Metastatic renal cell carcinoma presenting as an aural polyp

Renal cell carcinoma may metastasize to the head and neck region at different stages of its evolution. We present a case of an undiagnosed renal cell carcinoma presenting as an ear polyp, and discuss the difficulties of the diagnosis and the management of these tumours.     

Retained fetal lung liquid in congenital lobar emphysema: a possible predictor of polyalveolar lobe

The purpose of this study was to determine whether retention of fetal lung liquid is more prevalent in polyalveolar congenital lobar emphysema than in conventional congenital lobar emphysema. Two patients with congenital lobar emphysema were prospectively identified in a 3-year period. Twenty-five such patients were identified in a retrospective study covering 39 years. Medical records were available for 22 patients who had 23 emphysematous lobes. Both babies from the prospective study and six subjects from the retrospective group had respiratory symptoms and underwent chest X-ray in the first day of life. Six of the eight babies with respiratory symptoms and chest imaging in the first day of life had retention of fetal lung liquid in an emphysematous lobe. All six of these lobes were polyalveolar. The lobe in one child was a polyalveolar lobe but without retained fetal lung liquid, and one child exhibited conventional lobar emphysema also without retained fetal lung liquid. One polyalveolar lobe caused no neonatal symptoms and was not imaged until the child was 3 months old. No baby with conventional lobar emphysema was shown to have retained fetal lung liquid. There seems to be a correlation between polyalveolar lobe and onset of respiratory symptoms in the first day of life. Retention of fetal lung liquid within the affected lobe was documented only in cases of polyalveolar lobe.     

Non-functional variants of yeast mitochondrial ATP synthase subunit 8 that assemble into the complex

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.     

Diazepam alters caffeine-induced effects on beta-endorphin levels in specific rat brain regions

The present study was conducted to evaluate the effects of caffeine and the benzodiazepine agonist diazepam, and a combination of both on beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light: 12-hour dark illumination cycle were used in this study. Caffeine (10 mg/kg), diazepam (2 mg/kg) or a combination of caffeine (10 mg/kg) and diazepam (2 mg/kg) were administered intraperitoneally to rats at 11:00 hr. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection, the brains were immediately removed; the cortex, hippocampus, hypothalamus and midbrain were dissected and their B-EN levels measured by radioimmunoassay. Caffeine administration significantly increased B-EN levels in the cortex. Similarly, administration of diazepam alone resulted in a significant increase of B-EN levels in cortex. However, concurrent administration of diazepam and caffeine resulted in higher increase of B-EN levels in cortex. No significant changes in B-EN levels were detected in hippocampus and midbrain after administration of either caffeine or diazepam alone. On the other hand, when diazepam and caffeine were concurrently administered a significant increase of B-EN levels were observed in the midbrain. Moreover, administration of diazepam alone resulted in a significant increase of B-EN levels in hypothalamus. This increase was still observed following concurrent administration of diazepam and caffeine. These results clearly indicate that diazepam alters caffeine-induced effects on B-EN in specific rat brain regions.     

Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement

We have prepared casein conjugates of two BODIPY dyes for use as fluorogenic protease substrates in homogeneous assays. Both conjugates are labeled to such an extent that the dyes are efficiently quenched in the protein, yielding virtually nonfluorescent substrate molecules. These fluorogenic substrates release highly fluorescent BODIPY dye-labeled peptides upon protease digestion, with fluorescence increases proportional to enzyme activity. These quenched substrates are suitable for the continuous assay of enzymatic activity using standard fluorometers, filter fluorometers, or fluorescence microplate readers using either fluorescein excitation and emission wavelengths to measure BODIPY FL casein hydrolysis or Texas Red wavelengths to detect proteolysis of BODIPY TR-X casein. Most current techniques for detecting protease activity, such as the fluorescein thiocarbamoyl casein (FTC-casein) protease assay, require extensive manipulation, including separation steps, and are therefore labor intensive and error-prone. In comparison, we found the BODIPY dye-labeled casein protease assays to be simple and precise and to have greater sensitivity and a broader dynamic range of detection than the FTC-casein assay. We were able to sensitively detect the activities of a wide variety of enzymes with these new substrates, including serine, acid, sulfhydryl, and metalloproteases. We also found the assay suitable for quantitating protease inhibitor concentrations and for real-time analysis of proteolysis.     

Expression of matrix metalloproteinases and their inhibitors in aneurysms and normal aorta

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by degradation of collagen and elastin resulting from increases in matrix metalloproteinase (MMP) activity. Previous authors have identified isolated increases in expression of specific MMPs in AAAs, but none have compared relative levels of expression of particular MMPs to one another or to those of their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). This study proposes to quantify relative mRNA levels for interstitial collagenase (MMP-1), 72 kd type IV collagenase (MMP-2), 92 kd type IV collagenase (MMP-9), TIMP-1, and TIMP-2 in normal aorta (NA) and AAA to provide insight as to the relative importance of each in aneurysm formation. METHODS: Competitive polymerase chain reactions (PCRs) with gene-specific external standards and cDNA derived from AAAs (n = 8; mean age, 67.4 years) and NA (n = 5; mean age, 40.6 years) were used to quantify mRNA levels. Results were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels, determined by means of competitive PCR, and compared by means of Mann-Whitney statistics. RESULTS: Significant increases in MMP mRNA expression in AAA over NA were observed for MMP-1 (3.64 versus 0.3, p = 0.007), MMP-9 (78.03 versus 3.35, p = 0.003), TIMP-1 (835.32 versus 477.2, p = 0.027), and TIMP-2 (18.09 versus 4.14, p = 0.003). The ratio of MMP to TIMP mRNA levels was higher in AAA than NA (0.135 versus 0.045, p = 0.018). CONCLUSIONS: Increases in expression of MMP-1, MMP-9, and MMP/TIMP ratios may result in increased proteolysis and matrix degradation, which characterize AAAs. MMP-9 appears to be the predominant metalloproteinase expressed in AAA, because its mRNA levels were more than 20 times and 2 times higher than those of MMP-1 and MMP-2, respectively. TIMP-1 mRNA levels were in molar excess to those of any of the metalloproteinases studied.     

Na+ channel modulation and force-frequency relationship in human myocardium

Insect cell lines in culture are used for a variety of studies. In this laboratory imaginal disc cell lines have been established from primary cultures from third instar larvae, and used for a number of experiments. The effect of ageing on the morphology and physiology of Drosophila cell lines has received very little attention, although problems of genotypic or phenotypic changes in cell lines with age are recognized in other areas of animal cell culture. We tested our cell line Cl8+ for any difference in growth, morphology and response to 20-hydroxyecdysone (20HE) at different ages (passage numbers). The cells were found to multiply faster, adhere less firmly to the substrate and to lose the tendency to aggregate at higher passages. The response to 20HE in terms of cell numbers and induction of beta-galactosidase was similar at all passage numbers but morphological changes in hormone-treated cells were less obvious in the higher passages. Cell lines are likely to vary in the extent of ageing effects but workers are advised to be aware of the possibilities. We suggest the effects of age on cell lines should be established, and passage numbers noted in experimental reports.     

Anatomical suitability of abdominal aortic aneurysms for endovascular repair

BACKGROUND: Aortic aneurysm anatomy is crucial when considering patients for endovascular repair. The aim of this study was to determine the proportion of patients with aortic aneurysm suitable for endovascular repair with three different graft-stent systems. METHODS: Spiral computed tomographic angiography was used to assess the anatomy of 154 abdominal aortic aneurysms. Measurements were made of aneurysm neck length and diameter, renal artery to aortic bifurcation length, common iliac artery diameter and length, and external iliac artery diameter. Aneurysms were assessed for anatomical suitability for currently available aortoaortic, aortobi-iliac and aortouni-iliac devices. RESULTS: Six patients (4 per cent) had a distal aortic neck suitable for implantation of a straight aortic graft. Fifteen patients (10 per cent) had arterial anatomy suitable for implantation of a bifurcated graft and 85 (55 per cent) patients were suitable for endovascular repair with an aortouni-iliac graft. The primary reasons for unsuitability were: proximal neck length less than 1.5 cm (44 patients), proximal neck diameter greater than 3.0 cm (12), and angulation of the proximal neck (three). A further ten patients were considered unsuitable for an aortouni-iliac graft because of bilateral common iliac artery aneurysms (four), tortuous iliac arteries (four) and narrow external iliac arteries (two). CONCLUSION: The aortouni-iliac device has the widest applicability of the currently available endovascular systems but open repair remains the only option for a large proportion of patients.