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E Gonzales

Publications and source records attributed to E Gonzales.

At least 37 records · Page 2Linked to original sources

Analysis of Hox gene expression in the chick limb bud.

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.

Amino Acid Sequence↗

A model for technology assessment as applied to closed loop infusion systems. Technology Assessment Task Force of the Society of Critical Care Medicine.

OBJECTIVES: To test a model for the assessment of critical care technology on closed loop infusion control, a technology that is in its early stages of development and testing on human subjects. DATA SOURCES: A computer-assisted search of the English language literature and reviews of the gathered data by experts in the field of closed loop infusion control systems. STUDY SELECTION: Studies relating to closed loop infusion control that addressed one or more of the questions contained in our technology assessment template were analyzed. Study design was not a factor in article selection. However, the lack of well-designed clinical outcome studies was an important factor in determining our conclusions. DATA EXTRACTION: A focus person summarized the data from the selected studies that related to each of the assessment questions. The preliminary data summary developed by the focus person was further analyzed and refined by the task force. Experts in closed loop systems were then added to the group to review the summary provided by the task force. These experts' comments were considered by the task force and this final consensus report was developed. DATA SYNTHESIS: Closed loop system control is a technological concept that may be applicable to several aspects of critical care practice. This is a technology in the early stages of evolution and much more research and data are needed before its introduction into usual clinical practice. Furthermore, each specific application and each device for each application (e.g., nitroprusside infusion, ventilator adjustment), although based on the same technological concept, are sufficiently different in terms of hardware and computer algorithms to require independent validation studies. CONCLUSIONS: Closed loop infusion systems may have a role in critical care practice. However, for most applications, further development is required to move this technology from the innovation phase to the point where it can be evaluated so that its role in critical car practice can be defined. Each application of closed loop infusion systems must be independently validated by appropriately designed research studies. Users should be provided with the clinical parameters driving each closed loop system so that they can ensure that it agrees with their opinion of acceptable medical practice. Clinical researchers and leaders in industry should collaborate to perform the scientifically valid, outcome-based research that is necessary to evaluate the effect of this new technology. The original model we developed for technology assessment required the addition of several more questions to produce a complete analysis of an emerging technology. An emerging technology should be systematically assessed (using a model such as the model developed by the Society of Critical Care Medicine), before its introduction into clinical practice in order to provide a focus for human outcome validation trials and to minimize the possibility of widespread use of an unproven technology.

Algorithms↗

Coagulation profile in persons with long-standing spinal cord injury.

Acute spinal cord injury (SCI) is associated with a marked propensity to thromboembolism and a variety of coagulation abnormalities. However, data on blood coagulation profiles in patients with uncomplicated long-standing SCI are limited. These data were studied here. Eight men with uncomplicated chronic SCI and nine able-bodied normal men were studied. Plasma activities and/or antigen concentrations of high molecular weight kininogen (HMWK) and of factors XII, XI, IX, VIII, VII, X, V, II and XIII as well as von Willebrand factor (vWF), fibrinogen and fibronectin were measured by appropriate functional and or immunological assays. The SCI group exhibited normal values for factors XII, IX, VIII, vWF, VII, X and V as well as HMWK, vWF and fibronectin concentration. However, they showed slight reductions in plasma factor XI activity, factor XIII antigen concentration and modest increases in fibrinogen and factor II concentrations. No correlation was found between the parameters studied and either the duration or the level of injury. In conclusion, in contrast to acute SCI, the coagulation profile in uncomplicated chronic SCI is noted to be largely normal with only a few minor alterations of questionable clinical significance.

Adult↗

The beta-core fragment of chorionic gonadotropin is not complexed to macromolecules in amniotic fluid.

A prior report claimed that amniotic fluid contains substantial quantities of beta-core fragment, a major degradation product of CG metabolism, complexed to macromolecules. In an attempt to confirm this finding, we measured beta-core fragment concentrations in 36 second- and 22 third-trimester amniotic fluid samples in a direct beta-core fragment RIA as well as a total CG RIA and found that all of the apparent immunoreactivity could be accounted for by the cross-reaction of CG and CG beta in the beta-core fragment RIA. Chromatography of concentrated pools of amniotic fluid or pregnancy serum failed to reveal a peak of CG immunoreactivity in the beta-core fragment elution area. However, chromatography after incubation of amniotic fluid or pregnancy serum with 3 mol/L ammonium thiocyanate resulted in a peak of apparent CG immunoreactivity in the area coinciding with the elution of ammonium thiocyanate and not purified beta-core fragment. The addition of ammonium thiocyanate to the CG RIA tubes resulted in apparent, but spurious, CG immunoreactivity. We conclude that amniotic fluid does not contain appreciable amounts of free or complexed beta-core fragment. We also were unable to confirm the presence of beta-core fragment complexed to macromolecules in pregnancy serum. Our results suggest that the previous studies that purported to demonstrate beta-core fragment-macromolecular complexes in amniotic fluid and pregnancy serum were reporting artifacts introduced by the ammonium thiocyanate used to dissociate beta-core fragment from the putative complex or the in vitro generation of beta-core fragment.

Amniocentesis↗

The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system.

Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = -0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress.

Adult↗

Erythropoietin profile in spinal cord injured patients.

Patients with spinal cord injury (SCI) have a high incidence of anemia. Intact erythropoietin (EPO) production is essential to the maintenance of erythrocyte mass and prevention and correction of anemia. However, the effect of chronic SCI on EPO production remains unclear. We measured plasma EPO concentration in 83 men with longstanding SCI and a group of normal able-bodied individuals. The SCI patients showed a significant reduction in hematocrit, a high prevalence of anemia, and an increased plasma EPO concentration. Active smokers showed a significantly higher hematocrit and lower EPO concentration than nonsmokers. No significant difference was found in hematocrit or EPO between individuals with paraplegia and those with quadriplegia. A negative correlation was found between EPO and hematocrit in SCI patients lacking significant lung disease. Thus, in the absence of renal insufficiency, EPO response to anemia is qualitatively preserved in SCI patients and is largely independent of the level of injury.

Adult↗

Identification and analysis of a DNA fragment from Saccharomyces kluyveri that can complement the loss of CDC25 function in Saccharomyces cerevisiae.

In the budding yeast, Saccharomyces cerevisiae, the function of wild-type Ras proteins is dependent on the CDC25 protein, which promotes the exchange of guanine nucleotides bound to Ras. To facilitate the identification of proteins which similarly regulate Ras function in higher eukaryotes, we have identified the CDC25 gene from another budding yeast, Saccharomyces kluyveri, by low-stringency hybridization to an S. cerevisiae CDC25 restriction fragment. This protein, SKCDC25, shares significant amino acid homology with CDC25, SCD25, and Ste6 of Schizosaccharomyces pombe in the C-terminal portion of the protein. The expression of SKCDC25 in a temperature-sensitive cdc25 strain of S. cerevisiae complements the loss of endogenous CDC25 activity. The identification of the highly conserved C-terminal sequences, which direct bona fide CDC25 activity within these proteins, will aid in the isolation of CDC25 genes from higher eukaryotes.

ATP-Binding Cassette Transporters↗

Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae CDC25 gene encodes a nucleotide-exchange-factor (NEF) that can convert the inactive GDP-bound state of RAS proteins to an active RAS-GTP complex. CDC25 can activate the yeast RAS proteins as well as the human H-ras protein. CDC25 is a member of a family of yeast genes that likely encode NEFs capable of regulating the RAS-related proteins found in yeast. By aligning the amino acid sequence of CDC25-related gene products we found a number of conserved motifs. Using degenerate oligonucleotides that encode these conserved sequences, we have used polymerase chain reactions to amplify fragments of mouse and human cDNAs related to the yeast CDC25 gene. We show that a chimeric molecule, part mouse and part yeast CDC25, can suppress the loss of CDC25 function in the yeast S. cerevisiae.

Amino Acid Sequence↗

Plasma concentration and urinary excretion of erythropoietin in adult nephrotic syndrome.

PURPOSE: Nephrotic syndrome (NS) is associated with a significant alteration of protein metabolism. While lowering the plasma concentrations of certain proteins, the disease often raises the level of certain other proteins. The current study was undertaken to determine the effect of NS on erythropoietin (EPO) metabolism. PATIENTS AND METHODS: We measured the EPO concentration in plasma and urine of 26 patients with NS by an immunologic assay using a rabbit antiserum against recombinant human EPO. The results were compared with those obtained in a group of 12 normal control subjects. RESULTS: Despite a significant reduction in the hemoglobin concentration in the NS group compared with the control group (125 +/- 25 g/L versus 148 +/- 11 g/L, p less than 0.05), the plasma EPO concentration in the NS group was not significantly different from that seen in the control group (6.2 +/- 4.5 mU/mL versus 6.7 +/- 2.4 mU/mL, p = NS). No significant correlations were found between plasma EPO and hemoglobin concentration, serum creatinine, serum albumin, or urinary albumin excretion rate. Moreover, comparison of the NS patients with serum creatinine concentrations less than or equal to 1.5 mg/dL (133 mumol/L) with those exhibiting creatinine concentrations exceeding 1.5 mg/dL did not reveal a significant difference in mean plasma EPO concentration. Significant amounts of EPO were found in the urine of the patients with NS, while none was detected in the urine of the control subjects. CONCLUSION: We conclude that plasma EPO is inappropriately low in patients with NS. This is due, at least in part, to the urinary/renal losses of this protein and can potentially contribute to anemia in NS patients or compound the problem in those with concurrent renal insufficiency and diminished EPO production.

Adolescent↗

Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris.

BACKGROUND AND METHOD: The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. RESULTS: The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, alpha 2-macroglobulin activity, and alpha 1-antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal alpha 2-antiplasmin concentration. CONCLUSIONS: The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.

Adult↗

Pressure ulcer, fibronectin, and related proteins in spinal cord injured patients.

Pressure ulcer is a common occurrence in spinal cord injured (SCI) patients and can lead to serious complications. With proper management, some patients exhibit satisfactory healing whereas others show slow or nonhealing ulcers. Fibronectin has been shown to accumulate in wound, opsonize macroaggregate debris for phagocytosis, promote revascularization, and facilitate fibroblast migration and proliferation. We explored the relationship of plasma fibronectin with healing potential in 21 SCI men with pressure ulcer. They received standard wound care and were observed for eight weeks. Ten otherwise healthy SCI men without pressure ulcer (SCI-controls) and 32 able-bodied normal individuals (normal controls) were also studied. Plasma fibronectin and related proteins, ie, fibrinogen, plasminogen, alpha 2-antiplasmin and Factor XIII, were measured. Ten of 21 SCI patients with pressure ulcer showed rapid healing within four weeks and had significantly higher fibronectin levels as compared with the 11 patients with poor healing ulcers, SCI controls, and normal controls. Factor XIII and alpha 2-antiplasmin were mildly reduced and fibrinogen values were significantly increased in all SCI groups. Plasminogen concentrations were comparable in all groups studied. It thus appears that plasma fibronectin rises in patients with fast healing ulcers but fails to do so in those with poor healing ulcers and as such may be predictive of the course of pressure ulcers.

Adult↗

Use of the inferior epigastric artery for coronary bypass.

Between December 1988 and April 1991, 74 free inferior epigastric arteries were used in 73 patients for coronary artery bypass grafts. In addition, 72 of the patients received a left internal mammary artery for single or sequential grafting to the left anterior descending system and 62 a right internal mammary artery to the circumflex or the right coronary artery. Twenty-seven patients had no saphenous vein available, and two had no suitable internal mammary artery; in an attempt to make a complete arterial revascularization, we chose the inferior epigastric artery as an alternative conduit in 24 young patients and in 10 reoperations; bilateral internal mammary artery dissection was avoided in four patients with impaired lung function and in six patients with selected two-vessel disease to spare one internal mammary artery. The technique for harvesting the inferior epigastric artery is described. Fifty-three inferior epigastric artery grafts were anastomosed to the distal right coronary artery or to its branches, 18 to the distal obtuse marginals of the circumflex artery (three as sequential grafts and one as a natural Y graft), and three to the left anterior descending system. The mean number of distal anastomoses is 3.60 per patient. Seventy proximal anastomoses of the inferior epigastric artery were made to the aorta and four to one internal mammary artery. There were four early deaths and one nonfatal myocardial infarction. Four abdominal wound hematomas needed surgical drainage. Sixty-one patients underwent angiographic study on postoperative day 10:59 of 61 inferior epigastric artery grafts (63 of 65 inferior epigastric artery distal anatomoses) and 111 of 111 internal mammary artery grafts (155 of 156 internal mammary artery distal anastomoses) were patent. Clinical follow-up of all the survivors (100% follow-up) could be obtained with a mean period of 9 months (1 to 28 months). There was no late cardiac death, no infarction, and all the patients were free of angina. Nineteen patients underwent a 6-month postoperative angiographic study. Seventeen of 19 inferior epigastric artery grafts were patent and 16 of 19 were intact; 34 of 34 internal mammary artery grafts (46 of 47 internal mammary artery distal anastomoses) were patent and intact. In conclusion, free inferior epigastric artery grafts can reach the diaphragmatic ischemic areas of the heart. The early patency rate and the clinical results are encouraging but only long-term evolution and evaluation can determine the true efficacy of the inferior epigastric artery graft as a reliable conduit for coronary artery bypass graft operations.

Abdominal Muscles↗

Blood coagulation, fibrinolytic and inhibitory profiles in renal transplant recipients: comparison of cyclosporine and azathioprine.

Renal transplant recipients treated with cyclosporine (CS) have been reported to be at increased risk of thrombotic complications. The present study was intended to examine the blood coagulation, fibrinolytic, and inhibitory systems in such patients. Eight transplant recipients on maintenance immunosuppression with CS and prednisone were studied. Five transplant recipients maintained on azathioprine (AZA) and prednisone and 32 normal volunteers served as controls. Plasma antigen concentrations and/or activities of various proteins in the above pathways were measured. Both the CS and AZA groups exhibited significant elevations of factor IX activity, von Willebrand factor (vWF), D-dimer, protein C and tissue type plasminogen activator (t-PA) levels when compared with the normal controls. In addition, CS group showed a significant elevation of alpha 2-macroglobulin activity and AZA group showed a significant reduction in factor XII activity when compared with the normal controls. Comparison of data from CS and AZA groups revealed higher factor XII activity and vWF concentration in the former group. In conclusion, transplant recipients treated with long-term cyclosporine and prednisone exhibited significant elevation of plasma vWF, D-dimer and protein C concentrations. In addition, both CS and AZA-treated transplant recipients showed increased plasma concentrations of D-dimer and t-PA. The latter observations suggest in vivo thrombin generation, fibrin formation and degradation.

Adult↗

Local cerebral blood flow response to locally infused 2-chloroadenosine during hypotension in piglets.

Brain interstitial adenosine increases during hypotension in piglets. If adenosine is to participate in the regulation of neonatal cerebral blood flow (CBF) during hypotension, it must retain its vasodilatory action under that condition. To examine this issue, we studied the effects of locally infused 2-chloroadenosine (2-CADO), a stable adenosine analog, on local CBF in the piglet frontal cortex during normotension and graded hemorrhagic hypotension. We used the modified brain microdialysis/hydrogen clearance technique to simultaneously infuse 2-CADO into the frontal cortex and measure local CBF from the same area. When 2-CADO from 10(-8) M to 10(-3) M was infused under control conditions (n = 7), CBF increased 61% at 10(-5) M, 167% at 10(-4) M, and 210% at 10(-3) M. In hypotension experiments, local infusion of 10(-5) M 2-CADO (n = 8) caused significant increases in CBF (P less than 0.05) under control conditions (MABP = 65 mmHg) and at hypotensive blood pressures of 55 mmHg and 44 mmHg, respectively. At a blood pressure of 33 mmHg, however, infusion of the analog failed to increase CBF. Local infusion of 10(-3) M 2-CADO also produced a similar change in CBF during graded hypotension. These results indicate that 2-CADO dilates intracerebral vessels during normotension, and mild and moderate hypotension, and support the hypothesis that endogenous adenosine mediates autoregulatory adjustments of CBF during hypotension in newborn piglets.

2-Chloroadenosine↗

Functional cloning of BUD5, a CDC25-related gene from S. cerevisiae that can suppress a dominant-negative RAS2 mutant.

By searching for genes that behave like CDC25 of S. cerevisiae in their ability to counteract a dominant-negative RAS2 mutant in a wild-type RAS-dependent manner, we have isolated a CDC25-like homolog, BUD5. BUD5 is tightly linked to the MAT locus. Although overexpressed BUD5 cannot substitute for CDC25 function, we present evidence that its gene product can bind to the guanine nucleotide binding-deficient RAS2val19ala22 gene product and thereby counteract its dominant-negative effect. We propose that BUD5 is a member of a family of CDC25-related genes that encode activators of RAS and RAS-like proteins.

Amino Acid Sequence↗

Erythropoietin in preeclampsia.

To investigate the possible effect of preeclampsia on erythropoietin metabolism, we measured plasma and urine erythropoietin concentrations and complete blood count in 19 women with preeclampsia and nine healthy gravidas. Hemoglobin concentration and hematocrit values in the preeclamptic patients did not differ significantly from those of the normal pregnant controls. However, the plasma erythropoietin concentration tended to be higher in the preeclamptic group than in the normal pregnant controls (26.9 +/- 31.2 versus 11.2 +/- 9.9 mU/mL), though the difference was not statistically significant. Plasma erythropoietin concentration correlated negatively with both hemoglobin concentration and hematocrit (r = -0.85, P less than .01). The pattern and magnitude of the erythropoietin response to anemia paralleled that previously reported in individuals with iron deficiency anemia. No significant correlation was found between urinary erythropoietin excretion and blood pressure, qualitative albumin excretion, hematocrit, hemoglobin concentration, or plasma erythropoietin concentration. Based on our results, the erythropoietin response to anemia appears to be intact in preeclampsia, at least in the absence of renal failure.

Adult↗

Factor XIII and its substrates, fibronectin, fibrinogen, and alpha 2-antiplasmin, in plasma and urine of patients with nephrosis.

Plasma and urine concentrations of factor XIII and its circulating substrates (fibronectin, fibrinogen, and alpha 2-antiplasmin) were measured in a group of 36 patients with nephrotic syndrome. The results were compared with those obtained in a group of 32 normal volunteers (control group) and 12 patients with end-stage renal disease (ESRD). A mild but significant reduction in plasma level and an abnormal urinary excretion of alpha 2-antiplasmin was found in the nephrotic group. Plasma concentrations of factor XIII, fibronectin, and fibrinogen were significantly elevated in patients with nephrosis. In contrast, patients with ESRD showed no significant difference in the plasma concentrations of either factor XIII, fibronectin, or alpha 2-antiplasmin and only a modest elevation of fibrinogen when compared with normal controls. No significant correlation was found between serum creatinine concentration and plasma levels of factor XIII and its circulating substrates in the nephrotic group. No measurable quantities of factor XIII and only small quantities of fibronectin were found in the urine of patients with nephrosis. Elevation of plasma factor XIII, fibronectin, and fibrinogen concentrations in the nephrotic group is considered to be the result of a combination of increased synthesis and possibly contracted intravascular distribution of these macromolecular proteins in the face of their negligible urinary losses. The presence of the observed abnormalities in the nephrotic group and their absence in the non-nephrotic ESRD group tends to exclude renal failure as a cause of these abnormalities. Although the clinical significance of these abnormalities is uncertain, they can potentially contribute to the thrombophilic diathesis and platelet hyperaggregability in nephrotic syndrome.

Adolescent↗