Annexin A1, formyl peptide receptor,and NOX1 orchestrate epithelial repair

N-formyl peptide receptors (FPRs) are critical regulators of host defense in phagocytes and are also expressed in epithelia. FPR signaling and function have been extensively studied in phagocytes, yet their functional biology in epithelia is poorly understood. We describe a novel intestinal epithelial FPR signaling pathway that is activated by an endogenous FPR ligand, annexin A1 (ANXA1), and its cleavage product Ac2-26, which mediate activation of ROS by an epithelial NADPH oxidase, NOX1. We show that epithelial cell migration was regulated by this signaling cascade through oxidative inactivation of the regulatory phosphatases PTEN and PTP-PEST, with consequent activation of focal adhesion kinase (FAK) and paxillin. In vivo studies using intestinal epithelial specific Nox1^–/–IEC and AnxA1^–/– mice demonstrated defects in intestinal mucosal wound repair, while systemic administration of ANXA1 promoted wound recovery in a NOX1-dependent fashion. Additionally, increased ANXA1 expression was observed in the intestinal epithelium and infiltrating leukocytes in the mucosa of ulcerative colitis patients compared with normal intestinal mucosa. Our findings delineate a novel epithelial FPR1/NOX1-dependent redox signaling pathway that promotes mucosal wound repair.     

Prognoma of maxilla

Prognoma is a rare dysembryogenic tumour of infancy Very few cases have been recorded in the world literature so far A case report of this tumour affecting a female child with involvement of the right maxilla is being presented Histopathologically prognoma is a melanotic neuroectodermal tumour An increased level of a-fetoprotem m the serum and vanillylmendilic acid (V M A ) in a 24 hours urine sample have been reported with prognoma.     

Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange

The promise of bispecific antibodies (bsAbs) to yield more effective therapeutics is well recognized; however, the generation of bsAbs in a practical and cost-effective manner has been a formidable challenge. Here we present a technology for the efficient generation of bsAbs with normal IgG structures that is amenable to both antibody drug discovery and development. The process involves separate expression of two parental antibodies, each containing single matched point mutations in the CH3 domains. The parental antibodies are mixed and subjected to controlled reducing conditions in vitro that separate the antibodies into HL half-molecules and allow reassembly and reoxidation to form highly pure bsAbs. The technology is compatible with standard large-scale antibody manufacturing and ensures bsAbs with Fc-mediated effector functions and in vivo stability typical of IgG1 antibodies. Proof-of-concept studies with HER2×CD3 (T-cell recruitment) and HER2×HER2 (dual epitope targeting) bsAbs demonstrate superior in vivo activity compared with parental antibody pairs.     

Eating epilepsy: a study of twenty cases.

Twenty cases of eating epilepsy have been studied over a period of 5 years (1985-1989). Males outnumbered females (4:1). Heavy meal comprising conventional Indian diet (viz, rice, vegetables, etc), was found to be the most important provocating factor (14 out of 20 cases). The attacks occurred at lunch time in most cases (15). Thirteen cases had generalised seizures. Electro-encephalogram showed focal changes in 10 cases, generalised changes in 6 cases, while 4 cases had normal electro-encephalogram. Computerised tomography scan was normal in all the cases (7) when it was done.     

Equivalent recognition of HIV proteins, Env, Gag and Pol, by CD4+ and CD8+ cytotoxic T-lymphocytes.

OBJECTIVES: Cytotoxic T-lymphocytes (CTL) appear to be an important defense mechanism against HIV infection. This study proposes to examine the major histocompatibility complex (MHC)-restricted HIV-1 Env-, Gag- and Pol-specific CTL activities in HIV-infected asymptomatic patients. DESIGN: CD4+ and CD8+ CTL were examined to establish whether the same HIV-1 protein (Env, Gag or Pol) was recognized by both CD4+ and CD8+ CTL with MHC antigen restriction. METHODS: Peripheral blood mononuclear cells, CD4+ and CD8+ T-cells from 17 HIV-infected asymptomatic patients and 10 HIV-seronegative individuals were examined for HIV-1 Env-, Gag- and Pol-specific MHC-restricted cytotoxicity using autologous and heterologous B-lymphoblastoid cell lines infected with vaccinia recombinant expressing HIV-1 Env, Gag and Pol proteins as targets. RESULTS: CD4+ and CD8+ CTL specific for the HIV-1 Env, Gag and Pol were demonstrated in the peripheral blood. DR4 and DQw2 were possible sites of MHC class II restriction of CD4+ CTL. Possible MHC class I restriction sites of CD8+ CTL included A2 and B8 for Env, A1 and A2 for Gag, and A2 and B8 for Pol antigen. CONCLUSIONS: These observations should help to define more precisely the nature and elements of protective immunity and to evaluate AIDS vaccine strategies.     

Ramipril and methyldopa compared in patients with mild to moderate hypertension

Twenty-seven patients with mild to moderate essential hypertension were randomly assigned to receive 5 mg of ramipril once daily or 250 mg of methyldopa twice daily for eight weeks. Similar reductions in diastolic blood pressure and heart rate were noted in the two treatment groups during treatment. Perhaps because of the limited number of patients, no between-group differences in the results of a measure of quality of life were found, but on overall assessments of treatment outcome by patients and the investigator, slightly better outcome was apparent in the ramipril-treated patients. No side effects or clinically significant changes in laboratory test results were reported. It is concluded that ramipril is a safe and effective agent in mild to moderate hypertension when administered as a single daily dose.     

Antibody response of infants in tropics to five doses of oral polio vaccine

Sixty-two infants 1-12 months of age were administered five doses of trivalent oral polio vaccine (TOPV) at intervals of 4 weeks. The seroconversion achieved were 88.7, 93.5 and 96.5 per cent for type I, II, and III polioviruses. These seroconversion rates are significantly better when compared to seroconversion achieved after two and three doses of trivalent oral polio vaccine. Factors which were considered in previous studies to be responsible for low seroconversion rates viz. interference by enteroviruses, breast feeding, malnutrition, and age were found to be insignificant when five doses of oral polio vaccine were given. It is possible that these effects were overcome by increasing the number of doses of trivalent oral polio vaccine.     

Local segmentation of biomedical images

In this paper, a new algorithm for local segmentation of biomedical images is presented. First, a relatively small region is selected for segmentation on the basis of dispersion measurement of local gray values. This small region is then segmented using a segmentation algorithm based on quantization approach. While quantizing a signal, the range of input signal is divided into a number of segments. All signal values within a segment are assigned a unique reconstruction value. In segmentation of gray level images, the problem is to classify or code gray values of the pixels into two or more groups. An N-level threshold selection method for segmentation thus becomes the design of an N-level optimal quantizer. This new approach is suitable for a number of biomedical applications where the objects of interest appear as small and localized in the images. Some experimental results are also provided which illustrate the success of the new scheme.     

Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep

1. Administration of glucocorticoids to ewes early in pregnancy results in offspring with hypertension in adulthood. The hypertension in female offspring exposed to dexamethasone is associated with increased cardiac output, but whether this is also true in cortisol-exposed offspring is unknown.
2. Systemic haemodynamic variables were measured under basal conditions in castrated male and female adult sheep exposed to cortisol (5 mg/h) or saline (0.19 mL/h) from 26 to 28 days of gestation. To examine the contribution of the autonomic nervous system to maintenance of basal arterial pressure in established hypertension in cortisol-exposed sheep, responses to adrenoceptor blockade (intravenous infusion of 0.15 mg/kg per h phentolamine plus 0.4 mg/kg per h propranolol) and ganglionic blockade (intravenous infusion of 125 mg/h hexamethonium) were examined in castrated male offspring.
3. Mean arterial pressure and calculated systemic vascular resistance were 9% and 17% greater, whereas cardiac output tended to be 8% less, in cortisol-compared with saline-exposed sheep. These effects were not sex dependent. The depressor response to ganglionic blockade and the initial phase of the depressor response to adrenoceptor blockade were greater in cortisol-compared with saline-exposed sheep.
4. These results indicate that hypertension in offspring exposed prenatally to cortisol is associated with increased total peripheral resistance, mimicking observations in human patients with chronic hypertension. Furthermore, the increased vascular resistance appears to be dependent, at least in part, on an increased effect of sympathetic vasomotor drive. Taken together with previous findings, the present observations suggest that prenatal cortisol and dexamethasone programme altered adult cardiovascular function via distinct mechanistic pathways.