Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images

PURPOSE: To determine the accuracy of magnetic resonance (MR) cholangiography for demonstration of the biliary tract and detection of biliary complications in patients who have undergone orthotopic liver transplantation. MATERIALS AND METHODS: Breath-hold half-Fourier rapid acquisition with relaxation enhancement MR cholangiography was performed in 25 patients who had undergone orthotopic liver transplantation. MR cholangiograms were prospectively and independently interpreted by two radiologists for depiction of the biliary tract and ductal anastomosis and for complications (eg, biliary dilatation, stricture, stones). MR cholangiographic findings were correlated with findings from direct cholangiography (n = 24) and surgery (n = 1). RESULTS: MR cholangiography completely demonstrated first-order intrahepatic bile ducts in 23 (92%) patients, the donor extrahepatic bile duct in 25 (100%), the recipient extrahepatic bile duct in 17 of 18 (94%), and the anastomosis in 24 (96%). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of biliary dilatation and stricture were each 100%. Complete interobserver agreement occurred in the detection of biliary dilatation and stricture. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of stones were 100% for one radiologist and 86%, 100%, 96%, 100%, and 95%, respectively, for the other. Both radiologists agreed on the diagnosis of bile duct stones in six of seven cases (kappa = 0.90). CONCLUSION: MR cholangiography enables accurate depiction of the biliary tract and detection of biliary complications in patients with an orthotopic liver transplant.     

Familial mixed tumors of the parotid gland

BACKGROUND: The most common neoplasm of the parotid gland is the pleomorphic adenoma. The familial occurrence of such tumors arising within the parotid gland is rare, with only 3 previous reports in the literature. Bilateral synchronous pleomorphic adenomas of the parotid gland are also uncommon. We report 2 siblings with pleomorphic adenomas of the parotid gland, 1 of whom had bilateral synchronous mixed tumors. Patients and Methods Chromosomal analysis of tumor cells from the sibling with bilateral adenomas revealed the translocation t(3;12)(p21;q15). Chromosome 12q breakpoints have previously been identified in a wide variety of solid tumors including pleomorphic adenomas of the parotid gland. CONCLUSIONS: We discuss bilateral mixed tumors, familial parotid tumors, and the potential for a genetic predisposition for the recurrence of such parotid tumors, as suggested by characteristic chromosomal translocations associated with mixed tumors.     

Evaluation of the completeness of cancer case ascertainment in the Seoul male cohort study: application of the capture-recapture method.

Since the completeness of case ascertainment is directly related to the validity of a study, the evaluation of completeness is an essential feature of a cohort study. To estimate the completeness of cancer case ascertainment during a three year period (Jan. 1, 1993, to Dec. 31, 1995) in which the Seoul Male Cohort was followed up, we applied capture-recapture method. Data were obtained from the cancer registries, medical records and death certificates, with cases identified from each source numbering 103, 105, and 38, respectively. After eliminating duplicate cases, the total number was 141, and by using a log-linear model, the number of cases not detected by any of the three data sources was estimated to be 16. For all cancers, the estimated completeness of follow-up was 89.9%.     

Cadmium inhibits albumin endocytosis in opossum kidney epithelial cells

Chronic exposure to cadmium results in proteinuria. To gain insights into the mechanism by which cadmium inhibits the protein transport in the renal proximal tubule, we investigated the effects of cadmium on the receptor-mediated endocytosis of albumin, using fluorescein isothiocyanate-labeled bovine serum albumin (FITC-albumin) as a model substrate and opossum kidney cell line (OK cell) as a proximal tubular cell model. Cell monolayers grown to confluence were treated with 100 microM CdCl(2) for 60 min at 37 degrees C, washed, and tested for FITC-albumin uptake (37 degrees C) and surface binding (4 degrees C). The amounts of FITC-albumin uptake and binding were quantified by fluorimetrically determining the cell-adherent fluorescence. Both the binding and uptake of FITC-albumin by OK cells appeared to be saturable and inhibitable by unlabeled albumin in the medium, indicating that specific receptor sites were involved. The uptake of FITC-albumin was inhibited by agents that interfere with the formation of endocytotic vesicle (hypertonic mannitol), endosomal acidification (NH(4)Cl), and vesicular trafficking (cytochalasin D and nocodazole), confirming that the uptake occurred via the process of receptor-mediated endocytosis. In cells treated with cadmium, the specific FITC-albumin uptake was significantly attenuated, and this was due to a reduction in V(max) and a rise in K(m). These changes in kinetic parameters were similar to those induced by NH(4)Cl. The binding of FITC-albumin to the apical surface of OK cells was inhibited by cadmium treatment, and this was attributed to a reduction in B(max). The values of K(d) and its pH dependency were not altered by cadmium treatment. The formation of endocytotic vesicles, as judged by fluid phase endocytosis of FITC-inulin, was not changed by cadmium treatment. These results indicate that the receptor-mediated endocytosis of albumin is impaired in cadmium-treated OK cells most likely due to a defect in endosomal acidification and the attendant fall in ligand-receptor dissociation, which impairs receptor recycling and the overall efficiency of endocytosis.     

Effect of the aryl substituent on antitumor activity of 2-substituted-1,4-dihydroxy-9,10-anthraquinones and 2-substitutedanthracene-1,4,9,10-tetraones

2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).     

Glutathione conjugates of 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone derivatives: Formation and structure

Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DMNQ) were synthesized and their structure was determined. The yield of GSH conjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of alkyl side chain influenced the chemical shift of quinonoid protons; the quinonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl, 6.51-6.59 ppm vs. other ones with R=butyl to heptyl, 6.64-6.68 ppm. This was explained to be due to a folding effect of longer alkyl group. Glutathione (GSH) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathionyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then, the adduct was autooxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DMNQ derivatives to their hydrogenated products. It was suggested that such an organic reaction might play an important role for a study of metabolism or toxicity of DMNQ derivatives in the living cells.     

Synthesis andin vitro antitumor activity of isoazamitosene and isoiminoazamitosene derivatives

Seven isoazamitosene derivatives, mitomycin analogues, were synthesized and tested for cytotoxicities against leukemia and gastric cancer cell lines. Preparation of a pyrrolo[1,2-a]benzimidazole (3) (azamitosene ring system) was completed by utilizing the Lewis acid-catalized cyclization, witho-chloronitrotoluene as the starting material. Nitration of3 produced a mixture of two isomers (5-nitro isomer (4) and 7-nitro isomer (5)) in product ratio of 36∶52.4 was directly converted into quinone (7) by reduction and Fremy oxidaton. Finally, quinone derivatives (8, 9, 10, and11) were synthesized by 1,4-addition of7 with cyclic secondary amines. From above-mentioned5, 8-nitro compound (15) was prepared in 4 steps. At pH 3, Fremy oxidation of15 produced quinone (16), whereas iminoquinone derivatives (17a and17b) at pH 7. Isoazamitosene derivatives (8, 9, 10, and11), containing cyclic amino groups at the 7-position, showed potent cytotoxicity on P388, SNU-1, and KHH tumor cell lines. Among them,8 had stronger cytotoxicity against SNU-1 cell line than mitomycin and adriamycin. Considering these results, isoazamitosene derivatives may had unique cytotoxicity profiles. However, isoiminoazamitosene derivatives (17a and17b) revealed very weak cytotoxicity.     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure