Biomedical subjects
Publications and source records attributed to Z Wu.
A highly efficient and versatile solid-phase synthesis of 2,4-diaminoquinazoline library from 2,4-dichloroquinazolines and amines using 3,5-dimethoxy 4-formylphenoxy-polystyrene resin is described.
Pancreatic islets were encapsulated with sodium alginate-polylysine after procurement by collagenase digestion and Ficoll density-gradient-dispersion. The encapsulated islets were intact and during the first week of culture produced insulin 63 +/- 42 microU/d vs 69 +/- 42 microU/d by noncapsulated islets. Seven streptozotocin-induced diabetic rats each received 4.0-4.5 x 10(3) microencapsulated islets intraperitoneally. After transplantation, blood glucose dropped from 350 +/- 29 mg/dl to 142 +/- 12 mg/dl. To date, normoglycemia has been maintained for 222 days. Control animals either died or developed cataracts.
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Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) with different functional end groups, namely carboxyl, methyl ester, hydrazide, and amino groups, were prepared by chain transfer free-radical polymerization. 2,2'-Azobisisobutyronitrile (AIBN) was used as an initiator and 3-mercaptopropionic acid, methyl 3-mercaptopropionate, 3-mercaptopropionic hydrazide, and 2-mercaptoethylamine were used as chain-transfer agents. The semitelechelic polymers have been characterized by end-group analysis, size-exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The effects of the concentrations of the mercaptans and the initiator on the molecular weight of the polymers have been investigated. The higher the concentration of mercaptan, the lower the molecular weight of ST-PHPMA. The concentration of initiator did not have a significant effect on the molecular weight of the semitelechelic polymers. The end groups of the ST polymers can be readily transformed by polymeranalogous reactions. A model protein, alpha-chymotrypsin, has been modified with ST-PHPMA-CONHNH2 and ST-PHPMA-COOSu and the conjugates characterized by MALDI-TOF MS. The activity of modified chymotrypsins toward a high molecular weight substrate, P-Gly-Leu-Phe-NAp (where P is the HPMA copolymer backbone, and NAp is p-nitroanilide), was slightly lower than the activity of the native enzyme. The cleavage of a low molecular weight substrate, Z-Gly-Leu-Phe-NAp, by modified chymotrypsins was dependent on their structure. Whereas the activity of the amino group modified chymotrypsins was higher than that of the native enzyme, the activity of carboxyl-modified chymotrypsins was lower than that of the native enzyme. In summary, the data seem to indicate that ST-PHPMA is an effective protein-modifying agent.
Using data from the 1995 Canadian General Society Survey (GSS-95), we study the intention to have a third child among a sample of women and men who have already had two children (N = 505). Our results show that 15 per cent of the respondents intend to have a third child. Nearly 20 per cent of the respondents are uncertain about their fertility intentions. We found that the same factors that predict intentions also predict uncertainty, and that the effects of these predictors are remarkably similar. In particular, intentions and uncertainty generally decline with age, but increase with regular church attendance, remarriage, and being Catholic. Unlike earlier studies, we found that the sex of previous children has virtually no impact on third-birth intentions or uncertainty.
Nimbus Inc. (Rancho Cordova, CA) and the University of Pittsburgh have completed the second year of development of a totally implanted axial flow blood pump under the National Institutes of Health Innovative Ventricular Assist System Program. The focus this year has been on completing pump hydraulic development and addressing the development of the other key system components. Having demonstrated satisfactory pump hydraulic and biocompatibility performance, pump development has focused on design features that improve pump manufacturability. A controller featuring full redundancy has been designed and is in the breadboard test phase. Initial printed circuit layout of this circuit has shown it to be appropriately sized at 5 x 6 cm to be compatible with implantation. A completely implantable system requires the use of a transcutaneous energy transformer system (TETS) and a diagnostic telemetry system. The TETS power circuitry has been redesigned incorporating an improved, more reliable operating topography. A telemetry circuit is undergoing characterization testing. Closed loop speed control algorithms are being tested in vitro and in vivo with good success. Eleven in vivo tests were conducted with durations from 1 to 195 days. Endurance pumps have passed the 6 month interval with minimal bearing wear. All aspects of the program continue to function under formal quality assurance.
Triggered by the Olympic games in Sydney last year, many articles in the press suggested that recombinant human growth hormone (hGH) is one of the most popular performance enhancing drugs used by athletes. However, any hard facts on hGH abuse were provided by Australian customs officers--and not by laboratory assessment. The lack of an official test for hGH doping together with the widespread rumours on its tremendous beneficial effects seem to make this compound attractive for athletes. From a scientific point of view, there are two major questions about this issue: First, as there is no controlled study demonstrating a profound effect of hGH administration on workload capacity in healthy adults, why do athletes use hGH? Second, how could the application of a substance naturally occurring in the human body be detected? Both aspects are discussed in this article.
CONTEXT: In every country, contraceptive behavior has important implications for fertility and the prevalence of sexually transmitted diseases (STDs). There has been relatively little attention to contraceptive practices in Canada, however, particularly how patterns of method use may have changed. METHODS: Data on contraceptive use were collected from 5,315 women in the 1984 Canadian Fertility Survey, and from 3,220 women and 3,449 men in the 1995 General Social Survey. RESULTS: Among Canadian women aged 15-49, current contraceptive use declined from 69% to 60% between 1984 and 1995. Pill use dropped from 19% to 17%, and IUD use declined from 6% to 3%. However, during the same period, condom use increased from 6% to 10%; tubal ligation declined from 24% to 17%, while vasectomy increased. In addition, the proportion of women sterilized for reasons other than contraception rose between 1984 and 1995. Men were less likely to rely on sterilization than were women (31 % vs. 40%). Men reported higher levels of condom use (22%), but lower levels of pill use among their partners (9%), than did women (10% and 17%, respectively). CONCLUSIONS: Contraceptive behavior in Canada is unique: The decline in contraceptive use over the last decade has left Canada's overall contraceptive prevalence among the lowest in the industrialized world, and the rate of sterilization among the highest These changes in contraceptive behavior complicate efforts to plan for social and health needs, particularly policy decisions focusing on reducing infections with STDs.
This study provides a much-needed exploration of the determinants of age-discrepant unions in Canada. What little research has been conducted in this area of sociology of the family is now outdated. Further, the growing number of Canadians living in nonmarital cohabitation warrants their inclusion in any consideration of contemporary, heterosexual unions, and we have done so here. Utilizing multinomial logit modeling techniques, we analyze data drawn from the 1995 Canadian General Social Survey. We find that cohabitations and remarriages are more likely to be age-discrepant than marriages, and that as age at union formation increases, so does the likelihood that the union will be age-heterogamous. Although we hypothesized a positive relationship between education and the chances of age-heterogamous unions because the availability of eligible mates may decrease with education, we actually find an inverse association for women: a one-level increase in education decreases a woman's odds of entering an age-discrepant union by about 4 percent. We speculate that for women, greater education (economic position) may increase age-homogamy because they may be more economically attractive and thus more able to select a partner of their own age.
Biologically relevant interleukin-2 receptors (IL-2Rs) are present in two affinity states on responsive cells. High affinity receptors (HAR) apparently exist as heterotrimers (alpha, beta and gamma) while the other functional complex, the intermediate affinity receptor (IAR), is comprised of beta and gamma chains. The mechanisms by which the beta and gamma subunits contribute the formation of HAR and IAR are still unclear. Soluble forms of the beta and gamma chains were cloned, epitope-tagged, expressed in insect cells and purified. IL-2 binding and neutralization of IL-2 bioactivity by beta and gamma extracellular domains (ectodomains) was analyzed by several biochemical and biological approaches. The results indicate that beta clearly binds IL-2 with low affinity (KI-KD = 3 microM) whereas gamma binding is detectable, but of very low affinity (apparent KI > 15 microM) in the absence of beta. Interestingly, combinations of beta and gamma ectodomains interact to bind IL-2 with higher affinity and greater stability than either chain alone. An apparent stable binding complex is formed when beta, gamma, and IL-2 are combined. Ligand binding by the beta and gamma chains in solution is specific for IL-2 and is of sufficient affinity and stability to effectively neutralize IL-2 in biological assays (binding IC50 = biological IC50). Direct analyses of binding kinetics by surface plasmon resonance reveals that the increased affinity and biological neutralizing ability of beta gamma, as compared to beta, is due to a very slow dissociation rate contributed by the gamma ectodomain. While IL-2R beta and gamma cytoplasmic and transmembrane domains are not essential for interactive binding of IL-2, they may contribute to IL2 binding affinity. The recognition and association of IL-2 by the beta gamma IAR appears to be contributed primarily by the beta chain while the stability and dissociation is likely dominated by the gamma chain. It is anticipated that the gamma subunit functions in a similar manner when participating in high affinity IL-4 and IL-7 binding.
Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.
An axial-flow ventricular assist device (VAD) under development at the authors' facility is intended for use as a long-term implantable device. At high speeds axial-flow VADs can collapse the native ventricle and damage the heart muscle, lung tissue, and blood. A prototype algorithm was developed to maintain physiologic perfusion to the vital organs while preventing ventricular collapse, through analysis of the electrical current waveform of the motor. The premise of the control algorithm is that the hemodynamics of the patient are reflected in the shape of this waveform. This approach is intended to eliminate the need for invasive sensors, thus effectively using the pump itself as a transducer. The control algorithm regulates the speed of the pump by comparing the motor-current waveform with reference waveforms using a matched filter. The matched filter was evaluated by its classification and differentiation performance. Thus far, the authors have been able to classify the waveforms into one of the four physiologic regions (below, within, or above the optimal range, and ventricular suction) with over 90% reliability. Ongoing work is directed toward improving the detection of ventricular suction, as this condition must be strictly avoided.