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Biomedical subjects

M H Silver

Publications and source records attributed to M H Silver.

At least 19 recordsLinked to original sources

Cognitive functional status of age-confirmed centenarians in a population-based study.

The New England Centenarian Study is a population-based study of all centenarians in 8 towns near Boston, MA. Age was confirmed for 43 centenarians all alive on a designated date. To determine prevalence of dementia in centenarians, the authors analyzed neuropsychological, medical, and functional status data for 34 (79%) of the centenarians. Definition of dementia was based on the Consortium to Establish a Registry for Alzheimer's Disease criteria, and a Clinical Dementia Rating (CDR) score was formulated for each participant. Seven (21%) had no dementia (CDR score 0), and an additional 4 (12%) were assigned a CDR score of 0.5, uncertain or deferred diagnosis. The remaining 22 (64%) had at least some degree of dementia. The authors calculated Barthel Index scores to determine ability to perform activities of daily living. There was a statistically significant correlation between CDR scores and Barthel Index scores (r = -0.73). Correlation was strongest for those with no or severe dementia, with the greatest range of function measured among those with moderate dementia.

Activities of Daily Living↗

Validity of reported age and centenarian prevalence in New England.

INTRODUCTION: the age reported by or on behalf of centenarians may be suspect unless proven correct. We report the validity of age reports in a population-based sample of centenarians living in New England and the prevalence of centenarians in an area within the North Eastern USA. METHODS: cohort study. All centenarians in a population-based sample detected by local censuses. Ages were confirmed by birth certificate. Type of residence and whether the subject was living independently were also recorded. RESULTS: from a population of about 450,000 people, 289 potential centenarians were reported by the censuses of the eight towns participating in the study. Of these, 186 (64%) had died at the time centenarian prevalence was determined. Of the 80 still alive, 13 (16%) had incorrect birth years recorded by the censuses. The specificity of the censuses for stating the number of centenarians alive and living in the sample was 28-31%. Using additional sources, only four more centenarians were located, indicating that the sensitivity of the censuses approached 100%. We had an 83% success rate in obtaining proof of age in those families we interviewed. In all instances, age and birth order of children were an important source of corroborative evidence and in no case did we detect inconsistencies with the families' reported ages of the centenarian subjects. Therefore, there were at least 46 centenarians or approximately 1 centenarian per 10,000 people. CONCLUSIONS: age validation can be performed for most centenarians in the North Eastern USA. Self or family reports of those between the ages of 100 and 107 years were dependable.

Age Distribution↗

Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima indians.

The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala-->Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C-->T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 +/- 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium ( P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals >45 years of age were considered, heterozygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.

Adolescent↗

Patients' rights in England and the United States of America: The Patient's Charter and the New Jersey Patient Bill of Rights: a comparison.

The Patient's Charter has been in effect for nearly five years. This article considers the purpose and value of the document through a comparison with the New Jersey Patient Bill of Rights. Patient rights statements have been posted in American hospitals for more than twenty years. However, the New Jersey document and the patient rights programme it established seven years ago, have proven to be economically effective, successful in their representation of patients and enforceable, due to the adoption of state legislation and regulation to oversee the process. Several examples of how the programme works are included in the comparison, with a similar review of The Patient's Charter. In the comparison the author argues that for the programme to succeed as it has done in New Jersey, the government will need to develop legislative backing to ensure enforcement, and an efficient system for monitoring compliance. The programme will need to become credible in the eyes of the health service user. The author suggests this may be best achieved by developing an efficient, accessible and user-friendly means of redress, should the patient consider his or her rights have been violated. A "mish-mash" of quality assurance standards and levels of care which patients can "expect" from the health service providers only serves to distract the health service user from the government's failure to commit the resources that would empower the patients rights portion of The Patient's Charter.

Delivery of Health Care↗

Cells from Rana pipiens gastrulae and arrested hybrid gastrulae show differences in adhesion to fibronectin-sepharose beads.

Experiments were performed to examine adhesion of Rana pipiens gastrula cells and arrested hybrid gastrula cells to fibronectin-Sepharose beads (FN-beads). Blastula cells from both normal and hybrid embryos show poor adhesion to FN-beads. Beginning at the early gastrula stage, however, normal cells show a progressively increasing tendency to adhere to beads. In two different arrested hybrid embryos, cells from all developmental stages lack the ability to adhere to beads. A third hybrid shows an increase and then a decrease in cell-bead adhesion. A fourth hybrid shows a late increase in cell-bead adhesion in animal-half cells and no increase at all in vegetal-half cells. Blastula-stage cells have the ability to adhere to con A-beads and two kinds of Cytodex beads but will not adhere to FN-beads. Similarly, some cells from arrested hybrid embryos lack the ability to adhere to FN-beads but will adhere to con A-beads and cytodex beads. Observations in the light and scanning electron microscope show that normal cells form lamellipodia on FN-beads and move about actively on them, much like they do in vivo on surfaces coated by fibrils containing fibronectin. For adherent hybrid cells attached to beads, one kind does so by small pseudopodia but does not move on them and another kind forms active lamellipodia at the tips of fusiform cells and moves on beads.

Animals↗

Lentropin, a protein that controls lens fiber formation, is related functionally and immunologically to the insulin-like growth factors.

Lentropin, a factor present in the vitreous humor of the eye, stimulates lens fiber differentiation from chicken embryo lens epithelial cells in vitro. Lentropin has been partially purified but has not been isolated in sufficient quantity or purity for direct comparison with other growth and differentiation factors. Previous studies have shown that insulin and fetal bovine serum share with lentropin the ability to stimulate lens fiber formation from cultured epithelial cells. In the present study, a number of hormones and growth factors were assayed for lentropin activity. Of those tested, the only substances that had this activity were the insulin-like growth factors (IGFs) somatomedin C (Sm-C/IGF-I) and multiplication-stimulating activity (MSA/IGF-II). Sm-C/IGF-I was approximately 30 times more potent than insulin or MSA/IGF-II in promoting fiber cell formation. A monoclonal antibody to human Sm-C/IGF-I inhibited purified Sm-C/IGF-I, fetal bovine serum, and chicken vitreous humor from stimulating fiber cell differentiation in vitro. This antibody has been shown not to crossreact with insulin and did not block insulin-stimulated lens fiber formation. These findings indicate that lentropin is related to the IGFs and that these factors may play important roles in controlling cell differentiation, in addition to their better-known ability to stimulate cell division.

Animals↗

Cells from Xenopus laevis gastrulae adhere to fibronectin-sepharose beads and other lectin coated beads.

Cells from Xenopus laevis blastulae have a poorly developed ability to adhere to Sepharose beads covalently coupled to bovine plasma fibronectin (FN-beads). They do, however, have the ability to adhere to con A-beads and cytodex-1 and cytodex-3 beads. Beginning at the early gastrula stage, there is a progressively increasing ability of cells to adhere to FN-beads. Gastrula cells adhere to FN-beads by the formation of large ruffling lamellipodia. These cells can translocate on the surface of FN-beads; and when attached to both beads and the surrounding glass substratum of culture vessels, have the ability to move the beads extensively. Gastrula cells also have the ability to adhere to but not move upon con A-beads, wheat germ agglutinin-beads, and soy bean agglutinin-beads. They do not adhere significantly to Tetragonolobus purpureas agglutinin-beads. These results suggest that there are increasing numbers of fibronectin receptors present on the surface of embryonic amphibian cells during the period of gastrulation. They may explain the differential distribution of fibronectin-containing fibrils in vivo as observed by scanning electron microscopy.

Animals↗

Acute epiglottitis: evolution of management in the community hospital.

One hundred and forty-eight cases of acute epiglottitis in children treated at the University of Rochester's Strong Memorial Hospital and two affiliated community hospitals between 1965 and 1983 are reviewed retrospectively. Patients seen prior to 1975 were usually managed with tracheotomy and intravenous antibiotics, while those after 1975 with nasotracheal intubation, antibiotics and steroids. Tracheotomy and nasotracheal intubation were equally safe in controlling the upper airway. We compared our results with other series, primarily from children's hospitals, using nasotracheal intubation and found comparable results. Steroids provided no significant effect on the duration of intubation or infectious complications, but was associated with gastrointestinal bleeding. Long- and short-term complications of intubation, including self-extubation are discussed. We conclude that nasotracheal intubation is a safe method of management for acute epiglottitis in the community hospital.

Acute Disease↗

Epidermal growth factor stimulates type-V collagen synthesis in cultured murine palatal shelves.

The effects of epidermal growth factor (EGF) on the synthesis of collagen and fibronectin in murine palatal shelves in serum-free organ culture have been examined. Palatal shelves grown in the presence of EGF were substantially larger and showed dramatic increases in immunofluorescent localization of fibronectin, possibly reflecting increased synthesis compared to controls cultured without EGF. EGF also prevented the normal dissolution of the medial palatal epithelium. Net protein synthesis in experimental palatal shelves increased by 18%, whereas net collagen synthesis was approximately 10% of protein synthesis in both conditions. There was, however, an apparent shift in collagen isotypes. Under the influence of EGF, there was a significant increase in synthesis of the alpha 1 (V) and alpha 2 (V) chains of type-V collagen.

Animals↗

The isolation and partial characterization of chondronectin, an attachment factor for chondrocytes.

We have previously demonstrated that the adhesion of embryonic chick sternal chondrocytes to a type II-collagen substrate is not mediated by fibronectin but rather by a distinct attachment factor which we have named chondronectin. Here we describe the isolation, properties, and biological activity of chondronectin prepared from chicken serum. Chondronectin is shown to be a glycoprotein with an estimated Mr = 180,000. After reduction, it migrates as subunits of Mr = 70,000. Antibodies directed against chondronectin inhibited the attachment of chondrocytes to type II collagen. Chondronectin is immunologically distinct from either fibronectin or laminin. Immunofluorescence studies on frozen sections of embryonic chick sternal cartilage and of cultured sternal chondrocytes showed that chondronectin is cell-associated rather than a major matrix component.

Animals↗

Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. III. Immunostaining for laminin and its precursors.

Reichert's membrane and the endodermal cells of the parietal yolk sac were examined for the presence of laminin antigenicity using anti-laminin antibodies and the peroxidase-antiperoxidase sequence. Immunostaining was observed through the full width of Reichert's membrane and within endodermal cells. In these cells immunostaining was observed in rough endoplasmic reticulum (rER) cisternae and Golgi apparatus. The Golgi staining could occur in any saccule, but predominated in components interpreted as the last saccule of the stack, the GERL element, and associated prosecretory granules. The secretory granules found in the ectoplasm were also immunostained. Finally, multivesicular bodies showed some staining. The immunostaining of Reichert's membrane indicates the presence of laminin itself, while that of rER cisternae and the Golgi apparatus is attributed to laminin precursors. Presumably the biosynthesis of laminin occurs along the usual protein pathway, that is, from rER through Golgi saccules and the GERL element to secretory granules, which release their content into Reichert's membrane. The laminin immunostaining of Reichert's membrane and endodermal cells is similar to that of type IV collagen. It is, therefore, likely that the two substances are processed and secreted simultaneously.

Animals↗

The role of chondronectin and cartilage proteoglycan in the attachment of chondrocytes to collagen.

The interaction of cells with collagen has previously been demonstrated to be of importance in the growth and differentiation of various cells (reviewed by Hay 1981; Kleinman, et al 1981). Chondronectin has been demonstrated to be involved in mediating the interaction of chondrocytes with their matrix. Unlike fibronectin, which binds directly to collagen before the cell can interact with this macromolecular complex, chondronectin must interact with cartilage proteoglycan monomer in order to function efficiently as an attachment factor. Figure 4 is a schematic representation of the interaction between chondrocytes and their matrix components. We suggest that if these specific interactions are perturbed by the introduction of some outside factor, the phenotypic expression of the cells could be altered. For example, chondrocytes are not normally associated with fibronectin (Dessau, et al 1978; Stenman, Vaheri 1978). However, if chondrocytes are grown in the presence of fibronectin they will become more fibroblastic and stop making the cartilage-specific molecules of type II collagen and cartilage proteoglycan (Pennypacker, et al 1979; West et al 1979). Consequently, it is possible that the specific interactions seen between chondrocytes, chondronectin, type II collagen, and proteoglycan may be essential for the maintenance of the chondrocyte phenotype.

Animals↗

The cell binding fragment of fibronectin is chemotactic for fibroblasts.

The fibroblast chemoattractant property of fibronectin is retained in the proteolytically produced 160 kilodalton peptide that contains the heparin binding and cell binding domains of the molecule, while the 40 kilodalton collagen binding peptide is inactive. Further degradation of the 160 kilodalton peptide leads to destruction of chemoattractant activity. An analysis of the migration of fibroblasts in varied gradients of the 160 K peptide shows that the effect is chemotactic, i.e. directed migration of cells towards a higher concentration of the peptide.

Binding Sites↗

Distribution of fibronectin and collagen during mouse limb and palate development.

Indirect immunofluorescence has been used to study the distribution of fibronectin and collagen types I, II, and III in the developing primary and secondary palatal processes and forelimb buds of the Swiss Webster (NIH) mouse. In the palatal processes fibronectin and types I and III collagen are distributed throughout the mesenchyme. Fibronectin is present in the basement membrane, while types I and III collagen are localized in a linear, discontinuous fashion beneath the basement membrane. Fibronectin is not observed in the epithelium, including the presumptive fusion areas. In the forelimb bud these components show a similar distribution prior to chondrogenesis (early day 11). When chondrogenesis commences (late day 11 or early day 12) fibronectin and, to a lesser degree, types I and III collagen are apparently concentrated in the core mesenchyme, suggesting that fibronectin has a role in initiating chondrogenesis, perhaps by increasing cellular aggregation. Type II collagen is observed only in chondrogenic regions. The codistribution of fibronectin and types I and III collagen supports in vitro studies which indicate that cells use fibronectin to bind to collagen in the matrix. The developing chondrogenic regions appear to lose fibronectin gradually, concomitant with the appearance of type II collagen, suggesting that fibronectin is not involved in the maintenance of functional chondrocytes in their matrices.

Animals↗