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Biochemistry. 2000 Nov 7;39(44):13365-75.
Evaluation of the utility of NMR structures determined from minimal NOE-based restraints for structure-based drug design, using MMP-1 as an example.
Huang X, Moy F, Powers R.
Department of Biological Chemistry, Wyeth Research, 85 Bolton Street, Cambridge, Massachusetts 02140, USA.
The application of deuterium labeling and residual dipolar coupling constants in combination with other structural information has demonstrated the potential for significantly expanding the range of viable protein targets for structural analysis by NMR. A previous study by Clore et al. [(1999) J. Am. Chem. Soc. 121, 6513-6514] demonstrated that a significant improvement in the overall protein structure occurs with the combination of residual dipolar coupling constants and minimal tertiary long-range distance restraints. The analysis of NMR protein structures determined with minimal structural information is extended with a particular interest in the utility of these structures for a structure-based drug design program. As an example, the catalytic fragment of human fibroblast collagenase (MMP-1) was used to follow the effect of minimal restraint sets on the protein structure and its utility in drug design with a particular interest in the effect on the active site conformation. An MMP-1 structure that was calculated with the maximal number of restraints attainable with the constraint of a deuterated protein was shown to be very similar to a high-quality MMP-1 structure that was calculated from a complete set of restraints. The superposition of the active site backbone atoms for the high-quality and minimal restraint MMP-1 structures yielded an rmsd of 0.68 A where the size and shape of the S1' pocket are nearly identical. Additionally, an MMP-1-CGS-27023A complex based on a minimal set of NOE-based restraints reliably reproduced the structure of the complex, establishing the usefulness of the structures for drug design.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063573&dopt=Abstract
Ann Dermatol Venereol. 2000 Oct;127(10):814-7.
[Cutaneous neonatal lupus erythematosus: discordant expression in identical twins]
[Article in French]
Batard ML, Sainte-Marie D, Clity E, Belhabri S, Cotellon P, Pradinaud R.
Service de Dermatologie, Centre Hospitalier de Cayenne, rue des Flamboyants, BP 6006, 97306 Cayenne Cedex.
BACKGROUND: Neonatal lupus erythematosus is a rare syndrome characterized essentially by cutaneous lesions and/or congenital heart block occurring in infants at birth, or shortly after. It is related to transplacental crossing of maternal auto antibodies (usually anti Ro/SS-A, La/SS-B or rarely anti-U(1) RNP) from the mother to the infant. Mothers of affected children have signs of systemic lupus erythematosus or other collagenosis or are asymptomatic. CASE REPORT: We report a case of neonatal lupus erythematosus in one identical twin, revealed at the age of 3 months by erythematous and annular cutaneous lesions of the face and limbs. These lesions were preceded at birth by an asymmetrical livedo pattern of the lower limbs. Her twin sister was unaffected but both infants had a high rate of anti-Ro/SSA antibodies. The diagnosis of neonatal lupus erythematosus permitted to reveal a biological lupus syndrome in their asymptomatic mother. Cutaneous lesions cleared almost completely within 1 year whereas antiRo/SSA antibodies disappeared. CONCLUSION: Cases of neonatal lupus erythematosus in twins are rare and mostly described in heterozygotic twins. Clinical discordance is usual and could partly be explained by genetic factors. In monozygotic twins, like in our case, chromosome X inactivation could be an explanation of the differences observed.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11060383&dopt=Abstract
Osteoarthritis Cartilage. 2002 Nov;10(11):870-8.
Immunolocalization of carboxy-terminal type II procollagen peptide in regenerated articular cartilage of osteoarthritic knees after reduction of mechanical stress.
Kobayashi H, Saito T, Koshino T.
Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Japan. hayato-3.dion.ne.jp
OBJECTIVE: The purpose of this study was to investigate the immunolocalization of carboxy-terminal type II procollagen peptide (pCOL-II-C) in the regenerated articular cartilage grown 1-2 years after reduction of mechanical stress by correction of varus deformity with high tibial osteotomy (HTO) for knees with medial compartmental osteoarthritis. DESIGN: The series included 24 knees of 16 patients with a mean age of 70 (56-79) years. Synovial fluid and tissue specimens of the regenerated articular cartilage were obtained at the time of plate removal with arthrotomy. Tissue specimens were decalcified and stained with toluidine blue, safranin O, anti-type I and type II collagen and anti-pCOL-II-C. Pineda's histological grading of articular cartilage repair and Okada's grade of immunostaining were employed to assess the regenerated articular cartilage. RESULTS: In knees with regeneration of articular cartilage, there was a positive linear correlation between the grade of immunostaining and the concentration of synovial fluid pCOL-II-C (r=0.652; P< 0.001). Similarly, a positive linear correlation was observed between the grade of immunostaining and the histological grading score (r=0.683; P< 0.001). CONCLUSIONS: The immunostaining and synovial fluid concentration of pCOL-II-C decreased in accordance with the progression of articular cartilage regeneration observed after reduction of mechanical stress by correction of deformity with HTO. 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12435332&dopt=Abstract
ANA.AU.DK
Previous findings indicate that the thermal stability of bone collagen is related to age. In this study, collagen from rat bone with reported different turnover rates was investigated. Cortical and trabecular bone from femur were obtained from intact, ovariectomized, orchidectomized and multiparous breeder rats. Thermal stabilities of fibrillar collagen in decalcified bone matrix and molecular collagen obtained by pepsin treatment were measured as shrinkage (Ts) and 'melting' temperature (Tm), respectively. Both Ts and Tm of cortical collagen from intact female rats decreased in parallel with age as previously found in male rats indicating that Ts and Tm measurements are interchangeable techniques in characterizing the thermal stability of bone collagen. Tm of trabecular collagen from intact rats decreased with age, however, with a decay only one-third of that for cortical collagen. The different rates possibly reflect different ages of collagen due to remodeling activity present in trabecular and minimal in cortical bone. Compared with control rats the Tm of trabecular collagen from gonadectomized and multiparous rats with a reported increased trabecular turnover rate was elevated, whereas only minor variations in Tm of cortical collagen were found. In conclusion, the thermal stability of bone collagen decreases with the age of the collagen. Increased bone turnover implies elevated thermal stability of bone collagen. Thus, thermal stability of bone collagen appears to be an indicator of bone turnover.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063009&dopt=Abstract
Connect Tissue Res. 1998;39(4):269-79.
Human root dentin: structural anisotropy and Vickers microhardness isotropy.
Wang R, Weiner S.
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
The demanding mechanical functions and the variable structure of dentin make it an invaluable material for studying the structure-mechanical function relations of a mineralized collagen-containing tissue. The mineralized collagen fibril axes in human root dentin are mainly located on the incremental plane. Within this plane there is a preferred orientation in the general root-crown direction. The apatite crystals are aligned in three dimensions within an individual collagen fibril, but this orientation does not necessarily extend to the neighboring fibrils. Crystals are also present as aggregates without any preferred orientation. The structure is therefore clearly anisotropic with respect to the collagen fibril orientation, but less so with respect to overall crystal orientation. Vickers microhardness measurements of the root dentin are essentially the same on the three orthogonal planes with respect to the incremental plane. Knoop microhardness measurements are also the same on all three orthogonal planes when the major diagonal is aligned perpendicular to the collagen fibril axis preferred orientation direction. In-plane variations of up to 20% are observed in the orthogonal direction. The material is thus isotropic in the three main directions with respect to Vickers microhardness, but anisotropic in structure. This paradoxical situation is attributed mainly to the variable modes of crystal organization.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063007&dopt=Abstract
The average human scalp is covered by approximatey 100,000 hair follicles. Each hair undergoes
Loss of hair itself does not pose critical health problems because biological role of human hair is relatively marginal. Hair on our scalp protects the head from mechanical shock, heat loss, and exposure to UV-light. The eyelashes and eyebrowes protect the eyes, and hair in the ear canal or the nasal passages help filter out particles and pathogens, thus protecting our internal organs.
However, hair does play important social role: it is one of the major determinants of our appearance and identity in daily life. Fullness of hair also implicates or manifests physical integrity and youthfulness of the person. Losing hair could have more than just emotional impacts on individuals.
The hair is a unique organ that goes through a characteristic cycle consisting of an immature phase, a growing phase called anagen, a transitional phase between the growing phase and the resting phase called catagen, and finally a resting phase called telogen in which the hair stops growing, waiting to fall out. 85-90% of hairs on our body are in anagen phase or growing phase, which lasts anywhere from two to five years. This phase is followed by a short regression phase, or catagen, which lasts 2-3 weeks. Approximately 1% of hair follicles are in catagen. Approximately 10-15% of hair follicles are in the resting phase, the telogen, which lasts about 3-5 months. Hair follicles typically goes through 10-20 asynchronous cycles during the lifetime.
Persistent loss of more than 150 hairs would consist a state of hair loss, or alopecia, albeit it could be temporary.
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