PubMed Health⌕ Search

Biomedical subjects

M J Lysaght

Publications and source records attributed to M J Lysaght.

At least 19 recordsLinked to original sources
PubMed2005

Origin of insulin secreted from islet-like cell clusters derived from murine embryonic stem cells.

Islet-like cell clusters (ILCCs) were derived from murine embryonic stem cells using a slightly modified version of the protocol originally described by Lumelsky et al. in 2001. Analysis with enzyme-linked immunosorbent assays (ELISAs) that distinguish human from murine insulin demonstrated that insulin released from these ILCCs, upon initial in vitro glucose challenge, was of non-murine origin and in fact corresponded to the species of insulin, human or bovine, that had been added to the culture media used to derive ILCCs. This finding convincingly supports the hypothesis that ILCCs are not synthesizing insulin de novo, but rather simply regurgitating insulin taken up during tissue culture. In further experiments, ILCCs were derived in media in which insulin had been replaced by IGF-I with which it shares a common signaling pathway. These ILCCs failed to release any detectable insulin. In contrast, ILCCs produced by various protocols stained positive (dithizone and immunoselective antibodies) for intracellular insulin and, in some cases, C-peptide. Despite the presence of at least some level of de novo, synthesized insulin in ILCCs, the majority of insulin released by ILCCs was sequestered from the exogenous medium.

Animals↗
PubMed2001

The growth of tissue engineering.

This report draws upon data from a variety of sources to estimate the size, scope, and growth rate of the contemporary tissue engineering enterprise. At the beginning of 2001, tissue engineering research and development was being pursued by 3,300 scientists and support staff in more than 70 startup companies or business units with a combined annual expenditure of over $600 million. Spending by tissue engineering firms has been growing at a compound annual rate of 16%, and the aggregate investment since 1990 now exceeds $3.5 billion. At the beginning of 2001, the net capital value of the 16 publicly traded tissue engineering startups had reached $2.6 billion. Firms focusing on structural applications (skin, cartilage, bone, cardiac prosthesis, and the like) comprise the fastest growing segment. In contrast, efforts in biohybrid organs and other metabolic applications have contracted over the past few years. The number of companies involved in stem cells and regenerative medicine is rapidly increasing, and this area represents the most likely nidus of future growth for tissue engineering. A notable recent trend has been the emergence of a strong commercial activity in tissue engineering outside the United States, with at least 16 European or Australian companies (22% of total) now active.

Artificial Organs↗
PubMed1999

Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis.

Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. Significant changes in extracorporeal membranes have occurred over the past five decades in which hemodialysis (HD) has been available as a therapy for both acute renal failure (ARF) and end-stage renal disease (ESRD). For cellulosic membranes, these changes have included a reduction in thickness, hydroxyl group substitution, and an increase in pore size. These modifications have resulted in enhanced efficiency of small solute removal, a broader spectrum of overall solute removal, and an attenuation of complement activation in comparison to the thick, unsubstituted cellulosic membranes of low permeability used in the early days of HD therapy. Synthetic membranes, originally developed specifically for use in high-flux HD and hemofiltration, have also evolved during this same time period. In fact, the initially clear distinction between low-flux regenerated cellulosic and high-flux synthetic membranes has become blurred, as membrane formulators have developed products designed to appeal to enthusiasts for both membrane formats. The purpose of this review is to characterize both the solute removal and biocompatibility characteristics of dialysis membranes according to their composition (that is, polymeric makeup) and structure. In this regard, the manner in which membrane biocompatibility interacts with flux is highlighted.

Biocompatible Materials↗
PubMed1998

An economic survey of the emerging tissue engineering industry.

The contemporary scope of worldwide tissue engineering research and development was estimated by totaling the relevant annual spending and other economic parameters of firms involved the field. Operating expenses allocated to tissue engineering in 1997 exceed $450 million and fund the activities of nearly 2,500 scientists and support personnel. Growth rate is 22.5% per annum. Most activity is centered in the United States. Government spending in this field represents <10% of the total. The aggregate capital value of start-ups that have gone public was approximately $1.7 billion as of January 1, 1998; total capital value of all firms and business units in the field was estimated to be roughly $3.5 billion. The level of investment and valuation represents a remarkable act of faith in the future of a technology yet to produce its first significant revenue-generating product.

Artificial Organs↗
PubMed1996

Transport characterization of membranes for immunoisolation.

This study relates to the diffusive transport characterization of hollow fibre membranes used in implantable bio-hybrid organs and other immunoisolatory devices. Techniques were developed to accurately determine the mass transfer coefficients for diffusing species in the 10(2)-10(5) MW range, validated and then used to study one membrane type known to effectively immunoisolate both allografts and xenografts in vivo. Low-molecular-weight diffusing markers included glucose, vitamin B12 and cytochrome C; higher-molecular-weight molecules were bovine serum albumin, immunoglobulin G, apoferritin and a range of fluorescein-tagged dextrans. Overall and fractional mass transfer coefficients through the hollow fibres were determined using a resistance-in-series model for transport. A flowing dialysis-type apparatus was used for the small-molecular-weight diffusants, whereas a static diffusion chamber was used for large-molecular-weight markers. For diffusion measurements of small-molecular-weight solutes, convective artefacts were minimized and the effect of boundary layers on both sides of the membrane were accounted for in the model. In measuring diffusion coefficients of large-molecular-weight species, boundary layer effects were shown to be negligible. Results showed that for small-molecular-weight species (< 13,000 MW) the diffusion coefficient in the membrane was reduced relative to diffusion in water by two to four times. The diffusion rate of large-molecular-weight species was hindered by several thousand-fold over their rate of diffusion in water.

Animals↗
PubMed1996

Plasma therapy at Klinikum Grosshadern: a 15-year retrospective.

Immediately after the availability of highly permeable membranes in 1979, membrane plasma separation was introduced as a mode of extracorporeal blood purification by the nephrology group at Klinikum Grosshadern of the Ludwig Maximilians University of Munich (F.R.G.). The new therapy was applied primarily in the management of immunologically mediated renal and extrarenal disorders as well as in paraproteinemias. We also have witnessed a widespread application of this extracorporeal treatment as a last resort in otherwise refractory clinical conditions. Over the years, the group at Grosshadern has contributed to the development, as well as to the laboratory and clinical testing, of new plasma separation membranes, simplified plasmapheresis formats (e.g., spontaneous membrane plasma separation), and several plasma fractionation procedures (e.g., cascade filtration, adsorption). Whenever indicated and possible, plasma fractionation procedures, rather than unselective plasma exchange, are performed in an appropriate clinical situation.

Chemical Fractionation↗
PubMed1994

Recent progress in immunoisolated cell therapy.

Biohybrid implants represent a new class of medical device in which living cells, supported in a hydrogel matrix, and surrounded by a semipermiable membrane, produce and deliver therapeutic reagents to specific sites within a host. First proposed in the mid-1970s for diabetes, this treatment modality has progressed rapidly in the past four years and is now being investigated not just for endocrine disorders but also for alleviation of chronic pain, treatment of neurodegenerative disorders, and delivery of neurotrophic factors to sites within the blood brain barrier, and as a practical alternative to conventional ex vivo.

Alzheimer Disease↗
PubMed1991

Kinetic modeling as a prescription aid in peritoneal dialysis.

Methods for calculating fluid and mass removal in peritoneal dialysis are presented in order to aid clinicians in their care and management of patients and to assist them in their understanding of the physiological mechanisms which govern peritoneal transport. These methods are based on the Pyle-Popovich peritoneal mass transport model which encompasses both diffuse and convective transport as well as lymphatic flow and residual renal function. Algebraic solutions to the mass balance equations governing solute transport are provided. Since these solutions are expressed explicitly as functions of time, they are easily programmed for use on a personal computer or calculator. This offers considerable advantage over the more computer-intensive numerical solutions which had been previously required since one can now calculate both mass removal and changes in blood concentration at the end of an exchange without requiring any intermediate calculations. This computational advantage and the ability to model changes in blood concentration are shown to be of particular importance when modeling more dynamic therapies such as CCPD or Tidal peritoneal dialysis. Finally, the model and solutions, when assessed clinically among 5 patients on two separate occasions, resulted in predicted fluid and mass removals which were in high concordance with measured fluid and mass removals (concordance correlation coefficients in excess of 0.97). Our findings suggest that kinetic modeling can provide the kind of analytical tools necessary to guide clinicians in their care and management of peritoneal dialysis patients.

Algorithms↗
PubMed1989

The role of lymphatic drainage in peritoneal mass transfer.

Peritoneal lymphatic drainage has recently been shown to be a contributing factor to both clearance and fluid removal patterns during continuous ambulatory peritoneal dialysis. In this report peritoneal transport equations are derived and compared and contrasted with existing models that ignore this term. It was found that for solutes for which the sieving coefficient may be assumed to equal unity, such as urea and creatinine, the values of the mass transfer area coefficient (KoA) are overestimated by the value of the lymphatic drainage rate. In this instance, corrected KoA may be obtained simply by subtracting lymphatic flow rate from the KoA calculated by traditional methods. For larger solutes, such as beta 2-microglobulin, for which the sieving coefficient may be assumed to equal zero, the value of mass transfer coefficient was underestimated to varying degrees; however, for values of lymphatic drainage rate less than 60 ml/h the effect will not be clinically measurable. A theoretical model is used to plot the dependence of net fluid removal on peritoneal lymphatic flow, glucose KoA, and hydraulic permeability. Reduction in net ultrafiltered volume, and hence estimation of transperitoneal ultrafiltration, is directly proportional to accumulated lymphatic drainage.

Creatinine↗
PubMed1989

Mixed-mode therapy: kinetic analysis and acute clinical evaluation.

A mixed therapeutic modality was devised in which patients with chronic renal failure were treated with a combination of continuous ambulatory peritoneal dialysis (CAPD; two daily 4-hour exchanges per day; 16 h dry belly) and hemodialysis (1 session per week). Kinetic modeling analysis indicated that a time-averaged urea concentration equivalent to CAPD could be obtained with a Kt/V value of 1.2-1.6, depending on patient parameters, for the single-weekly hemodialysis. The therapy format was acutely evaluated in a 2-week clinical trial on 4 patients. Excursions in small-solute concentration were virtually equivalent to those predicted from theory. Adequate fluid removal was obtained in the 2 CAPD exchanges and blood pressure was well controlled. As a result of the success of the acute trials, and since this format may offer potential lifestyle advantages to patients who possess dual access, a chronic trial of mixed-mode therapy seems advised.

Aged↗
PubMed1989

Beta-2 microglobulin removal during continuous ambulatory peritoneal dialysis (CAPD).

Beta-2 microglobulin (B2M) handling in continuous ambulatory peritoneal dialysis (CAPD) was characterized in acute and chronic clinical studies. Average clearance rate was 0.7 mL/min and mean mass transfer coefficient, KoA, was calculated to be 0.95 cm2/min; these values are in the range expected from extrapolation of published data for other large solutes. In chronic studies with both anuric and oliguric populations, CAPD was shown to be much more effective than conventional hemodialysis in removing B2M and, in fact, CAPD removal rates were equivalent to those reported for high flux dialysis therapies. However, this greater extraction was not associated with any clinically significant reduction in circulating plasma concentrations. These trends remained valid in both the anuric and oliguric subsets of the study population.

Dialysis Solutions↗
PubMed1988

Evolution of transport theory in CAPD.

Current mathematical approaches describing solute and mass transfer during CAPD are based on a compartmental model, assuming the body and the peritoneal cavity to be different compartments and the peritoneal membrane to be a more or less complicated interface. Whereas simplified mathematical approaches may prove useful for routine clinical determination of mass transfer characteristics, more complex models may better serve developmental and theoretical purposes.

Biological Transport↗