Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation.

The neu protooncogene (also known as c-erbB2, NGL,and HER2) encodes a 185-kDa transmembrane glycoprotein with intrinsic tyrosinekinase activity that resembles the receptor for epidermal growth factor. Thep185 gene and protein were originally identified in the brain and are thought toplay a critical role in neurogenesis. Aberrant c-erbB2 protein overexpressionalso occurs in several human adenocarcinomas. A ligand for p185, neu-activatingfactor (NAF), specifically binds to neu receptor and increases the p185c-neutyrosine phosphorylation in vitro and in vivo in a dose-dependent manner. We nowshow that NAF specifically binds to purified p185 expressed in baculovirus.Direct binding analysis showed that NAF binds with high affinity (Kd = 1.3 nM).We have investigated changes in the structure and association state ofbaculovirus-produced neu holoreceptor that are induced by ligand binding. Inthis study, we used sucrose gradients to show that purified p185c-neu existsmainly in the monomeric form at low concentrations, whereas at higherconcentrations p185c-neu exists as dimers or multimers. At low concentrations,but in the presence of ligand, p185c-neu sediments as a dimeric or multimericform. Monomer-oligomer interconversion is absolutely ligand dependent at lowreceptor concentrations. The high molecular weight form of the receptor isenzymatically more active, as a consequence of ligand-driven activation of thereceptor kinase. Oncogenic p185neu receptors sediment predominantly as highmolecular weight forms and have constitutively active kinases.     

A Review on Basic Biology of Bacterial Biofilm Infections and Their Treatments by Nanotechnology-Based Approaches

Biofilms are responsible for causing 80% of human infections including chronic infections like-cystic fibrosis, endocarditis and osteomyelitis. The growing ability of the biofilm to resist most of the available antibiotics has caused a serious threat to different life forms. Plenty of research work has already been reported, and some are ongoing to combat this serious health issue worldwide. Recent developments in nanotechnology have given a great boost in dealing biofilm infections. The unique size-dependent properties for antibacterial and antibiofilm activities provide the nanoparticles better options to eradicate biofilms. Here, the authors have discussed the basic biology of bacterial biofilm and their impact on human health. In addition, different nanotechnology-based strategies to overcome serious health issues caused by biofilm infections have been highlighted.

     

Status of Hilsa Fishery in Hooghly-Bhagirathi River System and Associated Coastal Waters of Northern Bay of Bengal

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Hilsa, Tenualosa ilisha, is a popular fish in northern Bay of Bengal and Hooghly-Bhagirathi river system in...     

Direct observation of intermediates formed during steady-state electrocatalytic O2 reduction by iron porphyrins

Heme/porphyrin-based electrocatalysts (both synthetic and natural) have been known to catalyze electrochemical O₂, H⁺, and CO₂ reduction for more than five decades. So far, no direct spectroscopic investigations of intermediates formed on the electrodes during these processes have been reported; and this has limited detailed understanding of the mechanism of these catalysts, which is key to their development. Rotating disk electrochemistry coupled to resonance Raman spectroscopy is reported for iron porphyrin electrocatalysts that reduce O₂ in buffered aqueous solutions. Unlike conventional single-turnover intermediate trapping experiments, these experiments probe the system while it is under steady state. A combination of oxidation and spin-state marker bands and metal ligand vibrations (identified using isotopically enriched substrates) allow in situ identification of O₂-derived intermediates formed on the electrode surface. This approach, combining dynamic electrochemistry with resonance Raman spectroscopy, may be routinely used to investigate a plethora of metalloporphyrin complexes and heme enzymes used as electrocatalysts for small-molecule activation.     

Acute panuveitis with haemorrhagic hypopyon as a presenting feature of acquired immunodeficiency syndrome (AIDS)

Anterior uveitis is a known clinical entity in herpes zoster ophthalmicus associated with AIDS. However, reports of acute haemorrhagic hypopyon uveitis in such cases are lacking. Herein we describe a young male patient presenting with acute panuveitis with haemorrhagic hypopyon, who was found HIV positive on investigation.     

Human cytomegalovirus infection and expression in human malignant glioma

Malignant gliomas are the most common primary brain tumors in adults, have no known etiology, and are generally rapidly fatal despite current therapies. Human cytomegalovirus (HCMV) is beta-herpesvirus trophic for glial cells that persistently infects 50-90% of the adult human population. HCMV can be reactivated under conditions of inflammation and immunosuppression, and HCMV gene products can dysregulate multiple cellular pathways involved in oncogenesis. Here we show that a high percentage of malignant gliomas are infected by HCMV and multiple HCMV gene products are expressed in these tumors. These data are the first to show an association between HCMV and malignant gliomas and suggest that HCMV may play an active role in glioma pathogenesis.     

Evaluation of naphthal-NU,a 2-chloroethylnitrosourea derivative of naphthalimide,as a mixed-function anticancer agent

Naphthal-NU, 2-[2-[3-(2-chloroethyl)-3-nitrosoureido]ethyl]-1H-benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally designed new mixed-function anticancer agent from 1,8-naphthalic anhydride. Its chemical alkylating activity compared with CCNU as standard compound indicated that it possesses greater alkylating activity than the latter. Its antitumour efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Three clinical drugs namely CCNU (lomustine), endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Compound 1 has displayed excellent and reproducible antitumoural activity having curative effects in these tumours comparable with CCNU and 5-FU. It has also significantly increased the life span of mice bearing highly advanced tumour for 10 days before the drug challenge. Its toxicity was also assessed in vivo in normal and in S-180 bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. The results indicated that the compound did not adversely affect hematopoiesis. Drug-induced hepatotoxicity and nephrotoxicity were also evaluated at its optimum dose on those days but no such toxicities were detected. It was further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines.     

Prolonged delivery of ciprofloxacin hydrochloride from hydrophilic ocular inserts

Ocular inserts were developed with prolonged release of drug and minimum swelling within cul-de-sac using ciprofloxacin (CPF) hydrochloride as a model drug. The ocular inserts were fahricated with sodium alginate films loaded with drug and then treated with calcium chloride. A 4% w/v solution of calcium chloride and an exposure of 15 s to this solution was found to be the optimum treatment combination of inserts. Four types of inserts were produced: type-I contained CPF hydrochloride and alginate, type-II contained CPF crystals and alginate, type-III contained CPF hydrochloride inalginate and hydroxypropylmethylcellulose (HPMC) matrix and type-IV contained CPF crystals entrapped inalginate and HPMC matrix. In vitro release profile of drug from the inserts followed Higuchi and first-order kinetic models. Longer duration for 90% drug release were obtained from types-II and IV inserts than from types I and III, although type III had a longer duration than type-I inserts. In vivo studies were carried out in rabbit eyes by measuring the tear concentrations against time. From the pharmacokinctic parameters obtained types II and IV were found to prolong the duration of action more than 2 days while types I and II inserts the duration of action lasted for about 1.5 days.