Toxicity of polycyclic aromatic hydrocarbons. III. Effects of beta-naphthoflavone pretreatment on hepatotoxicity of compounds produced in the ozonation or NO2-nitration of phenanthrene and pyrene in rats

Male Sprague-Dawley rats were treated ip with beta-naphthoflavone (BNF, 40 mg/kg/day) in dimethylsulfoxide (DMSO, 26.7 mg BNF/ml) for three days. At 24 hr after the pretreatment DMSO (3.0 ml/kg), phenanthrene (150 mg/kg), ozonized or nitrated products of phenanthrene (150 mg/kg), pyrene (150 mg/kg), or ozonized or nitrated products of pyrene (150 mg/kg) were injected ip. Phenanthrene, pyrene, and their ozonized or nitrated products were dissolved in DMSO (50 mg/ml). No increase in the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or sorbitol dehydrogenase (SDH) was seen in the pretreated rats 48 hr after the treatment. This is in contrast to what was seen in previous work without the BNF pretreatment. BNF pretreatment induced a small but significant increase in gamma-glutamyl transpeptidase (GGTP) levels. No treatment group receiving BNF differed from another with respect to GGTP. A decrease in lactate dehydrogenase (LDH) levels was noted in the nitro-PAH treatment groups; the same phenomenon was observed earlier in rats treated with nitro-PAH without BNF treatment. These results suggest that the mixed-function oxidase systems specifically induced by BNF have a protective effect against the hepatotoxicity of the oxonized or nitrated products of phenanthrene and pyrene.     

Lexical judgments after right- or left-hemisphere injury

Patients with unilateral left- or right-hemisphere lesions were asked to make similarity judgments to visually presented words on the basis of rhyme, meaning or visual similarity. The left-hemisphere-injured group was significantly impaired, relative to controls, for all types of lexical judgments, with the greatest impairment in the rhyme condition. Patients with right-hemisphere injury were also impaired, but only when lexical judgments were based on meaning. The results are generally consistent with normal and split-brain lateralization findings, and provide evidence supportive of a right-hemisphere contribution to some aspects of lexical semantic processing.     

Colonoscopic diagnosis of an aorto-appendiceal fistula

A case of an aorto-appendicular, aorto-enteric fistula diagnosed by colonoscopy after presentation with colonic haemorrhage is reported. The role of colonoscopy in such patients is discussed and reported experience is reviewed.     

A novel G protein-coupled receptor kinase gene cloned from 4p16.3.

Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.     

Colonoscopy — how difficult,how painful?

Colonoscopy is sometimes painful for the patient and often difficult for the endoscopist, but it is hard to predict how difficult or painful the examination will be. The purpose of this study was to identify factors that influence difficulty and pain during colonoscopy.Some 1,284 consecutive patients undergoing office colonoscopy by three endoscopists were prospectively studied. A standard questionnaire was completed by the nursing staff, who assessed the degree of difficulty and pain associated with each exam on a four-point scale.There were 682 men and 551 women (sex not recorded in 51). There was no pain in 27%, mild pain in 39%, moderate pain in 25%, and severe pain in 9%. There was no difficulty in 25%, mild difficulty in 33%, moderate difficulty in 28%, and severe difficulty in 14%. Colonoscopy was significantly easier (P<0.001, chi square) and less painful (P<0.001, chi square) in patients after sigmoidectomy. It was more painful after hysterectomy (P<0.05, chi square) and more difficult and painful in women than in men (P<0.01, chi square). There were significant differences between endoscopists in the assessment of pain associated with colonoscopy.Most colonoscopies are associated with little or no pain (66%) and are easy or only mildly difficult to perform (58%). Patients who have had sigmoid resection are especially easy and painless to examine while women, especially after hysterectomy, are at higher risk of having a painful experience. Colonoscopy technique can influence the amount of pain experienced by the patient.     

Assignment of the lens intrinsic membrane protein MP19 structural gene to human chromosome 19.

We have isolated and characterized a bovine cDNA clone encoding the bovine lens intrinsic membrane protein, MP19. This cDNA was used as a probe to analyze a panel of Southern blots of human-Chinese hamster somatic cell hybrid DNAs to assign the gene coding for MP19 to its human chromosome. Control human and Chinese hamster DNAs displayed a distinct EcoR1 restriction fragment pattern when hybridized with the bovine MP19 cDNA. When somatic cell hybrid DNAs were restricted with Eco R1 and Southern blots hybridized with the bovine MP19 cDNA, the characteristic human restriction pattern was observed only when human chromosome 19 was present in the hybrid panel. This assignment was confirmed using a human chromosome 19-specific genomic library. A clone from this human chromosome 19-specific library was identified and further characterized. This clone contained a 7.9 kilobase fragment that contained identical DNA sequences with that of the authentic bovine MP19 cDNA, and with a separate human genomic clone containing the MP19 gene.     

Allergen activates peripheral blood eosinophil nuclear factor-κB to generate granulocyte macrophage-colony stimulating factor, tumour necrosis factor-α and interleukin-8

BACKGROUND: Allergic inflammation is characterized by the influx and activation of eosinophils. Cytokines generated by both resident and infiltrating cells are responsible for the initiation and maintenance of this pathogenesis. This study focuses on allergen-induced activation of eosinophil NF-kappaB and generation of granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-alpha, and IL-8. METHODS: Peripheral blood eosinophils were enriched to >99.9% by Percoll gradient sedimentation and negative magnetic affinity chromatography. NF-kappaB activation by 10 microg/mL house dust mite (HDM) extract was demonstrated immunocytochemically using a monoclonal antibody against the active form of NF-kappaB (NF-kappaBa). The authenticity of NF-kappaB was confirmed by Western blot. Cytokine production was assessed both by immuno-staining of eosinophils and by assay of cytokines in the cell supernatant. RESULTS: Activation of peripheral blood eosinophils from atopic, but not non-atopic, donors induced activation of NF-kappaB, which peaked at 4 h and was accompanied by a decline in IkappaB-alpha. The activation of authentic NF-kappaB was confirmed in gel shift assays. Supershift assays showed p65 to be the major subunit of eosinophil NF-kappaB. Immunofluorescent confocal microscopy demonstrated localization of NF-kappaBa to the nucleus. Following activation, cytokine immunoreactivity was seen in a fraction of the eosinophils and cytokines were released into the supernatant. The NF-kappaB inhibitors, calpain inhibitor 1 (10 microm), pentoxifylline (0.5 mm), pyrrolidine dithiocarbamate (PDTC, 10 microm) or gliotoxin (1 pg/mL) reduced the generation of GM-CSF, TNF-alpha and IL-8 in parallel with their inhibition of NF-kappaB. CONCLUSIONS: HDM allergen activates human eosinophil NF-kappaB leading to the production of the cytokines GM-CSF, TNF-alpha and IL-8. We speculate that a role for eosinophil NF-kappaB-dependent cytokines is to act as an autocrine loop augmenting the survival of eosinophils in vivo.     

Effect of inhaled frusemide on responses of airways to bradykinin and adenosine 5'-monophosphate in asthma.

BACKGROUND--Inhaled frusemide exerts a protective effect against bronchoconstriction induced by several indirect stimuli in asthma. This effect could be caused by interference with neural pathways. The effect of inhaled frusemide on bronchoconstriction induced by inhaled bradykinin, which is thought to cause bronchoconstriction via neural mechanisms, was studied and compared with the effects of adenosine 5'-monophosphate (AMP) which probably produces its airway effects by augmenting mast cell mediator release and interfering with neural pathways. METHODS--Patients first underwent AMP and bradykinin challenges. They were then studied in a randomised, placebo controlled, double blind fashion. Ten atopic asthmatic subjects, studied on four days, were pretreated with inhaled frusemide (40 mg) or placebo for 10 minutes, five minutes before challenge with increasing concentrations of nebulised AMP or bradykinin. RESULTS--On the open visit days the provocative concentrations required to reduce forced expiratory volume in one second (FEV1) by 20% from baseline (PC20) for AMP and bradykinin were 16.23 (1.42-67.16) and 2.75 (0.81-6.6) mg/ml. There was a significant correlation between baseline AMP and bradykinin PC20 values. For AMP the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 80.97 (9.97- > 400.0) and 14.86 (2.6-104.6) mg/ml respectively (95% CI 0.49 to 0.98). For bradykinin the geometric mean PC20 values following pretreatment with inhaled frusemide and matched placebo were 13.22 (2.53- > 16.0) and 2.52 (0.45-5.61) mg/ml respectively (95% CI 0.43 to 1.01). Frusemide afforded 5.45 and 5.24 fold protection against AMP and bradykinin-induced bronchoconstriction respectively. Furthermore, there was a significant correlation between protection afforded to the airways against AMP and bradykinin. CONCLUSIONS--These data suggest that inhaled frusemide affords protection against bradykinin-induced bronchoconstriction which is comparable to that against AMP, supporting a common mechanism of action for frusemide.     

Perioperative tumor localization for laparoscopic colorectal surgery

Background: Because of the inability to palpate colonic tumors during laparoscopy, their location must be precisely identified before resection is undertaken. Method: A retrospective study was performed of 58 patients in order to be able to describe our methods of tumor localization for laparoscopic colorectal operations and to review their effectiveness. Results: In all patients, the entire colon was examined preoperatively by colonoscopy. In one patient, preoperative colonoscopic localization was inaccurate. In 31 patients, tumors were easily detectable at surgery. In five patients with the tumor in the right colon, even though the lesion was not detectable at surgery, right colectomy was performed without marking because preoperative colonoscopy reliably identified the lesion adjacent to the ileocecal valve. Twenty-two patients required some type of procedure to localize the tumor. The procedures and their problems were as follows: preoperative tattoo (five)—tattoo not visualized (one); intraoperative colonoscopy alone (six), combined with intraoperative tattoo (four) or clip (three)—poor operative exposure due to bowel distension (nine), hard to see the clip (three), dislodged clip (two), inadequate resection margin (one); intraoperative proctoscopy alone (two), combined with laparoscopic stitch (two)—no problems. In no patient was tumor present at a resection line and in no patient was the wrong segment resected. Conclusions: Reliable preoperative identification of the tumor adjacent to the ileocecal valve can permit right colectomy without marking. Lesions in the upper rectum can be approached via intraoperative proctoscopy ± suture placement. If the surgeon anticipates intraoperative localization may be difficult, lesions other than rectal or cecal ones should probably be marked by preoperative tattooing. Further studies regarding the technique of tattooing are warranted. Received: 18 July 1996/Accepted: 10 March 1997     

Self-Concept and Satisfaction With Physical Appearance in Youth With and Without Oral Clefts

This study investigated relationships between child/parent dissatisfaction with child facial appearance and the self-concept/social competence of 8- to 15-year-old children with (N = 34) and without (N = 34) oral clefts. Children in both groups had normative psychosocial adjustment, but also reported moderate dissatisfaction with facial appearance. Cleft group parents were more likely to agree with their child's dissatisfaction. When cleft group parents were more dissatisfied with child facial appearance, their children reported better quality of life. Results suggest that parents of children with clefts reporting greater dissatisfaction may respond in positive ways that enhance quality of life.