bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligands and Signaling Through Receptor‐Type Tyrosine Phosphatases
Authors: Bixby John L. 
Published: August 2002

AbstractVirtually every aspect of cellular proliferation and differentiation is regulated by changes in tyrosine phosphorylation. Tyrosine phosphorylation, in turn, is controlled by the opposing activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). PTKs are often transmembrane proteins (receptor PTKs) whose enzymatic activities and signaling functions are tightly regulated by the binding of specific ligands. A variety of transmembrane PTPs has also been identified; these proteins are called receptor PTPs (RPTPs), but in most cases their roles as receptors are very poorly understood. This review discusses the evidence that RPTPs are actually receptors for extrinsic ligands, and the extent to which interactions with putative ligands are known or suspected to cause changes in enzymatic activity. Finally, some of the RPTP substrates believed to be physiologically important are described. The evidence gathered to date suggests that models derived from studies of receptor PTKs may be too simple to account for the diversity and complexity of mechanisms through which ligand binding controls RPTP function.
Vitamin E 80th Anniversary: A Double Life, Not Only Fighting Radicals
Authors: Ricciarelli Roberta , Zingg Jean‐Marc , Azzi Angelo 
Published: August 2002

AbstractRecent research on α‐tocopherol has revealed specific cellular functions of this compound belonging to the vitamin E family. α‐Tocopherol can act as a radical scavenger, as a pro‐oxidant, as an anti‐alkylation agent and, most important, by mechanisms that are independent of the above properties. To the last group belong protein kinase C and 5‐lipoxygenase inhibition at post‐translational level, as well as α‐tocopherol activation of protein phosphatase 2A and diacylglycerol kinase. Furthermore, at transcriptional level, several genes (CD36, α‐TTP, α‐tropomyosin, and collagenase) are modulated by α8‐tocopherol. These effects result in inhibition of smooth muscle cell proliferation, platelet aggregation, and monocyte adhesion and may be related to the alleged protection of atherosclerosis by vitamin E. On the other side, epidemiological and intervention studies have shown some inconsistent results. Rather than disregarding vitamin E as a means to protect against atherosclerosis progression, it would be wiser to better design clinical trials based on current knowledge of the biological properties of the molecule.
Human Heart Cytosolic Reductases and Anthracycline Cardiotoxicity
Authors: Mordente Alvaro , Meucci Elisabetta , Martorana Giuseppe Ettore , Giardina Bruno , Minotti Giorgio 
Published: August 2002

AbstractAnthracyclines are a class of antitumor drugs widely used for the treatment of a variety of malignancy, including leukemias, lymphomas, sarcomas, and carcinomas. Different mechanisms have been proposed for anthracycline antitumor effects including freeradical generation, DNA intercalation/binding, activation of signaling pathways, inhibition of topoisomerase II and apoptosis. A life‐threatening form of cardiomyopathy hampers the clinical use of anthracyclines. According to the prevailing hypothesis, anthracyclines injure the heart by generating damaging free radicals through iron‐catalyzed redox cycling. Although the “iron and freeradical hypothesis” can explain some aspects of anthracycline acute toxicity, it is nonetheless disappointing when referred to chronic cardiomyopathy. An alternative hypothesis implicates C‐13 alcohol metabolites of anthracyclines as mediators of myocardial contractile dysfunction (“metabolite hypothesis”). Hydroxy metabolites are formed upon two‐electron reduction of the C‐13 carbonyl group in the side chain of anthracyclines by cytosolic NADPH‐dependent reductases. Anthracycline alcohol metabolites can affect myocardial energy metabolism, ionic gradients, and Ca 2+ movements, ultimately impairing cardiac contraction and relaxation. In addition, alcohol metabolites can impair cardiac intracellular iron handling and homeostasis, by delocalizing iron from the [4Fe‐4S] cluster of cytoplasmic aconitase. Chronic cardiotoxicity induced by C‐13 alcohol metabolite might be primed by oxidative stress generated by anthracycline redox cycling (“unifying hypothesis”). Putative cardioprotective strategies should be aimed at decreasing C‐13 alcohol metabolite production by means of efficient inhibitors of anthracycline reductases, as short‐chain coenzyme Q analogs and chalcones that compete with anthracyclines for the enzyme active site, or by developing novel anthracyclines less susceptible to reductive metabolism.
Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions
Authors: SPILLER WOLFGANG , KLIESCH HOLGER , WÖHRLE DIETER , HACKBARTH STEFFEN , RÖDER BEATE , SCHNURPFEIL GüNTER 
Published: August 2002

The singlet oxygen luminescence method and the photochemical methods using 1,3-diphenylisobenzofuran ( DPBF ) or bilirubin ditaurate ( BDT ) as chemical quenchers were employed to determine the single oxygen quantum yields (ΦΔ) of different phthalocyanines and tris(2,2″-bipyridyl)ruthenium(II) dichloride in dimethylformamide ( DMF ) or aqueous micellar solution of 0.1 M CTAC (cetyltrimethylammonium chloride). Additionally, a perylenetetracarboxylic acid diimide derivative was examined in DMF . In a series of tetrasulfonated phthalocyanines ( PTS ) the following order was found: ZnPTS > GaPTS > AlPTS ≈ H2PTS > CoPTS . In general, the singlet oxygen quantum yields are higher in DMF than in 0.1 M CTAC/H2O . The results obtained with the photochemical systems are comparable with those obtained by the photophysical method.The photochemical DPBF method results in absolute values of ΦΔ. However, in micellar solution, chain reactions occur when DPBF is used as chemical quencher in the photo-oxidative process. This problem can be overcome by adding sodium thiosulphate which is able to destroy the endoperoxide initially formed. BDT can be used as quencher in different solvents to determine ΦΔrelative to a photosensitizer with known singlet oxygen quantum yield in the respective solvent.In comparison to the chemical methods the luminescence method exhibits the advantage that side reactions of the quencher are excluded. But normally the ΦΔvalues obtained are relative to a reference, since absolute determinations need much larger efforts.
Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders
Authors: Jensen Morten Krogh , de Nully Brown Peter , Thorsen Sixtus , Hasselbalch Hans Carl 
Published: August 2002

AbstractChronic myeloproliferative disorders (MPD) are characterized by a high incidence of thrombohaemorrhagic complications, possibly related to platelet abnormalities and disturbances of the coagulation system. In an attempt to define abnormalities in coagulation and fibrinolysis, we investigated risk markers for venous thromboembolism, fibrinolytic, and haemostatic system activation markers and antiphospholipid antibodies in blood samples from 50 MPD patients and 30 controls. Compared with controls median levels of protein S free and protein C were significantly decreased in the patients (0.27 vs. 0.38 arbitrary units; P < 0.001 and 0.86 vs. 0.99 arbitrary units; P < 0.001, respectively), and activated partial thromboplastin time was significantly prolonged in patients (33 vs. 27 sec; P < 0.001). No differences were observed in levels of antithrombin, thrombin–antithrombin complex, and fibrin D‐dimer. In patients the median value of thrombomodulin was significantly increased indicating perturbed endothelial function. Anticardiolipin antibodies of IgM subtype (median 38 U/mL, 33–99) were detected in 11 patients (22%) and only in one control (3%) (P < 0.021; patients vs. controls). Seven patients were heterozygous for the Factor V Leiden, one patient was heterozygous for the prothrombin G20210A mutation, and one patient was homozygous for the Factor V Leiden mutation. Among controls, two were heterozygous for the Factor V Leiden mutation. Comparing the allele frequency of the Factor V Leiden mutation in patients with MPD and the background population disclosed a significantly increased allele prevalence of the Factor V Leiden mutation in the patients (9% vs. 3.4%; P = 0.003). Alterations in the level of anticoagulant proteins, disturbances of endothelial cell function, and the presence of cardiolipin antibodies and Factor V Leiden mutation may increase the cumulative thrombotic risk in MPD besides the risk imposed by platelet activation. Am. J. Hematol. 69:185–191, 2002.© 2002 Wiley‐Liss, Inc.
Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti‐D and to IV gammaglobulin predict response to subsequent splenectomy?
Authors: Bussel James B. , Kaufmann Craig P. , Ware Russell E. , Woloski B.M.R. 
Published: August 2002

AbstractThe acute platelet response to Intravenous Gammaglobulin (IVIG) has been reported to predict response to subsequent splenectomy of patients with ITP. The current study was undertaken to determine if the platelet response to IV anti‐D (Winrho‐SDF) predicts response to subsequent splenectomy. The 61 HIV‐uninfected children and adults in this study had taken part in the pre‐licensing studies of IV anti‐D and were all those who not only had evaluable platelet responses to IV anti‐D but also had undergone splenectomy and had information available describing its 1‐year outcome. Results of treatment with IVIG were available in 38 of these 61 patients. Neither response to the initial infusion of IV anti‐D, nor response to the initial or last IVIG, predicted the response in either children or adults to subsequent splenectomy. However, response to the last anti‐D infusion in adults was strongly correlated (P = 0.003) to response to subsequent splenectomy as was hemolysis ≥2.0 gm/dl after IV anti‐D (P = 0.03). There was no overall relationship between response to IV anti‐D or IVIG, and response to subsequent splenectomy. However, a good platelet response in adults to the last IV anti‐D and a hemoglobin decrease ≥2.0 gm/dl both appeared to predict response to subsequent splenectomy. Am. J. Hematol. 67:27–33, 2001. © 2001 Wiley‐Liss, Inc.
Reversible sideroblastic anemia associated with the tetracycline analogue COL‐3
Authors: Rudek Michelle A. , Horne McDonald , Figg William D. , Dahut William , Dyer Valerie , Pluda James M. , Reed Eddie 
Published: August 2002

AbstractEight of 35 patients with cancer receiving COL‐3, a tetracycline derivative with antiangiogenic properties, developed anemia while on treatment. All of these patients were enrolled on an approved Phase I clinical trial at the National Cancer Institute. Three of these patients had bone marrow examinations that revealed ringed sideroblasts. This paper describes these cases. Am. J. Hematol. 67:51–53, 2001. Published 2001 Wiley‐Liss, Inc.
Bone marrow aspiration, biopsy, and culture in the evaluation of HIV‐infected patients for invasive mycobacteria and histoplasma infections
Authors: Akpek Görgün , Lee Shing M. , Gagnon David R. , Cooley Timothy P. , Wright Daniel G. 
Published: August 2002

AbstractBone marrow (BM) aspiration and biopsy are used commonly in clinical practice to diagnose invasive tissue infections caused by Mycobacterium avium intracellulare (MAC), Mycobacterium tuberculosis (TB), and Histoplasma capsulatum (HC) in patients with human immunodeficiency virus‐1 (HIV) infection. However, the value of these invasive procedures relative to other diagnostic approaches has not been clearly defined. To determine the value of BM culture and BM histology in the diagnosis of opportunistic MAC/TB and HC infections in immunosuppressed patients with HIV, we retrospectively reviewed the records of 56 adult patients with HIV who underwent a single BM aspiration, biopsy, and culture because of unexplained fever and/or other clinical features suggestive of MAC/TB or HC infection. Thirty‐two patients (57%) were ultimately diagnosed with MAC/TB or HC infection by positive cultures of BM, blood, sputum, or bronchoalveolar lavage fluid or by the histologic detection of organisms in biopsies of BM or other tissues. The diagnostic sensitivity of BM cultures was equal to that of blood cultures (20/32, or 63%). Granuloma and/or histologically apparent organisms were seen in BM biopsy specimens in 11 of 32 individuals (34%) ultimately diagnosed with MAC/TB or HC infections. Among these 11 cases, both granuloma and acid‐fast staining organisms were found in the BM biopsy specimens of 2 individuals for whom both BM and blood cultures were negative. Certain clinical symptoms and signs at the time of BM examination were found by logistic regression analysis to be significantly associated with a subsequent diagnosis of MAC/TB or HC infections; these included high fever, long duration of febrile days prior to BM examination, and elevated direct bilirubin. In conclusion, while the diagnostic sensitivity of BM cultures was found to be no greater than that of blood cultures in detecting MAC/TB or HC infections in immunosuppressed HIV+ patients, histopathologic examination of BM specimens resulted in the relatively rapid identification of nearly one third of infected patients who underwent BM examination, and also identified infections in some patients who were culture negative. These findings support the continued use of BM aspiration, biopsy, and culture for the diagnosis of opportunistic MAC/TB or HC infections in immunosuppressed HIV+ patients, particularly when selected clinical features are present. Am. J. Hematol. 67:100–106, 2001. © 2001 Wiley‐Liss, Inc.
Racial differences in prevalence of a supratypic HLA‐genetic marker immaterial to pre‐employment testing for susceptibility to chronic beryllium disease
Authors: Weston Ainsley , Ensey James , Kreiss Kathleen , Keshava Channa , McCanlies Erin 
Published: August 2002

AbstractBackgroundA beryllium materials manufacturer is conducting a limited pilot program that offers testing for HLA‐DPβ1E69 with genetic counseling through a third party to applicants for employment. An important consideration in this regard is the prevalence of this marker in the general population, and its consequent positive predictive value of disease susceptibility.MethodsPolymerase chain reaction and restriction fragment length polymorphism analyses were used to determine HLA‐DPβ1E69 population frequencies. Estimation of positive predictive values assumed a disease frequency among beryllium workers of either 5 or 15% and used an odds ratio for disease risk of 35 for the HLA‐DPβ1E69 marker.ResultsAllelic/carrier frequencies were found to be 0.21/0.33, 0.24/0.40, 0.27/0.47, and 0.38/0.59 for Caucasians, African‐Americans, Hispanics, and Chinese, respectively. Ranges of positive predictive values for a genetic test based on HLA‐DPβ1E69 in these populations were calculated to be 8.3–14.3% for carriers with an assumed disease frequency of 5%. For high risk subgroups with disease frequencies of 15%, the range of positive predictive values was found to span between 24.9–43.0%.ConclusionsThese estimates suggest that using HLA‐DPβ1E69 genotyping for general pre‐employment screening in the beryllium industry has a low positive predictive value, which varies little among racial groups where carrier frequencies differ significantly. Am. J. Ind. Med. 41:457–465, 2002. © 2002 Wiley‐Liss, Inc.
Occupational categories at risk for Parkinson's disease
Authors: Kirkey Kandace L. , Johnson Christine Cole , Rybicki Benjamin A. , Peterson Edward L. , Kortsha Gene X. , Gorell Jay M. 
Published: August 2002

AbstractBackgroundThe etiology of Parkinson's disease (PD) is considered to have a strong environmental component, but relatively few studies have investigated the potential association between occupation and the disease.MethodsIn a population‐based case‐control study, we collected comprehensive occupational histories from all study participants, 144 case and 464 control subjects.ResultsChi‐square analysis revealed that working in an agricultural occupation increased estimated PD risk (OR = 1.74; 95% CI = 0.85, 3.60). In contrast, a history of ever working in a service occupation was negatively associated with PD risk (OR = 0.69; 95% CI = 0.47, 1.00). Risk estimates were close to one for specific service occupations. Adjusted odds ratios for all non‐service occupational and industrial categories were similar, and working in a service occupation was the only significant inverse predictor of PD risk.ConclusionsFuture investigations focusing on lifestyle factors and environmental exposures within the agricultural and service occupational categories are warranted. Am. J. Ind. Med. 39:564–571, 2001. © 2001 Wiley‐Liss, Inc.
Evidence for the multigenic inheritance of schizophrenia
Authors: Freedman Robert , Leonard Sherry , Olincy Ann , Kaufmann Charles A. , Malaspina Dolores , Cloninger C. Robert , Svrakic Dragan , Faraone Stephen V. , Tsuang Ming T. 
Published: August 2002

AbstractSchizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy‐seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome‐wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the α7‐nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait‐locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. © 2001 Wiley‐Liss, Inc.
Patient with rheumatoid arthritis and MCA/MR syndrome due to unbalanced der(18) transmission of a paternal translocation t(18;20)(p11.1;p11.1)
Authors: Czakó Márta , Riegel Mariluce , Morava Éva , Schinzel Albert , Kosztolányi György 
Published: August 2002

AbstractA girl with psychomotor retardation and a pattern of minor anomalies was found to have a slightly enlarged short arm of chromosome 18 by conventional GTG‐banded chromosome examination. The 18p + chromosome has also been found in the father. FISH studies using chromosome 18–and chromosome 20–specific painting probes confirmed a reciprocal whole arm translocation between chromosomes 18 and 20 in the father, resulting in monosomy of the short arm of chromosome 18 and trisomy of the short arm chromosome 20 in the patient. FISH analysis using a chromosome 18 alpha‐satellite–specific probe showed a reduced signal intensity. The patient presented with a flat, oval face, upslanting palpebral fissures, periorbital fullness, and mental retardation; she also had chronic diarrhea with milk protein intolerance and juvenile rheumatoid arthritis at age 5 years. Juvenile rheumatoid arthritis, like several other immunologic disorders, has occasionally been reported in patients with deletion of 18p, and thus most likely loss of a gene or genes on 18p is responsible for various immunologic disorders occurring in these patients. © 2002 Wiley‐Liss, Inc.
Linkage genome scan for loci predisposing to panic disorder or agoraphobia
Authors: Gelernter Joel , Bonvicini Kathleen , Page Grier , Woods Scott W. , Goddard Andrew W. , Kruger Susan , Pauls David L. , Goodson Susan 
Published: August 2002

AbstractWe conducted a 10 cM linkage genome scan in a set of 20 American pedigrees (153 subjects), ascertained through probands with panic disorder (PD). Several anxiety disorders segregate in these families; they were diagnosed on the basis of Schedule for Affective Disorders and Schizophrenia interview. In this article, we describe results for panic disorder and agoraphobia, which are closely related, common, heritable anxiety disorders. This is the first complete linkage genome scan for agoraphobia and the third for PD. A total of 407 markers (389 autosomal, 18 X chromosome) were genotyped. Multipoint LOD score and NPL analysis were completed using GENEHUNTER2. For PD, two genomic regions meet criteria for suggestive linkage. One of these regions is on chromosome 1 (LOD score = 2.04). This region coincides with a region that generated a LOD score of 1.1 in a previous genome scan by Crowe et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:105–109]. The other (LOD score = 2.01) is located on chromosome 11p and occurs at marker CCKBR, one of eight candidate genes examined. For agoraphobia, the most promising potential linkage was on chromosome 3 (NPL score = 2.75; P = 0.005). This was accounted for primarily by a single family that by itself generated an NPL score of 10.01 (P = 0.0039) and a LOD score of 2.10. These results provide initial evidence for a genetic locus on chromosome 3 that contributes to risk for agoraphobia. They also support suggestive linkage to two risk loci for panic disorder. Additional potential loci were identified with lesser statistical support; several of these were consistent with previously reported panic disorder linkage results. Overall, the results presented here suggest that PD and agoraphobia are complex traits that share some, but not all, of their susceptibility loci. Published 2001 Wiley‐Liss, Inc.
Genetic relationship of Chinese ethnic populations revealed by mtDNA sequence diversity
Authors: Yao Yong‐Gang , Nie Long , Harpending Henry , Fu Yun‐Xin , Yuan Zhi‐Gang , Zhang Ya‐Ping 
Published: August 2002

AbstractThe origin and demographic history of the ethnic populations of China have not been clearly resolved. In this study, we examined the hypervariable segment I sequences (HVSI) of the mitochondrial DNA control region in 372 individuals from nine Chinese populations and one northern Thai population. A relatively high percentage of individuals was found to share sequences with those from other populations of the same ethnogenesis. In general, the populations of southern or Pai‐Yuei tribal origin showed high haplotype diversity and nucleotide diversity compared with the populations of northern or Di‐Qiang tribal origin. Mismatch distributions from these populations showed concordant features. All except the northern groups Nu, Lisu, Tibetan, and Mongolian showed typical signatures of ancient population expansions in the mismatch distributions and neutrality tests. Episodes of extreme size reduction in the past are one of the likely explanations for the absence of evidence of expansion in northern populations. Small sample sizes as well as samples from isolated subpopulations contributed to the bumpy mismatch distributions observed. Phylogenetic analysis and haplotype sharing among populations suggest that current mtDNA variation in these ethnic populations could reveal their ethnohistory to some extent, but in general, linguistic and geographic classifications of the populations did not agree well with classification by mtDNA variation. Am J Phys Anthropol 118:63–76, 2002. © 2002 Wiley‐Liss, Inc.