Selectively replicating adenoviruses targeting deregulated E2F activity are potent,systemic antitumor agents

We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastoma tumor suppressor protein (pRB) pathway. Early and late viral gene expression as well as DNA replication were significantly reduced in a functional pRB-pathway-dependent manner, resulting in a restricted replication profile similar to that of nonreplicating adenoviruses in normal cells both in vitro and in vivo. In contrast, the viral life cycle and tumor cell killing activity of ONYX-411 was comparable to that of wild-type adenovirus following infection of human tumor cells in vitro as well as after systemic administration in tumor-bearing animals.     

Ultrastructural identification of Ia positive dendritic cells in the lactating rat mammary gland

Summary Dendritic cells which express Ia antigen have been demonstrated for the first time in the lactating rat mammary gland. Ultrastructurally, the dendritic cells appear as electron-lucent pale cells interspersed among the epithelial cells of the alveoli, forming a cell population distinct from classical macrophages. They show morphological resemblance to the dendritic cells of lymphoid organs as well as the Langerhans cells of skin. The Ia antigen has been localised by electron microscopic immunocytochemistry on the cell membrane and endocytotic vesicles and tubules. Ia positive cells are also seen in the stroma of the mammary gland. It is proposed that the dendritic cells of the mammary gland belong to the lineage of epidermal Langerhans cells and lymphoid dendritic cells, subserving an immunological role in the lactating breast.     

Is Combined Therapy of Sympathomimetics and Theophylline Indicated?

Bronchodilator effect and toxicity of theophylline 300 mg twice a day (R₁), salbutamol 4 mg tid (R₂), their combination in higher (200/4mg, R₃), and lower doses (100/2mg R₄), and placebo (calcium lactate 300 mg) tid (R₅) were compared in 25 patients with bronchial asthma in a randomized crossover trial. Statistically significant improvement in forced expiratory volume in one second (FEV₁) was observed in all the active treatment groups (R₁ to R₄) compared with placebo (R₅). The mean improvement in FEV₁ was 29.0%, 22.0%, 28.0%, 30.0%, and 0.73% in regimen R₁, R₂, R₃, R₄, and R₅, respectively day 1, and corresponding improvement was 30.0%, 24.0%, 29.0%, 34.0%, and 4.4% on completion of one week therapy. On intergroup statistical comparison, mean improvement in pulmonary function test values were statistically significant or highly significant in regimens R₁ to R₄, as compared with placebo. However, improvement between any two regimens was not statistically significant in any of the regimens (R₁-R₄). Almost all the regimens were tolerated well and no patient showed major adverse reactions or cardiotoxicity necessitating withdrawal of the drug. On the other hand, minor adverse reactions were common and the high dose combination (R₃) was found to have more adverse reactions than the low dose combination and either drug used alone.     

Cold Adapted Fungi from Indian Himalaya: Untapped Source for Bioprospecting

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Cold adapted microorganisms are gaining importance in view of their ability to colonize extreme low...     

Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration: effects on protein-L-isoaspartyl methyltransferase activity

BACKGROUND/AIMS: Protein-L-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. METHODS: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1% betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. RESULTS: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. CONCLUSIONS: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios.     

GFAP-Immunoreactivity following hypothermic forebrain ischemia

This study investigated the effect of intra-ischemic hypothermia on astroglial reactions in the hippocampus following cerebral ischemia. Mongolian gerbils were subjected to forebrain ischemia by bilateral carotid occlusion of 10 min at a) 30°C and b) 37°C followed by normothermic reperfusion ranging from 1 to 3 days (d). The astrocytes were visualized by immunostaining against glial fibrillary acidic protein (GFAP), and neuronal injury was evaluated by using hematoxylin-eosin staining. In normothermic brains, reactive astrocytosis was noted in 1 and 2 d postischemic animals, becoming prominent in the 3 d postischemic group. Intense GFAP-positive cells with thickened processes were noted in all regions of the hippocampus, especially the CA1 region. These cells were seen to have migrated toward the stratum pyramidale which was normally devoid of such staining. Hypothermia significantly inhibited the GFAP-upregulation seen 3 d after normothermic ischemia. There was no significant neuronal damage in the 3 d hypothermic ischemic group. Since glial cell activation, as evidenced by GFAP-upregulation, precedes as well as accompanies neuronal damage, and since hypothermia, known to be neuroprotective, inhibits glial cell activation in the 3 d postischemic brain, it appears that glial cells play critical roles in neuronal survival or death following ischemia.     

Clear cell hidradenoma simulating breast carcinoma: A diagnostic pitfall in fine-needle aspiration of breast

Clear cell hidradenoma, a benign tumor of sweat gland, presented as a breast lump with ulceration of overlying skin in an elderly woman. Failure to identify its cytological features led to a wrong diagnosis of breast carcinoma on fine-needle aspiration of the lump. Retrospective review of cytology revealed the presence of many clear cells amidst polygonal tumor cells, but no tubular lumina were seen. Accurate diagnosis remains a problem. Diagn Cytopathol 1996;15:70–72. © 1996 Wiley-Liss, Inc.