Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 109 records · Page 6Linked to original sources

PubMed2001

Dystrophin-deficient myocardium is vulnerable to pressure overload in vivo.

OBJECTIVE: Dystrophin provides mechanical reinforcement to the membranes of myocytes. Dystrophin abnormalities are known to cause cardiomyopathy and skeletal muscle disorders; however, the pathogenesis of these abnormalities remains unclear. Dystrophin-deficient skeletal muscle is vulnerable to stresses such as stretch and hypo-osmotic shock. We investigated whether the myocardium of dystrophin-deficient (mdx) mice shows increased vulnerability to acute pressure overload in vivo. METHODS AND RESULTS: Abdominal aortic banding was performed in 12-week-old mdx and control mice. The aortic pressure was measured by cannulation of the right carotid artery at the time of sacrifice. Systolic pressures in mdx mice at 0, 1, 2, 7 and 14 days after aortic banding were 100 +/- 11, 119 +/- 7, 123 +/- 4, 134 +/- 11 and 130 +/- 10 mmHg, respectively. Microscopic analysis revealed focal lesions in the left ventricular wall in banded mdx mice. These lesions consisted of damaged myocytes and inflammatory cells, and also of fibrosis at a late stage. Similar lesions were not observed in non-banded or banded control mice. The proportion of areas of lesions to total left ventricular area increased over time: 1.0 +/- 0.6% in mdx mice without aortic banding (sham, n = 6), and 1.7+/-1.4% 1 day (n = 6, vs. sham, NS), 2.6 +/- 1.9% 2 days (n = 7, vs. sham, P < 0.05), 6.3+ /- 6.5% 7 days (n = 13, vs. sham, P < 0.05) and 9.9 +/- 8.3% 14 days after aortic banding (n=15, vs. sham, P < 0.01). Furthermore, linear regression analysis revealed a significant correlation between percentage of lesion area and systolic pressure in mdx mice (P < 0.05). CONCLUSION: Dystrophin-deficient myocardium is more vulnerable than normal myocardium to pressure overload in vivo. This result has two clinical implications: (1) the patients with dystrophynopathy, such as the Duchenne and the Becker types of muscular dystrophy and X-linked type of dilated cardiomyopathy, who develop arterial hypertension should be treated aggressively, and (2) they should avoid stresses that elevate blood pressure.

Animals↗

PubMed2001

Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.

BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

14-3-3 Proteins↗

PubMed2001

Can conditioned histamine release occur under urethane anesthesia in guinea pigs?

Many clinical and experimental data have shown that learning can occur under general anesthesia. To clarify this possibility with respect to allergic reactions, particularly asthmatic responses, we first established classical conditioned histamine release in response to a neutral odor by using pairings of the odor and an inhaled antigen for five sessions (Experiment 1) and then investigated whether conditioned histamine release into the plasma, bronchoalveolar lavage fluid (BALF), and lung tissue, which followed such a conditioning procedure, would be produced in urethane-anesthetized guinea pigs in the presence or absence of antigen (Experiment 2). Ovalbumin (OA) was used as the unconditioned stimulus (US) and dimethylsulfide (DMS) served as the conditioned stimulus (CS) in both experiments. In Experiment 1, the plasma histamine levels in the conditioned group increased significantly more than those of the unpaired control group in response to the CS during consciousness. In Experiment 2 in the absence of antigen, however, no significant differences in the histamine levels were found regarding the groups (DMS, triethylamine, saline, or unsensitized) or the time course (before, immediately, 5 min, and 10 min after the inhalations) during anesthesia, except for the finding that the histamine levels in the lung tissue specimens from the DMS group were significantly higher than those from the triethylamine group. In Experiment 2 in the presence of antigen, there was a significant increase in the plasma histamine levels after exposure to the US, irrespective of the presence of the CS, however, no significant difference in the histamine levels was observed between the US and the CS+US groups. These results indicated that a classically CS might not induce asthmatic responses under anesthesia.

Anesthesia, Intravenous↗

PubMed2001

Effect of phorbol ester and calcium ionophore on human thymocytes.

Positive selection of immature thymocytes is a developmental process in which TCR ligation with low avidity induces generation of mature T cells. In mouse thymocytes, CD4(+)8(+) double-positive (DP) cells which were treated with a proper combination of calcium ionophore ionomycin and phorbol 12-myristate 13-acetate (PMA) have been reported to differentiate into CD4 single positive cells. However, in human thymocytes the effects of PMA and ionomycin have remained unclear. Here we report that DP cells that were treated with PMA and ionomycin up-regulated bcl-2 and down-regulated CD1 expression. However, CD3 expression remained low. This treatment induced prolonged CD4 down-regulation in DP cells which was an effect also seen in mature peripheral blood T cells. PMA/ionomycin-treated DP cells showed high cell proliferation and resistance to dexamethasone-induced apoptosis. These results indicate that PKC activation and calcium elevation may be part of the biochemical signals that induce positive selection of human DP cells and the system described in this paper may be a useful model to study the signals involved in the selection of human thymocytes.

Antigens, CD1↗

PubMed2001

Intracellular cytokine profile of CD14 positive cells in patients with hematologic malignancies and solid tumors during hematologic recovery phase after intensive chemotherapy designed to mobilize peripheral blood stem cells.

We studied intracellular cytokines in monocytes by flow cytometry from 28 patients with hematologic malignancies and solid tumors to analyze the role of monokines in the hematologic recovery phase for peripheral blood stem cell harvest. The patients were divided into three groups: the first group, A, had a documented infection; the second group, B, had fever of unknown origin; and the third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL-6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured with lipopolysaccharide in all groups, but no increase was found with medium only when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL-8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but only in group A. The rate of intracellular cytokine positive cells was higher in monocytes cultured with only autologous serum from group A patients compared to those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha reached statistical significance (P < 0.05). However, increasing intracellular cytokine levels in the control group of patients exhibiting only infectious disease were observed. Thus, it appear that pro-inflammatory intracellular cytokine levels in monocytes are only related to microbial infections.

Adult↗

PubMed2001

The conserved residues of the ligand-binding domains of steroid receptors are located in the core of the molecules.

The relationship between conserved residues and biochemical functions of steroid receptors was investigated. Pairwise three-dimensional (3D) alignment of the ligand-binding domains of the human estrogen (1A52) and progesterone (1A28) receptors revealed two conserved domains; Asn313-Ser456 and Gln471-Lys531 (numbering reflects the sequence in the human estrogen receptor). Alignment of the protein sequences of 39 steroid receptors revealed 36 highly conserved residues (i.e., the residues commonly found in more than 80% of sequences aligned). They were distributed throughout the sequences but formed a contiguous 3D structure. Most of these highly conserved residues were buried in the ligand-binding domain, but several residues were exposed on the surface. The well-known functions commonly associated with the ligand-binding domain of steroid receptors are ligand binding, HSP90 binding, transcriptional activation and dimerization. The relationship between the residues and these functions were checked. To determine the residues involved in dimerization, the differences between the solvent accessibilities of the monomeric and dimeric forms were calculated. These results revealed 32 residues of 1A52 and 15 residues of 1A28 potentially involved in dimerization. Their distribution areas do not overlap greatly. Comparing these putative dimerization sites with highly conserved residues, many of the exposed conserved residues were observed on the side of the domain opposite are the dimerization sites. Some highly conserved residues are located in a steroid-binding site and in transcriptional activation domain. However, few of them were observed in the HSP90 binding site. These results indicate that the core structure made by most of the highly conserved residues among the ligand-binding domains of steroid receptors is important. These conserved residues may be essential for conformational change in the ligand-binding domain from its inactive to active form.

Amino Acid Motifs↗

PubMed2001

Detection of the exogenous hGDNF in gerbils under the treatment with AxCAhGDNF adenoviral vector.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors and promotes survival in many populations of cells. We examined the neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia [Brain Res. 885 (2000) 273-282]. Gerbils received AxCAhGDNF or an adenoviral vector encoding bacterial beta-galactosidase gene (AxCALacZ) through administration into the lateral ventricle. Two days later, occlusion of the common carotid arteries for 5 min bilaterally using aneurysm clips produced transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by the adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA-1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. In this paper, we describe in detail the techniques for the detection of the exogenous gene of hGDNF under the treatment with AxCAhGDNF.

Adenoviridae↗

PubMed2001

Ly49 and CD94/NKG2: developmentally regulated expression and evolution.

Murine natural killer (NK) cells express two families of MHC class I-specific receptors, namely the Ly49 family and CD94/NKG2 heterodimers. Stochastic co-expression of these receptors generates diverse receptor repertoires in adult NK-cell populations, whereas fetal NK cells have much more limited receptor diversity as they mostly express CD94/NKG2A but not Ly49. These receptors are also expressed on CD8-T cells and NK1.1+ T cells and regulate their functions, but their expression pattern on NK cells is significantly different from those on T cells. Thus, expression of Ly49 and CD94/NKG2 is developmentally regulated. NK cells acquire the Ly49 family of receptors in an orderly manner as they differentiate from bone marrow progenitors in vitro. Similarly, acquisition of CD94 and NKG2 by NK cells as they differentiate from embryonic stem cells is also orderly To gain insight into the mechanisms regulating Ly49 expression, potential regulatory regions of several Ly49 genes have been examined. Ly49 genes with different expression patterns have remarkably similar sequences in the putative regulatory regions. Finally, a functional Ly49 gene has been identified in baboon, and primate comparisons suggest that functional extinction of the Ly49 gene in the human lineage seems to have been a relatively recent event.

Amino Acid Sequence↗

PubMed2001

Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

Animals↗

PubMed2001

Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector.

We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.

Animals↗

PubMed2001

Nonsurgical treatment of an upper thoracic spinal subdural hemorrhage.

STUDY DESIGN: A case report of an upper thoracic spinal subdural hemorrhage which was managed successfully by conservative treatment. OBJECTIVES: Spinal subdural hemorrhage is rare and can cause serious neurologic symptoms. Surgery is the most common treatment and is believed to prevent further neurologic injury. A case of an upper thoracic spinal subdural hemorrhage which was managed successfully by conservative therapy is reported. SETTING: Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara, Japan. METHODS: A 29-year-old woman presented with acute severe back pain. She experienced acutely developed weakness of both lower extremities, hypesthesia below T6 and urinary retention. Magnetic resonance imaging performed on the day of hospital admission revealed the existence of a subdural hematoma in the upper thoracic spine. Muscle strength of the lower extremities was grade 0 on admission, but improved slightly on day 1. The decision was made to manage the patient nonoperatively by corticosteroid and diuretic administration. RESULTS: Improvement was gradual but progressive. Muscle strength was grade 4 out of 5 on the 28th day. Magnetic resonance imaging at 3 months except for mild urinary retention. CONCLUSIONS: Spinal subdural hemorrhage can be treated nonoperatively by correlating magnetic resonance image findings with the clinical condition.

Adult↗

PubMed2001

A fluorescent probe for monitoring nitric oxide production using a novel detection concept.

A fluorescent probe using a novel 'spin exchange' concept was developed for monitoring nitric oxide (NO) production. The probe is composed of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) labeled with acridine and N-dithiocarboxysarcosine (DTCS)-Fe(II) complex. When the non-fluorescent acridine-TEMPO was incubated with DTCS-Fe(II) complex in buffer solution, the nitroxide radical in the acridine-TEMPO interacted with the Fe(II) through a redox interaction. This interaction recovered the fluorescence based on the acridine moiety. The addition of an NO-releasing reagent caused a fluorescent decrease of the probe due to the irreversible binding of NO to the Fe(II), and the amount of the fluorescent decrease strictly corresponded to that of released NO. Using this probe, less than 100 nM of NO can be detected. This probe system is not only useful for monitoring direct production of NO in an aqueous solution, but is also interesting as a basic concept by which to construct new types of NO fluorescent probes.

Electron Spin Resonance Spectroscopy↗

PubMed2001

Pyrogenic cytokines injected into the rat cerebral ventricle induce cyclooxygenase-2 in brain endothelial cells and also upregulate their receptors.

Peripheral immunological insults induce interleukin (IL)-1 beta and IL-6 in the brain. To elucidate the mechanism(s) of fever evoked by these brain-derived cytokines, and possible interactions between them, we examined in rats: (i) whether cyclooxygenase-2 is responsible for fever evoked by central injection of these cytokines; (ii) if so, where in the brain cyclooxygenase-2 is induced; (iii) where the receptors for these cytokines are located; and (iv) how the expression of these receptors is influenced by the cytokines. Intracerebroventricular injection of these cytokines evoked fever that was suppressed by a cyclooxygenase-2 inhibitor. Brain endothelium was the site of cyclooxygenase-2 induction by these cytokines. IL-1 receptor (IL-1R) was constitutively expressed in brain endothelium, and its mRNA was further upregulated by either cytokine. IL-6R mRNA was constitutively expressed in the cerebral cortex, and was newly induced in as yet unidentified cells in brain blood vessels by either cytokine. Messenger RNAs for cyclooxygenase-2, IL-1R, and IL-6R were often observed in the same blood vessels. These results suggest that COX-2 induced in brain endothelium is, at least in part, involved in the fever evoked by these cytokines, and that one possible interaction between these two cytokines is mutual upregulation of their receptors in the endothelium or perivascular cells, resulting in augmentation of their actions.

Animals↗

PubMed2001

Lymph node micrometastasis and prognosis in patients with oesophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate whether the presence of lymph node micrometastasis in pathological lymph node-negative (pN0) oesophageal squamous cell carcinoma had prognostic value. METHODS: Some 1840 lymph nodes were obtained from 50 patients with pN0 oesophageal squamous cell carcinoma who underwent curative resection of the primary tumour with systematic lymphadenectomy. These lymph nodes were examined immunohistochemically with anticytokeratin antibody (AE1/AE3). Lymph node micrometastases newly detected by immunohistochemistry were classified as micrometastasis. Additionally, lymph node micrometastases were classified into three stages: stage 1, one individual AE1/AE3-positive cell; stage 2, multiple individual positive cells; stage 3, one or multiple positive clusters. RESULTS: Micrometastases were detected in 20 patients (40 per cent). A higher stage of micrometastasis was associated with greater pathological tumour (pT) size (P = 0.023). Recurrent tumours developed in nine patients. However, the frequency of recurrence was similar in patients with, or without, micrometastasis (five of 20 and four of 30 patients respectively; P = 0.25). Twenty-three of 30 patients without micrometastasis survived, whereas 15 of 20 patients with micrometastasis were still alive (5-year overall survival 75 and 78 percent respectively, P = 0.91). Twenty-six of 30 patients without micrometastasis had no recurrence, whereas 15 of 20 patients with micrometastasis had no recurrence (5-year relapse-free survival 86 and 73 per cent respectively, P = 0.37). There was no significant difference in prognosis with respect to the stages of micrometastasis. Multivariate analysis also showed that micrometastasis was not an independent prognostic factor (P = 0.73). CONCLUSION: Immunohistochemical detection of lymph node micrometastasis may be an indicator of lymphatic dissemination of tumour cells. However, the presence of micrometastasis had no impact on the prognosis of node-negative patients with oesophageal squamous cell carcinoma.

Aged↗

PubMed2001

Crk family adaptor proteins trans-activate c-Abl kinase.

BACKGROUND: c-Abl kinase is activated in response to a variety of biological stimuli. Crk family adaptor proteins can interact physically with c-Abl and be involved in the activation of c-Abl kinase. RESULTS: We report that the Crk family of adaptor proteins act as trans-acting activators of c-Abl kinase. The interaction of the amino-terminal Src-homology (SH) 3 domain of c-Crk and the proline-rich motifs of c-Abl is an essential step for the phosphorylation of c-Crk by c-Abl, as well as the activation of c-Abl by c-Crk. The activation of c-Abl by c-Crk is negatively regulated by phosphorylation of the tyrosine 221 of c-Crk. Our data suggest that, in the absence of phosphorylation of the tyrosine Y221, the SH2 domain of c-Crk becomes free to bind to target molecules while the carboxyl-terminal SH3 domain of c-Crk binds to the proline-rich region of c-Abl, inducing the activation of c-Abl by c-Crk. CONCLUSION: This study suggests that the Crk family functions as trans-acting activators of c-Abl kinase. The phosphorylation of c-Crk may regulate c-Abl kinase.

Animals↗

PubMed2001

Spatial expression patterns of genes involved in cyclic AMP responses in Dictyostelium discoideum development.

The spatial expression patterns of genes involved in cyclic adenosine monophosphate (cAMP) responses during morphogenesis in Dictyostelium discoideum were analyzed by in situ hybridization. Genes encoding adenylyl cyclase A (ACA), cAMP receptor 1, G-protein alpha2 and beta subunits, cytosolic activator of ACA (CRAC and Aimless), catalytic subunit of protein kinase A (PKA-C) and cAMP phosphodiesterases (PDE and REG-A) were preferentially expressed in the anterior prestalk (tip) region of slugs, which acts as an organizing center. MAP kinase ERK2 (extracellular signal-regulated kinase-2) mRNA, however, was enriched in the posterior prespore region. At the culmination stage, the expression of ACA, CRAC and PKA-C mRNA increased in prespore cells in contrast with the previous stage. However, no alteration in the site of expression was observed for the other mRNA analyzed. Based on these findings, two and four classes of expression patterns were catalogued for these genes during the slug and culmination stages, respectively. Promoter analyses of genes in particular classes should enhance understanding of the regulation of dynamic and coordinated gene expression during morphogenesis.

Animals↗

PubMed2001

Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement.

AIM: The aim of this study was to examine the effectiveness and toxicity of radiation therapy in combination with transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with extensive portal vein tumor thrombus (PVTT). METHODS: The combined therapy was performed in 24 HCC patients with extensive PVTT. External radiation targeted for PVTT (50 Gy in 2 Gy fractions) was performed in combination with repetitive TACE for intralobar lesions using 30-60 mg epirubicin every 3 months, and associations of the following variables with the survival rate were evaluated: gender, age, viral etiology, Child's class, performance status, extrahepatic metastasis, size and number of HCC, and location of PVTT. RESULTS: The local response confined to PVTT was complete response (CR) in four patients, partial response (PR) in eight patients, no change (NC) in eight patients, and progressive disease (PD) in four patients. By using the stepwise Cox's regression analysis, only Child's class was associated with the survival rate. The survival rates after 1 and 2 years were 73 and 21% in Child's A, 10 and 0% in Child B or C, and 61 and 21% in patients in whom the local response was CR or PR, and 19 and 9% in those in whom the local response was NC or PD, respectively. By using the multiple logistic regression analysis, Child's class was the only factor associated with the local response (P = 0.006). CONCLUSIONS: The combined therapy is feasible and may be useful to reverse PVTT in patients with good hepatic function reserve.

Antineoplastic Agents↗

PubMed2001

Reduced urinary excretion of intact osteopontin in patients with IgA nephropathy.

Osteopontin (OPN) is a phosphoprotein secreted by many cells of epithelial, mesenchymal, and hematopoietic origin. In the kidney, OPN is expressed in the renal tubules and collecting ducts and is excreted into the urine. A pathophysiologic role for urinary OPN has not been established. In this study, urinary excretion of OPN was analyzed in patients with primary glomerular diseases, including immunoglobulin A nephropathy (IgAN; n = 32), minimal change nephrotic syndrome (MCNS; n = 16), and membranous nephropathy (MN; n = 18). Compared with normal controls (n = 20), mean +/- SD of urinary OPN in IgAN patients was decreased significantly (21.4 +/- 6.2 versus 11.6 +/- 9.6 mg/g creatinine, P: < 0.001). In contrast, the levels of urinary OPN in patients with MCNS or MN did not differ significantly from normal values. Immunoblot analysis showed that OPN is present as a 55- to 60-kd molecule in normal urine. A 34-kd fragment of OPN was the major immunoreactive band in samples from IgAN patients. This fragment also was detectable in the urine from some patients with MCNS or MN but was absent in normal subjects. OPN has a thrombin-cleavage site near its central portion. Thrombin treatment of the urine from normal controls could result in 34-kd OPN fragments. Although the underlying mechanisms remain to be determined, these data provide evidence that secretion or processing (or both) of urinary OPN is altered in patients with IgAN.

Adult↗