Pattern integrations in young depressed women: Part I

Five nitro musk compounds widely used in cosmetics and detergents were examined for DNA-damaging and mutation-inducing properties. For this purpose two short-time assays were used, the SOS chromotest and the Salmonella/mammalian microsome test. Musk ambrette showed mutagenicity in Salmonella typhimurium TA 100 requiring metabolic activation by rat liver postmitochondrial supernatant (S9) but it lacked mutagenicity in the absence of S9 and genotoxicity in the SOS chromotest. Musk xylene, musk ketone, musk moskene and musk tibetene showed neither mutagenicity nor genotoxicity in the presence and absence of S9.     

DNA nick processing by exonuclease and polymerase activities of bacteriophage T4 DNA polymerase accounts for acridine-induced mutation specificities in T4

Acridine-induced frameshift mutagenesis in bacteriophage T4 has been shown to be dependent on T4 topoisomerase. In the absence of a functional T4 topoisomerase, in vivo acridine-induced mutagenesis is reduced to background levels. Further, the in vivo sites of acridine-induced deletions and duplications correlate precisely with in vitro sites of acridine-induced T4 topoisomerase cleavage. These correlations suggest that acridine-induced discontinuities introduced by topoisomerase could be processed into frameshift mutations. The induced mutations at these sites have a specific arrangement about the cleavage site. Deletions occur adjacent to the 3' end and duplications occur adjacent to the 5' end of the cleaved bond. It was proposed that at the nick, deletions could be produced by the 3'-->5' removal of bases by DNA polymerase-associated exonuclease and duplications could be produced by the 5'-->3' templated addition of bases. We have tested in vivo for T4 DNA polymerase involvement in nick processing, using T4 phage having DNA polymerases with altered ratios of exonuclease to polymerase activities. We predicted that the ratios of the deletion to duplication mutations induced by acridines in these polymerase mutant strains would reflect the altered exonuclease/polymerase ratios of the mutant T4 DNA polymerases. The results support this prediction, confirming that the two activities of the T4 DNA polymerase contribute to mutagenesis. The experiments show that the influence of T4 DNA polymerase in acridine-induced mutation specificities is due to its processing of acridine-induced 3'-hydroxyl ends to generate deletions and duplications by a mechanism that does not involve DNA slippage.     

A guide to safe corporotomy incisions in the presence of underlying inflatable penile cylinders: results of in vitro and in vivo studies

PURPOSE: Because iatrogenic injury to an underlying inflatable implant may be induced by electrocautery incision of the tunica during tunical release or cylinder reexploration, safe electrocautery guidelines are needed. MATERIALS AND METHODS: For the in vitro model silicone and polyurethane elastomer lined inflatable penile prosthetic cylinders were used, and cutting and coagulation electrocautery was applied directly on the device, on a tissue-implant interface, and at minimal, partial or full inflation with saline. For the in vivo study 10 patients with underlying inflatable prosthetic cylinders underwent tunical releases for treatment of secondary penile curvature (7) and reexploration for a malpositioned device (3) with a minimum 1 year of followup. RESULTS: In the in vitro study electrocautery injuries either did not occur when applied directly to silicone and polyurethane elastomer lined devices, occurred in both devices in the presence of a tissue-implant interface, occurred in polyurethane elastomer lined devices at a far less thermal energy setting than with silicone, occurred in both implants at lower wattages with increasing saline inflation or did not occur in 100% of polyurethane elastomer lined devices when coagulation electrocautery was less than 65 watts. In the in vivo study, by adhering to the aforementioned principles and using novel surgical techniques, no device malfunctions were created intraoperatively or observed within a mean followup of 22 months. CONCLUSIONS: Electrocautery can be used safely to create a tunical incision with any underlying inflatable cylinder. To avoid electrocautery injury, based on the clinical study results in polyurethane elastomer lined devices, one should deflate the cylinder before electrocautery, use coagulation current at 35 watts, apply the electrocautery only to the outer longitudinal tunical layer, bluntly dissect through the inner circular layer, and elevate the tunica, protect the device and incise the tissue under direct vision.     

Division of flexor tendons causes progressive degradation of tendon matrix in rabbits

Deep flexor tendons of 30 rabbits were divided at the ankle level. The effects of unloading on the synthesis and content of matrix components, the synthesis of DNA, and dry weight were investigated. The ability of the tendons to synthesize collagen during short-term culture and the contents of matrix components decreased inversely to the time of unloading. 12 weeks following division, the fibrocartilagnious segments had lost 2/5 of their dry weight, 2/3 of proteoglycan and 1/3 of collagen and non-collagen protein content. Less pronounced losses were observed in the non-fibrocartilaginous segments. A transient increase in cell proliferation in both types of segments was found. These findings indicate that divided flexor tendons undergo a progressive degradation, degradation, which may have implications for delayed suture of deep flexor tendon injuries.     

Electrodiagnosis in neuromuscular disease

This article provides a general approach to the electrodiagnostic evaluation of the patient with neuromuscular disease. The electrodiagnostic findings in patients with various forms of peripheral neuropathy, motor neuron disease, neuromuscular junction disorders, and myopathy are presented. The pediatric electrodiagnostic evaluation is also discussed.     

Developing a brief measure of smoking in the home: description and preliminary evaluation

The insulin-like growth factors (IGF-I and IGF-II) play a key role in cellular proliferation and are involved in cellular transformation. The expression of the IGF-I receptor has been demonstrated in a variety of human tumor cell lines including ovarian cancer cells. Phosphorothioate antisense oligodeoxynucleotides (S-ODNs) were analyzed for their potential to suppress the IGF-I receptor in the NIH: OVCAR-3 ovarian cancer cell line. The application of the antisense S-ODN reduced potently the cell growth of unstimulated NIH:OVCAR-3 cells, whereas sense and mismatch S-ODNs were without any effect. This effect resembled that of the monoclonal antibody (MAb) alphaIR-3. In contrast to the antisense compound, this MAb only partially inhibited the IGF-I-induced proliferation of ovarian cancer cells. The concentration of the antisense S-ODN to exhibit an identical inhibition of cell proliferation was reduced to 50 nM when the oligonucleotides were delivered by the cationic lipid formulation lipofectin. The specificity of the antisense S-ODN action was confirmed by reduction of the receptor protein and of the receptor mRNA, as assayed by flow cytometry and by Northern blot hybridizations. Our data demonstrate the potency of antisense S-ODNs to target the IGF-I receptor message and show that antisense strategies against the IGF-I receptor may provide new strategies for the therapy of ovarian cancer.     

Treatment options in Western hepatocellular carcinoma: a prospective study of 224 patients

BACKGROUND/AIMS: Though hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world, the optimal therapeutic strategy is still poorly defined. This is mainly due to geographic differences in HCC which may affect the validity of treatment regimens in differents areas of the world. The aim of the present study was to analyze the natural course of the disease as well as to assess the efficacy of different therapeutical schemes in HCC observed in Ljubljana (Slovenia) and Trieste (Italy), two cities in Western Europe situated close to each other. METHODS: During the period from January 1988 to December 1993, 224 consecutive patients (132 in Trieste and 92 in Ljubljana) with HCC were enrolled in the study. Patients were treated with the following 3 schemes: surgery 39 (17.4%), transcatheter chemoembolization (TACE) 116 (51.8%), and no treatment 69 (30.8%). The tumor was classified by Okuda staging and the liver disease by Child-Pugh score. Patients were followed up for 12-60 months, with an average of 40 months. The response rate to TACE and recurrence following surgery were evaluated. Comparative analysis of survival between different treatment groups was performed. RESULTS: The natural course of the disease, and other characteristics of the HCC, showed a typical Western type of tumor. Liver disease was scored as Child A in 58%, Child B in 30% and Child C in 12%, and the tumor was staged as Okuda I in 52%, Okuda II in 37% and Okuda III in 11%, respectively. Treatment with TACE was followed by an objective response in 27%, with a median survival of 31 months. Surgery was followed by a recurrence rate of 77% within 19.5 months and median survival of 49 months. The overall median survival of nontreated patients was 8 months. Survival in each group of patients differed significantly between all three consecutive stages of Okuda (p<0.001). In contrast, the differences in survival were significant only between Child A and B (p<0.02). The differences between Child B and C were not significant. CONCLUSIONS: This study emphasizes the importance of staging in the choice of treatment modality and diffusion of HCC in affecting an overall response to treatment and survival. Surgery is highly effective in monofocal HCC of Okuda I and II without cirrhosis. TACE is effective in Okuda I and II and Child A cirrhosis only. The treatment of HCC in Child B cirrhosis needs further studies. In Child C and/or Okuda stage III of HCC, any treatment except pure symptomatic relief is detrimental and should not be used.