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PubMed1998

Development of a prototype for a Center for Women's Health at an academic medical center.

The development of a centralized program in women's health is a challenge in a decentralized academic medical center and in the environment of healthcare transformation. The Center for Women's Health at the Columbia-Presbyterian Medical Center has allowed the clinical and educational abilities of an academic faculty interested in gender-specific health to operate in the delivery of coordinated care. Within the structure of an academic environment come advantages and unique opportunities for solving deficiencies in healthcare but also the need to overcome obstacles inherent in a large system. Flexibility and creative problem solving are key to meeting the challenges of the changing environment of healthcare. Here we describe ventures to develop a model program of clinical care and education in the gender science of women's health.

Academic Medical Centers↗
PubMed2006

Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate-substituted hydroxyapatite crystals and shaped by rapid prototyping to contain internal microchannels.

The next generation of tissue engineering scaffolds will be made to accommodate blood vessels and nutrient channels to support cell survival deep in the interior of the scaffolds. To this end, we have developed a method that incorporates microchannels to permit the flow of nutrient-rich media through collagen-based scaffolds. The scaffold matrix comprises nano-sized carbonate-substituted hydroxyapatite (HA) crystals internally precipitated in collagen fibers. The scaffold therefore mimics many of the features found in bone. A biomimetic precipitation technique is used whereby a collagen membrane separates reservoirs of calcium and phosphate solutions. The collision of calcium and phosphate ions diffusing from opposite directions results in the precipitation of mineral within the collagen membrane. Transmission electron microscopy analysis showed the dimension of the mineral crystals to be approximately 180 x 80 x 20 nm, indicating that the crystals reside in the intermicrofibril gaps. Electron diffraction indicated that the mineral was in the HA phase, and infrared spectroscopy confirmed type A carbonate substitution. The collagen-HA membrane is then used to make 3-dimensional (3D) scaffolds: the membrane is shredded and mixed in an aqueous-based collagen dispersion and processed using the critical point drying method. Adjusting the pH of the dispersion to 5.0 before mixing the composite component preserved the nano-sized carbonate-substituted HA crystals. Branching and interconnecting microchannels in the interior of the scaffolds are made with a sacrificial mold manufactured by using a 3D wax printer. The 3D wax printer has been modified to print the mold from biocompatible materials. Appropriately sized microchannels within collagen-HA scaffolds brings us closer to fulfilling the mass transport requirements for osteogenic cells living deep within the scaffold.

Absorbable Implants↗
PubMed1995

Mediterranean diet, Italian-style: prototype of a healthy diet.

Since Keys' first observations in the 1960s, the Mediterranean diet has been under scrutiny by researchers and public health specialists for its health-promoting qualities. Detailed analyses of food surveys carried out in Italy at that time permitted a definition of an Italian-style Mediterranean diet, characterized by low total fat (< 30% of energy), low saturated fat (< 10% of energy), high complex carbohydrates, and high dietary fiber. The importance of the plant components of this dietary pattern became increasingly recognized as a result of advances in the understanding of the pathophysiology of chronic and degenerative diseases. Thus, the Mediterranean diet was found not only to produce favorable effects on blood lipid profiles, but also to protect against oxidative stress and carcinogenesis. However, possible unwanted effects, such as those on micronutrient bioavailability, also must be taken into account. In recent years, despite an increase in consumption of animal foods, the dietary profile of southern Italy has maintained its basic features, and vital statistics still demonstrate a comparative advantage of eating behaviors in Mediterranean countries.

Antioxidants↗
PubMed1998

An initial trial of a prototype telepathology system featuring static imaging with discrete control of the remote microscope.

Routine diagnosis of pathology images transmitted over telecommunications lines remains an elusive goal. Part of the resistance stems from the difficulty of enabling image selection by the remote pathologist. To address this problem, a telepathology microscope system (TelePath, TeleMedicine Solutions, Birmingham, Ala) that has features associated with static and dynamic imaging systems was constructed. Features of the system include near real time image transmission, provision of a tiled overview image, free choice of any fields at any desired optical magnification, and automated tracking of the pathologist's image selection. All commands and images are discrete, avoiding many inherent problems of full motion video and continuous remote control. A set of 64 slides was reviewed by 3 pathologists in a simulated frozen section environment. Each pathologist provided diagnoses for all 64 slides, as well as qualitative information about the system. Thirty-one of 192 diagnoses disagreed with the reference diagnosis that had been reached before the trial began. Qf the 31, 13 were deferrals and 12 were diagnoses of cases that had a deferral as the reference diagnosis. In 6 cases, the diagnosis disagreed with the reference diagnosis yielding an overall accuracy of 96.9%. Confidence levels in the diagnoses were high. This trial suggests that this system provides high-quality anatomic pathology services, including intraoperative diagnoses, over telecommunications lines.

Diagnostic Imaging↗
PubMedDate not supplied

Experimental visna in Icelandic sheep: the prototype lentiviral infection.

A brief review of experimental infection of Icelandic sheep following intracerebral inoculation of neurotropic strains of visna virus is presented. In vivo replication of the virus is restricted, so that some cells carry the deoxyribonucleic acid provirus as an unexpressed genome. This cellular restriction plays a major role in the slow progression of the infection, abetted by neutralizing antibody in serum and spinal fluid. The latent provirus maintains the viral genome in the presence of an active immune response, since immune surveillance cannot recognize cells that are not synthesizing viral antigens. Infected Icelandic sheep experience two types of diseases of the central nervous system: a subclinical subacute encephalitis begins within weeks of infection in most sheep; and at irregular intervals from 0.5-8 years after infection, clinical paresis develops in the majority of Icelandic sheep and is accompanied by discrete focal demyelinating lesions in the spinal cord. The subacute encephalomyelitis is probably mediated by an antiviral cellular immune response, whereas the pathogenesis of the focal demyelinating lesions is still obscure. During persistent infection there is some selection for neutralization-resistant antigenic variants of the infecting serotype, and these are isolated at a frequency of approximately 15%. However, variants do not replace the infecting serotype, and antigenic drift does not appear essential for persistence of visna virus or for the occurrence of demyelinating lesions.

Animals↗
PubMed1998

Structure of proline iminopeptidase from Xanthomonas campestris pv. citri: a prototype for the prolyl oligopeptidase family.

The proline iminopeptidase from Xanthomonas campestris pv. citri is a serine peptidase that catalyses the removal of N-terminal proline residues from peptides with high specificity. We have solved its three-dimensional structure by multiple isomorphous replacement and refined it to a crystallographic R-factor of 19.2% using X-ray data to 2.7 A resolution. The protein is folded into two contiguous domains. The larger domain shows the general topology of the alpha/beta hydrolase fold, with a central eight-stranded beta-sheet flanked by two helices and the 11 N-terminal residues on one side, and by four helices on the other side. The smaller domain is placed on top of the larger domain and essentially consists of six helices. The active site, located at the end of a deep pocket at the interface between both domains, includes a catalytic triad of Ser110, Asp266 and His294. Cys269, located at the bottom of the active site very close to the catalytic triad, presumably accounts for the inhibition by thiol-specific reagents. The overall topology of this iminopeptidase is very similar to that of yeast serine carboxypeptidase. The striking secondary structure similarity to human lymphocytic prolyl oligopeptidase and dipeptidyl peptidase IV makes this proline iminopeptidase structure a suitable model for the three-dimensional structure of other peptidases of this family.

Amino Acid Sequence↗
PubMed1999

Drainin required for membrane fusion of the contractile vacuole in Dictyostelium is the prototype of a protein family also represented in man.

The contractile vacuole expels water by forming a channel with the plasma membrane and thus enables cells to survive in a hypo-osmotic environment. Here we characterize drainin, a Dictyostelium protein involved in this process, as the first member of a protein family represented in fission yeast, Caenorhabditis elegans and man. Gene replacement in Dictyostelium shows that drainin acts at a checkpoint of channel formation between the contractile vacuole and the plasma membrane. A green fluorescent protein fusion of drainin localizes specifically to the contractile vacuole and rescues its periodic discharge in drainin-null cells. Drainin is a peripheral membrane protein, requiring a short hydrophobic stretch in its C-terminal region for localization and function. We suggest that drainin acts in a signaling cascade that couples a volume-sensing device in the vacuolar membrane to the membrane fusion machinery.

Amino Acid Sequence↗
PubMed1999

Crystal structure of the surfactin synthetase-activating enzyme sfp: a prototype of the 4'-phosphopantetheinyl transferase superfamily.

The Bacillus subtilis Sfp protein activates the peptidyl carrier protein (PCP) domains of surfactin synthetase by transferring the 4'-phosphopantetheinyl moiety of coenzyme A (CoA) to a serine residue conserved in all PCPs. Its wide PCP substrate spectrum renders Sfp a biotechnologically valuable enzyme for use in combinatorial non-ribosomal peptide synthesis. The structure of the Sfp-CoA complex determined at 1.8 A resolution reveals a novel alpha/beta-fold exhibiting an unexpected intramolecular 2-fold pseudosymmetry. This suggests a similar fold and dimerization mode for the homodimeric phosphopantetheinyl transferases such as acyl carrier protein synthase. The active site of Sfp accommodates a magnesium ion, which is complexed by the CoA pyrophosphate, the side chains of three acidic amino acids and one water molecule. CoA is bound in a fashion that differs in many aspects from all known CoA-protein complex structures. The structure reveals regions likely to be involved in the interaction with the PCP substrate.

Amino Acid Sequence↗
PubMed2000

The Nepal National Vitamin A Program: prototype to emulate or donor enclave?

More than 250 million of the world's children suffer from vitamin A deficiency. Nepal is one of 60 countries in which this deficiency constitutes a significant public health problem. Each year in Nepal, vitamin A deficiency is responsible for the deaths of 9000 children and for 2500 children becoming permanently blind. The Nepal National Vitamin A Program (NVAP) was begun in 1993 in eight of the country's 75 districts. By the end of 1997, the programme covered 32 districts, and by 2003 its coverage will be nationwide. The Nepal NVAP is considered by many to be a highly successful, model programme. It consists primarily of distributing high-dose vitamin A capsules to all children 6 to 60 months of age during twice-yearly campaigns. The capsule distribution is carried out by a previously existing network of Female Community Health Volunteers (FCHVs) that has been reinvigorated by the highly visible and universally acclaimed success of the NVAP. An important strategy of the programme has been the empowerment of the FCHVs, which has been accomplished by organizing, training and motivating community workers and other representatives from education, agriculture and other sectors, as well as political representatives, to support the FCHVs. The annual cost of the NVAP is US$1.7 million. It costs $1.25 to deliver two vitamin A capsules to each participant. The cost per averted death is $327. The NVAP reduces the incidence and severity of diarrhoeal disease and measles, which in turn reduces the need for Ministry of Health services, thereby annually saving the Government of Nepal $1.5 million. Factoring in these cost savings, the net annual cost of the current NVAP is $167,000, and the net annual cost of the permanent, nationwide programme is estimated at $1.1 million. The NVAP is a highly cost-effective programme. The article concludes with a discussion of the sustainability and replicability of the programme.

Blindness↗
PubMed2003

Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.

Since 1998, five disorders involving enzyme defects in post-squalene cholesterol biosynthesis have been identified-desmosterolosis, X-linked dominant chondrodysplasia punctata, CHILD syndrome, lathosterolosis, and hydrops-ectopic calcification-moth-eaten skeletal dysplasia. They join the most common cholesterol biosynthetic disorder, Smith-Lemli-Opitz syndrome, whose underlying defect was identified in 1993. All are associated with major developmental malformations that are unusual for metabolic disorders. The existence of mouse models for five of these disorders is beginning to enable more detailed developmental and in vitro studies examining the mechanisms involved in disease pathogenesis. In this review, an overview of the cholesterol biosynthetic pathway will be presented. Clinical features of the human disorders and mouse models of post-squalene cholesterol biosynthesis will then be discussed.

Animals↗