Histidinemia in mice: A metabolic defect treated using a novel approach to hepatocellular transplantation

Histidinemia in mice and in humans is an autosomal recessive disorder of histidine metabolism that leads to high-histidine levels in both plasma and urine and is caused by a lack of hepatic histidine-α-deaminase (histidase). We have used a novel approach to hepatocellular transplantation to effect a complete phenotypic cure of histidinemia in a mouse model. Mice lacking histidase were treated with isolated liver cells (approximately 18 × 10⁶ hepatocytes and 9 x 10⁶ nonparenchymal cells) from histidase-competent donors transplanted into the peritoneum (active transplant group). Recipient mice showed a dramatic decrease, by more than 75%, in urinary histidine levels from day one throughout the course of the experiment, resulting in levels within the normal range for wild-type mice. In comparison, there was no change in urinary histidine levels in the control group of histidase-deficient mice treated with isolated liver cells from mice lacking histidase (statistical comparison between the two groups, P < .003, two-way ANOVA). Histologically, ectopic liver tissue was seen in the peritoneum in association with abdominal wall, pancreas, and peritoneal connective tissue; immunohistochemical evidence showed expression of histidase in the ectopic liver tissue in the active transplant group. This report is the first to show complete correction of a defective biochemical phenotype achieved by hepatocellular transplantation.     

Testing of sequential sera from HCV-ab positive patients by RIBA II

Serial serum samples (mean 4.3 per patient) from 79 patients with hepatitis C virus (HCV) antibodies in enzyme-linked immunosorbent assay (ELISA) were tested by recombinant immunoblot assay (RIBA) II. All but 17 patients had consistently the same results in all sera tested. Of consistently RIBA II positive patients 81% (n = 36) were also polymerase chain reaction (PCR) positive, while from 22 patients with consistently indeterminant RIBA only 45% were positive in PCR. An increase in RIBA II positivity in serial serum samples was found in 11 patients (only four PCR positive), and a decrease in RIBA II positivity was observed in six patients (only two PCR positive). RIBA II results were therefore found highly consistent even over several months but unfortunately also in terms of the inconclusiveness of the results.     

Preparation of brush border membrane vesicles from bovine choroid plexus

The purpose of this study was to establish a method for preparing brush border membrane vesicles (BBMV) from bovine choroid plexus epithelium. Using the technique of divalent cation precipitation and differential centrifugation, we established and validated a procedure. The specific activity of Na⁺/K⁺ ATPase, a specific marker for choroid plexus brush border membranes, was enhance greater than 14-fold in the final membrane preparation in comparison to its specific activity in the homogenate. The specific activities of marker enzymes for basolateral membranes, lysosomal membranes, and endoplasmic reticulum were enhanced less than fourfold in the final preparation. The presence of intact vesicles was ascertained by electron micrography and studies of osmotic sensitivity using isotopic uptake methods. Sodium-driven proline uptake was demonstrated confirming the presence of functional tightly sealed choroid plexus BBMV.     

“Energy Up”: A Novel Approach to the Weight Management of Inner-City Teens

There are few successful adolescent obesity prevention programs. We evaluated “Energy Up,” an innovative program for inner-city girls that focuses on addictive food avoidance, exercise, and self-esteem building. Over a 9-month period, obese participants lost 12.9 pounds and overweight participants lost 2.9 pounds, prompting expansion to other schools.