The ratio of Matriptase/HAI-1 mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals.Purpose: It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatic increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression rather than the expression level per set. Dysregulated matriptase/HAI-1 ratio has been shown to strongly potentiate chemical carcinogenesis. This aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine whether a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis. Experimental design: Using RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n=9), severe dysplasia (n=15), mild/moderate dysplasia (n=21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n=10). Matriptase and HAI-1 mRNA levels were normalized to beta-actin. Results: Matriptase levels showed a modest down-regulation in carcinomas, whereas HAI-1 expression was extensively down-regulated in tissue displaying mild/moderate dysplasia and in normal and affected tissue from individuals with severe dysplasia or carcinomas. Conclusions: Both colorectal adenomas and carcinomas displayed a higher matriptase/HAI-1 mRNA ratio than corresponding normal tissue from the same individuals or healthy controls. This shows that dysregulation of the matriptase/HAI-1 mRNA occurs early during carcinogenesis and is maintained during all stages of malignant progression.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.