Biomedical subjects

A Dardik

Publications and source records attributed to A Dardik.

At least 19 recordsLinked to original sources

PubMed2006

Presence of prostacyclin receptor in arteriosclerotic human femoral artery.

AIM: Prostacyclin, which is mainly synthesized by vascular endothelial cells, exerts antiplatelet and smooth-muscle-relaxant effects, thereby maintaining cardiovascular homeostasis. Prostacyclin analogues have been clinically proven to improve ischemic symptoms and prevent the occurrence of vascular events in the lower extremities of patients with arteriosclerosis obliterans. We examined the presence of prostacyclin receptor (IP receptor) in an arteriosclerotic human femoral artery. METHODS: Specimens of the femoral artery were obtained at the time of limb amputation from an 83-year-old woman. Atherosclerotic lesions and associated changes such as calcification were evident. The specimens were stained with hematoxylin and eosin, and processed for immunohistochemistry. RESULTS: A monolayer of cells was observed on the luminal side of the femoral artery. Single immunohistochemistry showed the presence of the IP receptors on cells of the luminal side of the femoral artery. Triple-immunofluorescence staining revealed colocalization of IP-receptor-positive cells and cells positive for von Willebrand factor, a marker of vascular endothelial cells. CONCLUSIONS: We investigated the presence of the IP receptor in the human femoral artery immunohistochemically, and demonstrated their strong expression in endothelial cells. This finding suggests that prostacyclin or prostacyclin analogues may act on their receptors on endothelial cells in patients with arteriosclerosis obliterans.

Aged, 80 and over↗

PubMed2006

Relationship between air-plethysmographic venous function and clinical severity in primary varicose veins.

AIM: The role of air plethysmography (APG) in the diagnosis of chronic venous insufficiency has not been well established. The purpose of this study was to elucidate the relationship between APG parameters and clinical severity in patients with chronic venous insufficiency. METHODS: Two hundred and ninety-four limbs in 154 patients with primary varicose veins were evaluated by APG. Limbs were categorized according to the clinical classification of chronic venous disease suggested by the Ad Hoc Committee on Reporting Standards in Venous Disease of the North American Chapter of the Society for Vascular Surgery and International Society for Cardiovascular Surgery (SVS/ ISCVS). RESULTS: The venous filling index (VFI) was significantly higher in classes 2, 3, 4, and 5+6 than in class 0 or 1, and did not differ among classes 2, 3, 4, 5+6. The ejection fraction did not differ significantly among the 6 classes, and the residual volume fraction was significantly higher in classes 2, 3, 5+6 than in class 0. CONCLUSIONS: APG is a reasonable method for distinguishing the presence or absence of chronic venous insufficiency, but it cannot discriminate the clinical severity. Among APG parameters, the VFI is the most useful diagnostic parameter in the evaluation of chronic venous insufficiency.

Adult↗

PubMed2001

Improved quality of life among patients with symptomatic carotid artery disease undergoing carotid endarterectomy.

BACKGROUND: Few studies have examined how carotid endarterectomy affects patients' view of their quality of life. METHODS: Patients undergoing carotid endarterectomy from January 1996 to March 1997 at the John Radcliffe Hospital completed the United Kingdom Short Form 36 (SF-36) Health Survey Questionnaire before undergoing the procedure and again at 3 months afterward. Scores were compared with population normal values. RESULTS: In 50 patients with symptomatic carotid artery disease, there was significant improvement in the SF-36 overall "change in health" score after the procedure compared with beforehand (61.0 +/- 3.7 vs 44.5 +/- 3.4, P =.003, Wilcoxon signed rank test). There were, however, no statistically significant differences in the group's mean SF-36 subscores after operation compared with before the procedure. The physical subscores were below age-adjusted healthy population means but similar to those for chronically ill patients (physical function subscore P =.015 vs normal, P =.89 vs ill; role limitation-physical subscore P =.007 vs normal, P =.89 vs ill). Patients with postoperative complications did not have an improved change in health score (-12.5 vs 22.0, P =.03, Mann-Whitney U test). There was no effect on change in health score because of other risk factors or in patients with contralateral carotid artery occlusion or a history of preoperative stroke. CONCLUSIONS: Patients with symptomatic carotid artery disease undergoing an uncomplicated carotid endarterectomy perceive improved quality of life and overall health. There is no perception of worsened pain, energy, or physical or mental function after the procedure. These results confirm that patients believe that performance of carotid endarterectomy improves their overall health, supporting the surgical approach to carotid artery disease.

Aged↗

PubMed2001

Aneurysmal expansion of the visceral patch after thoracoabdominal aortic replacement: an argument for limiting patch size?

INTRODUCTION: Thoracoabdominal aortic replacement requires visceral vessel revascularization and is usually performed with Crawford's inclusion technique or a large Carrel patch. This segment of retained native aorta may be prone to recurrent aneurysmal disease. We reviewed our experience with patients in whom aneurysmal expansion of the visceral patch was detected. METHODS: The records of 107 patients undergoing thoracoabdominal aortic replacement operations performed or followed up at the Johns Hopkins Hospital between 1992 and 2000 were reviewed. All patients had visceral patches created for type II, III, or IV aneurysms. Visceral patches were considered aneurysmal if the maximal diameter of the aortic prosthesis and patch was 4.0 cm or more. RESULTS: Patch aneurysmal expansion (mean, 5.4 cm) was detected in eight patients (7.5%). All three women had connective tissue disorders (mean age, 36 years), and all five men had atherosclerotic disease (mean age, 73 years). Five patients were symptom free with their aneurysms detected by surveillance computed tomography scans; two patients had back pain prompting computed tomography scans; and one patient presented with an emergency patch rupture. Aneurysmal patches were successfully revised in three patients. Two patients died in the operating room, and three patch aneurysms (< 5 cm) are still being observed. The mean time to the detection of aneurysmal expansion was 6.5 years after the original operation. Therapy consisted of replacement of a segment of the thoracoabdominal aortic graft and refashioning a smaller patch, including only the visceral artery orifices with separate attachment of the left and possibly right renal artery. CONCLUSIONS: Although Crawford's inclusion method of visceral patch construction is generally durable, patients undergoing thoracoabdominal aortic replacement require yearly surveillance for the detection of aneurysmal expansion of the visceral patch. We recommend limiting visceral patch size at the original operation by routinely excluding the orifice of the left renal artery. Patients at high risk for recurrent aneurysmal expansion, such as those with connective tissue disorders, will benefit from creating small visceral patches and possibly implanting both renal arteries separately during the original operation.

Adult↗

PubMed2000

Impact of race on the outcome of carotid endarterectomy: a population-based analysis of 9,842 recent elective procedures.

OBJECTIVE: To examine the influence of race and other potentially confounding variables on the outcome of carotid endarterectomy (CEA). SUMMARY: Previous studies have demonstrated that CEA is performed less frequently in black patients, although little attention has been focused on the influence of race on the outcome of surgery. METHODS: The Maryland Health Services Cost Review Commission database was reviewed to identify all elective CEA procedures performed in all nonfederal acute care hospitals in the state from 1990 through 1995 to examine the influence of race and other factors on the rates of in-hospital complications, in-hospital stroke, length of stay, and total hospital charges. RESULTS: Carotid endarterectomy was performed in 9,219 (94%) white and 623 (6%) black patients during this period. The in-hospital stroke rate was 1.7%-3. 1% among black patients and 1.6% among white patients. Black patients had a longer length of stay and higher mean hospital charges than white patients. Multivariate logistic regression analysis identified black race as an independent risk factor for in-hospital stroke. Performance of CEA by a high-volume surgeon was protective for the combined occurrence of in-hospital stroke or death, and whites were more than twice as likely to undergo surgery performed by high-volume surgeons. Conversely, undergoing surgery in a low-volume hospital was associated with in-hospital stroke, and blacks were four times as likely to use low-volume hospitals. CONCLUSIONS: Black patients who underwent elective CEA in Maryland from 1990 to 1995 had an increased incidence of in-hospital stroke, a longer hospital stay, and higher hospital charges than whites. Black race was identified as an independent risk factor for in-hospital stroke, although the reasons for this influence of race on outcome are undefined. The authors' observations also suggest the possibility of limited access to optimal surgical care among blacks, and this issue warrants further study.

Black or African American↗

PubMed2000

Acute abdomen with colonic necrosis induced by Kayexalate-sorbitol.

Colonic necrosis is an unusual complication after treatment of hyperkalemia with sodium polystyrene sulfonate (SPS, Kayexalate) in sorbitol. To increase awareness of this complication, we report a case of necrosis of the transverse colon in a patient given oral and rectal SPS-sorbitol for hyperkalemia. Colonic necrosis was manifested as an acute abdomen within 24 hours of initial administration. Prompt surgical resection of the necrotic transverse colon permitted rapid recovery of bowel function. Although SPS crystals are seen microscopically in the necrotic bowel, experimental evidence implicates the sorbitol component of the SPS-sorbitol in the pathogenesis of colonic necrosis. A high index of suspicion for the unusual complication of colonic necrosis after oral or rectal administration of SPS-sorbitol may allow prompt recognition and surgical cure.

Abdomen, Acute↗

PubMed2000

Accurate placement of microvascular guide sutures.

A simple technique to accurately place initial microvascular guide sutures is described. Enhanced suture placement enables anastomosis construction in situations in which the clamp must be placed very close to the vessel end or if the vessel lumen is distorted or poorly visualized. Because this technique eliminates the need for retraction on the guide suture tails, it is particularly useful for solo microvascular surgeons.

Anastomosis, Surgical↗

PubMed1999

Results of elective abdominal aortic aneurysm repair in the 1990s: A population-based analysis of 2335 cases.

OBJECTIVE: The safety and efficacy of conventional abdominal aortic aneurysm (AAA) repair are undergoing increased examination in parallel with the development of less invasive repair methods. Because most published studies of elective AAA repair report operations performed in tertiary referral institutions and thus may not reflect the outcome in the surgical community at large, the current population-based study was undertaken to document the results obtained across a broad spectrum of clinical practice in a defined geographic area and to examine the factors that influence the outcomes. METHODS: The Maryland Health Services Cost Review Commission database was used to identify all the elective AAA repairs that were performed in all the nonfederal acute care hospitals in the state from 1990 to 1995. RESULTS: Elective AAA repair was performed on 2335 patients (mean age, 70.4 years) in 46 of the 52 (88%) nonfederal acute care hospitals in the state, including seven high-volume (>100 cases), nine moderate-volume (50 to 99 cases), and 30 low-volume (<50 cases) institutions. The in-hospital mortality rate was 3.5% and increased significantly with advancing age: less than 65 years, 2.2%; 65 to 69 years, 2.5%; 70 to 79 years, 3.5%; and more than 80 years, 7.3% (P =.002). Mortality rates were higher for women (4.5% vs 3.2%; P =.17), for blacks (6.7% vs 3.2%; P =.046), and for patients with renal failure (11.8% vs 3. 4%; P =.11) but not for patients with hypertension, diabetes, heart disease, and pulmonary disease. The operative mortality rate was inversely correlated with hospital volume (4.3% in low-volume hospitals, 4.2% in moderate-volume hospitals, and 2.5% in high-volume hospitals; P =.08), although no differences were noted in the mean ages or comorbidity levels of patients who underwent operations in these three hospital populations. The operative mortality rate was inversely correlated with the experience of the individual surgeon: one case, 9.9%; two to nine cases, 4.9%; 10 to 49 cases, 2.8%; 50 to 99 cases, 2.9%; and more than 100 cases, 3.8% (P =.01). Multivariate analysis results identified patient age (P =. 002), low hospital volume (P =.039), and very low surgeon volume (P =.01) as independent predictors of operative mortality. The mean length of stay and mean hospital charges were 10.6 days and $17,589 and decreased with increasing surgeon volume: one case, 22.7 days/$32,800; two to nine cases, 10.6 days/$18,509; 10 to 49 cases, 10.0 days/$16,611; 50 to 99 cases, 10.9 days/$17,843; and more than 100 cases, 9.6 days/$16,682 (P <.0001/P <.0001). CONCLUSION: Elective AAA repair is a safe procedure in contemporary practice in Maryland. Operative risk is increased among the elderly and when operations are performed by surgeons with very low volumes or in low-volume hospitals. Hospital lengths of stay were shorter and charges were lower when elective AAA repair was performed by surgeons with higher volumes.

Adult↗

PubMed1999

Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness.

OBJECTIVE: The absence of endothelial cells at the luminal surface of a prosthetic vascular graft potentiates thrombosis and neointimal hyperplasia, which are common causes of graft failure in humans. This study tested the hypothesis that pretreatment with chronic in vitro shear stress enhances subsequent endothelial cell retention on vascular grafts implanted in vivo. METHODS: Cultured endothelial cells derived from Fischer 344 rat aorta were seeded onto the luminal surface of 1.5-mm internal diameter polyurethane vascular grafts. The seeded grafts were treated for 3 days with 1 dyne/cm2 shear stress and then for an additional 3 days with 1 or 25 dyne/cm2 shear stress in vitro. The grafts then were implanted as aortic interposition grafts into syngeneic rats in vivo. Grafts that were similarly seeded with endothelial cells but not treated with shear stress and grafts that were not seeded with endothelial cells served as controls. The surgical hemostasis time was monitored. Endothelial cell identity, density, and graft patency rate were evaluated 24 hours after implantation. Endothelial cell identity in vivo was confirmed with cells transduced in vitro with beta-galactosidase complementary DNA in a replication-deficient adenoviral vector. Histologic, scanning electron microscopic, and immunohistochemical analyses were performed 1 week and 3 months after implantation to establish cell identity and to measure neointimal thickness. RESULTS: The pretreatment with 25 dyne/cm2 but not with 0 or 1 dyne/cm2 shear stress resulted in the retention of fully confluent endothelial cell monolayers on the grafts 24 hours after implantation in vivo. Retention of seeded endothelial cells was confirmed by the observation that beta-galactosidase transduced cells were retained as a monolayer 24 hours after implantation in vivo. In the grafts with adherent endothelial cells that were pretreated with shear stress, immediate graft thrombosis was inhibited and surgical hemostasis time was significantly prolonged. Confluent intimal endothelial cell monolayers also were present 1 week and 3 months after implantation. However, 1 week after implantation, macrophage infiltration was observed beneath the luminal cell monolayer. Three months after the implantation in vivo, subendothelial neointimal cells that contained alpha-smooth muscle actin were present. The thickness of this neointima averaged 41 +/- 12 micrometer and 60 +/- 23 micrometer in endothelial cell-seeded grafts that were pretreated with 25 dyne/cm2 shear stress and 1 dyne/cm2 shear stress, respectively, and 158 +/- 46 micrometer in grafts that were not seeded with endothelial cells. CONCLUSION: The effect of chronic shear stress on the enhancement of endothelial cell retention in vitro can be exploited to fully endothelialize synthetic vascular grafts, which reduces immediate in vivo graft thrombosis and subsequent neointimal thickness.

Adenoviridae↗

PubMed1999

Neutralizing TGF-beta1 antibody infusion in neonatal rat delays in vivo glomerular capillary formation 1.

BACKGROUND: The interruption of transforming growth factor-beta (TGF-beta) signaling with dominant negative type II TGF-beta receptors in bovine glomerular endothelial cells abrogates capillary morphogenesis in vitro, and genetic defects in the TGF-beta1 signaling cascade in mice and humans result in abnormalities of blood vessel morphology. This study sought to determine whether TGF-beta1 participates in renal glomerular capillary development in vivo. METHODS: To inhibit TGF-beta1 action, neutralizing anti-TGF-beta1 IgG was infused intra-arterially into the suprarenal aorta of three-day-old rats, and the glomerular endothelial cell appearance was evaluated two days later by immunohistochemical detection of the endothelium-specific von Willebrand factor, in situ analysis of vascular endothelial growth factor receptor binding, and morphometric study of developing glomerular structures by transmission electron microscopy. RESULTS: The infusion of neutralizing the TGF-beta1 antibody markedly reduced the invasion of comma- and S-shaped bodies by endothelial cells, and inhibited organization of endothelial cells into capillaries in these structures. In addition, capillary lumen formation and endothelial cell fenestration in developing cortical, but not in deep, already mature glomeruli were inhibited by neutralizing TGF-beta1 antibody. Seven days after TGF-beta1 antibody infusion, glomeruli appeared normal, and no reduction in glomerular number was observed. CONCLUSIONS: These findings suggest that TGF-beta1 plays a critical role in the formation of glomerular capillaries during renal development in the rat, and that flattening and fenestration of glomerular capillaries require the action of TGF-beta1.

Animals↗

PubMed1998

Surgical repair of ruptured abdominal aortic aneurysms in the state of Maryland: factors influencing outcome among 527 recent cases.

PURPOSE: Abdominal aortic aneurysm (AAA) rupture has been historically associated with high operative mortality rates. In this community-based, cross-sectional study, we examined factors influencing outcome after operations performed for ruptured AAA (rAAA). METHODS: An analysis of a state database identified 3820 patients who underwent AAA repair between 1990 and 1995, including 527 (13.8%) who had an operation for an rAAA. Demographic variables examined included patient age, gender, race, associated comorbidity rates, operative surgeon experience with rAAA, and annual hospital rAAA and total AAA operative volumes. Outcomes measured included operative mortality rates, hospital length of stay, and charges. RESULTS: Operative mortality rates increased significantly with advancing age (P < 0.0001) but were not related to gender (P = 0.474) or race (p = 0.598) and were significantly lower among patients with hypertension (P = 0.006) or pulmonary disease (P = 0.045). There was no relationship between hospital rAAA or total AAA volume and rAAA repair mortality rate, although high-volume surgeons (i.e., performing more than 10 rAAA repairs) had decreased mortality rates and hospital charges compared with other surgeons. Hospital lengths of stay and charges increased with age among survivors, but not nonsurvivors, of rAAA repair. Despite a stable incidence of rAAA repairs during the study interval and no significant change in the mean age of patients undergoing operation or the percentage of operations performed by high-volume surgeons, the statewide mortality rate declined from 59.3% to 43.2% (P = 0.039). CONCLUSION: The incidence of rAAA does not appear to be declining. Although operative rAAA repair continues to be associated with substantial risk and remains an especially lethal condition among the elderly, the operative mortality rate has declined in recent years in Maryland. Lower operative mortality rates and hospital charges are associated with operations performed by high-volume surgeons.

Adult↗

PubMed1998

Influence of age and hospital volume on the results of carotid endarterectomy: a statewide analysis of 9918 cases.

PURPOSE: This study evaluated the impact of patient age and hospital volume on the results of carotid endarterectomy (CEA) in contemporary practice. METHODS: The Maryland Health Services Cost Review Commission (MHSCRC) database was reviewed to identify all patients who underwent elective CEA as the primary procedure in all acute care hospitals in the state over the past 6 years. RESULTS: From January 1990 through December 1995, 9918 elective CEAs were performed in 48 hospitals at a total charge of $68.9 million. Postoperative death and neurologic complications occurred in 90 (0.9%) and 166 (1.7%) cases, including 0.8% and 1.7%, 0.9% and 1.6%, 0.9% and 1.8%, and 1.4% and 1.3% of patients < 65 years, 65 to 69 years, 70 to 79 years, and > or = 80 years old, respectively. The mean length of stay and hospital charges increased linearly with increasing age: 4.2 days/$6550, 4.4 days/$6834, 4.8 days/$7059, and 5.6 days (p < 0.0001 vs others)/$7756 (p < 0.005 vs 70 to 79 years and p < 0.0003 vs < 70 years old), respectively, for patients < 65, 65 to 69, 70 to 79, and > or = 80 years old. The mortality rate was 1.9% in low-volume hospitals, 1.1% in moderate-volume hospitals, and 0.8% in high-volume hospitals. The neurologic complication rate was significantly higher (6.1%; p < 0.0001) in low-volume when compared with moderate-volume (1.3%) and high-volume (1.8%) hospitals. CONCLUSIONS: CEA is a safe procedure in the majority of hospitals in contemporary practice, even among the very elderly, who may experience a longer length of stay and higher charges correlating with their documented greater medical complexity.

Adult↗

PubMed1998

Successful delayed bilateral renal revascularization during active phase of Takayasu's arteritis.

Successful bilateral renal revascularization was performed 24 days after the development of angiotensin converting enzyme-inhibitor-induced bilateral renal artery thrombosis and anuric acute renal failure in a patient with Takayasu's arteritis. Excellent results were obtained after an unusually long ischemic time for a patient with active-phase disease. The outcome suggests that aggressive surgical revascularization can benefit patients with renal failure caused by renal arterial occlusion during the active phase of Takayasu's arteritis.

Acute Kidney Injury↗

PubMed1998

Shear stress and the endothelium.

Shear stress and the endothelium. Vascular endothelial cells (ECs) in vivo are influenced by two distinct hemodynamic forces: cyclical strain due to vessel wall distention by transmural pressure, and shear stress, the frictional force generated by blood flow. Shear stress acts at the apical cell surface to deform cells in the direction of blood flow; wall distention tends to deform cells in all directions. The shear stress response differs, at least partly, from the cyclical strain response, suggesting that cytoskeletal strain alone cannot explain it. Acute shear stress in vitro elicits rapid cytoskeletal remodeling and activates signaling cascades in ECs, with the consequent acute release of nitric oxide and prostacyclin; activation of transcription factors nuclear factor (NF)kappaB, c-fos, c-jun and SP-1; and transcriptional activation of genes, including ICAM-1, MCP-1, tissue factor, platelet-derived growth factor-B (PDGF-B), transforming growth factor (TGF)-beta1, cyclooxygenase-II, and endothelial nitric oxide synthase (eNOS). This response thus shares similarities with EC responses to inflammatory cytokines. In contrast, ECs adapt to chronic shear stress by structural remodeling and flattening to minimize shear stress. Such cells become very adherent to their substratum and show evidence of differentiation. Increased adhesion following chronic shear stress has been exploited to generate vascular grafts with confluent EC monolayers, retained after implantation in vivo, thus overcoming a major obstacle to endothelialization of vascular prostheses.

Animals↗

PubMed1997

Vena cava filter ensnarement and delayed migration: an unusual series of cases.

PURPOSE: To review delayed and guidewire-induced morbidity associated with vena cava filters. METHODS: The records from the Johns Hopkins Hospital, a tertiary care referral center, of all patients who had vena cava filter complications from August 1993 through July 1996 were retrospectively reviewed. RESULTS: Five patients had filter migration or ensnarement with a guidewire. One patient had delayed extrusion of a filter strut into the duodenum. Four patients had filters ensnared by guidewires, including one during initial filter placement and one several years after placement. CONCLUSIONS: Delayed complications of vena cava filters should be considered whenever unusual patient signs or symptoms cannot be easily explained, even in the absence of a history of filter placement. To prevent guidewire ensnarement of filters, simple techniques should modify endovascular procedures when vena cava filters are present.

Adult↗

PubMed1997

Impact of a critical pathway on the results of carotid endarterectomy in a tertiary care university hospital: effect of methods on outcome.

PURPOSE: A carotid endarterectomy critical pathway (CP) targeting a 3-day postoperative course was introduced in March 1994. This retrospective analysis assesses its impact on operative results, postoperative length of stay (POD), and cost of hospitalization (COH). METHODS: One hundred eighty-six patients who underwent 201 carotid endarterectomy procedures from Nov. 1992 to Feb. 1994 (Pre-CP; n = 67) and from Apr. 1994 to Jul. 1995 (Post-CP; n = 134) at Johns Hopkins Hospital, a tertiary care referral center, were evaluated. RESULTS: The Pre-CP and Post-CP groups had similar risk factors, postoperative morbidity rates, and mortality rates. Furthermore, they had similar mean POD (Pre-CP, 6.0 +/- 0.5 days; Post-CP, 5.7 +/- 0.6 days; p = 0.79) and COH. However, only 85 of the Post-CP (63%) patients were actually placed on the CP (CP-starters); the mean POD was 3.4 +/- 0.3 days among these CP-starters (p < 0.0001) and 2.8 +/- 0.1 days among the 74 Post-CP patients (55%) that remained on the pathway (CP-finishers; p < 0.0001). The mean COH was reduced from $12,881 (Pre-CP) to $9701 for the CP-starters (p = 0.01) and to $8572 for the CP-finishers (p = 0.0001). However, we found that only 47 of the Pre-CP patients (70%) would have been eligible for the CP, and the mean POD among those cases was 4.2 +/- 0.4 days, which was not different than the mean POD among the CP-starters (p = 0.17). The mean COH of the eligible Pre-CP cases, $9508, was not significantly different from the COH of the CP-starters (p = 0.97). CONCLUSIONS: This subset analysis emphasizes the importance of establishing an accurate "control" group when studying a CP, because using all of the Pre-CP cases as the "control" group in the original analysis, including patients who would not have been candidates for the CP, clearly overstated the beneficial impact of the CP.

Analysis of Variance↗

PubMed1993

Protein secretion by the mouse blastocyst: stimulatory effect on secretion into the blastocoel by transforming growth factor-alpha.

We have previously demonstrated that newly synthesized proteins are secreted into the mouse blastocoel [Dardik and Schultz (1991): Biol Reprod 45:328-333]. In the present study we examine the effect of transforming growth factor-alpha (TGF-alpha) on these proteins. We observe that TGF-alpha stimulates secretion of these newly synthesized proteins into the blastocoel and apical medium, which faces the zona pellucida, by about 65%. Although one-dimensional gel electrophoretic analysis does not reveal any marked differences in the patterns of newly synthesized proteins secreted into the blastocoel in response to TGF-alpha, zymography reveals a marked stimulation in the secretion of several gelatinases into the blastocoel and apical medium. These results suggest additional functions for TGF-alpha in mouse preimplantation development.

Animals↗

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↗