Biomedical subjects

A Dardik

Publications and source records attributed to A Dardik.

7 recordsLinked to original sources

PubMed1992

Changes in cAMP phosphodiesterase activity and cAMP concentration during mouse preimplantation development.

Cyclic nucleotide phosphodiesterase (PDE) activity and cAMP amounts were measured in mouse preimplantation embryos at the 1-cell, 2-cell, 8-cell/morula, and mid-blastocyst stages. PDE activity remained constant between the 1-cell and 2-cell stages. It decreased by the 8-cell stage and continued to decrease by the mid blastocyst stage to about 14% of the 1- and 2-cell values. By contrast, cAMP amounts remained essentially constant at 0.05 fmole/embryo (0.3 microM) from the 1-cell to the blastocyst stage and increased to 0.175 fmole in the fully expanded blastocyst that was close to hatching. Measurements of embryo volume indicated that intracellular volume remained essentially constant up to the blastocyst stage. The morphological changes in cell shape that accompany differentiation of the trophectoderm and that are coupled with blastocoel expansion decreased the intracellular volume. This decrease resulted in an increase in the cAMP concentration to about 0.4 microM by the mid-blastocyst stage. Previous studies indicate that either cAMP or TGF-alpha/EGF can stimulate the rate of blastocoel expansion. Although TGF-alpha/EGF can elevate cAMP levels in other cell types, TGF-alpha, at a concentration that maximally stimulates the rate of blastocoel expansion, did not elevate cAMP in blastocysts. Thus, it was unlikely that elevation of cAMP is the mechanism by which TGF-alpha stimulates the rate of blastocoel expansion.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Colocalization of transforming growth factor-alpha and a functional epidermal growth factor receptor (EGFR) to the inner cell mass and preferential localization of the EGFR on the basolateral surface of the trophectoderm in the mouse blastocyst.

Results of previous studies suggested that responses of mouse blastocysts to TGF-alpha/EGF treatment are mediated by EGF receptors (EGFR) located on the apical surface of the trophectoderm (TE). We report here results of experiments using gold-labeled EGF that confirm the presence of these apically located EGFRs. In addition, immunoelectron microscopy (IEM) studies using anti-EGFR antibodies indicate that the receptor is preferentially distributed on the basolateral surface of the TE. Furthermore, the receptor is also present on the inner cell mass (ICM) and is likely to be functional, since treatment of isolated ICMs with TGF-alpha affects [35S]methionine uptake and incorporation into acid-insoluble material. IEM was also used to demonstrate that EGF, which is not synthesized by the mouse preimplantation embryo, is present in both the oviduct and the uterus. Maternally derived EGF is present in both ICM and TE cells in freshly isolated blastocysts, but is present in greatly reduced amounts following overnight culture of blastocysts in vitro. Last, IEM was also used to demonstrate that TGF-alpha is preferentially localized to the ICM and polar TE. The co-localization of TGF-alpha and functional EGFRs to the ICM and polar TE suggests potential autocrine, juxtacrine, and paracrine roles for TGF-alpha in blastocyst development.

Amino Acids↗

PubMed1991

Protein secretion by the mouse blastocyst: differences in the polypeptide composition secreted into the blastocoel and medium.

To initiate studies on the protein microenvironment of the mouse blastocoel, we examined the electrophoretic profile of newly synthesized proteins secreted into the blastocoel, as well as those secreted into the medium. Although most polypeptides reveal no relative enrichment, some proteins (e.g., proteins of Mr = 155,000 and 33,000) are enriched in the blastocoel relative to those secreted apically into the medium. In addition, some proteins (e.g., proteins of Mr = 102,000 and 40,000) are enriched in the medium relative to the blastocoel. The relative amount of newly synthesized protein secreted into the blastocoel is about 2.5% of total protein synthesis. In addition, the trophectoderm and inner cell mass contribute to these proteins. Results of these studies suggest a potential function for these blastocoel-enriched proteins in inner cell mass development.

Animals↗

PubMed1991

Blastocoel expansion in the preimplantation mouse embryo: stimulatory effect of TGF-alpha and EGF.

The factors that promote blastocoel expansion in the preimplantation mouse embryo are not well understood. Since cAMP stimulates the rate of blastocoel expansion and, in other systems, EGF can elevate intracellular cAMP levels, we investigated the ability of either TGF-alpha or EGF to stimulate the rate of blastocoel expansion in the mouse. Picomolar concentrations of either TGF-alpha or EGF stimulate the rate of blastocoel expansion in a concentration-dependent manner, and the continual presence of the growth factor is required to observe the stimulatory effect. Neutralizing antibodies to either TGF-alpha or EGF inhibit the TGF-alpha or EGF stimulatory effect, respectively. An antibody to the extracellular domain of the EGF receptor stimulates the rate of blastocoel expansion in a concentration-dependent manner, whereas an antibody to the cytoplasmic domain of the receptor does not. Tyrphostin RG 50864, which inhibits the EGF receptor kinase activity, inhibits the TGF-alpha stimulation of the rate of blastocoel expansion in a concentration-dependent manner; the less active tyrphostin, RG 50862, has no inhibitory effect. In addition, TGF-alpha does not stimulate a precocious onset of cavitation. The stimulatory effect on the rate of blastocoel expansion elicited by TGF-alpha or EGF is observed in 70% of the embryos (responders). Responders and nonresponders have similar intracellular ATP levels and cell numbers. Whereas TGF-alpha stimulates the uptake of [35S]methionine into the acid-soluble and acid-insoluble pools in the responders, TGF-alpha has no stimulatory effect in the nonresponders. Results of these experiments suggest that an initial differentiative function of the first mammalian epithelium--fluid transport--is sensitive to peptide growth factor modulation.

Animals↗

PubMed1991

Infrapopliteal prosthetic graft patency by use of the distal adjunctive arteriovenous fistula.

From November 1979 through December 1989, 210 distal arteriovenous fistulas were constructed as adjuncts to tibial and peroneal vascular reconstructive procedures in 203 patients threatened with limb loss. Two-year cumulative patency rates were calculated by grouping patients on the basis of changing indications in sequential time periods: group 1 (n = 61): 1979 to 1983, 18%; group 2 (n = 80): 1983 to 1986, 33%; group 3 (n = 69): 1986 to 1989, 44%. Although the therapeutic results observed in these groups are not statistically comparable, they show a perceptible trend. Postoperative arteriography showed that flow is prograde in the distal vessels beyond the distal arteriovenous fistula. Graft surveillance by duplex ultrasonography also confirmed that flow in the distal arteries is prograde and that "steal" does not occur. Peak systolic velocity (174 +/- 38 cm/sec) and mean velocity (92 +/- 23) flow rates are increased in grafts with patent distal arteriovenous fistulas compared to those bypasses with closed distal arteriovenous fistulas (p less than 0.01). There were no differences in the flow measurements for the arteries beyond the distal anastomoses and distal arteriovenous fistulas, confirming the prograde nature of the distal flow. In 22 patients analysis of graft and fistula patency by duplex sonography showed that one fourth of all grafts were patent without fistulas at 1 and 2 years after operation. Alternatively, 68% of patent grafts at 1 year had patent fistulas and 58% had patent fistulas at 2 years. We conclude that the distal arteriovenous fistula will increase graft flow and simultaneously prevent distal arterial overload without causing "steal." This technique should be considered whenever a prosthetic graft is necessary for crural reconstruction and only in selected instances of revascularization with autologous veins.

Adult↗

PubMed1988

A decade of experience with the glutaraldehyde-tanned human umbilical cord vein graft for revascularization of the lower limb.

Between October 1975 and November 1985, 907 lower limb bypasses were constructed in 715 patients (799 limbs) with glutaraldehyde-stabilized umbilical veins (UV-G) used as the predominant, or sole, graft material. Each reconstruction was classified in one of eight categories depending on the site of the distal anastomosis: above- and below-knee popliteal, anterior and posterior tibial, peroneal, trifurcation, sequential, and crural (tibial or peroneal) bypasses with adjunctive distal arteriovenous fistulas. Primary and secondary cumulative graft patency rates were determined for each category as well as cumulative actual palliation that combines end points of graft failure, amputation, and death. Half-life patencies for popliteal, tibial, and peroneal bypasses were 6.5, 2.3, and 1.7 years, respectively. Perioperative graft thrombosis occurred in 11% of popliteal reconstructions compared with 22% for the crural group. Nonocclusive graft failure caused by infection, aneurysm, or progressive foot gangrene occurred in 87 grafts (8%). The overall infection rate was 4.3%. Anastomotic aneurysms (1.4%) and strictures (2.1%) occurred infrequently as isolated phenomena. The incidence of graft dilatation and aneurysms assumed significant proportion after 5 years (36% aneurysms and 21% dilation); the diagnosis was particularly facilitated by B-mode imaging. Nevertheless, the overall clinical impact of graft degradation remained minimal (6% after 5 years). Twenty-two of 26 graft aneurysms were excised with successful graft replacement achieved in 10. During this 10-year period, our attitudes did change with regard to the indication for UV-Gs in relation to the maturation of infrapopliteal reconstructive surgery, appreciation of the superior results attainable with in situ saphenous vein, recognition of morphologic changes in long-term UV-G implants, and the growing documentation of poor results with polytetrafluorethylene in the crural position. We believe that UV-G is an acceptable alternative to the absent or deficient autologous vein, particularly in patients with limited life expectancy and where expediency may be a critical factor.

Adolescent↗

PubMed1984

Microcomputer-based programs for the practicing vascular surgeon.

An inexpensive microcomputer system can be programmed in BASIC to provide convenient data storage, retrieval, and analysis for the practicing vascular surgeon. A personalized registry program permits input of key patient data that can be processed and retrieved in list form or groupings with operator control of variables. A second program, in which lower extremity revascularization procedures can be analyzed by various parameters, is described. Results can be obtained in life-table formats with comparative statistical analysis. For the private practitioner of vascular surgery, the use of various computer programs will allow management of information for self-assessment, record keeping, teaching, and publication with great accuracy and at significant cost savings. In addition, word processing can increase secretarial output and efficiency. Office management programs are available but need to be individually investigated to determine their use for a particular practice. The major advantages of the microcomputer for the practicing vascular surgeon are personal control and ready access to data that are easy to store, analyze, and retrieve.

Computers↗