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PubMed1997

[Carnitine deficiency in inborn errors of metabolism].

Several conditions, considered as inborn errors of metabolism, involve severe deficiencies in carnitine in both plasma and muscle. In the absence of evidence suggesting primary carnitine deficiency due to a biosynthetic enzymatic defect in the liver, the various diseases with carnitine deficiency are related to genetic defects in organic acid metabolism leading to blocked mitochondrial beta oxidation. We describe a 4.5-year-old boy and 2 female infants with glutaric aciduria type I, isovaleric acidemia, and long-chain acid dehydrogenase deficiency, in whom severe carnitine deficiency was apparent. In all 3, long-term carnitine treatment proved to be vital and eliminated most of the symptoms.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1998

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes--effect of clofibrate-feeding.

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes was investigated. In the control hepatocytes, NAD+ synthesis from tryptophan was not affected by nicotinic acid from 0.026 to 0.26 mM. NAD+ synthesis from nicotinic acid was slightly inhibited with varying concentrations of tryptophan from 0.1 to 1.0 mM. In the clofibrate-treated hepatocytes, NAD+ synthesis from tryptophan was greatly increased (234% of the control), while that from nicotinic acid was decreased (71.2% of the control). Both, NAD+ synthesis from tryptophan and that from nicotinic acid were decreased by the coexisting nicotinic acid or tryptophan. Total amount of NAD+ synthesized from tryptophan and nicotinic acid at their physiological concentrations was significantly higher than that in the control hepatocytes as a result of a large increase of NAD+ synthesized from tryptophan. When the metabolic flux of 0.1 or 0.5mM tryptophan was investigated, the glutarate pathway was suppressed in the clofibrate-treated hepatocytes, the quinolinic acid-NAD+ flux being elevated. Similarly to clofibrate, DEHP and CPP revealed an increase in NAD+ synthesis from tryptophan. Mutual relationship of NAD+ biosyntheses from tryptophan and nicotinic acid in rat hepatocytes is discussed and the relevance with peroxisomal proliferation is suggested.

Animals↗
PubMed1998

Capillary electrophoresis for rapid profiling of organic acidurias.

Organic acids analysis is a powerful technique in the diagnosis of inborn errors of metabolism. Clinically, patients present with severe symptoms, and early detection and appropriate treatment are often lifesaving. Most of the existing methods are based on gas chromatography in combination with mass spectrometry and require sophisticated equipment and complex sample pretreatment and derivatization. We propose a rapid, simple, and automated capillary electrophoretic method for routine analysis of urine to detect 27 organic acids related to metabolic diseases. With this method, direct measurements are performed on samples after initial centrifugation and dilution, if needed. Separation is performed in pH 6.0 phosphate buffer with methanol added as an organic modifier, -10 kV applied potential, and ultraviolet detection at 200 nm. The assay is completed in <15 min, and alternative separation conditions are proposed in case of overlapping peaks. The developed method allows the identification and quantitation of methylmalonic, pyroglutamic, and glutaric acids in samples of patients with diseases related to these acids.

Carboxylic Acids↗
PubMedDate not supplied

[Physical-mechanical and functional characteristics of xenograft during various methods of stabilization and treatment].

The paper gives the results of experimental studies of the elastic-strength and functional characteristics of xenotissue samples (the pericardium of the calf, pig and Glisson's capsule) stabilized with glutaric aldehyde and polyepoxy compounds. The paper discusses various treatments of biological materials (including Glisson's capsule) anticalcified with additives (sodium dodecyl sulfate, complexes of copper and zinc) and shows that their use improves proteolytic and calcinotic resistance without deteriorating the mechanical parameters of xenotissues. Comparative analysis of the physical-mechanic and functional characteristics of xenotissues treated in different ways allows one to make anticalcifying treatment of biological tissues with copper and zinc complexes physical-mechanic and functional characteristics of xenotissues (Glisson's capsule) for clinical application.

Animals↗
PubMed1994

Methylene blue-induced Heinz body hemolytic anemia.

OBJECTIVE: To describe the manifestations of methylene blue toxicity, with a review of the literature. DESIGN: A descriptive analysis of physical findings and significant laboratory tests in patients with methylene blue toxicity. SETTING: A pediatric referral center. PATIENTS: Two infants, one a neonate with trisomy 21 exposed to methylene blue as an intraoperative diagnostic marker and the other a neonate treated with methylene blue for type II glutaric acidemia. INTERVENTIONS: Laboratory tests to define the occurrence of methylene blue toxicity, phototherapy for hyperbilirubinemia, and transfusions for anemia. MEASUREMENTS AND RESULTS: Within hours after exposure to methylene blue, the infants voided green-blue urine, followed by hyperbilirubinemia, recurrent anemia requiring transfusions, and red blood cell dysmorphology, including the appearance of blister cells and Heinz bodies visible in both Wright's- and supravital-stained peripheral blood smears. After the initiation of phototherapy, both infants exhibited cutaneous bullae followed by desquamation. CONCLUSION: Significant neonatal morbidity may occur following postpartum administration of methylene blue. Toxic manifestations include hyperbilirubinemia, Heinz body hemolytic anemia, and possibly desquamation of the skin. In our infants toxicity was secondary to an overdose of methylene blue, as is true for most of the previously reported cases. Methods for defining the mechanism of dye-related hemolysis and simple screening tests for elucidating the unique sensitivity of certain individuals to dye toxicity are suggested.

Anemia, Hemolytic↗
PubMed1998

Improved local delivery of TGF-beta2 by binding to injectable fibrillar collagen via difunctional polyethylene glycol.

To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor beta2 (TGF-beta2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-beta2. Covalent binding was achieved in a two-step procedure: First, TGF-beta2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-beta2 (PEG-TGF-beta2) was bound to the fibrillar collagen (FC-PEG-TGF-beta2). Initial binding of TGF-beta2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-beta2 and Western blot analysis, using a TGF-beta specific antibody, demonstrated that at least 85% of the TGF-beta2 was bound to the fibrillar collagen. The activity of PEG-TGF-beta2 was fully stable in phosphate-buffered saline at 4 degrees C and 37 degrees C for at least up to 4 weeks. Unmodified TGF-beta2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-beta2 containing 40 microg/ mL TGF-beta2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-beta2-containing formulations showed the TGF-beta typical fibroblastic response at the day 7 time point. Covalent binding of TGF-beta2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-beta2 response than that observed with admixed formulations of collagen and TGF-beta. The TGF-beta response with FC-PEG-TGF-beta2 lasted up to day 42 but was not seen after day 7 for TGF-beta2 admixed to FC. These findings clearly demonstrate that TGF-beta2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-beta responses and stabilizes the TGF-beta in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents.

Animals↗
PubMed1997

Modification of swelling-contraction-aggregation processes in rat muscle mitochondria by the 1,4-dihydropyridines, cerebrocrast and glutapyrone, themselves and in the presence of azidothymidine.

The influence of the 1,4-dihydropyridines (DHPs), water-soluble glutapyrone available as sodium, potassium and ammonium salts of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-DHP-4-carboxamide)glutaric acid, from one side, and a lipophylic cerebrocrast, 2-propoxyethyl 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-DHP-3,5-dicarboxylate, from the other side, on partially damaged mitochondria of the Wistar rat hindlimb muscle was also studied. The following tests were made: (1) rates of endogenous respiration and substrate (succinate) oxidation and oxidative phosphorylation; (2) rates and amplitudes of high-amplitude swelling and contraction after the addition of ATP, ADP and succinate to the previously swollen mitochondria and (3) rate of reversible self-aggregation of mitochondria isolated in salt media after ATP-induced contraction without and in the presence of azidothymidine (AZT). Cerebrocrast (10-100 microM) partially normalized the endogenous respiration rate and slightly augmented the respiration rate after the addition of succinate and to lesser extent ADP. Cerebrocrast in a concentration-dependent manner (2.5-50 microM) increased (two-fold at 20-50 microM) the active contraction amplitude of swollen mitochondria, induced by single or repeated additions of ATP. The influence of cerebrocrast on the ADP- and succinate-induced contractions was less obvious. Unlike cerebrocrast glutapyrone caused a reduction of the ATP-induced contraction amplitude (two-fold at 0.5-5.0 mM), not impairing the mitochondrial contraction ability in response to ATP or succinate. Pre-exposure to 2.5 mM glutapyrone resulted in at least a 10-fold inhibition of the reversible aggregation rate in the presence of 99 and 198 microM AZT. The results suggest the usefulness of further study of cerebrocrast and glutapyrone in preventing AZT-induced and some other mitochondrial myopathies.

Adenosine Diphosphate↗
PubMed2001

Chemical synthesis of cross-linked poly(KGGVG), an elastin-like biopolymer.

Previous studies afforded on peptides and polypeptides containing repetitive sequences of elastin have largely demonstrated that their molecular and supramolecular properties are fully representative of those of tropoelastin, the soluble, linear precursor of elastin itself. In the attempt to synthesize cross-linked elastin-mimetic polypeptides, the repeating sequence VGGVG (V: valine; G: glycine), typical of elastin, was modified to incorporate lysine residues, yielding the polymer poly(KGGVG) (K: lysine). This imparts primary amine functionality susceptible to cross-linking reaction with appropriate bifunctional cross-linking reagents. We report herein the chemical synthesis and cross-linking of poly(KGGVG) with glutaraldehyde (GTA) and with disuccinimidyl glutarate (DSG). In both cases, the characterization of the polymers, both linear and cross-linked, has been carried out by CD spectroscopy and transmission electron microscopy measurements. The obtained results, although not conclusive, demonstrate that poly(KGGVG), both linear and cross-linked, may be considered very similar to tropoelastin and mature elastin, as concerns its molecular and supramolecular properties.

Animals↗
PubMed1987

Renal-hepatic-pancreatic dysplasia: a syndrome reconsidered.

Five infants, three dying neonatally and two later in the first year of life, had renal, hepatic, and pancreatic dysplasia, a combination of abnormalities first described by Ivemark et al [1959]. The renal malformation consisted of cystic dysplasia, with abnormally differentiated ducts, deficient nephron differentiation, and glomerular cysts. The hepatic abnormality consisted of enlarged portal areas containing numerous elongated biliary "profiles," with a tendency to perilobular fibrosis. Serial liver biopsies in one child with cholestasis from birth showed a progression from bile duct paucity at 1 1/2 wk to typical biliary "dysgenesis" at 7 mo. Four of the five children had intrahepatic ductal dilatation, diagnosed ante mortem in the two older children as Caroli disease. The pancreatic abnormality consisted of fibrosis and cysts, with a diminution of parenchymal tissue. The clinical and functional reflection of these abnormalities in the two children surviving the newborn period included renal insufficiency, chronic jaundice, and insulin-dependent diabetes mellitus. Similar renal, hepatic, and pancreatic abnormalities occur in other syndromes, including trisomy 9, Meckel syndrome, Jeune, Saldino-Noonan, and Elejalde types of chondrodysplasia, and glutaric aciduria II. After exclusion of identifiable syndromes, the remaining cases of renal-hepatic-pancreatic dysplasia do not necessarily constitute a homogeneous group.

Abnormalities, Multiple↗
PubMed1991

Antibody responses of mice exposed to low-power microwaves under combined, pulse-and-amplitude modulation.

Irradiation by pulsed microwaves (9.4 GHz, 1 microsecond pulses at 1,000/s), both with and without concurrent amplitude modulation (AM) by a sinusoid at discrete frequencies between 14 and 41 MHz, was assessed for effects on the immune system of Balb/C mice. The mice were immunized either by sheep red blood cells (SRBC) or by glutaric-anhydride conjugated bovine serum albumin (GA-BSA), then exposed to the microwaves at a low rms power density (30 microW/cm2; whole-body-averaged SAR approximately 0.015 W/kg). Sham exposure or microwave irradiation took place during each of five contiguous days, 10 h/day. The antibody response was evaluated by the plaque-forming cell assay (SRBC experiment) or by the titration of IgM and IgG antibodies (GA-BSA experiment). In the absence of AM, the pulsed field did not greatly alter immune responsiveness. In contrast, exposure to the field under the combined-modulation condition resulted in significant, AM-frequency-dependent augmentation or weakening of immune responses.

Animals↗
PubMed2006

A flexible method for preparation of peptide homo- and heterodimers functionalized with affinity probes, chelating ligands, and latent conjugating groups.

Dimerization of peptides can provide high binding entities to serve as targeted diagnostics or therapeutics. We developed methods for the preparation of homo- and heterodimer peptides bearing functional molecules (affinity probes, chelating ligands, or latent conjugating moieties). Monomer peptides, optionally bearing spacer groups, are tethered using a bifunctional linker, (di-succinimidyl glutarate, DSG) to provide the dimers. Protected or unprotected peptides can be employed for dimer assembly. Multiple lysine N(epsilon)-amino groups are controlled using the (4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde) protecting group. Functional molecules are optionally incorporated into the component peptides or into the assembled dimer. The methods are efficient and scaleable.

Amino Acid Sequence↗
PubMed1986

Mass spectrometric identification of 2-hydroxy-sebacic acid in the urines of patients with neonatal adrenoleukodystrophy and Zellweger syndrome.

The urines of children with neonatal adrenoleukodystrophy and Zellweger syndrome contained an excess of unusual even- and odd-numbered dicarboxylic acids with a chain length of from 5 to 15 carbon atoms, as well as 2-hydroxy-compounds, including 2-hydroxy-isocaproate, 2-hydroxy-glutarate and 2-hydroxy-sebacate. The latter product, not previously found in metabolic diseases, appears as an additional useful marker of these peroxisomal disorders.

Adrenal Gland Diseases↗
PubMed1991

Metabolism of deuterium-labeled nonanoic acids in the riboflavin-deficient rat model of multiple acyl-CoA dehydrogenase deficiency.

Riboflavin-deficient rats are used to study the metabolism of deuterium-labeled nonanoic acids under conditions mimicking the human disorder of multiple acyl-CoA dehydrogenase deficiency in which large amounts of ethyl-malonic, glutaric, adipic, suberic, 4-octenedioic, sebacic and 4-decenedioic acids are excreted. Both control and deficient rats convert the nonanoic acids to labeled azelaic and pimelic acids. The labeling pattern in pimelic acid is consistent with the omega-oxidation of nonanoic acids to azelaic acid followed by beta-oxidation to pimelic acid.

Acyl-CoA Dehydrogenases↗
PubMed2003

Hybrid organic-inorganic 1D and 2D frameworks with epsilon-Keggin polyoxomolybdates as building blocks.

Organic-inorganic hybrid materials based on polyoxometalate building blocks with capping La3+ ions and bidentate oxygenated ligands have been obtained by reaction at room temperature of the [epsilon-PMo12O36(OH)4[La(H2O)4]]5+ polyoxocation with glutarate (C5H6O(2)(2-)) and squarate (C4O(4)(2-)) organic ligands. [epsilon-PMo12O37(OH)3[La(H2O)4(C5H6O4)0.5]4].21 H2O (1) and [epsilon-PMo12O39(OH)[La(H2O)6]2-[La(H2O)5(C4O4)0.5]2].17 H2O (2) form unprecedented 1D chains built from alternating polyoxocations and organic ligands connected through LaO links. The structures of these materials are compared to the 2D hybrid organic-inorganic framework [NC4H12]2-[Mo22O52(OH)18[La(H2O)4]2[La(CH3CO2)2]4].8H2O (3) isolated from the hydrothermal reaction of elemental precursors (MoO(4)(2-), Mo, La3+) in acetate buffer. Compound 3 is built from previously undescribed polyoxometalate units with twenty-two MoV centers capped by six La3+ ions, four of which are bridged by acetate ligands.

Journal Article↗
PubMed2004

Glutamine-induced free radical production in cultured astrocytes.

Ammonia is a neurotoxin implicated in the pathogenesis of hepatic encephalopathy, Reye's syndrome, inborn errors of the urea cycle, glutaric aciduria, and other metabolic encephalopathies. Brain ammonia is predominantly metabolized to glutamine in astrocytes by glutamine synthetase. While the synthesis of glutamine has generally been viewed as the principal means of ammonia detoxification, this presumed beneficial effect has been questioned as growing evidence suggest that some of the deleterious effects of ammonia may be mediated by glutamine rather than ammonia per se. Since ammonia is known to induce the production of free radicals in cultured astrocytes, we investigated whether such production might be mediated by glutamine. Treatment of astrocytes with glutamine (4.5 mM) increased free radical production at 2-3 min (95%; P < 0.05), as well as at 1 and 3 h (42% and 49%, respectively; P < 0.05). Similarly treated cultured neurons failed to generate free radicals. Free radical production by glutamine was blocked by the antioxidants deferoxamine (40 microM) and alpha-phenyl-N-tert-butyl-nitrone (250 microM), as well as by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (500 microM). Free radical production was also blocked by 6-diazo-5-oxo-L-norleucine (1 mM), an inhibitor of glutaminase, suggesting that ammonia released by glutamine hydrolysis may be responsible for the generation of free radicals. Additionally, the mitochondrial permeability transition inhibitor, cyclosporin A, blocked free radical production by glutamine. The results indicate that astrocytes, but not neurons, generate free radicals following glutamine exposure. Glutamine-induced oxidative and/or nitrosative stress may represent a key mechanism in ammonia neurotoxicity.

Animals↗
PubMed1996

Use of a designer triple expression hybrid clone for three different lipoyl domain for the detection of antimitochondrial autoantibodies.

The detection of antimitochondrial autoantibodies (AMAs) is critical in the diagnosis of primary biliary cirrhosis (PBC). However, conventional laboratory assays to detect AMA are dependent on the time-consuming method of immunofluorescence microscopy, a method often plagued by problems of nonspecificity. AMAs react against mitochondrial autoantigens including the E2 components of the pyruvate dehydrogenase complex (PDC-E2), the branched-chain 2-oxo-acid dehydrogenase complex (BCOADC-E2), and the 2-oxo-glutarate dehydrogenase complex (OGDC-E2). Interestingly, the immunodominant epitopes of PDC-E2, BCOADC-E2, and OGDC-E2 are all conformational lipoate binding sites, but antibodies against them do not cross-react. Although 80% to 90% of sera from patients with PBC react to PDC-E2, approximately 10% patients with PBC react only to BCOADC-E2 and/or OGDC-E2. We have taken advantage of our epitope-mapping studies of the E2 components of PDC, BCOADC, and OGDC, and constructed a "designer" hybrid clone, designated as pML-MIT3, that coexpresses the immunodominant epitopes within the three distinct lipoyl domains. We examined a total of 321 sera, including 186 sera from patients with PBC, to test the immunoreactivity of pMIT3. Of 186 sera from patients with PBC, 152 sera (81.7%) reacted with recombinant fusion protein of PDC-E2, whereas 171 sera (91.9%) showed positive reactivities when probed by immunoblotting against the recombinant fusion protein expressed from the pML-MIT3 clone. Of 34 PBC sera that did not react with recombinant PDC-E2, 18 sera contained BCOADC-E2-specific AMA and 1 serum possessed only OGDC-E2-specific AMA. We also developed an enzyme-linked immunosorbent assay (ELISA), using affinity-purified recombinant fusion protein of pML-MIT3 clone as the antigen source, to quantify specific AMAs in patients with PBC. None of the 135 control sera from patients with primary sclerosing cholangitis (PSC), chronic autoimmune hepatitis (CAH), systemic lupus erythematosus (SLE), or healthy volunteers showed significant reactivity against pML-MIT3 recombinant fusion protein in the ELISA assay. Our results indicate that an ELISA using recombinant, cloned autoantigen of pML-MIT3 is a powerful and very specific method for the detection of AMA.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1998

Characterization of antimitochondrial antibodies in health adults.

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.

Adult↗
PubMed1999

In situ nucleic acid detection of PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1alpha, BCOADC-E1alpha, OGDC-E1, and the E3 binding protein (protein X) in primary biliary cirrhosis.

The characteristic serological feature of primary biliary cirrhosis (PBC) is the presence of antimitochondrial antibodies (AMAs), and the major proteins recognized by AMAs are subunits of the 2-oxo acid dehydrogenase complexes (2-OADC), including the E2 components of the pyruvate dehydrogenase complex (PDC), the 2-oxo-glutarate dehydrogenase complex (OGDC), the branched-chain 2-oxoacid dehydrogenase complex (BCOADC), the E3 binding protein (E3BP or protein X) and the E1a component of mammalian PDC. Previous work has postulated that either E3BP, or a molecule cross-reactive with the PDC-E2 molecule, is uniquely expressed on the surface of biliary epithelial cells in PBC. To address this issue, we performed in situ hybridization for all of the major 2-OADC components at the mRNA level, including PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1a, BCOADC-E1a, OGDC-E1, and E3BP using 13 PBC and 9 control livers using 7 mitochondrial antisense probes. In both PBC and controls, the expression of all 2-OADC component mRNA studied herein were found in hepatocytes and infiltrating mononuclear cells, without significant differences. Interestingly, however, despite published data on immunohistochemical staining, interlobular bile ducts including the injured bile ducts in PBC were generally negative or only faintly positive, with the exception of 1 bile duct in 1 of 13 cases of PBC and 1 of 9 control liver specimens. Moreover, confocal microscopic examination and image analysis revealed that the mRNA signal intensity of each of the 2-OADC components in the bile ducts of PBC was relatively lower in comparison with control liver diseases. These data suggest that continuous enhanced synthesis of the 2-OADC components is not likely to be occurring in the biliary epithelial cells in PBC, and that an increase of PDC-E2 or E3BP immunoreactivity in PBC is caused by exogenous imported or cross-reactive molecules.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗