The Application of Recombinant Human Collagen in Tissue Engineering

Collagen is the main structural protein in vertebrates. It plays an essential role in providing a scaffold for cellular support and thereby affecting cell attachment, migration, proliferation, differentiation, and survival. As such, it also plays an important role in numerous approaches to the engineering of human tissues for medical applications related to tissue, bone, and skin repair and reconstruction. Currently, the collagen used in tissue engineering applications is derived from animal tissues, creating concerns related to the quality, purity, and predictability of its performance. It also carries the risk of transmission of infectious agents and precipitating immunological reactions. The recent development of recombinant sources of human collagen provides a reliable, predictable and chemically defined source of purified human collagens that is free of animal components. The triple-helical collagens made by recombinant technology have the same amino acid sequence as human tissue-derived collagen. Furthermore, by achieving the equivalent extent of proline hydroxylation via coexpression of genes encoding prolyl hydroxylase with the collagen genes, one can produce collagens with a similar degree of stability as naturally occurring material. The recombinant production process of collagen involves the generation of single triple-helical molecules that are then used to construct more complex three-dimensional structures. If one loosely defines tissue engineering as the use of a biocompatible scaffold combined with a biologically active agent (be it a gene or gene construct, growth factor or other biologically active agent) to induce tissue regeneration, then the production of recombinant human collagen enables the engineering of human tissue based on a human matrix or scaffold. Recombinant human collagens are an efficient scaffold for bone repair when combined with a recombinant bone morphogenetic protein in a porous, sponge-like format, and when presented as a membrane, sponge or gel can serve as a basis for the engineering of skin, cartilage and periodontal ligament, depending on the specific requirements of the chosen application.     

Prognostic factors in well-differentiated thyroid carcinoma

OBJECTIVES: To test the prognostic significance of standard clinicopathologic factors in patients with well-differentiated thyroid carcinoma (WDTC). STUDY DESIGN: A retrospective chart review of the thyroid cancer database at Mount Sinai Hospital (Toronto, Canada 1963-2000) was carried out. METHODS: All patients consecutively treated for WDTC with a follow-up period of at least 5 years were eligible for inclusion. Relevant patient, tumor, treatment, and outcome data were collected. The main outcome measures were recurrence rate, actuarial overall, and disease-specific survival at 20 years. RESULTS: Three hundred and thirty-three patients (F 275, M 58) with a median age of 39.7 (range 9-82.9) years were eligible for inclusion in this study (median follow-up 10.4 years, range 5-34.4 years, minimum 5 years). The recurrence rate was 15.6% (52 /333). The overall and disease-specific survival at 10 years was 97.5% and 98.5%, respectively. Likewise, the overall and disease-specific survival at 20 years was 88.4% and 93.3%, respectively. Clinicopathologic factors significant on multivariate regression for the development of disease recurrence included family history of WDTC, advanced stage, and total thyroidectomy (all P < .05). Similarly, advanced stage on presentation was associated with a worse disease-specific survival on multivariate regression (all P < .05). There was a trend for age 60 or greater to predict disease-specific survival (P = .09). CONCLUSIONS: WDTC is associated with a significant recurrence rate but good disease-specific survival. The most important prognostic factors are family history of WDTC, extent of surgical treatment (i.e., total thyroidectomy), and advanced initial stage of disease, with a trend for age 60 years and older.     

Serum CA 125 combined with transvaginal ultrasonography for ovarian cancer screening

BACKGROUND: The aim of this study was to evaluate the combination of serum CA125 and Transvaginal Ultra Sonography (TVUS) score, as a screening procedure for ovarian cancer in premenopausal and postmenopausal women. PATIENTS AND METHODS: A retrospective case-control pilot study was conducted. The files of 120 women with ovarian neoplasia detected by TVUS and increased CA125 level, within the framework of a prevention program, were reviewed. The relationship between the above tests and epithelial malignancy was investigated using the SPSS-12 program for Windows. RESULTS: The combination of CA125 value exceeding 30U/ml and a TVUS score > or = 35 had a sensitivity of 81.7% and specificity of 100% in predicting ovarian cancer. Mathematical analysis of the logistic model of our variables revealed a mathematical model that can calculate the likelihood of ovarian cancer detection, by using a combination of CA125 > or = 30U/ml and TVUS score > or = 35. CONCLUSION: By combining TVUS and CA125, an accurate prediction for the presence of ovarian cancer may be achieved. Further investigation in a larger population is warranted.     

Synthesis,physicochemical investigation and cytotoxic activity of new Pt(II) complexes with hydantoin ligands

The interaction of cis-dichlorodiaminplatinum(II) (cis-DDP) with 2,4-imidazolidenedione-5-methyl-5-phenyl was studied. The method of preparation of the new Pt(II) complex consisted in precipitation of chloride ions from cis-DDP via a diaqua complex and reaction with the ligand in water-organic media. On the basis of IR spectra, (1)H- and (13)C-NMR analysis the coordination mode of the ligand and most fitting structures of two isomeric complexes were proposed. The pharmacological investigations revealed that the new Pt(II) complex with 5-methyl-5-phenylhydantoin (PtMPH) as well as the previously described Pt(II) complexes with cyclopentanespiro-5'-hydantoin and cyclohexanespiro-5'-hydantoin (PtCHH) exerted concentration-dependent cytotoxic effect in a panel of human tumor cell lines. On the basis of the IC(50) values obtained PtMPH proved to be the most active cytotoxic agent. The other investigated complexes were less active, and among them PtCHH was the least potent antineoplastic agent. The pharmacodynamic investigation of PtMPH showed that this compound induces programmed cell death (apoptosis), as evidenced by the detection of oligonucleosomal DNA fragmentation in HL-60 cells after treatment with PtMPH.     

Lead exposure biomarkers and mini-mental status exam scores in older men

BACKGROUND: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. METHODS: Lead exposure biomarkers and Mini-Mental Status Exam (MMSE) scores were measured among subjects in the Normative Aging Study. Multiple linear and logistic regression analyses were performed to examine the cross-sectional association of these 2 variables. RESULTS: We found an odds ratio (OR) of 2.1 for MMSE <24 with an increase from the lowest to the highest quartile of patella lead levels (95% confidence interval [CI] = 1.1 to 4.1). From the lowest to the highest quartile of blood lead the OR for low MMSE was 3.4 (CI = 1.6 to 6.2). There was an interaction between lead biomarkers and age. Among subjects in the lowest quartile of patella lead levels, MMSE score decreased by 0.03 points per year (CI = -0.07 to 0.005), whereas in the highest quartile, MMSE score decreased by 0.13 points per year (CI = -0.19 to -0.07). Similar interactions were found between blood lead levels and age. CONCLUSIONS: Increased levels of lead in bone and blood are inversely associated with cognitive performance among older men. Lead exposure might accelerate age-associated cognitive decline.     

Relationship of bone and blood lead levels to psychiatric symptoms: the normative aging study

Blood and bone lead levels were used to investigate lead's potential effect on psychiatric symptoms among middle-aged to elderly men from the Normative Aging Study. Symptoms were assessed using the Brief Symptom Inventory (BSI) and analyzed as individual outcomes as well as a measure that combined anxiety, depression, and phobic anxiety. Blood and bone lead averaged 6.3 microg/dL (standard deviation [SD] = 4.16), 21.9 microg/g (SD = 13.5), and 32.1 microg/g (SD = 19.8) for blood, tibia, and patella lead, respectively. In logistic regression models that adjusted for age, alcohol intake, employment status, and education status, we found that patella bone lead was significantly associated with an increased risk of phobic anxiety and the combined outcome measure at the P 相似文献