Significant non-alcoholic fatty liver disease is found in non-diabetic, pre-obese Chinese in Singapore.

INTRODUCTION: To characterise the anthropometrical and metabolic parameters of a group of non-diabetic and non-obese patients who had histologically-proven nonalcoholic steatohepatitis (NASH). METHODS: During September 1997 to November 1999, consent for liver biopsies were sought from a consecutive series of patients, whose body mass index (BMI) were equal to or less than 30 kg per square metres, and who had persistently elevated serum alanine transaminase (more than 2.5 times upper limit of normal for more than six months), with no associated viral hepatitis, alcohol or drug-induced liver disease, hereditary liver disease and diabetes mellitus. Patients who were found to have steatohepatitis histologically were further studied. Their body weight, height, waist and hip circumferences were taken, and fasting serum lipid and glucose measured. Serum insulin was measured in six patients and insulin resistance (IR) was calculated by homeostasis model assessment. Oral glucose tolerance tests were done if fasting glucose levels were greater than 6 mmol/L. All liver biopsies were reviewed by a single histopathologist. Three age- and sex-matched controls were randomly selected for each patient. RESULTS: 11 of 12 patients who underwent liver biopsies were found to have NASH. All 11 were Chinese: eight males and three females. 73 percent of them had hepatic fibrosis. Overall, compared to controls, they had significantly higher body weight, BMI, IR and triglyceridaemia. The female patients also had a higher waist-hip ratio than controls. None had diabetes mellitus, and one had impaired glucose tolerance/fasting glycaemia. Nine out of 11 had BMI between 25 and 30 kg per square metres. CONCLUSION: Significant histological changes of NASH with hepatic fibrosis were found in Singaporean Chinese non-diabetic patients with BMI of less than 30 kg per square metres.

CerbB2 status in breast cancer: pathologic issues.

INTRODUCTION: CerbB2 status determination in breast cancer is currently performed for predictive and prognostic information. However, much has yet to be learned about the accuracy, reproducibility and clinical correlation of the different testing methods available today. This is a review of the testing methods commonly in use and their applications in the management of breast cancer. METHODS: A Medline search for review articles with keywords cerbB2, Her2 testing, immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and breast cancer was done. Manual cross-referencing from the afore-mentioned articles and perusal of the package inserts, recommendations and manuals from the manufacturers of various commercially available test kits were also performed. RESULTS: The 2 main methods of testing in use in most routine laboratories are IHC and FISH on formalin fixed, paraffin embedded, breast cancer tissue. There is no single, universally accepted method and the plethora of testing and interpretative protocols has confounded the issue of clinical correlation of cerbB2 status with outcome and patient selection for therapy. The current consensus in the literature is leaning towards FISH; however, as pointed out in this paper, the use of FISH as a routine test in most diagnostic laboratories is not yet a reality mainly due to cost, technical and manpower constraints. In this regard, IHC is by default the preferred choice in many routine laboratories. CONCLUSION: Universal standardisation of testing methods for cerbB2 status determination, together with further clinical studies on the correlation of each method with outcome and response to therapy, will aid in the identification of the ideal method for stratifying patients with breast cancer into prognostic and optimal therapeutic groups.

Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining.

This study is an extension of in situ hybridization experiments showing expression of mRNA encoding CHIP28 in selected epithelial or endothelia in spleen, colon, lung, and eye (H. Hasegawa, R. Zhang, A. Dohrman, and A. S. Verkman. Am. J. Physiol. 264 (Cell Physiol. 33): C237-C245, 1993). Additional tissues from rat were screened by in situ hybridization, and tissues from rat and humans were stained with a polyclonal anti-CHIP28 antibody. Northern blot showed the 2.8-kilobase mRNA encoding CHIP28 in kidney, lung, and heart. In situ hybridization showed strong hybridization in epithelial cells in choroid plexus, iris, ciliary body, and lens and in epithelial and subepithelial layers of trachea. Except for colonic crypts, specific hybridization was not observed in the gastrointestinal tract, liver, thyroid gland, and muscle. Immunoblot of tissues from exsanguinated rats showed immunoreactive CHIP28 protein in kidney, lung, trachea, and heart. In fixed frozen rat and/or human tissues, the anti-CHIP28 antibody stained epithelial cells in kidney proximal tubule and thin limb of Henle, lung alveolus, bronchial mucosa and glands, choroid plexus, ciliary body, iris, lens surface, colonic crypt, sweat gland, pancreatic acini, gallbladder epithelium, and placental syncytial trophoblast cells. Endothelial cells were stained in many tissues. These studies indicate a wide and selective CHIP28 tissue distribution, suggesting an important role for CHIP28 in fluid transport. The absence of CHIP28 in many nonrenal membranes believed to be water permeable suggests the existence of non-CHIP28 water transporters.