bluuebunny/crossref_metadata_2025 huggingface dataset:
The pricing of innovations: An application to specialized corn traits
Authors: Alexander Corinne , Goodhue Rachael E.
Published: October 2002

One concern regarding the growing agricultural biotechnology industry is the potential for these firms to exercise market power when pricing their innovations, which would affect the magnitude and distribution of resulting welfare gains. We argue that competition across production systems limits the exercise of such market power by suppliers. In order to examine the demand for these innovations, we evaluate the producer's returns to planting patented seed innovations, using a calibrated optimization model of a south‐central Iowa corn producer's adoption decision. Overall, our results suggest that patented seed innovations do not increase the market power of biotechnology firms in the relevant market for production systems. [EconLit subject codes: L190, O330, Q120] © 2002 Wiley Periodicals, Inc.
Trisomies 8 and 9 not detected with fish in patients with mastocytosis
Authors: Swolin Birgitta , Rödjer Stig , Ögärd Inger , Roupe Gösta
Published: October 2002

Mastocytosis is a rare disease characterized by proliferation of mast cells in one or several organs. With conventional cytogenetics about 35% of the patients have chromosomally abnormal clones in bone marrow cells. It has been proposed to include the mast cell disease among the myeloproliferative disorders, in which trisomy for chromosome 8 and 9 can appear in the bone marrow cells. In this study bone marrow cells from eight patients with mastocytosis, two had as well an associated hematological disease, have been examined with fluorescence in situ hybridization (FISH) for enumeration of chromosome no8 and 9. In conventional cytogenetics two patients had clones with del(20) and 47,XY,+14/45, X,−Y, respectively. None of the patients with mastocytosis had clones with trisomy 8 or 9 with either cytogenetics or FISH. Am. J. Hematol. 70:324–325, 2002. © 2002 Wiley‐Liss, Inc.
Hydroxyurea treatment of sickle cell anemia in hospital‐based practices
Authors: Ferguson Robert P. , Arun Anuradha , Carter Chris , Walker Stanley D. , Castro Oswaldo
Published: October 2002

In a published randomized clinical trial, hydroxyurea (HU) improved clinical outcomes in patients with sickle cell anemia (SCA). The mean treatment duration of that trial was 21 months. Here we attempt to determine whether the benefits associated with HU therapy of SCA have led also to successful patient acceptance of HU treatment in community practices, and whether successful clinical outcomes persist beyond 2 years. This is an observational retrospective chart study of the computerized medical records of 60 men and women with SCA who had HU treatment for at least 3 months and who were treated at teaching hospital subspecialty clinics in Baltimore, Maryland, and Washington, D.C. Thirty had remained on therapy for at least 24 months. Admissions declined in this group by 30% (P = 0.04). Declines were seen also in transfusion requirements (−58%, P = 0.07). In 17 of these 30 patients, at least 48 months of follow‐up records were available. Fourteen of these remained on therapy the entire period, with similar and sustained reductions in admissions and transfusions. We conclude that hydroxyurea therapy of SCA applied in community settings leads to declining admissions and transfusion rates in many individuals for 4 years or more. Am. J. Hematol. 70:326–328, 2002. © 2002 Wiley‐Liss, Inc.
Split‐cord malformation in a girl with Angelman syndrome: A mere coincidence?
Authors: Mastroyianni Sotiria D. , Kontopoulos Eleftherios
Published: October 2002

We present a case of a girl with both Angelman syndrome and split‐cord malformation. The child was initially referred at the age of 2.5 years, for developmental delay and a possible diagnosis of spina bifida occulta, based on the presence of a hair tuft located on the midline of the lumbar area. Magnetic resonance imaging of the spine showed split‐cord malformation below L1, whereas a cytogenetically detected deletion of chromosome bands 15q11‐q13 (SNRPN) confirmed the clinical diagnosis of Angelman syndrome. Split‐cord malformation or diastematomyelia is a rare form of spina bifida occulta that occurs sporadically and is not particularly related to specific syndromes. Hair patches or other distinctive cutaneous stigmata such as those seen in the present case have not, to our knowledge, been reported in other patients with Angelman syndrome; therefore, the association of Angelman syndrome and split‐cord malformation in this child is probably coincidental. Spinal cord abnormalities have not been consistently reported in patients with Angelman syndrome; only one adult patient with Angelman syndrome and spina bifida occulta has been reported, and this association was probably considered fortuitous. However, some relatively uncommon clinical features such as deterioration of gait, lower limb malformations, and bladder dysfunction, particularly as the patients age, although nonspecific, are reminiscent of such a cause. We therefore urge clinicians to look for cutaneous stigmata along the spine and consider the evaluation of the spinal cord in children with apparent paraparesis, out of proportion to that usually seen in Angelman syndrome, should our case report not just be a coincidental observation. © 2002 Wiley‐Liss, Inc.
Expanding phenotype of XNP mutations: Mild to moderate mental retardation
Authors: Yntema Helger G. , Poppelaars Francis A. , Derksen Esther , Oudakker Astrid R. , van Roosmalen Tanja , Jacobs Anja , Obbema Hanneke , Brunner Han G. , Hamel Ben C.J. , van Bokhoven Hans
Published: October 2002

Mutations in the XNP gene have been reported in alpha thalassemia/mental retardation (MR) syndrome (ATR‐X) and other severe X‐linked MR conditions with facial dysmorphisms. In this report, we describe a missense mutation in exon 18 in a family with borderline to moderate MR. Like other disorders associated with an XNP mutation, skewed X‐inactivation was found in all carrier females in this family. Only retrospective examination revealed childhood facial hypotonia and HbH inclusions in some of the affected males. These results expand the spectrum of clinical phenotypes known to be due to mutations in the XNP gene, and indicate that XNP mutation analysis should not be restricted to patients with severe MR and characteristic facial features. © 2002 Wiley‐Liss, Inc.
Association study of the short tandem repeat in the 5′ upstream region of the cholecystokinin gene with mood disorders in the Japanese population
Authors: Hattori Eiji , Yamada Kazuo , Ebihara Mitsuru , Toyota Tomoko , Nankai Masahiro , Shibuya Haruo , Yoshikawa Takeo
Published: October 2002

We have recently identified a novel polymorphic short tandem repeat (STR) in the 5′ upstream region of the cholecystokinin (CCK) gene and reported its association with panic disorder. A linkage study of affective disorder showed a modest linkage signal on the short arm of chromosome 3, the location of the CCK gene. Furthermore, clinical comorbidity of depression and anxiety disorders have been documented. In the present study, we examined a possible association of the CCK STR with mood disorders. We genotyped 165 subjects with mood disorders consisting of unipolar and bipolar disorders and 253 control samples. However, no significant allelic associations were detected between the STR and either the combined mood disorders (P = 0.885), the unipolar group (P = 0.296), or the bipolar group (P = 0.605). These data suggest that the CCK promoter STR is unlikely to have a major genetic effect on the development of mood disorders in the Japanese population. © 2002 Wiley‐Liss, Inc.
Genitopatellar syndrome: A recognizable phenotype
Authors: Reardon William
Published: October 2002

Genitopatellar syndrome is a newly described condition, subject of a single literature report to date. The condition comprises absent patellae, genital and renal malformations, joint dislocation, and mental retardation. Recurrence has been recorded in two kindreds, consistent with autosomal recessive inheritance. © 2002 Wiley‐Liss, Inc.
Demonstration of acute ischemic lesions in the fetal brain by diffusion magnetic resonance imaging
Authors: Baldoli Cristina , Righini Andrea , Parazzini Cecilia , Scotti Giuseppe , Triulzi Fabio
Published: October 2002

The possibility of detecting acute hypoxic‐ischemic brain lesions by prenatal magnetic resonance imaging or ultrasound is low. We present a case of a fetus with a vein of Galen arteriovenous malformation in whom prenatal diffusion‐weighted magnetic resonance imaging at 33 weeks of gestation clearly detected cerebral acute ischemic lesions, associated with remarkable decrease of the average apparent diffusion coefficient, whereas T2‐weighted imaging was still not informative.
Differences in membrane properties of axonal and demyelinating Guillain‐Barré syndromes
Authors: Kuwabara Satoshi , Ogawara Kazue , Sung Jia‐Ying , Mori Masahiro , Kanai Kazuaki , Hattori Takamichi , Yuki Nobuhiro , Lin Cindy S.‐Y. , Burke David , Bostock Hugh
Published: October 2002

Guillain‐Barré syndrome is classified into acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) by electrodiagnostic and pathological criteria. In AMAN, the immune attack appears directed against the axolemma and nodes of Ranvier. Threshold tracking was used to measure indices of axonal excitability (refractoriness, supernormality, and threshold electrotonus) for median nerve axons at the wrist of patients with AMAN (n = 10) and AIDP (n = 8). Refractoriness (the increase in threshold current during the relative refractory period) was greatly increased in AMAN patients, but the abruptness of the threshold increases at short interstimulus intervals indicated conduction failure distal to the stimulation (ie, an increased refractory period of transmission). During the 4 week period from onset, the high refractoriness returned toward normal, and the amplitude of the compound muscle action potential increased, consistent with improvement in the safety margin for impulse transmission in the distal nerve. In contrast, refractoriness was normal in AIDP, even though there was marked prolongation of distal latencies. Supernormality and threshold electrotonus were normal in both groups of patients, suggesting that, at the wrist, membrane potential was normal and pathology was relatively minor. These results support the view that the predominantly distal targets of immune attack are different for AMAN and AIDP. Possible mechanisms for the reduced safety factor in AMAN are discussed.
Sequential interpenetrating polymer networks of poly(2‐hydroxyethyl methacrylate) and polydimethylsiloxane
Authors: Abbasi F. , Mirzadeh H. , Katbab A. A.
Published: October 2002

The preparation of interpenetrating polymer networks (IPNs) from silicone rubber and hydrogel forming poly(2‐hydroxyethyl methacrylate) (HEMA) were studied. The HEMA monomer was polymerized with simultaneous crosslink formation in the presence of the swollen silicone rubber. To minimize the required number of experiments, the Taguchi method of experimental design involving the factors of temperature, monomer concentration, initiator concentration, and crosslinker concentration was used. Upon removal of the swelling solvent, an IPN was obtained which absorbed water in the manner of a hydrogel but had mechanical properties superior to a hydrogel. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1825–1831, 2002
Study on the adsorption of hemoglobin onto bentonite clay surfaces
Authors: Bajpai A. K. , Sachdeva R.
Published: October 2002

The adsorption behavior of a hemoglobin (Hb) solution onto bentonite powder was studied from its alkaline solution (pH 12.6) and at room temperature. Different types of adsorption isotherms are discussed and various adsorption parameters, such as the adsorption coefficient, rate constants for adsorption and desorption, diffusion constant, penetration rate constant, were evaluated. The effects of pH and temperature of the adsorption medium on the extent of adsorption and the influence of solvents were studied, and the effect of salt concentrations on the rate of adsorption were also observed. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1607–1618, 2002
Effect of chemical modification of cotton fabrics on dyeing properties
Authors: Micheal M. N. , Tera F. M. , Ibrahim S. F.
Published: October 2002

The presented research deals with modifying the chemical structure of the cellulosic cotton fabrics by introducing amino groups as new active centers. The properties of the resulting aminated cotton, dimethylaminoethyl (DMAE)‐cotton, are evaluated and discussed by studying the dyeability, light fastness characteristics, and fading kinetics. The goal of this study was achieved. The modification succeeded in saving energy by decreasing both the dyeing time and temperature, and the dyeability and light fastness characteristics were improved. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1897–1903, 2002
Time‐dependent rheological behavior of low‐density polyethylene white color masterbatches under dynamic stress field
Authors: Lei Caihong , Chen Dahua , Huang Rui , Li Guangxian , Lu Yuben
Published: October 2002

The time‐dependent behavior of low‐density polyethylene (LDPE) white color masterbatches (WCMBs), which were concentrated suspensions filled with titanium dioxide (TiO2), was found using dynamic stress rheometer. The viscosity first decreased slightly with time then continuously increased with time, and Tg(δ) (δ was the angle of loss) decreased with time, which meant the time‐dependent behavior of the elastic contribution was more pronounced than that of the viscous contribution. The higher the experimental frequency and temperature, the more pronounced the viscosity increase. However, the higher experimental stress did not lead to pronounced viscosity increase, which was attributed to the existence of small defects at higher stress. The 30 wt % of TiO2 content was critical to obvious time‐dependent behavior. The viscosity increase with time was related to the formation of a hard shell around the melt sample during the test. It was verified by thermogravimetric analysis that the TiO2 concentration at the outer surface was higher than that at the core of the sample and, because the outer surface contained more TiO2, a hard shell was formed, which impeded further deformation of the sample. This was completely different from the other reported systems with time‐dependent behavior. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2793–2799, 2002
Surface structures of solvent‐cast films prepared from poly(ethylene oxide)‐segmented nylons
Authors: Mochizuki Akira , Senshu Kazuhisa , Yamashita Shuzo , Koshizaki Naoto
Published: October 2002

The surface structures of three kinds of poly(ethylene oxide)‐segmented nylon (PEO‐Ny) films prepared by the solvent‐cast method were investigated with electron spectroscopy for chemical analysis (ESCA). The PEO‐Ny's used were high‐crystalline PEO‐segmented poly(iminosebacoyliminohexamethylene), low‐crystalline PEO‐segmented poly(iminosebacoylimino‐m‐xylene), and amorphous PEO‐segmented poly(iminoisophthaloyliminomethylene‐1,3‐cyclohexylenemethylene), and the PEO contents in the bulk polymers were approximately 10 wt %. The ESCA results showed that the PEO segment was enriched on the top surfaces of all the films, and the degrees of enrichment were different. The mechanism of the PEO enrichment was examined. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 10–16, 2002
Miniemulsion and macroemulsion copolymerization of vinyl acetate with vinyl versatate
Authors: Wu X. Q. , Hong X. M. , Cordeiro Cajetan , Schork F. J.
Published: October 2002

The miniemulsion and macroemulsion polymerization of vinyl acetate with vinyl versatate in batch and semibatch systems was investigated. Vinyl versatate was added either as an emulsion with the vinyl acetate, or as a neat liquid stream. In the batch runs, there is a poor dispersion of vinyl versatate during the nucleation period for the runs in which the vinyl versatate was added neat at the beginning of the polymerization. This led to smaller particles, lower polymerization rate, and different polymer composition evolution when compared with runs in which the vinyl versatate was emulsified with the vinyl acetate. In seeded semibatch runs, residual surfactant in the seed latex, along with the propensity for homogeneous nucleation in vinyl acetate emulsions, resulted in continuing nucleation during the entire semibatch interval. The polymerization rate was primarily affected by monomer feed rate rather than the feeding mode. The effect of monomer feeding mode on copolymer composition was weak when the semibatch feed rate was low, indicating some level of vinyl versatate mass transfer resistance. In all runs, only one glass transition temperature was observed, indicating effective copolymerization. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2219–2229, 2002
Experimental investigation of the morphology development and mechanical properties of waste ethylene propylene diene monomer/polypropylene blend in modular intermeshing corotating twin‐screw extruder
Authors: Kim Jin Kuk , Lee Sung Hyo , Hwang Sung Hyuk
Published: October 2002

Nowadays, with the increase in the number of automobiles, waste EPDM (ethylene propylene diene monomer) is causing a significant environmental problem. From environmental and economical perspectives, recycling is one of the popular methods to solve environmental problems. This study, which involved waste EPDM/PP (polypropylene) blends with the ratio range of 70/30 and 75/25, set out to ascertain the relevance of the mass percentage of the dispersed phase, the influence of the screw geometry, the screw rpm, and the melting temperature of PP materials on the morphology and mechanical properties of the waste rubber blend. The purpose of this study is to develop a high‐value thermoplastic elastomer from waste EPDM. This investigation concentrated on determining the optimum conditions for producing a blend by extrusion, relative to screw geometry, screw rational speed, and operating temperature. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2276–2282, 2002
On the issue of urea phase connectivity in formulations based on molded flexible polyurethane foams
Authors: Aneja Ashish , Wilkes Garth L.
Published: October 2002

Lithium chloride was added to systematically alter the phase separation behavior, and hence, the nature of urea phase connectivity, in a series of plaques based on molded flexible polyurethane foam formulations. The plaques prepared were found to possess varied levels of urea phase connectivity that was examined at different length scales using several characterization techniques. SAXS, TEM, and t‐AFM were used to show that addition of LiCl systematically reduced the formation of the urea aggregate structures typically observed in flexible polyurethane foam formulations and thus led to a loss in urea phase connectivity at the macrolevel. SAXS, DSC, and DMA revealed that formulations with and without LiCl exhibited similar interdomain spacings and soft segment glass transitions, suggesting that incorporation of LiCl did not prevent the plaques from undergoing partial microphase separation. WAXS demonstrated that addition of LiCl led to a loss in the local ordering of the hard segments within the microdomains, i.e., it led to a reduction of microlevel connectivity or the regularity in segmental packing of the urea phase. High‐magnification t‐AFM images showed that increasing the LiCl content dispersed the urea component more homogeneously and in a more uniform manner in the polyol matrix, and thus altered the connectivity of the urea phase at the microdomain level. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2956–2967, 2002
Delivery of bupivacaine included in poly(acrylamide‐co‐monomethyl itaconate) hydrogels as a function of the pH swelling medium
Authors: Bernardo M. V. , Blanco M. D. , Olmo R. , Teijón J. M.
Published: October 2002

Copolymeric hydrogels of poly(acrylamide‐co‐monomethyl itaconate) (A/MMI) crosslinked with N,N′‐methylenbisacrylamide (NBA) were synthesized as devices for the controlled release of bupivacaine (Bp). Two compositions of the copolymer, 60A/40MMI and 75A/25MMI, were studied. A local anesthetic was included in the feed mixture of polymerization (2–8 mg Bp/tablet) and by immersion of the copolymeric tablets in an aqueous solution of the drug. A very large amount of Bp (36–38 mg Bp/tablet) was included in the gels by sorption due to interactions between the drug and the side groups of the hydrogels. Swelling and drug release were in accordance with the second Fick's law at the first stages of the processes. The swelling behavior of these copolymers depended on the pH of the medium. The equilibrium swelling degree (W∞) was larger at pH 7.5 (W∞ ≈ 90 wt %) than at pH 1.5 (W∞ ≈ 52–64 wt %) due to the ionization of the side groups of the copolymer. Release of the drug also depended on the pH of the swelling medium; at pH 7.5, about 60% of the included drug was released, and at pH 1.5, about 80% was released. Bp release was controlled by the comonomer composition of the gels, their drug‐load, and the pH of the swelling medium. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 327–334, 2002
Co‐development of Encarsia formosa (Hymenoptera: Aphelinidae) and the greenhouse whitefly, Trialeurodes vaporariorum (Homoptera: Aleyrodidae): A histological examination
Authors: Blackburn Michael B. , Gelman Dale B. , Hu Jing S.
Published: October 2002

Using histological techniques, we have simultaneously examined the co‐development of the Aphelinid parasitoid Encarsia formosa and its host the greenhouse whitefly, Trialeurodes vaporariorum. Previously we have determined that regardless of the whitefly instar parasitized, parasitoid larvae would not molt to their final instar until the whitefly reaches its maximum dimensions. In unparasitized T. vaporariorum, this point in development corresponds to the initiation of the adult molt. In part, this study was conducted to determine the developmental state of parasitized whiteflies at the time they achieve their maximum dimensions. It was found that parasitized final instar T. vaporariorum do, in fact, undergo a final molt and that E. formosa larvae will not molt to their final instar until this has occurred. The timing of the final whitefly molt appears unaffected by parasitization. The commonly observed melanization of parasitized whiteflies appears to be a consequence of this molt. In addition, we have discovered that the adult wasp oviposits within the ventral ganglion of the whitefly, and that major organ systems of the whitefly persist very late into parasitoid development. We also report the presence of possible endosymbiotic bacteria residing in the fatbody of E. formosa. Arch. Insect Biochem. Physiol. 51:13–26, 2002. Published 2002 Wiley‐Liss, Inc.
Joint damage and inflammation in c‐Jun N‐terminal kinase 2 knockout mice with passive murine collagen‐induced arthritis
Authors: Han Zuoning , Chang Lufen , Yamanishi Yuji , Karin Michael , Firestein Gary S.
Published: October 2002

Objective

Previous studies have demonstrated that inhibition of c‐Jun N‐terminal kinase (JNK) decreases joint destruction in the rat adjuvant arthritis model. The present study was undertaken to investigate whether selective loss of JNK‐2 function decreases joint destruction in JNK‐2 knockout mice, in order to determine the role of this isoform in inflammatory arthritis.

Methods

Passive collagen‐induced arthritis (CIA) was induced in Jnk2−/− and wild‐type mice by administering anti–type II collagen antibodies. Arthritis was assessed daily using a semiquantitative clinical scoring system. Fibroblast‐like synoviocytes (FLS) were prepared from Jnk2−/− and wild‐type mice, and JNK protein expression was determined by Western blot analysis. Matrix metalloproteinase 13 (MMP‐13) expression was determined by Northern blot analysis, and activator protein 1 (AP‐1) binding activity by electromobility shift assay (EMSA).

Results

The JNK protein level in Jnk2−/− mice with CIA was 22% of that in wild‐type mice with CIA (P < 0.001), and mainly the 46‐kd isoform was expressed in the former group. Surprisingly, clinical arthritis was slightly more severe in the Jnk2−/− mice. Histologic scores for synovial inflammation were not significantly different. However, Safranin O–stained sections from the Jnk2−/− mice exhibited significantly less joint damage. Although joint destruction was decreased in Jnk2−/− mice with CIA, EMSA and Northern blot analysis of total joint extracts revealed similar levels of AP‐1 binding and MMP‐13 expression in Jnk2−/− and wild‐type mice. The lack of correlation with AP‐1 activity and MMP expression was probably because non‐FLS cells in the joint may express more JNK‐1 than do FLS.

Conclusion

JNK‐2 is a determinant of matrix degradation, but it has little effect on inflammation in arthritis. Complete inhibition of MMP expression and joint destruction will likely require combined JNK‐1 and JNK‐2 inhibition.
Immunization of naive BALB/c mice with human β2‐Glycoprotein I breaks tolerance to the murine molecule
Authors: Tincani A. , Gilburd B. , Abu‐Shakra M. , Blank M. , Allegri F. , Ottaviani R. , Riboni M. , Meroni P. L. , Balestrieri G. , Shoenfeld Y.
Published: October 2002

Objective

Immunization of naive mice with β2‐glycoprotein I (β2GPI) leads to the generation of pathogenic anticardiolipin antibodies associated with clinical manifestations of the antiphospholipid syndrome (APS). The aim of this study was to determine whether immunization of naive mice with human β2GPI, which shares homology with mouse β2GPI molecules, breaks tolerance to murine β2GPI and leads to the generation of anti‐mouse β2GPI.

Methods

Twenty‐four female BALB/c mice were immunized in the footpads with 10 μg of human β2GPI. Twelve age‐ and sex‐matched BALB/c mice were immunized in the same manner with Freund's complete adjuvant and served as controls. The reactivity of whole sera, polyclonal IgG, and affinity‐purified anti‐β2GPI IgG antibodies against human, bovine, and mouse β2GPI was evaluated by enzyme‐linked immunosorbent assay.

Results

High titers of anti‐human β2GPI IgG antibodies were detected 1 month after immunization. Progressively increasing titers against murine and bovine β2GPI were recorded 1–4 months after injection.

Conclusion

Immunization of mice with human β2GPI resulted in the generation of antibodies reacting with human, bovine, and murine β2GPI. The loss of tolerance to mouse β2GPI is attributable to the high interspecies homology of β2GPI. These results may point to molecular mimicry as a possible cause of APS.
Suppression of tumor necrosis factor α–induced matrix metalloproteinase 9 production in human salivary gland acinar cells by cepharanthine occurs via down‐regulation of nuclear factor κB: A possible therapeutic agent for preventing the destruction of the acinar structure in the salivary glands of Sjögren's syndrome patients
Authors: Azuma Masayuki , Aota Keiko , Tamatani Tetsuya , Motegi Katsumi , Yamashita Tsuyoshi , Ashida Yuki , Hayashi Yoshio , Sato Mitsunobu
Published: October 2002

Objective

Our previous results suggested that suppression of tumor necrosis factor α (TNFα)–induced matrix metalloproteinase 9 (MMP‐9) could prevent the destruction of acinar tissue in the salivary glands of patients with Sjögren's syndrome (SS). The present study was undertaken to investigate the effect of cepharanthine on the suppression of TNFα‐induced MMP‐9 production in NS‐SV‐AC, an SV40‐immortalized normal human acinar cell clone.

Methods

After pretreatment with or without cepharanthine, NS‐SV‐AC cells were treated with TNFα alone or with a combination of TNFα and cepharanthine. The expression of MMP‐9 was then examined at the protein and messenger RNA levels. In addition, the effect of cepharanthine on the morphogenetic behavior of NS‐SV‐AC cells cultured on type IV collagen–coated dishes in the presence of TNFα was examined.

Results

Although TNFα induced the production of MMP‐9 in NS‐SV‐AC cells, this production was greatly suppressed when cells were pretreated with cepharanthine, followed by treatment with both TNFα and cepharanthine. In addition, cepharanthine suppressed the TNFα‐stimulated NF‐κB activity by partly preventing the degradation of IκBα protein in NS‐SV‐AC cells. When NS‐SV‐AC cells were seeded on type IV collagen–coated dishes in the presence of both TNFα and plasmin, type IV collagen interaction with the cells was lost and the cells entered apoptosis. However, pretreatment with cepharanthine restored the aberrant in vitro morphogenesis of the NS‐SV‐AC cells.

Conclusion

These results may indicate a molecular mechanism by which cepharanthine is able to protect against the destruction of the acinar structure in salivary glands from patients with SS.
Genetic linkage and association of Fcγ receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus
Authors: Edberg Jeffrey C. , Langefeld Carl D. , Wu Jianming , Moser Kathy L. , Kaufman Kenneth M. , Kelly Jennifer , Bansal Vipin , Brown W. Mark , Salmon Jane E. , Rich Stephen S. , Harley John B. , Kimberly Robert P.
Published: October 2002

Objective

Although low‐affinity alleles of human Fcγ receptor types IIA and IIIA (FcγRIIA and FcγRIIIA, respectively) polymorphisms have been associated with systemic lupus erythematosus (SLE) in case–control studies, the relative contribution of these genes to SLE susceptibility has not been resolved.

Methods

We analyzed the distribution of alleles of FcγRIIA, FcγRIIIA, and FcγRIIIB in 126 multiplex‐SLE pedigrees and FcγRIIA and FcγRIIIA in a case–control replication study, using allele‐specific polymerase chain reaction and direct sequencing of genomic DNA. Statistical tests of association were performed to detect evidence of linkage between the single nucleotide polymorphisms and SLE.

Results

We found evidence for linkage at both the FcγRIIIA (single‐point nonparametric linkage [NPL] 1.8, P = 0.038; multipoint NPL 2.7, P = 0.004) and the FcγRIIA (single‐point NPL 2.0, P = 0.021; multipoint NPL 2.6, P = 0.006) loci, but not the FcγRIIIB locus. Family‐based tests of association demonstrated increased transmission of the low‐affinity F176 allele at the FcγRIIIA locus (odds ratio [OR] 2.18, P = 0.0005 by transmission disequilibrium test and P = 0.002, by pedigree disequilibrium test [PDT]), but little evidence of preferential transmission of alleles at FcγRIIA (P = 0.089 by PDT). Stratification by ethnicity showed preferential transmission of the associated FcγRIIIA allele both in families of African American ancestry and in those of European American ancestry. Despite significant linkage disequilibrium between these genes, 2‐ and 3‐locus haplotype analysis of the extended Fcγ receptor cluster did not reveal any significant association beyond that observed with FcγRIIIA alone. In a large case–control replication study of 438 patients with SLE and 219 controls, FcγRIIIA provided the strongest evidence of an FcγR–SLE association (additive model: V/V 176 versus V/F 176 OR 1.51, V/V 176 versus F/F 176 OR 1.98, P = 0.007).

Conclusion

To our knowledge, these data are the first to demonstrate linkage and both family‐based and case–control–based association of FcγRIIIA with SLE. These data provide genetic evidence supporting a role for the physiologically relevant single nucleotide polymorphism of the FcγRIIIA gene in the pathophysiology of this complex genetic disease.
Inducible expression of Bcl‐XL restricts apoptosis resistance to the antibody secretion phase in hybridoma cultures
Authors: Jung Daniel , Côté Serge , Drouin Mathieu , Simard Carl , Lemieux Réal
Published: October 2002

B‐cell hybridomas are widely used to produce monoclonal antibodies via large‐scale cell culture. Unfortunately, these cells are highly sensitive to apoptotic death under conditions of nutrient deprivation observed at the plateau phase of batch cultures. Previous work has indicated that constitutive high‐level expression of antiapoptotic genes in hybridoma cells could delay apoptosis, resulting in higher cell densities and prolonged viability. However, the constitutive high‐level expression of antiapoptotic genes has been shown to have detrimental effects on genomic stability of other types of cultured cells. Inducible gene expression may be used to avoid this problem. In the present study, we first constructed an expression vector in which the promoter of a mammalian metallothionein (MT) gene drives the expression of bcl‐XL in response to metal exposure. The vector was then used to exogenously control the expression of bcl‐XL in D5 hybridoma cells. Our data show that stably transfected D5 cells (4G1.D9) expressed high levels of Bcl‐XL following overnight exposure to ZnSO4 concentrations (50 to 100 μM) that did not affect control cells. The level of Bcl‐XL expressed after ZnSO4 induction was sufficient to prevent apoptosis experimentally induced by cycloheximide and allowed 4G1.D9 cells to grow at higher densities and remain viable for prolonged periods in suboptimal culture conditions. The use of inducible bcl‐XL expression permits extension of the viability of cultured B‐cell hybridomas during the antibody secretion phase without the adverse genetic effects associated with constitutive long‐term bcl‐XL expression. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 180–187, 2002.
Development of (R)‐4‐hydroxymandelonitrile synthesis in an aqueous–organic biphasic stirred tank batch reactor
Authors: Willeman W. F. , Neuhofer R. , Wirth I. , Pöchlauer P. , Straathof A. J. J. , Heijnen J. J.
Published: October 2002

A relatively new hydroxynitrile lyase‐catalyzed reaction was optimized to be suitable for rapid and efficient development of a full‐scale production process. The conversion of 4‐hydroxybenzaldehyde into (R)‐4‐hydroxymandelonitrile, catalyzed by Prunus amygdalus hydroxynitrile lyase, was carried out in a biphasic system of aqueous buffer (pH 5.5) and methyl tert‐butyl ether and is described with a process model. The process model consists of a description of the reaction kinetics, mass transfer kinetics, and mass balances for both the aqueous and the organic phase. Values are determined for the equilibrium constant, the enzyme kinetic parameters, the lumped mass transfer coefficient for benzaldehyde, and the partition coefficients. By using estimated prices of enzyme and reactor use, the optimum aqueous phase volume fraction and required enzyme concentration were calculated at a temperature of 20°C for a batch‐operated stirred tank reactor. According to the process model it was possible to convert 90% of the 4‐hydroxybenzaldehyde into (R)‐4‐hydroxymandelonitrile with 95% enantiomeric excess. The price optimum for this reaction was found at an aqueous phase volume of 17% of the total volume. The required enzyme concentration to meet the targets was 28.6 g/L aqueous phase. At the predicted optimum, the synthesis was performed experimentally and the results were in accordance with the simulation regarding the extent of conversion and the enantiomeric excess. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 154–164, 2002.
Kinetics of benzene biotransformation under microaerophilic and oxygen‐limited conditions
Authors: Yerushalmi Laleh , Lascourreges Jean‐Francois , Guiot Serge R.
Published: October 2002

A special microbial consortium adapted to degrade petroleum hydrocarbons at limited availability of oxygen, transformed benzene, a highly toxic and carcinogenic contaminant of groundwater and soil, at low initial dissolved oxygen (DO) concentrations of 0.05–2 mg/L. The employed initial concentrations of dissolved oxygen were considerably lower than the previously reported values. Under these conditions, the overall transformation of benzene ranged from 34% ± 1.7% to 100%, considerably higher than the theoretical predictions for complete mineralization of benzene based on the requirement of 3.08 mg oxygen/mg benzene. Unlike biotransformation that proceeded at the lowest examined DO concentration of 0.05 mg/L, the mineralization of benzene, defined by its conversion to CO2 and water, required a minimum DO concentration of 0.2 mg/L. The mineralization of benzene under microaerophilic conditions (DO < 2 mg/L), ranged from 0.83% ± 0.06% to 89% ± 1.3%, which was less than the theoretical predictions at any given initial DO concentration. The regulatory effects of dissolved oxygen concentration or its partial pressure on the activities of enzymes catalyzing the biotransformation of aromatic hydrocarbons was postulated to account for the reduced mineralization of benzene. The ratio between the transformed benzene and the consumed oxygen increased with the decrease of initial DO concentration, reaching a value of 2.8, considerably higher than the theoretical value of 0.33 obtained for a complete aerobic oxidation of benzene. Phenol was the major and the most stable intermediate metabolite during the biotransformation of benzene at low concentrations of DO. While benzene transformation stopped after the depletion of oxygen in the experimental system, phenol continued to accumulate under strictly anaerobic conditions, indicating its formation from an alternative carbon source, possibly biomass. © 2002 Government of Canada. Exclusive worldwide publication rights in this article have been transferred to Wiley Periodicals, Inc. Biotechnol Bioeng 79: 347–355, 2002.
Overexpression of an archaeal protein in yeast: Secretion bottleneck at the ER
Authors: Smith Jason D. , Robinson Anne Skaja
Published: October 2002

Archaeal enzymes have great potential for industrial use; however, expressing them in their natural hosts has proven challenging. Growth conditions for many archaea are beyond typical fermentation capabilities, and to compound the problem, archaea generally achieve much lower biomass yields than Escherichia coli or Saccharomyces cerevisiae. To determine whether a eukaryotic host, S. cerevisiae, would be a suitable alternative for archaeal protein production, we examined the expression of the tetrameric β‐glucosidase from the hyperthermophilic archaeon Pyrococcus furiosus. We engineered the β‐glucosidase to facilitate secretion into the culture medium and have demonstrated the β‐glucosidase's secretion and activity. We determined the dependence of β‐glucosidase secretion on gene copy number and obtained a transformant capable of secreting ∼10 mg/L in batch culture. All transformants retained large intracellular fractions of β‐glucosidase, indicative of an intracellular bottleneck. Cell fractionation by sucrose density centrifugation and immunofluorescence identified the endoplasmic reticulum as the secretion bottleneck. Preliminary evidence indicates that the cause of this bottleneck is misfolding of the monomeric β‐glucosidase, rather than tetrameric association. Expression at moderately elevated temperatures (between 30 and 40°C) improved β‐glucosidase yields, suggesting that higher temperature expression may improve folding and secretion yields. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 713–723, 2002.
Jay Bailey as mentor—The students' perspective
Authors: Reardon Kenneth F. , Lee Kelvin H. , Wittrup K. Dane , Hatzimanikatis Vassily
Published: October 2002

Professor James E. Bailey was not only a world‐renowned leader and pioneer in biochemical engineering but also a mentor to the many graduate students and postdoctoral researchers in his group. To provide non‐“Bailey‐ites” with an impression of Jay as a mentor, we begin with a brief review of his career, focusing on the dynamics of the research group. Typical student experiences of being part of the Bailey group are then discussed, including the recognition of a particular research style and Jay's expectations for hard work. Finally, we provide some thoughts on Jay's mentoring style, which was marked by an ability to foster independence, a sense of quality, and passion for research. Jay's contributions as a mentor can perhaps be recognized as being as significant as his research achievements. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 484–489, 2002.
Inguinal canal ‘lipoma’
Authors: Heller C. Ann , Marucci Damian D. , Dunn Tirith , Barr Elizabeth M. , Houang Michael , Dos Remedios Cristobal
Published: October 2002

Groin dissection was performed in adult male post‐mortem subjects to establish the prevalence of inguinal canal ‘lipoma.’ Thirty‐six body halves (age range 24–92 years) were studied. Of these, 27 (75%) contained a discrete mass of fat within the inguinal canal. This mass was always continuous with the preperitoneal fat through the deep inguinal ring. Nineteen of these 27 masses (70%), displayed a characteristic pedunculated form with a bulbous distal end. Eighteen of the 36 dissections (50%), revealed a mass more than 4 cm in length. Six dissections showed extension of the mass beyond the superficial inguinal ring and three of these six (8% of the 36 groins studied) showed distortion of the proximal spermatic cord with a mass at the superficial inguinal ring. The masses submitted for histology comprised mature adipose tissue and all but two of these were reported as having an adherent capsule. No significant correlation was found between mass length and either subject age or body mass index (BMI) but a statistically significant correlation between the length of the fat mass on the left and right sides was shown. This study demonstrates that the inguinal canal ‘lipoma’ is a common feature in an adult male population and may be of sufficient size to cause clinical misdiagnosis. The high prevalence, characteristic location and appearance of the ‘lipoma’ suggest a developmental etiology. Clin. Anat. 15:280–285, 2002. © 2002 Wiley‐Liss, Inc.
Development of instructional software for the calculation of form stress concentration factors
Authors: Prater Glen , Shahhosseini Ali M.
Published: October 2002

Mechanical engineering curricula include a number of required courses in solid mechanics and machine design that involve the determination of stresses in components with geometric irregularities. This article documents the development of a Windows‐based computer program, ME‐StressCon, that allows rapid calculation of form stress concentration factors and nominal stresses for a wide variety of geometry and load cases. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 1–10, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10009
Potential goals for the dimensions of the pulmonary arteries and aorta with stenting after the Fontan operation
Authors: Tomita Hideshi , Yazaki Satoshi , Kimura Kohji , Ono Yasuo , Yamada Osamu , Ohuchi Hideo , Yagihara Toshikatsu , Echigo Shigeyuki
Published: October 2002

The purpose of this study was to clarify desired stent sizes for stenotic lesions in the post‐Fontan circulation. Using angiograms from 22 patients before and at late follow‐up (≥ 15 years) after the Fontan operation, we measured the maximum diameters of the proximal pulmonary arteries (PA) and the descending aorta. The diameters of the PA ipsilateral to the inferior vena cava, contralateral to the inferior vena cava, and descending aorta after the Fontan were 10.6–22.6 (15.8 ± 3.3), 8.0–19.1 (12.9 ± 3.1), and 12.1–18.9 (15.8 ± 2.0) mm, respectively, while the percent of normal predicted diameters (% N) were 55%–104% (70% ± 14%), 38%–99% (66% ± 17%), and 46%–74% (60% ± 7%), respectively. Despite somatic growth, the % N of all vessel diameters decreased significantly after the Fontan operation. In conclusion, smaller‐sized stents should be acceptable for both the pulmonary artery and descending aorta in the Fontan circulation. Cathet Cardiovasc Intervent 2002;56:246–253. © 2002 Wiley‐Liss, Inc.
Directional atherectomy of a calcified lesion using a new atherectomy device
Authors: Reimers Bernhard , Stankovic Goran , Prati Francesco , Sommariva Luigi , Karvouni Evangelia , Takagi Takuro , Albiero Remo , Angelini Annalisa , Di Mario Carlo , Thiene Gaetano , Colombo Antonio
Published: October 2002

We report on a case of directional atherectomy performed on a calcified coronary lesion using a novel device with a hardened titanium cutter. The successful removal of calcified plaque was documented by intravascular ultrasound assessment and confirmed by histopathological analysis of the obtained plaque specimen. Cathet Cardiovasc Intervent 2002;56:222–226. © 2002 Wiley‐Liss, Inc.
Intra‐atrial thrombolytic therapy for dissolution of chronic left atrial thrombi in patients undergoing balloon mitral commissurotomy
Authors: Chiang Cheng‐Wen , Chu Po‐Hsien , Hsu Long‐An
Published: October 2002

The purpose of this study was to evaluate the solubility of left atrial thrombi to thrombolytics after failure of long‐term anticoagulant therapy in patient with mitral stenosis. One hundred and eighty‐one consecutive patients with mitral valve area ≤ 1.5 cm2 and without severe mitral regurgitation were screened with echocardiography; 30 were found to have left atrial thrombi. Follow‐up echocardiography performed 7.4 ± 5.6 months after warfarin therapy revealed that 8/30 of patients had complete dissolution and 3/30 had partial dissolution of the thrombi. Thirteen patients with residual isolated appendageal thrombi underwent balloon mitral commissurotomy and were randomized into four groups at the end of balloon mitral commissurotomy: group A, receiving intra‐atrial infusion of heparin and tissue plasminogen activator (t‐PA; n = 4); group B, heparin and streptokinase (n = 3); group C, heparin (n = 3); and group D, acting as control (n = 3). It was found that only two patients in the t‐PA group had their thrombi either completely or partially dissolved within 48 hr. Thus, this study suggests that t‐PA may have the potential of dissolving chronic left atrial thrombi. Cathet Cardiovasc Intervent 2002;56:460–465. © 2002 Wiley‐Liss, Inc.
Elderly patients have a favorable outcome after intracoronary radiation for in‐stent restenosis
Authors: Ajani Andrew E. , Waksman Ron , Cheneau Edouard , Cha Dong‐Hun , Pinnow Ellen , Pichard Augusto D. , Satler Lowell F. , Kent Kenneth M. , Lindsay Joseph
Published: October 2002

Intracoronary radiation therapy (IRT) reduces recurrent in‐stent restenosis (ISR) by inhibition of smooth muscle cell proliferation. The ability of these cells to replicate is limited with age due to changes in the telomeres. The purpose of this study was to assess the effect of age on outcomes following IRT for ISR. We evaluated 1,088 patients with 6‐month clinical follow‐up who were enrolled in radiation trials for ISR using γ‐ and β‐emitters. Patients were analyzed within and between IRT (n = 861) or placebo therapy (n = 227) in four age groups (< 55, 55–65, 66–75, > 75 years). Baseline characteristics were similar within each age group of IRT patients, except elderly patients (> 75 years) had a lower rate of diabetes (28% in patients > 75 years; P = 0.008) and a higher rate of previous CABG (59% in patients > 75 years; P < 0.001). The rate of target lesion revascularization (TLR) was reduced in the elderly. TLR at 6 months was 18% in patients < 55 years, 21% in 55–65 years, 12% in 66–75 years, and 10% in patients > 75 (P = 0.009). The MACE rate at 6 months was 21% in patients < 55 years, 29% in 55–65 years, 26% in 66–75 years, and 17% in patients > 75 (P = 0.03). No effect of age was seen in placebo patients. IRT‐treated patients had reduced MACE compared to placebo in all age groups, driven by reduced target vessel revascularization. Age was an independent predictor of MACE at 6 months (OR = 0.8; CI = 0.70–0.93; P = 0.004). Angiographic restenosis was not clearly associated with need for TLR in patients > 75 years. In elderly patients (> 75 years) treated with IRT for ISR, the rate of TLR was significantly reduced compared to younger patients. However, this reduction in TLR was not associated with a reduction in angiographic restenosis, suggesting that TLR should not be used as a surrogate for angiographic evaluation. Cathet Cardiovasc Intervent 2002;56:466–471. © 2002 Wiley‐Liss, Inc.