Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma

BACKGROUND: Asthma is the most common chronic disease of childhood and has a strong genetic component. OBJECTIVE: To identify gene expression signatures that reflect asthma-related processes and to determine whether these genes were similar or distinct between stable asthma and acute exacerbations in childhood, we profiled gene expression patterns in nasal respiratory epithelial cells. METHODS: Children who had stable asthma (asthma-S; n = 10) and children experiencing an asthma exacerbation (asthma-E; n = 10) were recruited along with nonatopic children without asthma (n = 10). RNA was prepared from nasal respiratory epithelial cells isolated from each child, initially analyzed as pooled samples from the 3 groups, and further validated by using microarrays and RT-PCR with individual patient samples. RESULTS: Distinct gene clusters were identifiable in individual and pooled asthma-S and asthma-E samples. Asthma-E samples demonstrated the strongest and most reproducible signatures, with 314 genes of 34,886 measured as present on the chip demonstrating induction or repression of greater than 2-fold with P < .05 in each of 4 individual samples. Asthma-S-regulated genes encompassed genes that overlapped with those of asthma-E but were fewer (166) and less consistent with respect to their behavior across the asthma-E patient samples. CONCLUSION: Exacerbated asthma status is readily distinguished based on the occurrence of strong gene expression signatures in nasal epithelial samples. Stable asthma status also exhibits differential signatures. The results suggest that there are independent gene expression signatures reflective of cells and genes poised or committed to activation by an asthma attack.     

Mitochondrially targeted vitamin E and vitamin E mitigate ethanol-mediated effects on cerebellar granule cell antioxidant defense systems

Ethanol (EtOH) disrupts the structure and function of the developing nervous system, sometimes leading to birth defects associated with fetal alcohol syndrome (FAS). Animal FAS models indicate that cellular membrane peroxidation, intracellular oxidant accumulation, and suppression of endogenous antioxidant enzymes contribute to the toxic effects of EtOH. Mitochondrially targeted vitamin E (MitoVit E), a chemically engineered form of vitamin E (VE) designed to accumulate in the mitochondria, has been shown to inhibit intracellular oxidant accumulation and cell death more effectively than VE. In previous investigations, we have shown that, in vivo, VE reduces neuronal death in the developing cerebellum of EtOH-exposed animals, and, in vitro, VE prevents apoptotic and necrotic death of EtOH-exposed cerebellar granule cells (CGCs). The present investigation shows that, in a FAS CGC model, 1 nM MitoVit E renders significant neuroprotection against EtOH concentrations as high as 1600 mg/dL. The present study also demonstrates that, in this same model, MitoVit E mitigates EtOH-induced accumulation of intracellular oxidants and counteracts suppression of glutathione peroxidase/glutathione reductase (GSH-Px/GSSG-R) functions, protein expression of gamma-glutamylcysteine synthetase (gamma-GCS), and total cellular glutathione (GSH) levels. In the presence and absence of EtOH, VE amplifies the protein expression levels of gamma-GCS, an enzyme that performs the rate-limiting step for GSH synthesis, and total GSH levels. These results suggest that MitoVit E and VE ameliorate EtOH toxicity through non-oxidant mechanisms-modulations of endogenous cellular proteins-and antioxidant means.     

A case of extensive linear porokeratosis with evaluation of topical tretinoin versus 5-flourouracil as treatment modalities

A 19-year-old male presented with linear raised lesions over extensive areas of his body that followed Blaschko's lines. The lesions were asymptomatic with ridged borders. Histopathology confirmed a diagnosis of porokeratosis. He was given topical tretinoin and topical flourouracil for local application on specified areas. The cosmetic acceptability and the safety profile of tretinoin were found to be better than those of flourouracil. However, both the agents were equally efficacious. A rare case of extensive porokeratosis with comparative evaluation of two treatment modalities is hereby presented.     

Mental health status of runaway adolescents

There are 47.22 million homeless and runaway adolescents roaming on the streets of our country (Voluntary Health Association of India — VHAI) of which one lakh are in Delhi. Very little is known about them, their needs or their experiences.Objective: (1) To assess the psychological problems amongst the runaway adolescent boys. (2) To determine possible risk factors.Methods: This study was cross-sectional in design and done at a child observation home for boys in Delhi. All runaway boys aged 10 to 16 years of age were included in the study. The study was conducted from 15^th June to 15^th July 2001. A comprehensive schedule consisting of five parts, viz identification data, hopelessness scale for children by Kazdin, Beck depression inventory, Psychological survey questionnaire and RUTTER-B2 scale were used to assess various mental health problems.Results: 20.7% of children were found to have high hopelessness and 8% of children had depression. 2% of children revealed that they had attempted suicide at any point of time in life. Among children with high hopelessness, 3.2% had ever attempted suicide. 8.3% of the depressed children gave history of suicidal attempts. 38% of children gave history of physical abuse, 14.6% of sexual abuse and a large number reported substance abuse. 69.33% were found to have behavioral problems (i.e. scored above the recommended cut off score of 9). 81% of children had antisocial behavior, 7.8% were neurotic and 10.5% remained undifferentiated.Conclusion: Runaway adolescents suffer from a wide array of mental health problems and there is a need for a broad based psychosocial intervention programme.     

A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypovolemia after aneurysmal subarachnoid hemorrhage (SAH) may be mediated by natriuretic peptides and can further impair cerebral perfusion in dysautoregulated and vasospastic arterial territories. Dendroaspis natriuretic peptide (DNP), derived from the venom of Dendroaspis augusticeps, the Green Mamba snake, has recently been discovered in human plasma and atrial myocardium. There is no information regarding the presence or putative role of this peptide in patients with aneurysmal SAH. METHODS: A sensitive and specific DNP radioimmunoassay was performed on venous blood samples obtained on post-SAH Days 1, 3, and 7 from 10 consecutive SAH patients (cases) and randomly from 9 healthy volunteers (controls). Clinical and laboratory data, including daily serum sodium concentration and fluid balance, were collected prospectively up to 7 days after the ictus. RESULTS: Increase in plasma DNP levels occurred in five (63%) of eight patients who had DNP levels measured on Days 1 and 3 (mean increase, 29%). An increase in DNP level was significantly associated with development of a negative fluid balance (P = 0.003) and hyponatremia (P = 0.008). Three (75%) of the four patients who developed cerebral vasospasm during this study experienced an increase in DNP levels from Days 1 to 3. CONCLUSION: The present study is the first to find a significant association between elevated levels of DNP, a new member of the natriuretic peptide family, and the development of diuresis and natriuresis in patients with aneurysmal SAH. Our findings warrant further investigation by means of a large-scale, prospective, case-control study.     

Gamna Gandy bodies of spleen seen in CML: a causal association--a case report

Gamna Gandy bodies are usually seen in spleen in cases of chronic venous congestion. We present a case of CML showing gamna gandy bodies. These may have occurred as a part of evolving portal hypertension which maybe due to antileukemic therapy or CML per se or due to a combination of both factors.     

Primary chondrosarcoma of the breast: a case report

Mammary sarcomas are uncommon tumors. Of these pure chondrosarcoma without any other area of epithelial or mesenchymal differentiation feature as even rarer. This excludes tumors like malignant cystosarcoma phyllodes and metaplastic carcinoma where malignant cartilaginous areas may be present. Further primary chondrosarcoma arises from breast stroma and not from underlying bone or cartilage. Only five cases of pure and primary chondrosarcoma have been reported so far. The sixth case is reported here.