Isoforms In Patients Research Articles

Increased blood plasma concentrations of TGF-β isoforms after treatment with intravenous immunoglobulins (IVIG) in patients with multiple sclerosis

To assess whether TGF-β isoforms are significantly increased after intravenous immunoglobulin (IVIG) infusion in the plasma of patients with multiple sclerosis (MS), 19 patients with clinically definite MS were enrolled in a double blind placebo controlled IVIG study. TGF-β1, TGF-β2, TGF-β3 plasma concentrations were measured prior and directly after IVIG infusions by specific ELISA. Compared to the placebo group, we found a significant increase in the plasma levels of all three TGF-β isoforms in patients treated with IVIG. The significantly increased TGF-β plasma concentrations in treated patients suggest an additional, immediate mechanism of action that may accompany the molecular effects of IVIG therapy in MS. The variable amount of the potent anti-inflammatory TGF-β isoforms within the IVIG preparations may exert a differentiated view regarding the manifold indications of IVIG therapy.

Induced shift in myosin heavy chain expression in myosin myopathy by endurance training.

We recently described a new autosomal dominant myopathy (OMIM #605637) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene ( MYH2), which encodes for the fast myosin isoform that is expressed in type 2A muscle fibers. There was a correlation between muscle pathology and expression of MyHC IIa. Low expression of the mutation was associated with a milder phenotype. Since physical activity influences MyHC isoform expression in normal individuals, we investigated whether endurance training can alter the expression of MyHC isoforms in patients with the MYH2 mutation. The expression of MyHC I, IIa and IIx was analysed in muscle specimens from six patients before and after an eight-week endurancetraining program by SDS-polyacrylamide gel electrophoresis and immuno-histochemistry. There was a clear and consistent shift from fast to slow MyHC isoform expression, but the training program did not result in the desired reduction of MyHC IIa, which may be due to the limited time period of training. Fiber type transition was further illustrated by the appearance of hybrid muscle fibers expressing more than one MyHC isoform after the training period. All patients showed an increase in maximal workload but no significant change in isometric muscle strength.We conclude that endurance training in patients with myosin myopathy may be an important way to alter the expression of defective MyHC isoforms.

Decreased nitric oxide production after intravenous immunoglobulin treatment in patients with Kawasaki disease

Objective: To assess nitric oxide (NO) production and different displays of NO synthase (NOS) isoforms in patients with Kawasaki disease (KD) before and after intravenous immunoglobulin (IVIG) treatment. Study design: Blood and urine samples were collected from patients with KD before IVIG treatment and 3 days afterward. Age-matched febrile patients with various diseases served as control patients. Plasma NOx (NO3- + NO2-) levels were measured as NO production. Real-time reverse transcriptase–polymerase chain reaction and immunohistochemical staining were used to detect differential NOS isoform expression in mononuclear leukocytes (MNCs). Results: Patients with KD (n = 40) had higher levels of NOx than the non-KD febrile control patients. The elevated NOx levels in patients with KD were significantly associated with the occurrence of coronary artery dilation (>3 mm). These elevated NOx levels significantly decreased after IVIG treatment (157.8 ± 15.9 μmol/L vs 57.0 ± 4.27 μmol/L, P <.01). However, excretion of urinary NOx levels was not changed after IVIG treatment. Inducible but not constitutive NOS mRNA and protein in MNCs were prominently expressed but significantly decreased after IVIG treatment. Conclusions: IVIG may suppress iNOS expression of MNCs in patients with KD, thus decreasing NO-mediated inflammatory responses and coronary artery dilation.( J Pediatr 2002;141:560-5)

Expression of myosin heavy chain isoforms in skeletal muscle of patients with peripheral arterial occlusive disease

Peripheral arterial occlusive diseases (PAODs) not only compromise blood flow but lead to a series of subsequent metabolic and structural changes in the relevant muscles. Changes in myofibrillar proteins (eg, of myosin heavy chain [MHC] isoforms), one of the determinants of muscle structure as well as of muscular function, have not been reported in patients with PAOD and were therefore the aim of this study. Thirteen consecutive patients with PAOD were examined (clinical stage according to Fontaine II, three patients; III, three patients, and IV, seven patients) and compared with five age-matched control patients who had been in traffic accidents. A calf muscle sample (gastrocnemius muscle) in the ischemic region was taken for MHC isoform analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver stain, and the relative content of MHC isoforms was measured. Compared with the control patients, there was no significant change of MHC isoforms in patients with PAOD II. In patients with PAOD III, MHC IIb decreased significantly (P <.05) although MHC IIa remained unchanged; in patients with PAOD IV, both MHC IIa and IIb decreased significantly (P <.05). Accordingly, there was a progressive increase of the relative amount of MHC I with more critical ischemia in PAOD. In patients with PAOD, the content of MHC II decreased with a higher grade of ischemia. That seems to be consistent with an increased resistance to ischemia for myosin isoforms in the order of I more than in IIa more than IIb. Whether the decrease of MHC II in patients with PAOD is related to atrophy of muscle fibers or to muscle-fiber transition must be investigated further.

Expression of myosin heavy chain isoforms in skeletal muscle of patients with peripheral arterial occlusive disease

Purpose: Peripheral arterial occlusive diseases (PAODs) not only compromise blood flow but lead to a series of subsequent metabolic and structural changes in the relevant muscles. Changes in myofibrillar proteins (eg, of myosin heavy chain [AMC] isoforms), one of the determinants of muscle structure as well as of muscular function, have not been reported in patients with PAOD and were therefore the aim of this study.Methods: Thirteen consecutive patients with PAOD were examined (clinical stage according to Fontaine II, three patients; III, three patients, and IV, seven patients) and compared with five age-matched control patients who had been in traffic accidents. A calf muscle sample (gastrocnemius muscle) in the ischemic region was taken for MHC isoform analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver stain, and the relative content of MHC isoforms was measured.Results: Compared with the control patients, there was no significant change of MHC isoforms in patients with PAOD II. In patients with PAOD III, MHC Ilb decreased significantly (P < .05) although MHC IIa remained unchanged; in patients with PAOD IV, both MHC IIa and IIb decreased significantly (P < .05). Accordingly, there was a progressive increase of the relative amount of MHC I with more critical ischemia in PAOD.Conclusion: In patients with PAOD, the content of AMC II decreased with a higher grade of ischemia. That seems to be consistent with an increased resistance to ischemia for myosin isoforms in the order of I more than in IIa more than IIb. Whether the decrease of MHC II in patients with PAOD is related to atrophy of muscle fibers or to muscle-fiber transition must be investigated further.

Follicular fluid prolactin isoforms in patients submitted to in vitro fertilization

International Journal of Gynecology & ObstetricsVolume 70, Issue S2 p. B153-B153 Physiology of reproduction 2 Follicular fluid prolactin isoforms in patients submitted to in vitro fertilization G.S. Romão, G.S. RomãoSearch for more papers by this authorM.D. Moura, M.D. MouraSearch for more papers by this authorA.R. Marius, A.R. MariusSearch for more papers by this authorR.A. Ferriani, R.A. FerrianiSearch for more papers by this author G.S. Romão, G.S. RomãoSearch for more papers by this authorM.D. Moura, M.D. MouraSearch for more papers by this authorA.R. Marius, A.R. MariusSearch for more papers by this authorR.A. Ferriani, R.A. FerrianiSearch for more papers by this author First published: 10 December 2003 https://doi.org/10.1016/S0020-7292(00)83219-1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, IssueS22000Pages B153-B153 RelatedInformation

Expression of Myosin Heavy Chain Isoforms in Skeletal Muscle of Patients with Peripheral Arterial Occlusive Disease.

Abstract Purpose : Peripheral arterial occlusive diseases (PAODs) not only compromise blood flow but lead to a series of subsequent metabolic and structural changes in the relevant muscles. Changes in myofibrillar proteins (eg, of myosin heavy chain [MHC] isoforms), one of the determinants of muscle structure as well as of muscular function, have not been reported in patients with PAOD and were therefore the aim of this study. Methods : Thirteen consecutive patients with PAOD were examined (clinical stage according to Fontaine II, three patients; III, three patients, and IV, seven patients) and compared with five age-matched control patients who had been in traffic accidents. A calf muscle sample (gastrocnemius muscle) in the ischemic region was taken for MHC isoform analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver stain, and the relative content of MHC isoforms was measured. Results : Compared with the control patients, there was no significant change of MHC isoforms in patients with PAOD II. In patients with PAOD III, MHC IIb decreased significantly ( P P Conclusion : In patients with PAOD, the content of MHC II decreased with a higher grade of ischemia. That seems to be consistent with an increased resistance to ischemia for myosin isoforms in the order of I more than in IIa more than IIb. Whether the decrease of MHC II in patients with PAOD is related to atrophy of muscle fibers or to muscle-fiber transition must be investigated further. (J Vasc Surg 2000;31:443-9.)

Lipoprotein(a) and apolipoprotein(a) isoforms and proteinuria in patients with moderate renal failure

Atherosclerotic diseases are a major cause of death in patients with renal failure. Increased serum concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases and have been demonstrated in patients with moderate renal failure, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. Variable alleles at the apolipoprotein(a) [apo(a)] gene locus are the main determinants of the serum Lp(a) level in the general population. The purpose of this study was to investigate apo(a) isoforms in patients with moderate renal failure and mild proteinuria (less than 1.0 g/day). In 250 consecutive subjects recruited at a hypertension clinic, we assessed the renal function by 24-hour creatinine clearance, proteinuria, and microalbuminuria, as well as the prevalence of atherosclerotic disease, and we also measured apo(a) isoforms, serum albumin, and Lp(a) concentrations. Moderate impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) was found in 97 patients. Lp(a) levels were significantly greater in patients with moderate renal failure (21.7+/-23.9 mg/dl) as compared with patients with normal renal function (15.6+/-16.4 mg/dl, P<0.001), and an inverse correlation was observed between log Lp(a) and creatinine clearance (r = -0.181, P <0.01). However, no difference was found in the frequency of low molecular weight apo(a) isoforms between patients with normal (25.5%) and impaired (27.8%) renal function. Only patients with the smallest size apo(a) isoforms exhibited significantly elevated levels of Lp(a), whereas the large-size isoforms had similar concentrations in patients with normal and impaired renal function. No significant relationship was found between serum Lp(a) and proteinuria. Clinical and laboratory evidence of one or more events attributed to atherosclerosis was found in 9.8% of patients with normal renal function and 25.8% of patients with moderate renal failure (P<0.001). These results indicate that renal failure per se or other genes beside the apo(a) gene locus are responsible for the elevation of serum Lp(a) levels in patients with moderate impairment of renal function. The elevation of Lp(a) levels occurs independently of the level of proteinuria and may contribute to the risk for atherosclerotic disease in these patients.

Increased Serum Lipoprotein(a) Levels in Patients with Early Renal Failure

Letters15 June 1999Increased Serum Lipoprotein(a) Levels in Patients with Early Renal FailureLeonardo A. Sechi, MD, Laura Zingaro, MD, and Ettore Bartoli, MDLeonardo A. Sechi, MDUniversity of Udine School of Medicine; 33100 Udine, Italy (Sechi)University of Udine School of Medicine; 33100 Udine, Italy (Zingaro)University of Udine School of Medicine; 33100 Udine, Italy (Bartoli)Search for more papers by this author, Laura Zingaro, MDUniversity of Udine School of Medicine; 33100 Udine, Italy (Sechi)University of Udine School of Medicine; 33100 Udine, Italy (Zingaro)University of Udine School of Medicine; 33100 Udine, Italy (Bartoli)Search for more papers by this author, and Ettore Bartoli, MDUniversity of Udine School of Medicine; 33100 Udine, Italy (Sechi)University of Udine School of Medicine; 33100 Udine, Italy (Zingaro)University of Udine School of Medicine; 33100 Udine, Italy (Bartoli)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-12-199906150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Both Elisaf and colleagues and Dr. De Lima report data that confirm elevation of serum Lp(a) levels in patients with early renal failure. Other groups have also reported similar data on patients with renal failure treated conservatively (1, 2). Elisaf and colleagues noted similar frequency distribution of apolipoprotein(a) isoforms in patients with normal and moderately impaired renal function. This finding is consistent with our observations. They also showed that serum Lp(a) levels are significantly increased only in the patients expressing the high-molecular-weight apolipoprotein(a) isoforms, whereas the patients expressing low-molecular-weight isoforms have Lp(a) levels similar to those in persons ...

Lipoprotein (a) and apolipoprotein (a) isoforms in patients with coronary artery disease documented by angiography

Lipoprotein (a) and apolipoprotein (a) isoforms in patients with coronary artery disease documented by angiography

Differential level of platelet amyloid beta precursor protein isoforms: an early marker for Alzheimer disease.

To determine whether a differential level of platelet amyloid beta precursor protein (APP) isoforms is specifically related to Alzheimer disease (AD) and whether it shows a correlation with the progression of clinical symptoms. After subjects were grouped according to diagnosis and severity of dementia, APP isoform levels in platelets were compared. University medical centers. Thirty-two patients who fulfilled diagnostic criteria for probable AD, 25 age-matched control subjects, and 16 patients with non-AD dementia. The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. Messenger RNAs for APP transcripts were also evaluated by means of reverse transcriptase polymerase chain reaction. The ratio between the intensity of the 130-kd and 106- to 110-kd APP isoforms was significantly lower in the AD group (0.31 +/- 0.15, mean +/- SD) compared with both controls (0.84 +/- 0.2) and non-AD subjects (0.97 +/- 0.4). The ratio of platelet APP isoforms in patients with AD grouped by Clinical Diagnostic Rating score significantly correlated with the severity of the disease (Pearson correlation coefficient, followed by Bonferroni correction, P = .01). Reverse transcriptase polymerase chain reaction experiments showed that APP transcripts in all experimental groups were equally expressed. The pattern of platelet APP isoforms is specifically altered in patients with AD. In addition, the alteration of platelet APP isoforms shows a positive correlation with the progression of clinical symptoms, supporting the possibility to consider this peripheral parameter as a marker of progression of the disease. These alterations are not related to abnormalities of APP isoforms messenger RNAs in platelets.

Serum apolipoprotein(a) concentrations and apo(a) phenotypes in patients with liver cirrhosis

Objective: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. Methods: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. Results: Apo(a) serum levels were significantly lower ( p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations ( p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. Conclusion: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apoliprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.

Serum apolipoprotein(a) concentrations and apo(a) phenotypes in patients with liver cirrhosis

Objective: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. Methods: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. Results: Apo(a) serum levels were significantly lower (p< 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p= 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. Conclusion: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apoliprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.

Serum lipids, lipoprotein(a) and apo(a) isoforms in patients with established coronary artery disease and their relation to disease and prognosis after coronary by-pass surgery

Consecutive patients ( n=964) undergoing coronary angiography were studied and compared with a random population sample regarding serum lipids and lipoproteins with focus on lipoprotein(a) (Lp(a)) levels and apo(a) isoforms. The patients were also followed for 5 years after the angiography, and the progostic value of serum lipoproteins were analyzed. The patients were divided in two groups: Group 1 ( n=814) consisted of patients with angina pectoris and at least one coronary artery with 50% stenosis and group 2 ( n=150) patients with none of the coronary arteries significantly obstructed (<50%). As controls a random population sample was selected ( n=197). Blood samples were collected before coronary angiography for determination of serum lipids, Lp(a) and isoforms of apo(a). When group 1 and group 2 patients were compared, group 1 was found to have higher serum cholesterol, triglycerides, apoB and Lp(a) as well as lower HDL and apoAI. When group 1 was compared with the random sample, after correction for age and sex, similar differences were observed, except that the difference in Lp(a) was not significant. The high Lp(a) levels among patients was found to be primarily due to the female patients, where the difference compared to both group 2 and controls was highly significant ( P=0.007 and P=0.001, respectively). There was a significant difference in the apo(a) isoform distribution between group 1 patients and control subjects ( P=0.0003), with a higher frequency of low molecular weight isoforms among patients. This was also significant for the male subgroup ( P=0.001). Lp(a), LDL, total cholesterol, triglycerides, apoB, HDL and apoAI were significantly related to the number of major coronary arteries with >50% stenosis. Mortality during follow-up was,in a univariate analysis, significantly correlated to several factors related to the degree of heart disease and to LDL ( P=0.02) and apoB ( P<0.01). Increased mortality was, however, related to low levels of apoB and LDL. For cardiac mortality no significant correlation to lipoprotein variables were found. In conclusion established lipoprotein risk factors were more frequent among patient with angina pectoris and verified coronary stenosis. Furthermore high Lp(a) levels and a high frequency of low molecular weight isoforms of apo(a) were found in coronary patients. Higher Lp(a) levels were observed both for female and male patients, the differences were, however, significant only for the female patients. None of the lipoprotein variables could predict coronary death during the follow-up period.

Fcγ Receptor IIA H/R131 Polymorphism in Patients with Antiphospholipid Antibodies

A role for Fcgamma receptor in the pathophysiology of thrombosis in APS has been hypothesized. The polymorphism of this receptor, FcgammaRIIA H/R131, is associated with the binding affinity for human IgG2 (i.e. FcgammaRIIA-H131 isoform has a higher affinity than FcgammaRIIA-R131). Since anti-beta2 glycoprotein I antibodies (anti beta2GPI), which play a major pathogenic role in APS, show IgG2 dominant distribution, we investigated the prevalence of receptor isoforms in patients with antiphospholipid antibodies (aPL) by a PCR-RFLP method. We studied 100 Caucasian patients with aPL (57 primary APS, 32 secondary APS to SLE and 11 other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131 and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 29 (29%) in the patient group, and 9 (22%), 23 (56%) and 9 (22%) in control group, respectively. Thus there was no statistically significant difference in the prevalence of each genotype in these groups. None of the clinical manifestations of primary APS (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was significantly correlated with any FcgammaRIIA genotype. In conclusion, FcgammaRIIA polymorphism did not correlate with the manifestations of APS, and FcgammaRIIA genotype is not a genetic marker of APS.

G protein subunit levels in fibroblasts from familial Alzheimer's disease patients: lower levels of the high molecular weight Gs α isoform in patients with decreased β-adrenergic receptor stimulated cAMP formation

Abnormalities in G protein linked signal transduction pathways have been detected in fibroblasts from individuals with familial and sporadic Alzheimer's disease. The present study used Gs α, Gi α, Gq α and Go α G protein subunit antisera, immunoblotting and densitometry to quantify levels of these proteins in control fibroblasts and in fibroblasts from individuals with familial Alzheimer's disease (FAD). The FAD fibroblasts were from individuals with the APP K670N,M671L mutation, different presenilin 1 (PS1) mutations and one fibroblast cell line from an individual with FAD of unknown genetic aetiology. Results revealed a significant reduction in the large Gs α subunit in fibroblasts with the PS1 mutations and in the fibroblast cell line of unknown genetic aetiology, when compared to control levels. This decrease was not apparent in the APP K670N,M671L FAD fibroblasts. Immunoreactivity for Go α was not detected in any of the fibroblast cell lines. No differences were observed in Gi α or Gq α levels when comparing any of the control and Alzheimer's disease fibroblast groups. We conclude that with the exception of decreased levels of the large Gs α subunit, gross alterations in the levels of the Gi α, Gq α and Go α are not associated with the G protein-coupled signal transduction disturbances described previously for some of these FAD fibroblasts.

Association of Serum Lipoprotein(a) Levels and Apolipoprotein(a) Size Polymorphism With Target-Organ Damage in Arterial Hypertension

To investigate the association between lipoprotein(a) [Lp(a)] and other plasma lipids and apolipoproteins and target-organ damage (TOD) in patients with arterial hypertension. Cross-sectional study of a case series. University medical center. Lipoprotein(a) and apolipoproteins were analyzed in 277 untreated patients with mild to moderate essential hypertension and in 102 healthy controls. Apolipoprotein(a) [apo(a)] phenotypes were additionally analyzed in an independent sample set of 106 hypertensive and 105 control subjects. Staging of TOD obtained according to World Health Organization guidelines by clinical evaluation, and laboratory tests including measurments of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries; levels of lipids, apolipoproteins, Lp(a), fibrinogen, and apo(a) phenotypes. Blood pressure, duration of hypertension, and levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, Lp(a), and fibrinogen were significantly related to the presence and severity of TOD in univariate analysis. Stepwise multivariate analysis showed Lp(a) levels (P<.001) to be the best discriminator of the presence of TOD, followed by systolic blood pressure (P<.001), duration of hypertension (P=.01), and low-density lipoprotein cholesterol (P=.04). The Lp(a) levels were related to TOD independent of the level of blood pressure. We confirmed this association between Lp(a) concentrations and severity of TOD in a second independent sample set and observed a significantly higher frequency of low-molecular-weight apo(a) isoforms with increasing severity of TOD (P=.02). Lipoprotein(a) and apo(a) phenotype are sensitive indicators of the severity of TOD in patients with essential hypertension, and their evaluation might permit identification of hypertensive subjects liable to the development of organ damage. The higher frequency of low-molecular-weight apo(a) isoforms in patients with TOD demonstrates a genetically determined risk for the development of TOD in hypertensive patients.

Changes in expression of transforming growth factor beta mRNA isoforms in patients undergoing tamoxifen therapy - reply

Changes in expression of transforming growth factor beta mRNA isoforms in patients undergoing tamoxifen therapy - reply

Circulating standard CD44 isoform in patients with liver disease: Relationship with other soluble adhesion molecules and evaluation of diagnostic usefulness

Objectives: To verify the diagnostic usefulness of soluble CD44 (sCD44) in liver diseases. Methods: We studied 142 subjects (90 male, 52 female): 14 had acute hepatitis (AH); 45, noncirrhotic chronic liver disease (CLD); 34, cirrhosis; 35 had extrahepatic diseases (EHD); and 14 were healthy controls. sCD44, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured immunoenzymatically. Results: Patients with AH or cirrhosis had higher sCD44 in comparison to CLD, EHD, and controls ( t < 0.01). On univariate analysis, sCD44 was associated with sVCAM-1, sICAM-1, bilirubin, cholinesterase, aspartate aminotransferase, and alkaline phosphatase ( t < 0.001). By stepwise discriminant analysis, a set of variables, including sCD44 and sVCAM-1, were entered into a model that allocated correctly 79% of observations ( t < 0.0001). However, when adhesion molecules were excluded, the model could still allocate correctly 72% of observations. Conclusion: Although sCD44 concentration increases during severe acute or chronic liver disease, its measurement adds little to the clinical information provided by traditional liver biochemistry.

FcγRIIA H/R131 Polymorphism, Subclass-Specific IgG Anti-Heparin/Platelet Factor 4 Antibodies and Clinical Course in Patients With Heparin-Induced Thrombocytopenia and Thrombosis

AbstractThe explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross-linking of FcγRIIA by anti-heparin/platelet factor 4 (PF4) antibodies is central to the pathogenesis of thrombosis. The observation that a common functional polymorphism of FcγRIIA, involving either an arginine (R) or histidine (H) at amino acid 131, may underlie disease susceptibility prompted us to investigate the prevalence of receptor isoforms in patients with HIT and HITT. Furthermore, because these isoforms reportedly differ in their avidity for immune complexes containing human IgG2 , we also analyzed sera from patients with HIT and HITT for the prevalence of various subclass-specific IgG anti-heparin/PF4 antibodies. No difference in the allele frequency of FcγRIIA-H131 or R131 was identified among 13 patients with HIT or 23 with HITT compared with 102 controls (χ2 = 1.21, P = .8). Furthermore, although most patients had IgG2 antibodies (62%), IgG1 was the predominant subclass in 30 of the 34 patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive subclass found. Also, there was no association between the concordance of IgG2 anti-heparin/PF4 antibodies and the expression of FcγRIIA-H131 in patients with HITT compared with patients with thrombocytopenia alone. These results make it unlikely that the FcγRIIA-H131 isoform or IgG2 anti-heparin/PF4 antibodies are required to develop HITT, suggesting that factors in addition to cross-linking of FcγRIIA receptors contribute to the pathogenesis of thrombosis in patients with heparin-dependent antiplatelet antibodies.