was considerable larger than the amount resorbed during a same unit of time at steady-state. These data call attention to the fact that the absorption rate is higher before steady state is attained.