bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent and overlapping transcriptional activation during liver development and regeneration in mice
Authors: Kelley-Loughnane Nancy , Sabla Gregg E. , Ley-Ebert Catherine , Aronow Bruce J. , Bezerra Jorge A.
Published: August 2002

Liver development and regeneration share the requirement for simultaneous proliferation and acquisition of highly specialized cellular functions. However, little is known about molecules with regulatory roles in both processes. We hypothesized that transcriptional reprogramming induced by regeneration recapitulates that of developing liver. To address this hypothesis, we determined global hepatic gene expression at embryonic day 14.5, postnatal day 14, and 6 to 24 hours following partial hepatectomy using microarrays containing 8,635 cDNAs. Analysis of genes overexpressed during these conditions revealed 3 unique expression patterns. The first was predominantly signature gene clusters specific for each growth phase. Major groups were hematopoiesis-related genes in embryonic livers, metabolic genes during postnatal liver development, and growth/inflammation and metabolic genes during regeneration. The second pattern consisted of dual overexpression during regeneration and at least one phase of development. Consistent with potential regulatory roles in liver growth, most of these transcripts control cell-cell contact, membrane trafficking, cell growth, metabolism, and inflammatory response. The third pattern, revealed by surveying their expression across 76 hepatic and extra-hepatic tissues, uncovered a restricted temporospatial pattern of liver overexpression for CD14, orosomucoid 1, hepcidin, Spi 2.1, Ith3, and Tim-44. In conclusion, these results provide a basis for the identification of gene and gene groups that play critical roles at different phases of liver development and regeneration, and underscore the importance of maintaining metabolic demands during organ growth.
Hepatic HCV RNA before and after treatment with interferon alone or combined with ribavirin
Authors: McHutchison John G. , Poynard Thierry , Esteban-Mur Rafael , Davis Gary L. , Goodman Zachary D. , Harvey Joann , Ling Mei-Hsiu , Garaud Jean Jacques , Albrecht Janice K. , Patel Keyur , Dienstag Jules L.
Published: August 2002

The clinical use of measuring hepatic hepatitis C virus (HCV) RNA before and after therapy in patients with chronic hepatitis C has been assessed in a number of small clinical trials. Viral clearance from the liver may be a better marker of long-term response than eradication of serum HCV RNA. The aim of this study was to evaluate quantitative hepatic HCV-RNA measurements before and after antiviral therapy. Two thousand eighty-nine chronic hepatitis C patients were enrolled in 3 published clinical trials evaluating interferon alfa-2b alone or with ribavirin either as initial therapy or for interferon relapse. Hepatic HCV-RNA quantitation was performed with a modified reverse-transcription polymerase chain reaction (RT-PCR) before and 24 weeks after therapy in 951 and 1,316 patients, respectively. Pretherapy hepatic HCV-RNA concentrations correlated best with serum HCV-RNA concentrations (R = .236, P = .0001) and negatively correlated with alanine transaminase (ALT) values (−0.178, P = .0001), duration of infection (−0.09, P = .02), parenchymal injury (−0.135, P = .0001), histologic activity index (HAI) inflammatory score (−0.085, P = .01), Knodell fibrosis score (−0.072, P = .03), and body weight (−0.078, P = .02). In paired liver biopsy specimens (n = 534), change in hepatic HCV RNA correlated with the change in the HAI (R = .346, P = .0001). Of 400 sustained virologic responders (SVR), 393 (98%) had undetectable hepatic HCV RNA, whereas 7 (2%) had detectable hepatic HCV RNA; 5 have been followed and 2 have had reappearance of serum HCV RNA 12 months after therapy. In conclusion, measurement of hepatic HCV RNA before or after therapy reflects changes observed in serum HCV RNA, and correlates inversely with hepatic inflammation and fibrosis, but otherwise has minimal clinical use.
Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2
Authors: Baffy György , Zhang Chen-Yu , Glickman Jonathan N. , Lowell Bradford B.
Published: August 2002

Nonalcoholic fatty liver disease (NAFLD), a prevalent condition associated with obesity, has the potential of evolving into end-stage liver disease. The biochemical mechanisms that define the progression of NAFLD are not well known, but reactive oxygen species (ROS) have been implicated in this process. Uncoupling protein (UCP) 2 is a mitochondrial inner-membrane protein that mediates proton leak, uncouples adenosine triphosphate (ATP) synthesis, and negatively regulates ROS production. UCP2 expression is increased in various animal models of NAFLD. Up-regulation of UCP2 may compromise cellular ATP levels and worsen liver damage, or it may be protective by ROS reduction in NAFLD. This study aimed to obtain a definitive answer as to whether increased UCP2 expression contributes to NAFLD. UCP2−/− mice were exposed to obesity by crossbreeding with ob/ob mice and by long-term high-fat feeding to study the effect of UCP2 deficiency on the outcome of NAFLD. Steatohepatitis score of crossbred mice (ob/ob/ko) was similar to that of ob/ob mice at 25 weeks. No compensatory increase was observed in the expression of UCP5 in ob/ob/ko livers. To unmask the effects of absent leptin and its potential proinflammatory actions, steatosis was also induced in UCP2−/− mice by a high-fat diet continued for 6 months. Serum alanine aminotransferase (ALT) levels remained normal, and the steatohepatitis score in UCP2−/− mice was the same as in wild-type controls. We conclude that increased expression of UCP2 in the livers of mice with genetically or diet-induced obesity exerts neither protective nor deleterious effects on the severity of fatty liver disease.
Uroporphyria in mice: Thresholds for hepatic CYP1A2 and iron
Authors: Gorman Nadia , Ross Kerry L. , Walton Heidi S. , Bement William J. , Szakacs Juliana G. , Gerhard Glenn S. , Dalton Timothy P. , Nebert Daniel W. , Eisenstein Richard S. , Sinclair Jacqueline F. , Sinclair Peter R.
Published: August 2002

In mice treated with 5-aminolevulinic acid (ALA) and polyhalogenated aromatic compounds, the levels of both hepatic cytochrome P450 (CYP)1A2 and iron—which can be quite different among inbred strains—are critical in causing experimental uroporphyria. Here we investigate the development of uroporphyria as a function of CYP1A2 and iron levels in the liver of mice having a common C57BL/6 genetic background. We compared Cyp1a2(−/−) knockout mice, Cyp1a2(+/−) heterozygotes, Cyp1a2(+/+) wild type, and Cyp1a2(+/+) mice pretreated with a low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) (4 μg/kg). Cyp1a2(+/−) mice contain about 60% of the hepatic CYP1A2 content of Cyp1a2(+/+) mice, and the PCB126-pretreated Cyp1a2(+/+) mice have about twice the wild-type levels of CYP1A2. ALA- and iron-treated Cyp1a2(+/+) mice are known to accumulate hepatic uroporphyrin; this accumulation was increased 7-fold by pretreatment with the low dose of PCB126. ALA- and iron-treated Cyp1a2(+/−) heterozygote mice accumulated no uroporphyrin in 4 weeks, but by 8 weeks accumulated significant amounts of uroporphyrin. As previously reported, the ALA- and iron-treated Cyp1a2(−/−) knockout mouse has no CYP1A2 and exhibits no detectable uroporphyrin accumulation. Iron dose-response curves in ALA- and PCB126-treated Cyp1a2(+/+) mice showed that hepatic iron levels greater than 850 μg/g liver were required to produce significant uroporphyrin accumulation in the liver. Other measures of hepatic effects of iron (iron-response element-binding protein [IRP]-iron response element [IRE] binding activity and accumulation of protoporphyrin from ALA) decreased when the level of iron was considerably lower than 850 μg/g liver. At low iron doses, accumulation of iron was principally in Kupffer cells, whereas at the higher doses (required to stimulate uroporphyrin accumulation), more iron was found in parenchymal cells. We conclude that small changes in hepatic CYP1A2 levels can dramatically affect uroporphyria in C57BL/6 mice, providing the animals have been sufficiently loaded with iron; these data might be clinically relevant to acquired (sporadic) porphyria cutanea tarda, because humans show greater than 60-fold genetic differences in hepatic basal CYP1A2.
Hemolysis and bilirubin conjugation in association with UDP-glucuronosyltransferase 1A1 promoter polymorphism
Authors: Kaplan Michael , Hammerman Cathy , Rubaltelli Firmino F. , Vilei Maria T. , Levy-Lahad Ephrat , Renbaum Paul , Vreman Hendrik J. , Stevenson David K. , Muraca Maurizio
Published: August 2002

Hemolysis may contribute to hyperbilirubinemia in Gilbert's syndrome. The authors examined blood carboxyhemoglobin corrected for inspired CO (COHbc) to index heme catabolism and serum conjugated bilirubin fractions to reflect bilirubin conjugation. Both parameters were related to UDP-glucuronosyltransferase 1A1 (UGT) promoter polymorphism, associated with Gilbert's syndrome, in term male newborns. COHbc was expressed as percentage of total hemoglobin, and total conjugated bilirubin (TCB) value as a percentage of serum total bilirubin (STB), (TCB/STB[%]). A production/conjugation index, COHbc/(TCB/STB[%]), represented bilirubin production divided by conjugation. UGT promoter genotype was designated according to the number of promoter TA insertions in each allele: 6/6, homozygous normal; 6/7, heterozygous; 7/7, homozygous variant. STB and COHbc values were higher in the 7/7 subgroup than the other counterparts (P < .01). The COHbc/(TCB/STB[%]) was higher in the 7/7 than either the 6/6 or 6/7 subsets (1.93 [1.31-2.88] vs. 0.85 [0.51-1.72] and 0.84 [0.53-1.87], respectively; P < .01). In conclusion, 7/7 UGT promoter polymorphism was associated with increased blood COHbc values (unexpected finding) as well as diminished serum total conjugated bilirubin ratios (expected finding). The increased hemolysis may contribute to the pathogenesis of increased STB values seen in Gilbert's syndrome, and exacerbate neonatal hyperbilirubinemia associated with the promoter polymorphism.
Esophageal Obstruction Caused by a Left Aortic Arch and an Anomalous Right Patent Ductus Arteriosus in Two German Shepherd Littermates
Authors: Holt David , Heldmann Eileen , Michel Kathryn , Buchanan James W.
Published: August 2002

Objective—To present details of surgical management of an unusual vascular ring anomaly in two German Shepherd littermates.

Study Design—Clinical case report.

Study Population—Three‐month‐old intact male and female German Shepherd littermates.

Results—In each dog, the esophagus was obstructed by a vascular ring comprised of the left aortic arch, an anomalous patent right ductus arteriosus, and the pulmonary artery ventrally. Surgical treatment consisted of dividing and oversewing the patent right ductus arteriosus. Neither dog has clinical signs of esophageal disease one year after treatment.

Conclusion and Clinical Relevance—This vascular ring anomaly should be considered a possibility in any young dog with esophageal obstruction and a machinery murmur.
Arthrodesis of the Equine Proximal Interphalangeal Joint: A Biomechanical Comparison of Two 7‐Hole 3.5‐mm Broad and Two 5‐hole 4.5‐mm Narrow Dynamic Compression Plates
Authors: Watt Bruce C. , Edwards Ryland B. , Markel Mark D. , McCabe Ron , Wilson David G.
Published: August 2002

Objective—To compare the biomechanical characteristics and mode of failure of two different dynamic compression plate (DCP) techniques for proximal interphalangeal joint (PIPJ) arthrodesis in horses.

Study Design—Randomized block‐design blocking on horse (1–5), method of fixation (two 7‐hole, 3.5‐mm broad DCP vs two 5‐hole, 4.5‐mm narrow DCP), side (left, right), and end (front, hind). Constructs were loaded to failure in 3‐point bending in a dorsal‐to‐palmar (plantar) direction.

Sample Population—Ten paired limbs from 5 equine cadavers.

Methods—Two 7‐hole, 3.5‐mm broad dynamic compression plates (bDCP) were used in 1 limb of a pair, and two 5‐hole 4.5‐mm narrow dynamic compression plates (nDCP) were used on the contralateral limb. Plates were positioned abaxially across the dorsomedial and dorsolateral aspect of the PIPJ. Arthrodesis constructs were loaded (19 mm/s) in 3‐point bending in a dorsal‐to‐palmar (plantar) direction using a materials‐testing machine. Composite stiffness, yield point, and maximal bending moment at failure were obtained from bending moment—angular deformation curves. Data were analyzed using ANOVA, χ2analysis, and Fisher's exact tests; the power of the test was calculated when differences were not significant.

Results—There were no significant differences in composite stiffness (P> .05; power = 0.8 @δ= 21.9%), yield point (P> .05; power = 0.8 @δ= 34.4%), or maximal bending moment (P> .05; power = 0.8 @δ= 17.8%) between the two fixation techniques. For bDCP constructs, 11% (15 of 140) of the 3.5‐mm screws were damaged; 7 of the screw heads pulled through plates where the plates bent, 1 screw head broke off, and 7 screws were bent or pulled out of the phalanx. For nDCP constructs, 8% (8 of 100) of the 4.5‐mm screws were damaged; 1 screw head pulled through a plate, 1 screw head broke off, and 6 screws were bent or pulled out of the phalanx.

Conclusions—There were no biomechanical or failure differences between bDCP and nDCP fixation of the PIPJ in horses when evaluated in single‐cycle 3‐point bending to failure.

Clinical Relevance—There is no biomechanical advantage to the use of two 7‐hole, 3.5‐mm bDCP in equine proximal interphalangeal arthrodesis compared with two 5‐hole, 4.5‐mm nDCP. Two 5‐hole, 4.5‐mm nDCP may be easier to place, whereas two 7‐hole, 3.5‐mm bDCP may provide more versatility in fracture repair.
Steamrollers, Sports Cars and Security: Phthalocyanine Progress Through the Ages
Authors: GREGORY P.
Published: August 2002

Serendipity has been a major player in most dye discoveries, and phthalocyanines are no exception. The true account of their discovery in 1928 is given using information provided by one of the individuals involved (Ron Greig). One of the inventors, Drescher, after making a key observation as to the nature of the insoluble blue impurity formed in the routine manufacture of phthalimide from phthalic anhydride, was killed weeks later when, on his beloved Sunbeam motorcycle, he had a head-on collision with a steamroller on his way to work. The unique properties of phthalocyanine dyes and pigments make them the colorant of choice for most blue and green colours. Thus most blue and green cars, including sports cars, are coloured by phthalocyanine pigments. In addition to these traditional uses, phthalocyanines are also finding extensive use in modern hi-tech areas. They are used for their colour as, for example, cyan dyes in ink jet printing, and in colourless applications such as infrared absorbers in security. The discovery, traditional and hitech applications of phthalocyanines are described in detail in this paper.
The effect of direct mail framing strategies and segmentation variables on university fundraising performance
Authors: Berger Paul D. , Smith Gerald E.
Published: August 2002

This paper provides guidelines to charitable marketers in general, and university fund-raising managers in particular, regarding the effects of direct mail framing strategies and direct mail segmentation variables on the performance of university fundraising efforts. Several direct mail framing strategies (factors) were empirically tested in a designed fractional factorial experiment that allowed the determination of not only the (main) effect of each factor, but also their interaction effects. These framing strategies included four factors: size of anchor (suggested donation), frame valence (whether a frame is expressed in positive vs. negative terms), and inclusion or not of two independent types of reference information. In addition, we studied the impact of the traditional direct marketing variables, recency, frequency, and monetary (RFM), as well as various demographic factors. Two performance measures were considered: 1) response rate, and 2) size of gift. Results indicated, among other things, that to a large extent the two measures are affected by different factors.
Co‐Participation: Affordance and engagement at work
Authors: Billett Stephen
Published: August 2002

Bases for a workplace pedagogy need to go beyond models of guided learning to include factors that account for participation at work.
Comparisons of memories for traumatic events and other experiences
Authors: Byrne Christina A. , Hyman Ira E. , Scott Kaia L.
Published: August 2002

In the present study, we examined the similarities and differences between memory ratings for traumatic, negative, and positive life experiences. A sample of 113 female undergraduates completed a packet of questionnaires that included memory rating scales for all three types of experiences and measures of psychological functioning. Analyses revealed that traumatic experiences and negative experiences were less well‐recalled than positive experiences with regard to some sensory information and some aspects of the narrative structure of the event. In addition, there were no differences between some memory ratings for different types of life events. Additionally, no clear relationships emerged between memory ratings and measures of psychological functioning. Findings tend to support theoretical perspectives that emphasize more limited memory for traumatic experiences relative to memory for other experiences. Copyright © 2001 John Wiley & Sons, Ltd.
A brief look at the Tsypkin criterion: from analysis to design
Authors: Larsen Michael , Kokotović Petar V.
Published: August 2002

Tsypkin was among the first to recognize the importance of the Popov criterion and to extend it to discrete‐time systems in the form now known as the Tsypkin criterion. This paper briefly reviews the evolution of the Tsypkin criterion from its original use in absolute stability analysis to its current application as a design tool. Copyright © 2001 John Wiley & Sons, Ltd.
Towards a better understanding of the cathodic disbondment performance of polyethylene coatings on steel
Authors: Roy D. , Simon G. P. , Forsyth M. , Mardel J.
Published: August 2002

Polyethylene is one of the most widely used corrosion‐protection thermoplastic coating materials that protects steel by providing a barrier to oxygen, water, and corrosive ions and performs very well. In order to further improve medium density polyethylene (MDPE) properties with regard to cathodic disbondment (CD), i.e., the loss of adhesion that takes place in the presence of cathodic protection (CP), various blends with functionalized polyethylenes containing polar functional groups such as maleic anhydride‐grafted‐polyethylene (MAH‐g‐PE) and other thermoplastic elastomers such as EPDM have been formulated to increase CD performance. Using compression molding and strew coating, the above modified polyethylenes have been applied on steel plate and pipe, respectively. The CD performance and 90° peel strength (dry and wet) of these formulations are investigated in this study. It is observed that dry bond strength does not correlate with CD performance. The improvement of CD performance for compression‐molded materials and strew‐coated samples is demonstrated. Also discussed, for comparison, is the performance of MDPE applied by a commercially relevant fluidized bed technique. Wet adhesion strength is shown to be an important parameter in assessing the CD performance of coatings. The disbondment mechanism of failed polymer surfaces has also been investigated using X‐ray photoelectron spectroscopy, which allows us to monitor the mass transfer of the sodium cations along the crevice during CD. © 2002 John Wiley & Sons, Inc. Adv Polym Techn 21: 44–58, 2002; DOI 10.1002/adv.10010
Rh genotyping: Avoiding false‐negative and false‐positive results among individuals of African ancestry
Authors: Ekman G.C. , Billingsly R. , Hessner M.J.
Published: August 2002

High homology, variant alleles, and silent alleles have made the development of completely reliable genotyping assays for the RHD and RHC alleles difficult. An RHD pseudogene (RHDψ) possessing a 37‐bp insertion within exon 4 is common among serologically RhD‐negative individuals of African descent and generates false‐positive results in previously reported RhD genotyping assays. Genotyping RhC is problematic due to exon 2 homology between RHD and RHC; however, an RHC‐specific 109‐bp insertion within intron 2 has been reported useful for genotyping. Primers flanking the exon 4 insertion point were used for detection of RHD and RHDψ among a total of 231 serotyped individuals: 134 African American, 85 Caucasian, and 12 RhD serotype‐negative/genotype‐positive, D‐sensitized women. Primers flanking the RHC‐specific intron 2 insertion were used to genotype 282 serotyped individuals (128 African American, 154 Caucasian) and were compared to RHC genotyping using the exon 1 RhC‐specific nt48 cytosine polymorphism. Complete correlation was observed between genotyping with the RHDψ primer pair and serotyping among 219 individuals and 10/12 previous RHD false‐positive genotyping results were resolved. RHDψ was detected in 19% (n = 4/21) of RhD seronegative African Americans and 4.4% (n = 5/113) of RhD seropositive African Americans. When using the 109‐bp intron 2 insertion for genotyping of RHC, a 23.9% (n = 11/46) false‐negative rate was observed among African American RhCc serotyped heterozygotes. Utilization of the exon 1 nt48 cytosine for indirect genotyping of RHC yielded a 7.2% (n = 4/55) and 56.3% (n = 45/80) false‐positive rate among Rhcc Caucasians and African Americans, respectively. We conclude that these additional reactions, though not sufficient alone, can be useful supplements to existing Rh genotyping assays. Am. J. Hematol. 69:34‐40, 2002. © 2002 Wiley‐Liss, Inc.
Expression of the TEL/EVI1 fusion transcript in a patient with chronic myelogenous leukemia with t(3;12)(q26;p13)
Authors: Nakamura Yuichi , Nakazato Hiroshi , Sato Yuko , Furusawa Shinpei , Mitani Kinuko
Published: August 2002

The t(3;12)(q26;p13) translocation is a recurrent chromosomal aberration observed in myeloid malignancies. It has been shown that the translocation results in the fusion of the TEL (ETV6) gene at 12p13 and the EV11 gene at 3q26. We report the first case with Philadelphia (Ph)‐positive chronic myelogenous leukemia (CML) expressing the TEL/EVI1 fusion transcript. A 26‐year‐old man was initially diagnosed as having the chronic phase of Ph‐positive CML. The t(3;12)(q26;p13) emerged 16 months prior to the myeloid blastic crisis. Reverse transcriptase‐polymerase chain reaction detected the TEL/EVI1 transcript without the intervening 5′ non‐coding exon of EVI1, suggesting that inappropriate expression of the EVI1 protein driven by the TEL promotor could play a critical role in progression to the blast crisis of CML. Am. J. Hematol. 69:80‐82, 2002. © 2002 Wiley‐Liss, Inc.
Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C)
Authors: Freedman J. , Mody M. , Lazarus A.H. , Dewar L. , Song S. , Blanchette V.S. , Garvey M.B. , Ofosu F.A.
Published: August 2002

Activation of platelets and coagulation in vivo was studied in nine patients with hemophilia A and inhibitors to human Factor VIII, prior to and following treatment with porcine Factor VIII (PFVIII; HYATE:C). In addition, six hemophiliac patients were similarly studied after treatment with recombinant Factor VIII (rFVIII). Platelet activation was also examined in vitro using porcine von Willebrand factor (PvWF)‐enriched and PvWF‐depleted fractions obtained by fractionation of PFVIII. Coagulation was assessed by measuring the concentrations of plasma prothrombin fragment 1+2 concentrations (prothrombinase generation) and Factor Xa‐ATIII. Patients treated with PFVIII had significantly increased numbers of circulating platelets expressing CD62 and CD63 (markers of platelet activation) and annexin V (marker of platelet procoagulant activity) compared to patients treated with rFVIII; the former patients also demonstrated an increase in plasma coagulability after therapy. In in vitro experiments it was observed that the platelet‐activating and procoagulant capacity of PFVIII resided in the PvWF‐enriched fraction, and the same was true for the plasma hypercoagulability following exposure of platelets to PFVIII. These results support the hypothesis that PFVIII‐induced platelet activation provides a mechanism for enhancing hemostasis, separate from, and additional to, that due to increased circulating Factor VIII, and it is due to residual PvWF in the PFVIII preparation. Am. J. Hematol. 69:192–199, 2002. © 2002 Wiley‐Liss, Inc.
Relationship of venous thromboembolism and myocardial infarction with the renin‐angiotensin system in African‐Americans
Authors: Hooper W. Craig , Dowling Nicole F. , Wenger Nanette K. , Dilley Anne , Ellingsen Dorothy , Evatt Bruce L.
Published: August 2002

Genetic polymorphisms/mutations associated with venous thrombosis have largely been confined to the genes that encode for proteins in either the coagulant or the anticoagulant pathway. Although genetic alterations in the renin–angiotensin system have been reported to have a role in myocardial infarction and hypertension, there is recent evidence to suggest that there may also be an association with venous thrombosis. To extend our earlier observation of an association between the ACE DD genotype in African‐American males and venous thrombosis, other genes in the renin–angiotensin pathway were investigated for possible disease association and were compared with African‐Americans with myocardial infarction. African‐American patients with a documented history of venous thrombosis or a history of myocardial infarction were eligible for participation as cases in the study. Control subjects were African‐American outpatients attending a clinical laboratory for routine blood tests who had comparable age and gender distributions to the cases. Persons with a history of myocardial infarction, stroke, or thrombosis were excluded. Genes that were analyzed for known polymorphisms included angiotensinogen, angiotensin‐converting enzyme (ACE), and the angiotensin II type I receptor. Our results showed that the ACE DD genotype was also associated with MI in African‐American males but not in females. Racial/ethnic and sex differences were also found with respect to the genotype distribution of the ACE 4656(CT)2/3 poly‐ morphism. It was observed that the 2/2 genotype had a protective effective in males for myocardial infarction and venous thrombosis. The data also demonstrated that the allele frequencies of the A1166C variant of the angiotensin II type I receptor were different in African‐Americans as compared to Caucasians. Am. J. Hematol. 70:1–8, 2002.
Immune thrombocytopenia: A rare presenting manifestation of tuberculosis
Authors: Ghobrial M.W. , Albornoz M.A.
Published: August 2002

We report the case of a 49 year‐old male who presented with immune thrombocytopenia (ITP)‐induced epistaxis and generalized purpura. During the same hospitalization the patient was also found to have clinical, microbiological, histological, and roentgenographic evidence of disseminated mycobacterial tuberculosis (TB). The hematological and infectious abnormalities, which did not respond to high‐dose intravenous corticosteroids and immune globulin (IVIg), resolved after anti‐tuberculous treatment. Herein we review the characteristics of this rarely documented association. Am. J. Hematol. 67:139–143, 2001. © 2001 Wiley‐Liss, Inc.
Antibody against platelet membrane glycoprotein VI in a patient with systemic lupus erythematosus
Authors: Takahashi Hoyu , Moroi Masaaki
Published: August 2002

Platelet–collagen interaction is important in primary hemostasis and collagen receptors on the platelet surface include membrane glycoprotein (GP) Ia/IIa and VI. Platelets from a 47‐year‐old woman with systemic lupus erythematosus (SLE) and a mild bleeding symptom showed a defective collagen‐induced aggregation and an impaired adhesion to collagen surface. The patient's platelets had a markedly decreased content of GPVI. The patient had an antibody against GPVI in serum and the patient's plasma induced aggregation and release reaction of normal platelets. These findings indicate that GPVI is an important receptor for collagen on the platelet surface, and that anti‐GPVI antibody activates the platelets, resulting in aggregation. This is the first documented case of SLE who acquired a platelet‐aggregating anti‐GPVI antibody. Am. J. Hematol. 67:262–267, 2001. © 2001 Wiley‐Liss, Inc.
Molecular pathogenesis and clinical variability of β‐thalassemia syndromes among Indians
Authors: Nadkarni Anita , Gorakshakar A.C. , Lu C.Y. , Krishnamoorthy R. , Ghosh K. , Colah Roshan , Mohanty Dipika
Published: August 2002

Sixty‐four homozygous β‐thalassemia patients comprising 40 patients with β‐thalassemia major and 24 patients with β‐thalassemia intermedia were investigated for the nature of their β‐thalassemia mutations, associated α‐thalassemia, and XmnI polymorphism in the gamma gene which are known to affect the clinical course of the disease. This study was undertaken to look for the contribution of these associated factors in reducing the clinical severity of homozygous β‐thalassemia from a severe disease to a β‐thalassemia intermedia phenotype. Clinical severity of these patients was assessed by the degree of transfusion dependency and the age at which the patient presented with symptoms. Globin chain synthetic ratio was taken as the biochemical pointer of severity of the disease. Eleven different β‐thalassemia mutations were encountered among 128 β‐thalassemia chromosomes. It was observed that the nature of the β‐thalassemia mutations was not very different between the β‐thalassemia major and β‐thalassemia intermedia groups in our patients, but co‐inheritance of one or more α‐globin gene deletions (−α3.7) and the presence of the XmnI polymorphism were associated with lesser severity of the disease in Indians. Am. J. Hematol. 68:75–80, 2001. © 2001 Wiley‐Liss, Inc.
Cyclic immune thrombocytopenia responsive to thrombopoietic growth factor therapy
Authors: Rice Lawrence , Nichol Janet L. , McMillan Robert , Roskos Lorin K. , Bacile Margaret
Published: August 2002

We report a patient with cyclic thrombocytopenia and antiplatelet antibodies, a variant of chronic immune thrombocytopenic purpura (ITP), with a several year history of periodic fluctuation of the platelet count, megakaryocytic hyperplasia and high‐titer anti‐GPIb‐specific antiplatelet antibodies. The patient was resistant to multiple forms of therapy but has responded to the thrombopoietic growth factor, pegylated recombinant human megakaryocyte growth and development factor (PEG‐rHuMGDF). This case suggests that some patients with classic ITP may respond to thrombopoietic growth factors. Am. J. Hematol. 68:210–214, 2001. © 2001 Wiley‐Liss, Inc.
Genetic admixture in three mexican mestizo populations based on D1S80 and HLA‐DQA1 Loci
Authors: Cerda‐Flores Ricardo M. , Villalobos‐Torres Maria C. , Barrera‐Saldaña Hugo A. , Cortés‐Prieto Lizette M. , Barajas Leticia O. , Rivas Fernando , Carracedo Angel , Zhong Yixi , Barton Sara A. , Chakraborty Ranajit
Published: August 2002

This study compares genetic polymorphisms at the D1S80 and HLA‐DQA1 loci in three Mexican Mestizo populations from three large states (Nuevo León, Jalisco, and the Federal District). Allele frequency distributions are relatively homogenous in the three samples; only the Federal District population shows minor differences of the HLA‐DQA1 allele frequencies compared with the other two. In terms of genetic composition, these Mestizo populations show evidence of admixture with predominantly Spanish‐European (50–60%) and Amerindian (37–49%) contributions; the African contribution (1–3%) is minor. Together with the observation that in Nuevo León, the admixture estimates based on D1S80 and HLA‐DQA1, are virtually the same as those reported earlier from blood group loci, suggests that DNA markers, such as D1S80 and HLA‐DQA1 are useful for examining genetic homogeneity/heterogeneity across Mestizo populations of Mexico. The inverse relationship of the proportion of gene diversity due to population differences (Gst) to within population gene diversity (Hs) is also consistent with theoretical predictions, supporting the use of these markers for population genetics studies. Am. J. Hum. Biol. 14:257–263, 2002. © 2002 Wiley‐Liss, Inc.
Performance and quality measurement in occupational health services: Current status and agenda for further research
Authors: Pransky Glenn , Benjamin Katy , Dembe Allard E.
Published: August 2002

Background

There is growing interest in evaluating the impact and effectiveness of occupational healthcare services (OHS). Managed care networks, case and disease management, worker health promotion, and utilization review services have proliferated in OHS, usually without scientifically based, objective measures of their impact on the quality of care, outcomes, or costs. Performance and quality improvement (QI) efforts in OHS are different from those in general health care because the population, range of conditions, setting of care, and primary outcomes of interest differ considerably. However, scientific knowledge resulting from the application of QI in general health care can provide a useful framework for the development of measures in OHS.

Methods

We describe the development, selection, and evaluation of OHS performance and quality measures, and propose a research agenda.

Conclusions

Quality and performance measures in OHS should address common work‐related conditions with high costs, suboptimal outcomes, or unclear parameters for ideal practices. They should reflect stakeholder priorities. Measures should be precise and quantifiable, clearly specified, reliable, valid, and sensitive to important changes. They should be based upon data that can be collected and analyzed at a reasonable cost and effort. The focus of measurement should be on situations where improvement can be achieved by those directly involved in OHS delivery, through defined approaches. Appropriate severity and case‐mix adjustment may be especially problematic in OHS. Confidentiality, regulatory concerns, and appropriate use of results must be considered in the development and use of OHS measures. Research is needed to identify, develop, and validate OHS‐specific measures, to establish risk adjustment methods, and to test the utility of this information in improving OHS. Am. J. Ind. Med. 40:295–306, 2001. © 2001 Wiley‐Liss, Inc.
Hereditary intraosseous vascular malformation of the craniofacial region: An apparently novel disorder
Authors: Vargel Ibrahim , Cil Barbaros E. , Er Nuray , Ruacan Sevket , Akarsu A. Nurten , Erk Yucel
Published: August 2002

Primary intraosseous vascular anomaly, previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is exclusively described in sporadic cases and no hereditary component has yet been reported. The most commonly affected bones in the skull are the mandible and the maxilla, and life‐threatening bleeding after a simple tooth extraction is frequently observed. Here, we report two consanguineous families containing a total of four affected patients manifesting primary intraosseous vascular malformation (VMOS (vascular malformation osseous)) of the craniofacial region. The phenotypic expression is remarkably similar in both families. The characteristic findings include severe blood vessel expansions within the craniofacial bones and midline abnormalities such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation is restricted to the mandibular and maxillary area in the prepubertal age, and rapid expansion starts after age 12 or 13. A 15‐year follow‐up of one of the patients demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull. Detailed clinical and radiological evaluation provided neither evidence of soft‐tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region. An antibody against a universal proliferation marker, Ki‐67, detected nonproliferative, single‐layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. α‐actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly. Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22‐p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11‐q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2‐q21, 7p15‐p13, and 3q35.2‐q27, respectively. To the best of our knowledge, this is a new disorder, which we call hereditary intraosseous vascular malformation of the craniofacial region. © 2002 Wiley‐Liss, Inc.
Relationship of the delta‐opioid receptor gene to heroin abuse in a large Chinese case/control sample
Authors: Xu Ke , Liu Xie‐he , Nagarajan Saumya , Gu Xiao‐Yong , Goldman David
Published: August 2002

Pharmacological and electrophysiological evidence has shown that opioid receptors are involved in the mechanism of heroin dependence. Thus, opioid receptors are appropriate candidate genes for case‐control association studies of heroin dependence. Previously, two single nucleotide polymorphisms (SNPs), OPRD1 921T > C and 80G > T, of the human δ opioid receptor gene were used in population‐based studies of heroin dependence. One study in a German population found that OPRD1 921T > C was associated with heroin dependence. This finding, however, was not replicated in a different German sample. To test the hypothesis that OPRD1 or a closely linked gene is associated with heroin dependence, we used 5′ nuclease assays to genotype both OPRD1 SNPs in 450 Chinese heroin dependent patients and 304 unaffected controls from the same population. In addition, five SNPs distributed in four other genes: ADH2, ALDH2, OPRM1, and DRD1, were used as genomic control loci to test the case and control populations for stratification bias. Genotype and allele frequencies at OPRD1 921T > C were not significantly different, and the OPRD1 80G was absent from both Chinese opioid dependence patients and controls. Based on the genotype and allele frequencies of the genomic control loci, there was no evidence for stratification bias capable of masking an association of OPRD1 to heroin dependence in this large and homogenous Chinese sample. Therefore, these data do not support an association between the OPRD1 gene and heroin dependence in the Chinese population. Published 2002 Wiley‐Liss, Inc.
Genetic counseling for sex chromosome abnormalities
Authors: Linden Mary G. , Bender Bruce G. , Robinson Arthur
Published: August 2002

Sex chromosome abnormalities (SCAs) are the most frequently occurring chromosomal abnormalities encountered at both prenatal diagnosis and at birth. Approximately 1/400 newborns has an SCA, and incidence at prenatal diagnosis is even greater, 1/250 to 1/300. Physicians and health providers from various specialties are encountering diagnoses of SCAs with increased frequency as more individuals are becoming identified, both prenatally and postnatally. Because these conditions generally have relatively few serious physical implications and because they are extremely variable, genetic counseling is often more complex and challenging than that occurring with an autosomal abnormality. It is imperative that health professionals have the knowledge of content and methodology to provide appropriate counseling to such individuals and their families. During the period from 1964 to 1975, seven international groups (including the Denver group) screened a total of 199,898 consecutive births and identified 307 individuals with SCA. The Denver group has followed more than 40 such individuals from birth to adulthood. In addition, the Denver group has experience in counseling over 1,000 families with a prenatal diagnosis of SCA. Based on these studies and contacts, guidelines for the counseling of individuals and families with SCA are provided. Accurate information must be presented and the variability and imprecise prognosis recognized. Successful counseling strategies include interfamily contact, viewing photographs, and utilizing support groups. Issues of disclosure, follow‐up, and anticipatory guidance should be addressed. © 2002 Wiley‐Liss, Inc.
Additional evidence that genetic variation of MAO‐A gene supports a gender subtype in obsessive‐compulsive disorder
Authors: Camarena Beatriz , Rinetti Gina , Cruz Carlos , Gómez Amalia , de la Fuente Juan R. , Nicolini Humberto
Published: August 2002

Studies have recently reported a sexually dimorphic association between obsessive‐compulsive disorder (OCD) and a polymorphism related with variations in MAO‐A activity. These observations suggest the possibility of gender differences in genetic susceptibility for OCD. We thus reexamined the MAO‐A/EcoRV polymorphism in a sample of 122 OCD patients and 124 healthy subjects. An excess of allele 1 in OCD females with major depression disorder was confirmed as previously reported. This difference was more strongly associated with OCD females than males in the total sample. Finally, we analyzed a sample of 51 OCD trios. Haplotype‐based haplotype relative risk (HHRR) analysis of the inheritance of the MAO‐A variants revealed in the female probands that 14 out of 19 transmitted the allele 1, providing significant evidence for an allelic association between OCD and MAO‐A gene. In conclusion, our findings may provide molecular evidence to identify a clinically meaningful gender subtype. However, an effort should be made to replicate the analysis in larger samples of informative parents using strategies such as transmission disequilibrium test to allow definite conclusions. © 2001 Wiley‐Liss, Inc.
Serotonin transporter gene polymorphisms are associated with anxiety‐related personality traits in women
Authors: Melke Jonas , Landén Mikael , Baghei Fariba , Rosmond Roland , Holm Göran , Björntorp Per , Westberg Lars , Hellstrand Monika , Eriksson Elias
Published: August 2002

Several studies have reported an association between anxiety‐related personality traits and a promoter polymorphism in the human serotonin transporter (5‐HTT) gene (5‐HTT gene‐linked polymorphic region, 5‐HTTLPR). In the present study, a population of 251 subjects was assessed with the Karolinska Scales of Personality (KSP) and genotyped both for the 5‐HTTLPR and for a variable number of tandem repeats polymorphism in the second intron of the same gene. The interpretation of previous studies has to some extent been confounded by the studied subjects differing with respect to ethnicity, sex, and age. To circumvent this problem, all included subjects were Caucasians, women, and born in the same year (1956). Associations were found between the 5‐HTTLPR and four of the five anxiety‐related KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of assertiveness), subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype. In addition, an association was found between the intron 2 polymorphism and one anxiety‐related personality trait (somatic anxiety). © 2001 Wiley‐Liss, Inc.
Mutation screening of the dopamine D2 receptor gene in attention‐deficit hyperactivity disorder subtypes: Preliminary report of a research strategy
Authors: Todd Richard D. , Lobos Elizabeth A.
Published: August 2002

Attention‐deficit hyperactivity disorder (ADHD) is a highly heritable syndrome with onset in childhood that is associated with clinical response to drugs, which increase the release of monoamines, especially dopamine. A variety of studies have reported on genetic associations of ADHD with polymorphisms for various component genes of the dopamine pathway. The promise of preliminary associations found with several genes is mitigated by the significant controversy that exists over what are the appropriate clinical characteristics of ADHD associated with its familial transmission. In the current report, we describe a strategy for mutation screening in common, complex disorders and its application to the systematic screening for coding region variation in the dopamine D2 receptor (DRD2) gene. We used groups of individuals who met diagnostic criteria for DSM‐IV–defined ADHD subtypes, as well as recently defined latent class criteria for pure familial forms of ADHD. No coding region sequence variations were identified in the DRD2 gene that met our requirements for prevalence to be considered a candidate variant contributing to susceptibility for ADHD. © 2001 Wiley‐Liss, Inc.
Sources of variation in the nesting behavior of chimpanzees (Pan troglodytes schweinfurthii) in the Budongo forest, Uganda
Authors: Brownlow A.R. , Plumptre A.J. , Reynolds V. , Ward R.
Published: August 2002

Data on nesting behavior and nests of the Sonso community of chimpanzees (Pan troglodytes schweinfurthii) living in the Budongo Forest, Uganda, were collected between October 1995 and December 1996. Analysis of the selection of nests shows a preference for particular tree species, especially Cynometra alexandri. Male chimpanzees nested lower than females. Day nests were found to be structurally simpler than night nests and were built in tree species used for feeding, at the same height as feeding activity. Day and night nests serve different functions, and should be clearly distinguished in studies of nesting behavior. Am. J. Primatol. 55:49–55, 2001. © 2001 Wiley‐Liss, Inc.
Characterization and screening of microsatellite loci in a wild lemur population (Propithecus verreauxi verreauxi)
Authors: Lawler Richard R. , Richard Alison F. , Riley Margaret A.
Published: August 2002

Sixteen dinucleotide microsatellite loci were isolated from the genome of Propithecus verreauxi verreauxi. All loci were polymorphic when genotyped on a minimum of 16 animals. The number of alleles across these loci ranges from two to 11. Additionally, seven of these loci were genotyped across a minimum of 200 animals in order to estimate heterozygosity and their potential for parentage assignment in this population. Using these seven loci, the mean heterozygosity in this population is 0.705, and the combined probability of these seven loci to exclude a random individual from parentage, when one parent is known, is 0.996. These data suggest that these loci will be useful for estimating a variety of population genetic and genealogical parameters in P. v. verreauxi populations. Am. J. Primatol. 55:253–259, 2001. © 2001 Wiley‐Liss, Inc.
Sperm quality differences between the rainy and dry seasons in captive black‐handed spider monkeys (Ateles geoffroyi)
Authors: Hernández‐López Leonor , Parra Gerardo Cerezo , Cerda‐Molina Ana Lilia , Pérez‐Bolaños Stephanella C. , Sánchez Vicente Díaz , Mondragón‐Ceballos Ricardo
Published: August 2002

The present work provides an assessment of sperm measures (concentration, motility, viability, etc.) of three black‐handed spider monkeys (Ateles geoffroyi) during the rainy and dry seasons in Mexico City, as well as an evaluation of the between‐subjects variability of sperm quality. Twenty samples obtained by rectal electroejaculation and digested with trypsin were evaluated. The results showed that during the dry season (n = 9) the semen samples were of better quality than those obtained during the rainy season (n = 11). The individual animals showed differences in sperm concentration, although there were no differences in sperm quality. Am. J. Primatol. 57:35–41, 2002. © 2002 Wiley‐Liss, Inc.