The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation.

The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma.     

Karapandzic flap for reconstruction of lip defects.

PURPOSE: Systematic evaluation of the Karapandzic flap in the reconstruction of lip defects after ablative surgery. PATIENTS AND METHODS: Patients who had a Karapandzic flap to reconstruct lip defects were analyzed with reference to demographic details, histology and location of the tumor, and dimensions of resection. The functional aspects of the reconstruction were assessed in terms of the size of the oral stoma, preservation of oral competence, and facial expression, in addition to speech, diet and ease of cutlery, and denture usage. The esthetic outcome was assessed with a 4-point scale and in addition the symmetry of the commissure at rest and function, preservation of the philtrum, and lip projection also were assessed. The complications were noted. RESULTS: Seven patients underwent Karapandzic flap reconstruction (4 males, 3 females) with an age range of 43 to 98 years. Three tumors were located in the upper lip, 4 in the lower lip, and there were 5 squamous and 2 basal cell carcinomas. The lip defects ranged from 40% to 75% of the lip circumference. The oral stoma was of a reduced circumference in all cases but did not lead to any functional compromise in terms of oral competence, facial expression, speech, diet, denture and cutlery usage, and sensation. There were no wound complications in our series. The esthetic outcome was considered excellent/good in 85% of cases. The commissure was symmetrical in all except 1 patient, the philtrum was preserved in all cases of lower lip reconstruction, and the projection of the lip was reduced in edentulous patients. CONCLUSIONS: The Karapandzic flap is a reliable technique that offers consistently good functional and esthetic outcomes after reconstruction of lip defects.     

Reference frames for reach planning in macaque dorsal premotor cortex

When a human or animal reaches out to grasp an object, the brain rapidly computes a pattern of muscular contractions that can acquire the target. This computation involves a reference frame transformation because the target's position is initially available only in a visual reference frame, yet the required control signal is a set of commands to the musculature. One of the core brain areas involved in visually guided reaching is the dorsal aspect of the premotor cortex (PMd). Using chronically implanted electrode arrays in two Rhesus monkeys, we studied the contributions of PMd to the reference frame transformation for reaching. PMd neurons are influenced by the locations of reach targets relative to both the arm and the eyes. Some neurons encode reach goals using limb-centered reference frames, whereas others employ eye-centered reference fames. Some cells encode reach goals in a reference frame best described by the combined position of the eyes and hand. In addition to neurons like these where a reference frame could be identified, PMd also contains cells that are influenced by both the eye- and limb-centered locations of reach goals but for which a distinct reference frame could not be determined. We propose two interpretations for these neurons. First, they may encode reach goals using a reference frame we did not investigate, such as intrinsic reference frames. Second, they may not be adequately characterized by any reference frame.     

Detection of circulating parasite antigen in bancroftian filariasis by counterimmunoelectrophoresis

We used counterimmunoelectrophoresis (CIEP) with rabbit antibodies to Dirofilaria immitis and Brugia malayi to detect soluble filarial antigen in sera collected in a Wuchereria bancrofti-endemic area in South India. Filarial antigen was detected in 38 of 38 sera from microfilaremic patients, 3 of 48 sera from amicrofilaremic patients with lymphatic pathology, and 3 of 5 sera from former microfilaria carriers with negative blood examinations 6 months or more after diethylcarbamazine therapy. One of 32 endemic control sera, 0 of 35 nonendemic sera, and 0 of 20 B. malayi sera were positive. Antigenemia was equally detectable in sera collected at night or during the day (when microfilariae are absent from the blood). Parasite antigen was also detected in the urine of patients with positive serum tests. Antibodies to circulating filarial antigen (also detected by CIEP) were absent in all but 2 antigen-positive sera but present in 22 of 45 antigen-negative sera from clinical filariasis patients and in 9 of 31 antigen-negative sera from endemic controls. Parasite antigen detection by CIEP appears to be a sensitive, specific, and practical diagnostic test for active W. bancrofti infection.     

Identification of N-(deoxyguanosin-8-yl)-4-azobiphenyl by (32)P-postlabeling analyses of DNA in human uroepithelial cells exposed to proximate metabolites of the environmental carcinogen 4-aminobiphenyl

DNA adducts formed in human uroepithelial cells (HUC) following exposure to N-hydroxy-4-aminobiphenyl (N-OH-ABP), the proximate metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP), were analyzed by the (32)P-postlabeling method. Two adducts detected by (32)P-postlabeling were previously identified as the 3',5'-bisphospho derivatives of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) and N-(deoxyadenosin-8-yl)-4-aminobiphenyl (dA-C8-ABP) (Frederickson S et al. [1992] Carcinogenesis 13: 955-961; Hatcher and Swaminathan [1995b] Carcinogenesis 16: 295-301). In contrast to the dG-C8-ABP adduct, which was 3'-dephosphorylated by nuclease P1, dA-C8-ABP was resistant to nuclease P1, thus providing an enrichment step before postlabeling. Autoradiography of the two-dimensional thin-layer chromatogram of the postlabeled products obtained following nuclease P1 digestion revealed several minor adducts, one of which has been identified in the present study. Postlabeling analyses following nuclease P1 digestion of the products obtained from the reaction of N-acetoxy-4-aminobiphenyl with deoxyguanosine-3'-monophosphate (dGp) demonstrated the presence of this minor adduct. The 3'-monophosphate derivative of the adduct was subsequently chromatographically purified and subjected to spectroscopic analyses. Based on proton NMR and mass spectroscopic analyses of the synthetic product, the chemical structure of the adduct has been identified as N-(deoxyguanosin-N(2)-yl)-4-azobiphenyl (dG-N==N-ABP). (32)P-Postlabeling analysis of the nuclease P1-enriched DNA hydrolysate of HUCs treated with N-OH-ABP or N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) showed the presence of the dG-N==N-ABP adduct. It was also detected in calf thymus DNA incubated with HUC cytosol and N-OH-ABP in the presence of acetyl-CoA, or incubated with HUC microsomes and N-OH-AABP. These results demonstrate that in the target cells for ABP carcinogenesis in vivo, N-OH-ABP and N-OH-AABP are bioactivated by acyltransferases to reactive arylnitrenium ions that covalently interact at the N2 position of deoxyguanosine in DNA.