Limited value of fluorine-18-fluorodeoxyglucose PET for the differential diagnosis of focal liver lesions in patients with chronic hepatitis C virus infection

AIM: The differentiation of HCC from liver metastasis or benign disorders by imaging studies based upon morphological aspects may be difficult. METHOD: In order to evaluate the role of tumour metabolism, we performed FDG-PET (whole-body PET and transmission-corrected regional scans of the liver as well as the SUV determined 60 min after injection of FDG) in ten consecutive patients with HCV-associated focal liver lesions. Definite diagnosis was established after ultrasound-guided liver biopsy followed by histopathological examination. These results were compared with ultrasound, computed tomography, serum anti-p53, and p53 protein expression. RESULTS: The histologic examination revealed a HCC in five patients, regenerative nodules in three patients, and liver metastasis (primary malignancy: one adenocarcinoma and one neuroendocrine tumour) in the remaining two patients. Three of ten lesions were detectable by FDG-PET: two HCCs and one metastatic adenocarcinoma. Seven lesions were not distinguishable by FDG-PET (three HCCs, three regeneration nodules and one metastatic neuroendocrine tumour). In each patient hepatic lesions were visible either by ultrasound or CT. Both tumours (metastatic adenocarcinoma, moderately well-differentiated HCC) with the strongest expression of p53 also presented with highly increased FDG uptake. CONCLUSIONS: FDG-PET is not superior to ultrasound or CT and therefore does not allow the non-invasive differentiation of HCV-associated focal liver lesions. Tissue-diagnosis by means of liver-biopsy followed by histopathological examination remains the gold-standard for the differentiation of HCV-related liver lesions. The finding of the relationship of p53 protein overexpression with the SUV needs further confirmation.     

Potential for an external vaginal antiitch cream containing benzocaine to cause methemoglobinemia in healthy women

OBJECTIVES: Our purpose was to assess the potential for an external vaginal antiitch cream (20% benzocaine, 3% resorcinol) to significantly increase levels of methemoglobin above normal in healthy women. STUDY DESIGN: Fifty-five women reporting external vaginal itch were recruited for the study. Each patient was used as her own control with methemoglobin levels being measured before and after use of the cream. Women were instructed to apply a 1-inch strip of cream by fingertip to the external genital area three or four times a day for 7 consecutive days. RESULTS: There were no significant differences in methemoglobin levels before and after use or in levels from a subgroup of women aged > 50 years compared with levels in a younger population. CONCLUSIONS: This preparation appears to be safe when used as directed; however, the results cannot be extrapolated to the very young. Nevertheless, lavish or frequent application over wide areas of excoriation might lead to toxic concentrations and methemoglobinemia. Therefore patients with serious vaginal disease should be advised against self-treatment beyond the 7-day limit imposed by the Food and Drug Administration for over-the-counter external analgesic medications.     

Variation in the ratio of physical to genetic distance in intervals adjacent to the Mla locus on barley chromosome 1H

Variants of the pulsed-field gel electrophoresis technique were used in conjunction with two-dimensional DNA gel electrophoresis (2-DDGE) to determine the ratio of physical to genetic distance in two genetically defined intervals on barley chromosome 1H.2-DDGE analysis demonstrated that two loci that define a 0.3 cM interval, as determined by hybridization with BCD249, reside on a single 450-kb MluI fragment. This result indicates a maximum ratio of physical to genetic distance in this interval of 1500 kb/cM as compared to 3.7-4.2 Mb/cM for the barley genome as a whole. High molecular weight (HMW) DNA restricted with NotI and probed sequentially with MWG068 and BCD249 yield diffuse bands at approximately 2.8 Mb and 3.0 Mb in the C.I. 16151 and C.I. 16155 parental lines, respectively. These results suggest the maximum ratio of physical to genetic distance in the interval defined by these probes is 7.8 Mb/cM. Unique HMW DNA restriction fragment length polymorphisms (RFLP) were attributed to the presence of recombination breakpoints. Data from the recombination breakpoint analysis were used to estimate a ratio of physical to genetic distance of 2.5 Mb/cM in the Xbcd249.2-Xmwg068 interval and 0.465 Mb/cM in the Xbcd249.1-Xbcd249.2 interval. Both physical linkage and recombination breakpoint analysis indicate the Xbcd249.1-Xbcd249.2 interval is approximately five-fold smaller, physically, than the Xbcd249.2-Xmwg068 interval.     

Response of Brazilian crossbred cows to varying doses of bovine somatotropin

The effect of n-methionyl bovine somatotropin (bST) on milk yield was evaluated in crossbred cows (40 1/2 Bos indicus x 1/2 Bos taurus and 18 1/4 B. indicus x 3/4 B. taurus) in Brazil. Cows were randomly assigned to treatments within stage of lactation [stage 1 = 56 to 100 d in milk (DIM); stage 2 = 101 to 199 DIM] and breed groups (1/2 vs. 1/4 B. indicus blood). Treatments were 250 or 500 mg of bST administered every 14 d. Cows in the control group did not receive bST or a placebo. Treated cows received bST injected subcutaneously in the postscapular region, alternating between the left and right sides. The 26-wk experiment consisted of 2 wk of pretreatment and 24 wk of treatment. Cows were housed in an open lot with regulated access to pasture. Cows were milked twice daily and scored for body condition at 2-wk intervals. Compared with controls, milk yield increased equally (22%) for cows receiving 250 or 500 mg of bST. Milk yield response to bST was higher and persisted longer during stage 1 of lactation than during stage 2 of lactation. No difference in response to bST was noted between cows with 1/2 or 1/4 B. indicus blood. Cows treated with 500 mg of bST tended to have more mastitis, but no other adverse health effects were observed. The potential use of 250-mg doses of bST at 14-d intervals in crossbred cattle in Brazil and other subtropical regions throughout the world is suggested, particularly before about 220 DIM.     

Binding and incision activities of UvrABC excinuclease on slipped DNA intermediates that generate frameshift mutations

Previous in vivo studies involving sequence 5'-CCCG1G2G3-3' (SmaI site) have demonstrated that adducts of N-2-acetylaminofluorene (AAF) to any of the three guanine residues of the SmaI sequence induce, with different efficiencies, two classes of -1 frameshift events, namely -G and -C mutations, referred to as targeted and semitargeted mutations, respectively. It has been proposed that both events occur during replication as a consequence of slippage events involving slipped mutagenic intermediates (SMIs). In order to evaluate the potential role of the UvrABC excinuclease in frameshift mutagenesis, we have studied the interaction of this enzyme with DNA molecules mimicking SMIs in vitro. In all of our constructions, when present, the AAF adduct was located on the third guanine residue of the SmaI site (5'-CCCG1G2G3-3'). This strand was referred to as the top strand, the complementary strand being the bottom strand. Double-stranded heteroduplexes mimicking the targeted and semitargeted SMIs contained a deletion of a C and a G within the SmaI sequence in the bottom strand and were designated deltaC/3 and deltaG/3 when modified with the AAF on the third guanine residue in the top strand or deltaC/O and deltaG/O when unmodified. The modified homoduplex was designated SmaI/3. deltaC/O and deltaG/O were weakly recognized by UvrA2B, but not incised. All three AAF-modified substrates were recognized with similar efficiency and much more efficiently than unmodified heteroduplexes. With AAF-monomodified substrates, dissociation of UvrA2 from the UvrA2B-DNA complex occurred more readily in heteroduplexes than in the homoduplex. SmaI/3 and deltaC/3 were incised with equal efficiency, while deltaG/3 was less incised. The position of the AAF lesion dictated the position of the incised phosphodiester bonds, suggesting that the presence of a bulge can modulate the yield but not the incision pattern of AAF-modified substrates. The finding that UvrABC excinuclease acts on substrates that mimic SMIs suggests that the nucleotide excision repair pathway may help in fixing frameshift mutations before the following round of replication.     

Clemontanoside-C, a saponin from Clematis montana

Clemontanoside-C, a new hederagenin-based saponin isolated from the stems of Clematis montana, was identified by chemical and spectroscopic methods as hederagenin-3-O-alpha-L-arabinopyranosyl (1-3)-alpha-L-rhamnopyranosyl (1-2)-alpha-L-arabinopyranoside.