Tn, a carcinoma-associated antigen, reacts with anti-Tn of normal human sera

Tn antigen is the immediate precursor of the carcinoma (CA)-associated T antigen; both are masked in non-CA tissues. Tn antigen was detected by absorption of human anti-Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn-positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti-Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti-Tn and anti-T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

pH-sensitive polymers that enhance intracellular drug delivery in vivo.

Cytosolic delivery from endosomes is critical for those drugs that are susceptible to attack by lysosomal enzymes, such as DNA, RNA, oligonucleotides, proteins and peptides. Therefore, we have designed pH-sensitive, membrane-disruptive polymers to enhance the release of drugs from the acidic endosomal compartment to the cytoplasm. We have found that one polymer in particular, poly(propylacrylic acid) (PPAA), is very effective at membrane disruption at pHs below 6.5, based on hemolysis studies. PPAA also significantly enhances in vitro transfections of lipoplex formulations in cell culture, and does so in the presence of as much as 50% serum. In this study, we have extended our in vitro hemolysis and cell culture studies to an in vivo murine excisional wound healing model. A pilot study with a green fluorescent protein (GFP)-encoding plasmid indicated that injection of formulations containing PPAA into healing wounds resulted in increased GFP expression. Subsequently, by administering sense and antisense DNA for the angiogenesis inhibitor thrombospondin-2 (TSP2), we were able to alter the wound healing response in TSP2-null and wild type mice, respectively. Our findings showed that when PPAA was added to lipoplex formulations, expression of TSP2 was enhanced in TSP2-null mice compared to control formulations. These results show that PPAA can enhance in vivo transfections and that inhibition of TSP2 expression may lead to improved wound healing. These results suggest that PPAA can provide significant improvements in the in vivo efficacy of drugs such as DNA.     

Peroxidase: A novel pathway for chemical oxidation in human term placenta

Hydrogen peroxide-dependent oxidation of xenobiotics in a crude fraction of human term placental membranes (nuclei, mitochondria and microsomes) was investigated. Guaiacol was employed as a model substrate. The rate of its oxidation was found to be dependent on the concentration of protein, H2O2 and the substrate as well as the pH of the buffer. Several other classical substrates for peroxidases from different sources viz. pyrogallol, benzidine, p-PDA, DMBD, ABTS, TMPD and TMBD and endogenous chemicals such as bilirubin and epinephrine were also found to undergo oxidation. The xenobiotic oxidizing capacity of the membranes was retained by CaCl2 (0.5 M) extract as well as by the partially purified enzyme obtained by affinity (Con A) chromatography. The H2O2-dependent chemical oxidation by the partially purified peroxidase was inhibited by NaN3 and KCN (IC50 values 41 and 23 microM respectively). These results suggest that peroxidase may be a major enzyme in human term placenta capable of oxidation of endogenous chemicals and xenobiotics.     

Partial nephrectomy in mice with milliwatt carbon dioxide laser and its influence on experimental metastasis

We have developed a surgical model to perform partial nephrectomy in mice using the milliwatt CO2 laser and have used this model for studying the influence of the sequel of surgery on experimental tumor metastasis. Strain A mice were subjected to partial nephrectomy using the milliwatt CO2 laser. The surgical procedure was time efficient, the blood loss was minimal, and the postoperative mortality was 6%. Immediately after surgery, the wound consisted of a superficial layer of charring and a deeper layer of thermal damage (coagulative necrosis). The wound healing was completed within 30 days and was accompanied by fibroblast infiltration and tubular regeneration but minimal inflammatory response. Seventy surgical mice were injected I.V. with TA3Ha murine mammary adenocarcinoma cells at different intervals (immediately to 30 days) after surgery. Among 38 mice inoculated with tumor cells immediately or up to 3 days after surgery, 18 (47%) showed histologically confirmed tumors at the site of surgical trauma. None of the 38 unoperated kidneys showed any evidence of tumor. This difference is statistically significant at a P value of less than 0.001. As the interval between surgery and tumor inoculation was increased to 7, 15, and 30 days, the frequency of tumor formation at the site of surgery decreased to 20% (2/10), 14% (2/14), and 0% (0/8), respectively. The results demonstrate that a) partial nephrectomy in mice is feasible with minimal mortality or apparent morbidity, b) the laser-induced surgical trauma favors implantation and growth of tumors, c) the frequency of tumor formation is related to the stage of wound healing, and d) the tumors are anatomically related to the healing wound but do not invade into the parenchymal tissue.     

Actinomycosis of the parotid gland

Abstract - Actinomycosis is a slowly progressive infection caused by anaerobic bacteria with relatively decreasing incidence now-a-days. The Parotid gland is a quite rere site to be involved in cervico-facial actinomycosis as compared to the other sites in the face & neck region. We report a successfully managed case of Actinomycosis involving the parotid gland.