Pyloric atresia associated with epidermolysis bullosa--three cases presenting in three months

Three neonates presenting with pyloric atresia and epidermolysis bullosa are described in this report. Two babies underwent surgery for pyloric atresia, and 1 of these has survived until 3 months of age with no complications. The clinical presentation and complications of the pyloric atresia-epidermolysis bullosa syndrome are discussed with a brief review of literature.     

Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic

Recently, several human cancers including leukemia and breast and brain tumors were found to contain stem-like cancer cells called cancer stem cells (CSC). Most of these CSCs were identified using markers that identify putative normal stem cells. In some cases, stem-like cancer cells were identified using the flow cytometry-based side population technique. In this study, we first show that approximately 30% of cultured human cancer cells and xenograft tumors examined ( approximately 30 in total) possess a detectable side population. Purified side population cells from two cell lines (U373 glioma and MCF7 breast cancer) and a xenograft prostate tumor (LAPC-9) are more tumorigenic than the corresponding non-side population cells. These side population cells also possess some intrinsic stem cell properties as they generate non-side population cells in vivo, can be further transplanted, and preferentially express some "stemness" genes, including Notch-1 and beta-catenin. Because the side population phenotype is mainly mediated by ABCG2, an ATP-binding cassette half-transporter associated with multidrug resistance, we subsequently studied ABCG2+ and ABCG2- cancer cells with respect to their tumorigenicity in vivo. Although side population cells show increased ABCG2 mRNA expression relative to the non-side population cells and all cancer cells and xenograft tumors examined express ABCG2 in a small fraction (0.5-3%) of the cells, highly purified ABCG2+ cancer cells, surprisingly, have very similar tumorigenicity to the ABCG2- cancer cells. Mechanistic studies indicate that ABCG2 expression is associated with proliferation and ABCG2+ cancer cells can generate ABCG2- cells. However, ABCG2- cancer cells can also generate ABCG2+ cells. Furthermore, the ABCG2- cancer cells form more and larger clones in the long-term clonal analyses and the ABCG2- population preferentially expresses several "stemness" genes. Taken together, our results suggest that (a) the side population is enriched with tumorigenic stem-like cancer cells, (b) ABCG2 expression identifies mainly fast-cycling tumor progenitors, and (c) the ABCG2- population contains primitive stem-like cancer cells.     

Gene transfer with three amphiphilic glycol chitosans--the degree of polymerisation is the main controller of transfection efficiency

A number of studies have examined the possibility of delivering genes for the treatment of genetic diseases using various polymers and lipids. We have previously demonstrated the gene transfer ability of amphiphilic polymers (a soluble amine polymer covalently bound to lipid pendant groups). In the current communication we explore the gene transfer activity of amphiphilic glycol chitosans. Glycol chitosan was acid depolymerised to give polymers of various molecular weights. Palmitoyl or hexadecyl and in some cases additional N-methyl quaternary ammonium groups were attached to the polymers. DNA binding was studied by measuring the reduced fluorescence of ethidium bromide and the polyplex particle size and zeta potential. Biological characterisation of the polyplexes involved haemolysis, cytotoxicity and gene transfer assays. For the 22 polymers tested, DNA binding was optimum at a nitrogen to phosphate ratio of 2:1 and above. Polyplexes were 200-500 nm in diameter with a neutral or positive zeta potential. The haemolytic activity of the N-methyl polymers was studied and no haemolysis was detected up to a concentration of 10 mg ml-1. Cytotoxicity studies showed that the biocompatibility of glycol chitosan was adversely affected by a combination of a palmitoyl group and depolymerisation and that biocompatibility was subsequently restored with the introduction of N-methyl groups. In vitro transfection efficiency superior to the cationic lipid formulation N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulphate (DOTAP) was seen with depolymerised glycol chitosan in the A431 cell line only and with the depolymerised N-methyl quaternary ammonium amphiphilic derivatives in both the A431 and A549 cell lines. Degree of polymerisation (DP) was the most important controller of transfection efficiency and transfection resided within polymers with a DP of 73-171. High DP polymers diminished DNA-cell association, the first step in the cellular gene transfer process, thus apparently diminishing cell uptake. In vivo transfection with the N-methyl quaternary ammonium amphiphile was best at a DP of 86 and this glycol chitosan amphiphile gave superior liver and heart gene expression levels when compared to both Exgen 500 (linear polyethylenimine) and Superfect (a polyamidoamine dendrimer).     

Treatment histories of patients with a syndrome putatively prodromal to schizophrenia

Recent reports suggest that a symptomatic state that is often prodromal to schizophrenia can be identified prospectively. We examined treatment-seeking histories and psychiatric services received among patients with a syndrome similar to a prodromal state. The records of 47 patients who met the criteria for a prodromal state were reviewed. Most patients had previously sought and received psychiatric services (90 percent), including medications (64 percent), and 51 percent had previously received a psychiatric diagnosis. These data suggest that patients who present with a syndrome putatively prodromal to schizophrenia constitute a clinical population. Research into treatment interventions is indicated.     

Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas

The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3'5' cyclic monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked amylase secretion, tritiated choline ([3H]-choline) release and on intracellular free calcium concentration ([Ca2+]i) in the isolated rat pancreas were investigated. Electrical field stimulation (EFS; 10 Hz) and ACh (1 x 10(-5) M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1 x 10(-5) M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1 x 10(-6) M) abolished the secretory effect of EFS. Either SNP (1 x 10(-3) M) or 8-Br-cyclic GMP (1 x 10(-4) M) inhibited amylase secretion compared to basal. Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP had no significant effect on the amylase response to ACh. When extracellular Ca2+ concentration ([Ca2+]o) was elevated from 2.56 mM to 5.12 mM, SNP failed to inhibit the response to EFS. EFS stimulated the release of 3H from pancreatic segments preloaded with [3H]-choline. Either SNP or 8-Br-cyclic GMP had no effect on basal 3H release but significantly reduced the EFS-evoked response. In fura-2 loaded acinar cells, SNP elicited a small decrease in [Ca2+]i compared to basal and had no effect on the ACh-induced [Ca2+]i peak response. Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas.     

Loss of two new loci on chromosome 8 (8p23 and 8q12-13) in human prostate cancer

Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alterations in prostatic carcinogenesis. Loss of sequences on the short arm of chromosome 8 (8p) has been reported in human cancers, especially of 8p22 and 8p12-21 in prostate cancer. By using PCR analysis of polymorphic microsatellite repeat markers at four 8p loci and three 8q loci in 60 tumors, we observed deletion of sequences at two other deletion domains (8p23, and 8q12-13). There was loss in 51 of 60 cases (85%) with at least one marker. Four distinct regions of loss detected were: i) at 8p23, at locus D8S262; ii) at 8p22, on locus D8S259; iii) at 8p12, on loci D8S255 and D8S285; iv) at 8q12-13, on loci between D8S260 and D8S528. We found that 29% of the tumors showed LOH at 8p23; 19% LOH on 8p22; 54% had LOH at 8p12; and 48% had LOH at 8q12-13. There was higher frequency of LOH at 3 or more loci in samples of T3 stage (62%) as compared to T2 stage (13.3%) which suggests higher incidence of LOH in advanced stage of prostate cancer. We report deletion of two novel loci at 8p23 and 8q12-13, these regions may contain putative tumor suppressor genes in prostate cancer.     

Comparison of two radiation dose schedules in post mastectomy carcinoma of the breast

In 108 histopathologically proved breast cancer patients, after surgical treatment with modified radical mastectomy, two radiation dose schedules have been compared. Radiation therapy was given on a 60Co teletherapy machine using gent pair technique for chest wall irradiation and direct fields for lymphatic drainage areas. The patients were randomly divided into two groups (Group A and Group B). 54 patients were given external radiotherapy 40 Gy/17 F/3.2 weeks and remaining 54 patients were given 45 Gy/20 F/4 weeks. Results of treatment in Group A versus Group B were as follows; chest wall failure 5/50(10%) versus 3/54 (5.6%), axillary lymphnods failure 3/50(6%) versus 4/54(7%), distant metastasis 16/50(32%) versus 15/54(28%). Radiation reactions were almost similar in both the groups. Skin reactions were most common radiation effects [45/50 (90%) in Group A and 43/54 (79.6% in Group B]. Thus no statistically significant difference in local control and efficacy of these two radiation dose schedules was observed in postmastectomy carcinoma of the breast.     

Correction to: Optimization of Ultrasonic Extraction of Major Phenolic Components from Flowers of Ghav-Patta (Argyreia Speciosa Linn.) Via Response Surface Model

Pharmaceutical Chemistry Journal -