46117096
ras protein p21 processing enzyme farnesyltransferase in chemical carcinogen-induced murine skin tumors.
Farnesylation of ras protein p21 is crucial for the protein's membrane localization, which is essential for its cell-transforming activity, which in turn is thought to be critical for the ultimate induction of cancer. The cytosolic enzyme farnesyltransferase plays a major role in posttranslational modification of p21, but the level of farnesyltransferase activity in mammalian tumors and its relationship to the processing of cytosolic p21 that leads to tumorigenesis are unknown. We report here that farnesyltransferase activity was significantly higher in chemical carcinogen-induced benign skin papillomas in SENCAR mice than in the epidermises of control animals. The enzyme is primarily epidermal in origin, and kinetic studies with cytosol from epidermis and papillomas showed that the reaction was linear with respect to time, substrate concentration, and protein content. Skin papillomas showed significantly elevated levels of both cytosolic and membrane-bound Ha-ras p21, whereas far lesser cytosolic and almost negligible amounts of membrane-bound p21 were present in the epidermis of control mice. There was a positive correlation between increased enzyme activity in papilloma cytosol and the processing of overexpressed cytosolic Ha-ras p21 for its localization to membrane.
12257571
Protection against ultraviolet B radiation-induced effects in the skin of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea.
In prior studies we and others have shown that oral feeding of a polyphenolic fraction isolated from green tea (GTP) or water extract of green tea affords protection against ultraviolet B (UVB) radiation-induced carcinogenesis in SKH-1 hairless mice (Wang et al., Carcinogenesis 12, 1527-1530, 1991). It is known that exposure of murine skin to UVB radiation results in cutaneous edema, depletion of the antioxidant-defense system and induction of ornithine decarboxylase (ODC) and cyclooxygenase activities. In this study we assessed the protective effect of GTP on these UVB radiation-caused changes in murine skin. Oral feeding of 0.2% GTP (wt/vol) as the sole source of drinking water for 30 days to SKH-1 hairless mice followed by irradiation with UVB (900 mJ/cm2) resulted in significant protection against UVB radiation-caused cutaneous edema (P < 0.0005) and depletion of the antioxidant-defense system in epidermis (P < 0.01-0.02). The oral feeding of GTP also resulted in significant protection against UVB radiation-caused induction of epidermal ODC (P < 0.005-0.01) and cyclooxygenase activities (P < 0.0001) in a time-dependent manner. Our data indicate that the inhibition of UVB radiation-caused changes in these markers of tumor promotion in murine skin by GTP may be one of the possible mechanisms of chemopreventive effects associated with green tea against UVB-induced tumorigenesis. The results of this study suggest that green tea, specifically polyphenols present therein, may be useful against inflammatory responses associated with the exposure of skin to solar radiation.
5785486
Identification of the site of photocross-linking formed in the absence of magnesium nucleotide from SH2 (Cys-697) in myosin subfragment 1 labeled with 4'-maleimidylbenzophenone.
The site of photocross-linking between Cys-697 (SH2), prelabeled with 4'-[14C]maleimidylbenzophenone, and the 50-kDa segment of myosin S1 on irradiation in the absence of nucleotide has been determined by isolation of the 20-50-kDa adduct and subsequent tryptic proteolysis. Isolation and partial sequencing of the radioactively labeled peptide indicate that the site of cross-linking is Arg-239. This result indicates that, in the absence of nucleotide, Arg-239 resides at about 1.0 nm from SH2 and, on the basis of the recent work of Sutoh and Hiratsuka (Sutoh, K. and Hiratsuka T. (1988) Biochemistry 27, 2964-2969) places Arg-239 at no more than 1.45 nm from either Lys-184 or Lys-189 of the nucleotide-binding "glycine-rich" loop prior to the binding of nucleotide.
6837472
Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.
Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.
37464296
Introduction to Special Issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer--an International Journal.
The advance of technology and understanding of the process of cancer development suggests that the reported lesser incidence and death due to cancer in countries other than the Western and European countries might also be due to under- diagnosed and under-represented cases. Further, increases in life span as well as ignorance about the disease puts populations in South and South East Asian countries at higher risk to develop cancer. With the increasing rate of cancer incidence every year in non -Western countries, cancer is estimated to become the deadliest disease in coming decades. Conventional chemo- and radio-therapies during the past three decades have not been able to contain the disease, and also have serious side effects. Many natural agents, especially small molecules from plants are non-toxic, easily available and may have anticancer potential. Thus, screening phytochemicals as anticancer agents could be a better approach in cancer prevention and treatment. This chemoprevention approach may have translational significance for prevention and treatment of cancer. 
 
Therefore to emphasize the potential role of phytochemicals in cancer prevention and therapy, it was our privilege to host the International Symposium on Recent Advances in Cancer Research: Therapeutics to Chemoprevention, at Central University of Gujarat (CUG), Gandhinagar. The conference was co-organized by the University of Colorado Denver, USA; University of Pittsburgh, USA; University of Oklahoma, USA, during 8–9 February, 2012. Modern biological strategies, specifically the latest developments for the targeted prevention and treatment of cancer via dietary, natural and synthetic agents were discussed in detail. The symposium also emphasized the translational aspect of cancer chemoprevention strategies for various cancers. 
 
The symposium deliberations include the ideas for combinatorial chemoprevention by phytochemicals as a promising approach for cancer control and emerging trends for the use of herbal radio-modulators to sensitize the cancer cells for apoptotic cell death. Many bioactive phytochemicals such as silibinin, benzyl isothiocyanate, anthocyanidins, nexrutine, tocopherol, etc. were discussed for their in vivo efficacy in animal tumor models, associated mechanisms and translational potential. Targeting tumor microenvironment with small molecules was found promising and having translational potential for prostate and breast cancer chemoprevention. 
 
The novel work and ideas presented at the symposium were helpful in guiding the research orientation of scientists, especially the young researchers who will be benefitted at all levels of their career development. Since chemoprevention of cancer is becoming an attractive approach for controlling cancer, we felt that the deliberations of this symposium should reach to the wider section of the researchers. Therefore, it was planned to bring out a special issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer – An International Journal. We appreciate the researchers for contributing their novel work and ideas to this special issue. We are grateful to the Editor of Nutrition and Cancer – An International Journal, for his initiative to bring out this special issue on this relevant topic. We believe that this volume will be enlightening for the researchers working in the area of cancer chemoprevention.
35457752
Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes.
Nordihydroguaiaretic acid (NDGA), a plant lignan and phenolic antioxidant, is a known lipoxygenase inhibitor. In this study, we investigated the effect of NDGA on rat epidermal and hepatic monooxygenase activity and its interaction with rat hepatic microsomal cytochrome P-450. The addition of NDGA to epidermal microsomes prepared from control and 3-methylcholanthrene (3-MC)-pretreated rats and hepatic microsomal preparations from control, 3-MC-pretreated, and phenobarbital (PB)-pretreated rats resulted in a concentration-dependent inhibition of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (ERD) activities. The 50% inhibitory dose for NDGA ranged from 4.1 x 10(-5) to 13.1 x 10(-5) M for AHH and ERD activities in these microsomal preparations. The addition of NDGA to hepatic microsomes prepared from PB-pretreated rats resulted in spectral changes characterized by absorbance maxima at 380 nm and minima at 414 nm, typical of type I binding difference spectra. It also showed time- and concentration-dependent inhibition of the binding of carbon monoxide to dithionite or NADPH-reduced cytochrome P-450. We speculate that perhaps hydroxyl groups present in NDGA play an important role in inhibiting the monooxygenase activity and suggest that NDGA may have potential as an antimutagen and/or anticarcinogen. Furthermore, caution must be exercised in elucidating the role of lipoxygenase in metabolic pathways based solely on the criterion of inhibition by NDGA.
206198477
A new technique for repair of acquired split-ear-lobe deformity: the free conchal cartilage sandwich graft.
BACKGROUND
Split-ear-lobe repair is one of the commonest requests in cosmetic facial surgery. Frequently, the ear lobe split is prone to recurrence following surgical repair. A new technique is described that strengthens the ear lobe tissues using locally available conchal cartilage to prevent recurrence. A new classification of split ear lobe is also presented.


METHODS
Twenty-two women in the age range from 18 to 62 years with varying grades of split ear lobe were operated using the technique of conchal cartilage reinforcement of ear lobe. Eight females had bilateral involvement, and a total of 30 split ear lobes were repaired. A conchal cartilage disc was harvested at the time of repair of the ear lobe. This disc was placed in a pocket created in the ear lobe, and the ear lobe was repaired over this pocket. Simultaneous re-perforation of the ear lobe was done in a central location through the implanted conchal disc, and stud earring was applied.


RESULTS
Satisfactory aesthetic and functional results have been obtained in the series using the technique of conchal cartilage-graft augmentation of the ear lobe. All patients had high degree of satisfaction in being able to come out of the operating room with earrings on. There has been no stretching or re-tear of the ear lobe following implantation of conchal cartilage, over a follow-up period of 36 months.


CONCLUSION
The conchal cartilage-graft sandwich procedure allows immediate re-perforation of the repaired ear lobe at the time of repair in a central aesthetic location, as well as providing necessary strength to the ear lobe; thus preventing recurrence in primary and recurrent, acquired split-ear-lobe deformity.
30313777
It's Pneumocystis jiroveci not Pneumocystis carinii.
2006;129;498 Chest Saxena Ritesh Agarwal, Chandana Reddy, Ashutosh N. Aggarwal and Akshay K. carinii Pneumocystis Not Pneumocystis jiroveci It's http://chestjournal.chestpubs.org/content/129/2/498.full.html services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright2006by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest
20316893
Structure of human dual specificity protein phosphatase 23, VHZ, enzyme-substrate/product complex.
Protein phosphorylation plays a crucial role in mitogenic signal transduction and regulation of cell growth and differentiation. Dual specificity protein phosphatase 23 (DUSP23) or VHZ mediates dephosphorylation of phospho-tyrosyl (pTyr) and phospho-seryl/threonyl (pSer/pThr) residues in specific proteins. In vitro, it can dephosphorylate p44ERK1 but not p54SAPK-beta and enhance activation of c-Jun N-terminal kinase (JNK) and p38. Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date (150 residues), is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T). We present the crystal structure of VHZ determined at 1.93A resolution. The polypeptide chain adopts the typical alphabetaalpha PTP fold, giving rise to a shallow active site cleft that supports dual phosphorylated substrate specificity. Within our crystals, the Thr-135-Tyr-136 from a symmetry-related molecule bind in the active site with a malate ion, where they mimic the phosphorylated TY motif of the MAPK activation loop in an enzyme-substrate/product complex. Analyses of intermolecular interactions between the enzyme and this pseudo substrate/product along with functional analysis of Phe-66, Leu-97, and Phe-99 residues provide insights into the mechanism of substrate binding and catalysis in VHZ.
20628925
Chronic kidney disease is associated with oxidative stress independent of hypertension.
BACKGROUND
Oxidative stress is implicated in the pathogenesis of chronic kidney disease (CKD) and essential hypertension (EHTN). However, the role of hypertension in causing increased oxidative stress in patients with CKD is unknown.


METHODS
We performed a case control study in patients with EHTN and those with equal blood pressure assessed by ambulatory blood pressure monitoring but with concomitant CKD. Those with diabetes mellitus and those taking renin angiotensin inhibitors were excluded. Biomarkers of oxidative stress, malondialdehyde (MDA) and protein carbonylation and total glutathione levels were measured.


RESULTS
Average (SD) 24-hour ambulatory blood pressure in 12 patients with CKD was 134 (17)/75 (16) compared to 134 (10)/80 (9) in 11 patients with EHTN (p = NS). Plasma MDA in CKD was 0.89 +/- 0.38 micromol/l compared to 0.68 +/- 0.16 micromol/l in EHTN (p = 0.07). Urinary MDA/creatinine ratio was 1.78 (0.31) in CKD vs 1.43 (0.69) micromol/g in those with EHTN (p = 0.04). Thus, lipid peroxidation was increased in urine of CKD patients. Patients with CKD had higher (1.04 (0.20) nmol) carbonyl/mg protein compared to those with EHTN (0.80 (0.21) nmol carbonyl/mg protein) (p = 0.03). Thus, protein carbonylation was increased in CKD patients. Total glutathione in CKD and EHTN patients was 6.6 (1.8) ng/ml and 7.3 (3.1) ng/ml (p = NS). There was a good correlation between biomarkers of lipid (MDA) and protein oxidation (protein carbonyls) (r = 0.6, p = 0.004).


CONCLUSIONS
Biomarkers of lipid and protein oxidation are higher in patients with CKD compared to EHTN despite similar blood pressure. Thus, nonhemodynamic factors such as inflammation and altered cellular redox state may play a greater role in the generation of oxidative stress in CKD.
25550116
Noninvasive estimation of clinically asymptomatic pulmonary hypertension in idiopathic pulmonary fibrosis.
OBJECTIVES
To determine the prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis (IPF) by noninvasive methods.


PATIENTS AND METHODS
Twenty seven patients with IPF attending the Chest Clinic over a period of one-and-a-half-years underwent echocardiography for evidence of pulmonary hypertension, which was defined as pulmonary artery systolic pressure > or = 40 mmHg by Doppler echocardiography, or pulmonary acceleration time < or = 100 milliseconds or two-dimensional echocardiographic findings of right ventricular hypertrophy or overload.


RESULTS
Two patients with clinical evidence of pulmonary hypertension were excluded from analysis. Their mean age (n = 25) was 53.8 years. The mean duration of symptoms before presentation was 2.1 years. Pulmonary hypertension was diagnosed by echocardiography in nine of the 25 patients (36%). There was a statistically significant difference between the duration of illness, arterial oxygen tension (PaO2) levels and forced vital capacity in patients with pulmonary hypertension than in those without pulmonary hypertension. Logistic regression analysis showed a significant association between the duration of illness, decreasing forced vital capacity and hypoxemia with the development of pulmonary hypertension.


CONCLUSIONS
Echocardiography detects pulmonary hypertension in clinically asymptomatic individuals, and should be used routinely for the diagnosis of pulmonary hypertension in patients with IPF.