Ballistic CTLA4 and IL-4 gene transfer into the lower lid prolongs orthotopic corneal graft survival in mice.

PURPOSE: To explore outflow from the eye and to determine and modulate the influence of lymphatic drainage on corneal graft survival in mice. METHODS: Tracer experiments were conducted in BALB/c mice using the (99m)Tc colloidal albumin Nanocoll. Count rates were determined in the eyes, submandibular lymph nodes, spleen, liver and blood 24 h after subconjunctival, intracorneal, intracameral (anterior chamber), intravenous and subcutaneous lower-lid or upper-lid injections ( n=6 each). Four groups of BALB/c mice ( n=8) received corneal transplants from C3H mice; two of them were treated ballistically with vector CTLA4+IL-4 onto the leg or the lower lid, one group was untreated and the other control group was treated with an empty minimalistic, immunologically defined, gene expression (MIDGE) vector. RESULTS: Radioactivity was detected in the liver, spleen and ipsilateral submandibular lymph node after intracameral injection as follows: 91.9%, 6.6% and 1.2% respectively. Radioactivity uptake of the ipsilateral submandibular lymph node was also low after intravenous injection (0.1%) but high after intracorneal (33.8%), lower-lid (62.0%) and subconjunctival (71.2%) injection. Vector CTLA4+IL-4 treatment of the lower lid but not of the leg prolonged graft survival ( P=0.004). CONCLUSION: These tracer studies confirmed for the first time identical lymphatic drainage from the cornea and the lower lid. Logically, lymphatic drainage could be manipulated and graft survival improved by gene transfer to the lower lid.

Assessment of liver function in chronic liver diseases and regional function of irradiated liver by means of 99mTc-galactosyl-human serum albumin liver scintigraphy and quantitative spectral analysis.

Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) was performed on 102 patients, then the hepatic extraction fraction (HEF), the rate constant for liver uptake of the tracer from the blood (K1) and the hepatic blood flow index (HBFI) were determined by spectral analysis. The HEF, K1 and HBFI values correlated moderately or closely with various indices of hepatic function, and the HEF and K1 values decreased according to the stage of liver dysfunction. The HEF and K1 values linearly and nonlinearly correlated with HH15 and LHL15, respectively. The HEF, K1 and HBFI values for the irradiated portion of 20 patients before and alter irradiation were compared. The HEF value in patients with a cirrhotic liver significantly (p < 0.002) decreased compared with that in patients with a normal liver at a dose of less than 40 Gy, whereas the HBFI value in patients with a normal liver significantly (p < 0.05) decreased compared with that in patients with a cirrhotic liver at a dose of 40 Gy or greater. This method appears to be a simple, non-invasive and useful tool with which to quantitatively evaluate liver function and it also helps clarify changes in regional function of the irradiated liver.

Nontumorous decrease in Tc-99m GSA accumulation.

Nontutimorous decrease in 99mTc-GSA accumulation has not been well covered in the literature. Understanding of this phenomenon is, however, essential for accurate evaluation of regional hepatic function. Scintigrams (transaxial SPECT) of 269 patients who underwent 99mTc-GSA liver scintigraphy were reviewed for the presence of nontumorous decreases in 99mTc-GSA accumulation. Nontumorous decreases in 99mTc-GSA accumulation were seen in 32 of 269 patients (12%). In 16 of the 32 patients (6%), nontumorous decreases in 99mTc-GSA accumulation corresponded to regional decrease in portal venous flow. The causes of such decrease in portal venous flow were portal thrombus of hepatocellular carcinomas in eight patients, portal venous stenosis or occlusion by hilar cholangiocarcinomas in five patients, inter alia. In eight patients (3%), the regions with decreased 99mTc-GSA accumulation correlated with massive hepatic necrosis in fulminant hepatitis, scar in hepatitis, or confleuent in portal venous flow, lobar biliary stasis, or both. In four patients (1.5%), the exact causes of nontumorous decrease in 99mTc-GSA accumulation could not be determined.