Absence of a differential induction of cytochrome P450 2E1 by different alcoholic beverages in rats: implications for the aetiology of human oesophageal cancer

Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds, could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine) adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1 revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively, compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1 substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration. There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls, but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage. Received: 10 February 1997 / Accepted: 26 May 1997     

Sonographic and computerized tomography study of congenital choledochal cyst

In the neonatal period ultrasound and hepatobiliary functional scintigraphy are used to diagnose choledochal cysts. Initial sonography demonstrates hepatobiliary anatomy, hepatobiliary function is assessed by subsequent scintigraphy. The diagnosis can be confirmed by additional computed tomography as shown in this case report.     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Field evaluation of polycarbonate versus conventional safety glasses

Of all the causes of eye injury, gunshot has recently been cited as resulting in the highest rate of blindness and the lowest rate of visual recovery. Many of these cases are hunting accidents in which safety glasses could have prevented or lessened ocular damage. To evaluate the effectiveness of various types of safety glasses, we fired a Remington automatic shotgun at mannequin heads fitted with one of four types of safety lenses. From a distance of 10 yards, only polycarbonate lenses provided even partial protection. At 30 yards, polycarbonate and heat-treated lenses provided the best protection, whereas chemically treated and CR39 lenses provided significantly less protection. We recommend that hunters using shotguns in areas of poor visibility wear widely available polycarbonate safety glasses as well as "hunter's orange" to minimize their risk of devastating ocular gunshot injury.     

Eye injury: prevalence and prognosis by setting

Although an estimated 1 million Americans suffer ocular injuries each year, the setting of injury and its prognostic implications have not been closely examined. Using data compiled by the Eye Injury Registry of Alabama (EIRA) from 514 cases of serious eye injury, we examined the demographics and prognosis of ocular injury by setting of injury. Work-related injuries accounted for only 28% of total injuries, and injuries occurring at home accounted for 27%, followed by situations related to recreation (25%), assault (11%), travel (5%), and "other" (school, unknown, etc) (4%). The poorest initial vision, poorest final vision, and highest rate of enucleation occurred in patients injured by assault, whereas the lowest rate of enucleation and loss of light perception was found in patients who had work-related injuries. Patients in the "other" category had the highest rate of return to 20/100 or better vision.     

Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells.

The effect of two synthetic lipid A partial structures, compound 406 (or LA-14-PP, identical in structure to the lipid A precursor, known as Ia or IVa) and compound 401 (lipid X), on the in vitro modulation of endotoxin (lipopolysaccharide)-induced interleukin-6 production by human blood mononuclear cells was investigated. Lipopolysaccharide of Salmonella abortus equi and synthetic Escherichia coli-type lipid A (compound 506, or LA-15-PP) had potent interleukin-6-inducing capacities. The maximum release of interleukin-6 was found after stimulation with 1 to 10 ng of lipopolysaccharide or 10 to 100 ng of synthetic E. coli-type lipid A per ml. Both synthetic lipid A partial structures (compounds 406 and 401) failed to induce interleukin-6 release. However, they inhibited lipopolysaccharide- or lipid A-induced interleukin-6 production in a dose-dependent manner. Inhibition was found not only in mononuclear cells but also in purified monocytes and was not due to a shift in the kinetics of cytokine production. Suppression was manifested in the early stage of interleukin-6 production. Inhibition was also found in the presence of recombinant gamma interferon, indicating that compound 406 and recombinant gamma interferon act in different, independent pathways. Our data, therefore, indicate that the inhibition of interleukin-6 production by lipid A partial structures may help elucidate the mechanism of interaction of the lipid A component of lipopolysaccharide with immune cells in the inflammatory reaction during gram-negative infection.     

Histologic distinction between malignant mesothelioma,benign pleural lesion and carcinoma metastasis

Summary Thirty men and 7 women with malignant mesothelioma seen at the Free University Hospital from 1st January 1960 until 1st July 1981 were reviewed.The histological, histochemical and morphometrical findings are reported. These findings are compared with 25 cases of pleural metastatic carcinoma and 25 cases of reactive pleural lesions.Fourty-nine percent of malignant mesotheliomas produced hyaluronic acid, however all cases of pleural metastatic carcinomas failed to produce this substance. All cases of malignant mesothelioma were D-PAS negative while 15 cases of pleural metastatic carcinoma showed reactivity to D-PAS. All cases of malignant mesothelioma and 9 cases of metastases were CEA negative.To distinguish malignant mesothelioma from metastases it is advisable to perform the D-PAS staining first. If it is negative mesothelioma can be confirmed by showing hyaluronic acid activity. A positive CEA staining rules out mesothelioma. In our study it was shown that with these methods 18 of 37 mesotheliomas could be identified with certainty, and 22 of the 25 carcinoma metastases.Morphometrically the malignant mesotheliomas could not be distinguished from the metastases, however the reactive pleural lesions had smaller nuclei than the malignant cells with mean values below 30 mu². In the malignant cases these values had a range from 36 to 101 mu².In distinguishing between reactive pleural lesions and malignant mesothelioma the production of hyaluronic acid points to the malignant character of the lesion.Thus histochemistry and immunostaining are important in the distinction of malignant mesothelioma from metastases, while the value of morphometry lies mainly in the separation of reactive lesions from malignant mesothelioma.     

So-called "superficial" bladder tumors. Which classification in 2003? Part 2: Flat urothelial lesions

Flat urothelial lesions of the urinary bladder have been recently discussed by the International Society of Urological Pathology (ISUP) in 1998 and more recently redefined by an international consultation held in Ancona, Italy in 2001. This paper summarizes and illustrates the recent literature about non-papillary lesions of the urinary bladder. Flat urothelial lesions include: epithelial abnormalities (reactive urothelial atypia and flat hyperplasia), preneoplastic lesion (dysplasia) and neoplastic non invasive carcinoma (carcinoma in situ) and a new category of presumed neoplastic lesions and conditions; the latter points out to a notion of tumor biology, which may help to the understanding of urothelial carcinogenesis.