Biochemical and molecular medicine最新文献

{"title":"Structure–Function Relationships of the PEA3 Group of Ets-Related Transcription Factors","authors":"Yvan de Launoit ,&nbsp;Jean-Luc Baert ,&nbsp;Anne Chotteau ,&nbsp;Didier Monte ,&nbsp;Pierre-Antoine Defossez ,&nbsp;Laurent Coutte ,&nbsp;Hélène Pelczar ,&nbsp;Frauke Leenders","doi":"10.1006/bmme.1997.2605","DOIUrl":"10.1006/bmme.1997.2605","url":null,"abstract":"<div><p>The PEA3 group of transcription factors belongs to the Ets family and is composed of PEA3, ERM, and ER81, which are more than 95% identical within the DNA-binding domain—the ETS domain—and which demonstrate 50% aa identity overall. We present here a review of the current knowledge of these transcription factors, which possess functional domains responsible for DNA-binding, DNA-binding inhibition, and transactivation. Recent data suggest that these factors are targets for signaling cascades, such as the Ras-dependent ones, and thus may contribute first to the nuclear response to cell stimulation and second to Ras-induced cell transformation. The expression of the PEA3 group members in numerous developing murine organs, and, especially, in epithelial–mesenchymal interaction events, suggests a key role in murine organogenesis. Moreover, their expression in certain breast cancer cells suggests a possible involvement of these genes in the appearance, progression, and invasion of malignant cells.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 127-135"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and Nucleotide Sequence of Canine Glucose-6-phosphatase mRNA: Identification of Mutation in Puppies with Glycogen Storage Disease Type Ia","authors":"Priya S. Kishnani ,&nbsp;Yong Bao ,&nbsp;Jer-Yuarn Wu ,&nbsp;Amy E. Brix ,&nbsp;Ju-Li Lin ,&nbsp;Yuan-Tsong Chen","doi":"10.1006/bmme.1997.2600","DOIUrl":"10.1006/bmme.1997.2600","url":null,"abstract":"<div><p>Two Maltese puppies with massive hepatomegaly and failure to thrive had isolated deficient glucose-6-phosphatase (G-6-Pase) activity in liver and kidney and pathological findings compatible with GSD-Ia. To identify the mutation, we cloned G-6-Pase canine cDNA by RT–PCR with primers from the murine G-6-Pase gene sequence. The canine G-6-Pase cDNA is 2346 bp, with a 5′ untranslated region of 87 bp, a coding region of 1071 bp, and a 3′ untranslated region of 1185 bp. The difference between the canine and human sequences is in the 3′ untranslated region. A greater than 90% amino acid sequence homology was seen with canine, human, murine, and rat G-6-Pase. G-6-Pase cDNA from affected and control puppies revealed complete homology except at nt position 450, which showed a guanine to cytosine (G to C) transversion resulting in substitution of a methionine by isoleucine at codon 121 (M121I) in all five clones studied. The loss of an<em>Nco</em>I restriction site on genomic DNA amplified with primers flanking the mutation allowed us to prove that affected puppies were homozygous for the mutation and parents were heterozygous carriers. The mutant G-6-Pase cDNA had 15 times less enzyme activity than wild-type cDNA following transient transfection. Northern blot analysis of puppies with GSD-Ia revealed increased G-6-Pase mRNA, compared to normal controls. Increased G-6-Pase mRNA was also seen in normal fasted puppies compared to littermates in the fed state, suggesting that the increased G-6-Pase mRNA is a physiologic response to fasting. This is the first report of a molecularly confirmed naturally occurring animal model of GSD-Ia. The establishment of a breeding colony of this dog strain will facilitate studies on the role of G-6-Pase gene in glucose homeostasis, in pathophysiology of disease, and development of novel therapeutic approaches such as gene therapy.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 168-177"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical Features of a Patient with Zellweger-like Syndrome with Normal PTS-1 and PTS-2 Peroxisomal Protein Import Systems: A New Peroxisomal Disease","authors":"Inderjit Singh ,&nbsp;Robert G. Voigt ,&nbsp;Faruk G. Sheikh ,&nbsp;Karl Kremser ,&nbsp;Frank R. Brown III","doi":"10.1006/bmme.1997.2593","DOIUrl":"10.1006/bmme.1997.2593","url":null,"abstract":"<div><p>The peroxisomal disorders represent a group of inherited metabolic disorders that derive from defects of peroxisomal biogenesis and/or from dysfunction of single or multiple peroxisomal enzymes. We described earlier an 8 <span><math><mtext>1</mtext><mtext>2</mtext></math></span>-year-old with a history of progressive developmental delay, micronodular cirrhosis, and elevated very long chain fatty acids in plasma and skin fibroblasts. These findings were felt to be compatible with both neonatal adrenoleukodystrophy (nALD) and Zellweger syndrome (ZS). This patient is now 21 years old and his clinical course, inconsistent with either nALD or ZS, led us to examine his peroxisomal status in light of a possible new peroxisomal disease. The normal levels of bile acid precursors found in this patient suggest that peroxisomal β-oxidation is functional. The activities of dihydroxyacetone phosphate acyltransferase and oxidation of lignoceric acid and phytanic acid were 14, 17, and 15% of the control, respectively. This partial activity for oxidation and the normal levels of bile acid precursors suggests that this patient has peroxisomes containing β-oxidation enzymes. Western blot analysis of subcellular organelles showed that β-oxidation enzyme proteins are present at normal levels in catalase-negative peroxisomes of density equivalent to normal peroxisomes. The presence of acyl-CoA oxidase and 3-ketoacyl-CoA thiolase in catalase-negative peroxisomes suggests that both peroxisomal targeting signal-1 (PTS-1)- and peroxisomal targeting signal-2 (PTS-2)-mediated protein transport processes into peroxisomes are normal in this patient. These findings of catalase-negative peroxisomes of normal density and normal PTS-1 and PTS-2 import machinery with partial peroxisomal functions clearly demonstrate that this patient differs from those with known disorders of peroxisomal biogenesis.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 198-207"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20202546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Inducible Nitric Oxide Synthase in Skeletal Muscle Biopsies from Patients with Chronic Heart Failure","authors":"Volker Adams,&nbsp;Jiangtao Yu,&nbsp;Sven Möbius-Winkler,&nbsp;Axel Linke,&nbsp;Claudia Weigl,&nbsp;Lutz Hilbrich,&nbsp;Gerhard Schuler,&nbsp;Rainer Hambrecht","doi":"10.1006/bmme.1997.2598","DOIUrl":"10.1006/bmme.1997.2598","url":null,"abstract":"<div><p>In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 152-160"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Investigation of the Use of Dried-Blood Spots for the Assessment ofin UteroExposure to Environmental Pollutants","authors":"V.W. Burse ,&nbsp;M.R. Deguzman ,&nbsp;M.P. Korver ,&nbsp;A.R. Najam ,&nbsp;C.C. Williams ,&nbsp;W.H. Hannon ,&nbsp;B.L. Therrell","doi":"10.1006/bmme.1997.2603","DOIUrl":"10.1006/bmme.1997.2603","url":null,"abstract":"<div><p>We determined the concentration of dichlorodiphenyldichloroethylene (<em>p,p</em>′-DDE) in dried-blood spot specimens from 2-day-old infants from rural Texas who had never been breast fed. Anonymous, residual whole blood spots on filter paper, previously used for routine newborn screening procedures, were soaked in a phosphate buffer, extracted with an organic solvent, and eluted through silica gel. The concentrated eluates were analyzed by capillary gas chromatography with electron capture detection (ECD). The blood collected from 10 newborns was analyzed and found to contain DDE concentrations ranging from 0.13 to 1.87 pg/μl with a mean of 0.72 pg/μl. One of the 10 newborns had a whole blood DDE concentration of 1.87 pg/μl, which was greater than the concentration of 1.34 pg/μl in a freshly drawn sample from an adult donor whose blood serum was shown to contain DDE. With improvement in detection limits, this approach has the potential to displace the analyses of mothers’ blood (as a surrogate indicator of infants’ exposures) and cord blood as standard procedures for determining the newborns’ body burden of environmental pollutants.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 236-239"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20202550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Index for Volume 61","authors":"","doi":"10.1006/bmme.1997.2624","DOIUrl":"https://doi.org/10.1006/bmme.1997.2624","url":null,"abstract":"","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 240-241"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92015045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal Metabolism of Mannose in Families with Carbohydrate-Deficient Glycoprotein Syndrome Type 1","authors":"K. Panneerselvam ,&nbsp;James R. Etchison ,&nbsp;Flemming Skovby ,&nbsp;Hudson H. Freeze","doi":"10.1006/bmme.1997.2599","DOIUrl":"10.1006/bmme.1997.2599","url":null,"abstract":"<div><p>Patients with carbohydrate-deficient glycoprotein syndrome (CDGS) Type 1 underglycosylate many glycoproteins by failing to add entire N-linked carbohydrate chains to them. The primary defect in these patients has been reported as a &gt;90% deficiency in phosphomannomutase activity (PMM), the enzyme that converts mannose-6-phosphate to mannose-1-phosphate. This lesion reduces both the amount and the size of the lipid-linked oligosaccharide precursor. We have now analyzed the activity of PMM and the level of glycosylation in cultured fibroblasts as well as the level of blood mannose in seven CDGS Type 1 patients and their parents. All of these patients were ∼95% deficient in PMM activity and their parents had an average of 51% of control PMM activity. Furthermore, parental fibroblasts showed reduced glycosylation and a higher proportion of truncated N-linked chains compared to those made by control fibroblasts. Addition of 0.25 m<span>m</span>mannose to the culture medium corrected both the underglycosylation and size of the oligosaccharide chains in CDGS Type 1 patients and their parents. Finally, serum from CDGS patients had considerably reduced mannose levels (5–40 μ<span>m</span>) compared to normal controls (40–80 μ<span>m</span>) and some parents were below normal (16–103 μ<span>m</span>). These results suggest that the reduced blood mannose level is a consequence of the PMM deficiency. This is the first inherited disorder in human metabolism that shows a decrease in available mannose. Increasing blood mannose levels might correct some protein underglycosylation in these patients.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 161-167"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Science and Medicine at the Millennium","authors":"Arthur Kornberg","doi":"10.1006/bmme.1997.2606","DOIUrl":"10.1006/bmme.1997.2606","url":null,"abstract":"","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 121-126"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20202706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Physiological Importance of Two Classic Residual Products: Carbon Monoxide and Bilirubin","authors":"Gilca Marilena","doi":"10.1006/bmme.1997.2610","DOIUrl":"10.1006/bmme.1997.2610","url":null,"abstract":"<div><p>Heme oxygenase the rate-limiting step in the degradation of heme to bilirubin, generates carbon monoxide. This gaseous molecule plays important roles in neuronal signaling and modulation of vascular tone. Additionally, carbon monoxide is involved in some pathological conditions (e.g., ischemia, endotoxic shock, excitotoxicity) as a protective or toxic factor. Bilirubin, another heme metabolite, exhibits intriguing biological activities as an antioxidant, an antimutagen, and an anti-complement agent. Vital functions and the dual nature displayed by these two heme metabolites are discussed.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 136-142"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Evaluation of the Use of Dried Blood Spots from Newborn Screening for Monitoring the Prevalence of Cocaine Use among Childbearing Women","authors":"L.Omar Henderson ,&nbsp;Mary K. Powell ,&nbsp;W.Harry Hannon ,&nbsp;John T. Bernert Jr. ,&nbsp;Kenneth A. Pass ,&nbsp;Paul Fernhoff ,&nbsp;Cynthia D. Ferre ,&nbsp;Louise Martin ,&nbsp;Elizabeth Franko ,&nbsp;Roger W. Rochat ,&nbsp;Mary D. Brantley ,&nbsp;Eric Sampson","doi":"10.1006/bmme.1997.2609","DOIUrl":"10.1006/bmme.1997.2609","url":null,"abstract":"<div><p>A collaborative March of Dimes study was designed to examine the utility of dried blood spot (DBS) materials routinely collected from newborns as a source for monitoring cocaine exposure and to assess the prevalence of cocaine use among childbearing women in Georgia. We used a modified urinary radioimmunoassay (RIA) to anonymously detect the cocaine metabolite benzoylecgonine (BE) in DBSs. Extensive efforts were undertaken to assure absolute nonlinkage of BE data to any individual. The positive results found by RIA were confirmed by a mass spectrometry (MS) method specifically developed to detect BE in DBSs. BE was measured in 23,141 DBSs collected during 2 months of routine newborn screening in Georgia. A good correlation was observed for RIA results versus MS results (<em>r</em>²= 0.97). The estimated minimal statewide BE prevalence was 4.8 per 1000 childbearing women. We demonstrated that immunoassay testing for cocaine without confirmatory testing can yield falsely elevated prevalence rates. When proper confirmatory testing is done, DBSs are a valuable source for population-based monitoring of substance abuse among childbearing women.</p></div>","PeriodicalId":8837,"journal":{"name":"Biochemical and molecular medicine","volume":"61 2","pages":"Pages 143-151"},"PeriodicalIF":0.0,"publicationDate":"1997-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/bmme.1997.2609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20203256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}