bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved treatment of sudden hearing loss by specific fibrinogen aphaeresis
Authors: Ullrich Heidrun , Kleinjung Tobias , Steffens Thomas , Jacob Peter , Schmitz Gerd , Strutz Jürgen 
Published: July 2004

AbstractThe etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14–16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1–15, 1986; Harris and Sharp, Laryngoscope 100:516–524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41–45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94–100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763–766, 1999; Suckfüll, Lancet 360:1811–1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641–645, 1996; Suckfüll et al., Otol. Neurotol. 23:309–311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1–3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80–100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 ± 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 ± 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen.In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss. J. Clin. Apheresis 19:71–78, 2004. © 2004 Wiley‐Liss, Inc.
Plasma exchange conditioning for ABO‐incompatible renal transplantation
Authors: Winters J.L. , Gloor J.M. , Pineda A.A. , Stegall M.D. , Moore S.B. 
Published: July 2004

AbstractThe supply of deceased donor kidneys is inadequate to meet demand. To expand the pool of potential donors, ABO‐incompatible transplants from living donors have been performed. We present the Mayo Clinic experience with such transplants. Enrollment was open to patients when the only available potential living kidney donor was ABO‐incompatible. Conditioning consisted of plasma exchanges followed by intravenous immunoglobulin. Splenectomy was performed at the time of transplant surgery. Post‐transplant immunosuppression consisted of anti‐T lymphocyte antibody, tacrolimus, mycophenolate mofetil, and prednisone. Isoagglutinin titers and scores were determined before and after each plasma exchange. Transplant outcomes were determined. Twenty‐six ABO‐incompatible transplants were performed. No hyperacute rejection occurred. Mean patient follow‐up was 400 days. Patient and graft survivals at last follow‐up were 92 and 85%, respectively. Antibody‐mediated rejection occurred in 46% and was apparently reversed in 83% by plasma exchange and increased immunosuppression. The initial plasma exchange reduced immediate spin and AHG hemagglutination reactivity scores by 53.5 and 34.6%, respectively. Over the course of the pretransplant plasma exchanges, the immediate spin and AHG hemagglutination reactivity scores decreased by 96.4 and 68.5%, respectively. At 3 and 12 months, the immediate spin and AHG hemagglutinin reactivity scores and titers were less than those at baseline but greater than or equal to those on the day of transplantation. Despite an increase in scores and titers, antibody‐mediated rejection was not present. Pre‐transplant plasma exchange conditioning combined with other immunosuppressives can be used to prepare patients for ABO‐incompatible kidney transplantation from living donors, but antibody‐mediated rejection post‐transplant is a common occurrence and allograft survival may be reduced. Controlled clinical trials are needed to identify the optimum conditioning for ABO‐incompatible renal transplants. J. Clin. Apheresis 19:79–85, 2004. © 2004 Wiley‐Liss, Inc.
Effect of different LDL‐apheresis methods on parameters involved in atherosclerosis
Authors: Hershcovici Tiberiu , Schechner Vered , Orlin Jerome , Harell Daniella , Beigel Yitzhak 
Published: July 2004

AbstractLDL‐apheresis lowers the LDL level in patients with severe hypercholesterolemia. The present study compared three apheresis methods—DSA, DALI, and plasma exchange—for effectiveness in removal of LDL and effect on various blood parameters involved in atherogenesis. The study group included 6 patients with primary hypercholesterolemia unresponsive to maximal drug therapy. All were treated first with 4 consecutive plasma exchange sessions followed by 4 DSA sessions; in four out of six, an additional 4 sessions of DALI were then performed. Levels of lipoproteins, apoproteins, CRP, homocysteine, fibrinogen, and blood count were determined before and after each session. All 3 procedures yielded a significant reduction in total cholesterol and ApoB‐containing lipoproteins, with DALI being the most effective. Also, a significant reduction in triglycerides, HDL, and ApoA1 was observed with all the methods. The reduction in HDL‐C with DSA and DALI was greater than previously reported. The LDL/HDL‐cholesterol ratio decreased significantly with DSA and DALI and increased with plasma exchange. There was a significant decrease in CRP, fibrinogen, and platelets with all three methods, and a significant decrease in homocysteine only with DSA and DALI. All three procedures effectively reduced the concentration of various compounds involved in atherosclerosis. Plasma exchange is nonselective and cannot be recommended as the procedure of choice. J. Clin. Apheresis 19:90–97, 2004. © 2004 Wiley‐Liss, Inc.
Relapsed thrombotic thrombocytopenic purpura presenting as an acute cerebrovascular accident
Authors: Downes Katharine A. , Yomtovian Roslyn , Tsai H.M. , Silver Bernard , Rutherford Cynthia , Sarode Ravindra 
Published: July 2004

AbstractThrombotic thrombocytopenic purpura (TTP) is an uncommon but severe disorder that classically presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and fluctuating neurological changes. Previously, it was impossible to make a diagnosis of TTP in the absence of thrombocytopenia or microangiopathic hemolysis (MAHA). We describe two cases of relapsing TTP that presented with acute cerebrovascular accident (CVA) without concurrent thrombocytopenia or MAHA after initial classical presentation of TTP. In both cases, the diagnosis of TTP as the cause of the CVA was attributed to severe deficiency of the von Willebrand factor cleaving protease, ADAMTS13 in plasma (11 and 12%, normal 79–127%). Each patient had a dramatic clinical improvement in response to therapeutic plasma exchange. The experience in these two cases suggests that TTP should be considered as a potential cause among patients presenting with a CVA, particularly if the patients have a history of TTP. J. Clin. Apheresis 19:86–89, 2004. © 2004 Wiley‐Liss, Inc.
L‐carnitine improves pH and decreases surface phosphatidylserine expression in extended stored apheresis platelets
Authors: Sweeney Joseph D. , Kouttab Nicola M. , Arduini Arduino 
Published: July 2004

AbstractExtension of the storage period of apheresis platelets to seven or ten days may be possible with the implementation of screening for bacteria. This, however, may impair platelet quality, and additive compounds that improve storage parameters would be desirable. Apheresis platelets were harvested using the Cobe LRS device. Part of the product was aliquoted into two CLX® bags, 60 ml into each, on day 0. L‐carnitine (LC) to a final concentration of 5 mM was added to one container and saline to the other. pH, morphology score, and surface expression of phosphatidylserine were measured on day 1, and, in addition, hypotonic shock response (HSR) and the extent of shape change (ESC) on days 5, 10, and 13. Differences between test and controls were analyzed using paired t‐tests. The addition of LC improved pH by day 5, but was more evident by days 10 and 13. By day 10, significant differences (<0.01) were observed in pH (6.54 ± 0.3 vs. 6.75 ± 0.3), lactate (176 ± 31 vs. 150 ± 24 mg %), morphology score (213 ± 27 vs. 229 ± 35) and ESC (7 ± 6 vs. 11 ± 6). Percent surface phosphatidylserine expression was less in the LC treated platelets (16 ± 7 vs. 12 ± 4, P<0.03). Much of the benefit observed was attributable to improved parameters in some donors. LC improves the quality of extended stored apheresis platelets. J. Clin. Apheresis 19:98–102, 2004. © 2004 Wiley‐Liss, Inc.
Hematopoietic progenitor cell large volume leukapheresis (LVL) on the Fenwal Amicus blood separator
Authors: Burgstaler Edwin A. , Pineda Alvaro A. , Winters Jeffrey L. 
Published: July 2004

AbstractA technique for large volume leukapheresis (LVL) for hematopoietic progenitor cell (HPC) collection using the Fenwal Amicus is presented. It was compared to standard collections (STD) with regard to CD34+ cell yields and cross‐cellular content. Optimal cycle volumes and machine settings were evaluated for LVL procedures. A total of 68 patients underwent 80 HPC collection procedures. Because of differences in CD34+ cell yields associated with peripheral white blood cell counts (WBC), the comparison was divided into groups of 20 with WBC ≤35 × 109/L (≤35 K) and those >35 × 109/L (>35 K). Baseline CD34+ cell counts (peripheral count when patient started HPC collection) were used (median 18–23 cells/μl). Significantly more whole blood (corrected for anticoagulant) was processed with LVL (LVL 20 l vs. STD 13.5 l). For ≤35 K, median CD34+ × 106, WBC × 109, RBC ml, Plt × 1011 yields/collection were 183, 21.2, 14, 0.8, respectively, for STD vs. 307, 22.1, 11, 1.0, respectively, for LVL. For >35 K, median CD34+ × 106, WBC × 109, RBC ml, Plt × 1011 yields/collection were 189, 32.7, 15, 1.4, respectively, for STD vs. 69, 40.8, 21, 1.3, respectively, for LVL. We have described a method of LVL using the Amicus that, in patients with pre‐procedure WBC ≤35×109/L, collects more CD34+ cells than a standard procedure with acceptable cross‐cellular content. This method is not recommended when pre‐procedure WBC counts are >35 × 109/L. J Clin Apheresis 19:103–111, 2004. © 2004 Wiley‐Liss, Inc.
Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development
Authors: Fischer Andrew H. , Young Kyle A. , DeLellis Ronald A. 
Published: July 2004

AbstractA wide variety of alterations in cell and tissue structure still form the basis for cancer diagnosis by pathologists. Cancer development is recognized to be an evolutionary process [Foulds, 1954; Cairns, 1975; Nowell, 1976; Sager, 1982; Tomlinson et al., 1996; Cahill et al., 1999; Tomlinson and Bodmer, 1999], but the phenotypic changes diagnostic of cancer (pathologists' “criteria of malignancy”) have not been integrated into the existing evolutionary framework. Since phenotypic changes bear an important relationship to the genetic and physiologic changes underlying Darwinian evolution, we propose that diagnostic structural alterations also bear an important and predictable relation to both the cancer genes and the functional alterations active at any particular step in the development of a cancer. Cancer genes are predicted to mediate the acquisition of cellular‐level diagnostic criteria and the diagnostic cellular‐level structural changes should reflect in a useful manner the altered cell physiology required for the cell to achieve increased “cellular fitness” at any particular step of colonal evolution. Tissue‐level criteria of malignancy should relate less directly to specific cancer genes, but tissue‐level criteria should still provide essential insight into the interplay of the altered cellular fitness with the constraints imposed by the cells' microenvironment. The evolutionary framework allows tissue‐level criteria of malignancy to be expressed in terms of viable hypotheses for the mechanism of clonal expansion at any particular step in cancer development. This approach to conveying the tissue‐level criteria of malignancy complements pattern recognition approaches to diagnosis, and establishes common ground between pathology and cell biology. When viewed from this perspective, the functions of cancer genes appear quite different from those predicted by the “Gatekeeper, Caretaker” or “Hallmarks of Cancer” models. Finally, a full evolutionary framework incorporating the criteria of malignancy restores congruity between the histogenetic classification and the emerging molecular classification of cancer. © 2004 Wiley‐Liss, Inc.
Histone modification in constitutive heterochromatin versus unexpressed euchromatin in human cells
Authors: Jiang Guanchao , Yang Fan , Sanchez Cecilia , Ehrlich Melanie 
Published: July 2004

AbstractHistone modifications are implicated in regulating chromatin condensation but it is unclear how they differ between constitutive heterochromatin and unexpressed euchromatin. Chromatin immunoprecipitation (ChIP) assays were done on various human cell populations using antibodies specific for acetylated or methylated forms of histone H3 or H4. Analysis of the immunoprecipitates was by quantitative real‐time PCR or semi‐quantitative PCR (SQ‐PCR). Of eight tested antibodies, the one for histone H4 acetylated at lysine 4, 8, 12, or 16 was best for distinguishing constitutive heterochromatin from unexpressed euchromatin, but differences in the extent of immunoprecipitation of these two types of chromatin were only modest, although highly reproducible. With this antibody, there was an average of 2.5‐fold less immunoprecipitation of three constitutive heterochromatin regions than of four unexpressed euchromatic gene regions and about 15‐fold less immunoprecipitation of these heterochromatin standards than of two constitutively expressed gene standards (P < 0.001). We also analyzed histone acetylation and methylation by immunocytochemistry with antibodies to H4 acetylated at lysine 8, H3 trimethylated at lysine 9, and H3 methylated at lysine 4. In addition, immunocytochemical analysis was done with an antibody to heterochromatin protein 1α (HP1α), whose preferential binding to heterochromatin has been linked to trimethylation of H3 at lysine 9. Our combined ChIP and immunocytochemical results suggest that factors other than hypoacetylation of the N‐terminal tails of H4 and hypermethylation of H3 at lysine 9 can play an important role in determining whether a chromatin sequence in mammalian cells is constitutively heterochromatic. © 2004 Wiley‐Liss, Inc.
Candidate cis‐elements for human renin gene expression in the promoter region
Authors: Konoshita Tadashi , Makino Yasukazu , Wakahara Shigeyuki , Ido Kanako , Yoshida Masahiro , Kawai Yasuyuki , Miyamori Isamu 
Published: July 2004

AbstractThe regulation of renin gene expression, the rate‐limiting enzyme of the system, is thought to be fundamental to the total system. Previously, we mapped six putative cis‐elements in the promoter region of the human renin gene with nuclear proteins from human chorionic cells and human renal cortex by DNase I protection assay (footprint A–F). Each footprint contains Ets motif like site (A), HOXñPBX recognition sequence (B), unknown sequence as DNA binding consensus (C), CRE (D), COUP‐TFII (ARP‐1) motif like site (E), and AGE3 like site (F). Footprint D has been characterized by means of functional studies as the genuine human renin gene CRE interacting with CREB in cooperation with the site of footprint B. To obtain further clues to the specific expression in the promoter region, these putative cis‐elements were conducted to a consensus‐specific binding assay to compare renin‐producing and non‐renin‐producing cells by EMSA and electromobility super‐shift assay. Different sequence‐specific DNA/protein binding was obtained among the different cell lines with footprint B site, with COUP‐TFII (ARP‐1) motif like site and possibly with footprint F site. The results implicate these putative cis‐elements and each corresponding trans‐factor in the specific expression of the human renin gene in the promoter region. Further functional characterization of these elements would provide important data for a better understanding of human renin gene expression. © 2004 Wiley‐Liss, Inc.
Inhibitory helix‐loop‐helix transcription factors Id1/Id3 promote bone formation in vivo
Authors: Maeda Yukiko , Tsuji Kunikazu , Nifuji Akira , Noda Masaki 
Published: July 2004

AbstractBone formation is under the control of a set of transcription factors. Ids are inhibitory helix‐loop‐helix (HLH) transcription factors and expression of Id genes in osteoblasts is under the control of calciotropic agents such as BMP and vitamin D. However, the function of Ids during bone formation in vivo has not yet been elucidated. We, therefore, examined the role of Id1 and Id3 in the regulation of bone metabolism in vivo. Using wild type and Id1/Id3 heterozygous knockout mice, we analyzed calvarial bone formation in the suture by X‐ray picture, proliferation, and mineralization activities of primary calvarial osteoblasts by MTT assay and alizarin red staining and onthotopic in vivo bone formation by BMP injection onto calvaria and micro CT analysis. The width of calvarial sutures was reduced by more than 50% in Id1/Id3 heterozygous knock out mice. Analyses on the cellular basis for the mechanism underlying the defects in the mutant mice revealed suppression of proliferation and mineralization in osteoblasts derived from Id1/Id3 heterozygous knock out mice. Furthermore, Id1/Id3 heterozygous knock out mice suppressed BMP‐induced bone formation in vivo. These results indicated that Id1 and Id3 are positive factors to promote bone formation in vivo. © 2004 Wiley‐Liss, Inc.
Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells
Authors: Jaiswal Aruna S. , Narayan Satya 
Published: July 2004

AbstractIn the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild‐type adenomatous polyposis coli (APC) protein at the post‐translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT‐116 cells (which express the wild‐type APC gene) after treatment with ZnCl2. Increased levels of wild‐type but not truncated APC proteins were required for the ZnCl2‐mediated G2/M phase arrest in different colon cancer cell lines. We further tested whether serum‐stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl2‐induced G2/M phase arrest of HCT‐116 cells. Results showed that in the HCT‐116 cells pretreated with ZnCl2, the serum‐stimulation neither changed the distribution of G2/M phase arrested cells nor the increased levels of APC protein. The G2/M phase arrest correlated with retarded growth of HCT‐116 cells. To further establish that wild‐type APC protein plays a role in ZnCl2‐induced G2/M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl2 treatment did not induce G2/M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E‐cadherin and α‐tubulin levels. These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild‐type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase. On the other hand, ZnCl2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability. © 2004 Wiley‐Liss, Inc.
PTH and phospholipase A2 in the aging process of intestinal cells
Authors: Gentili Claudia , Morelli Susana , de Boland Ana Russo 
Published: July 2004

AbstractIn this study we analyzed, for the first time, alterations in phospholipase A2 (PLA2) activity and response to parathyroid hormone (PTH) in rat enterocytes with aging. We found that PTH, rapidly stimulate arachidonic acid (AA) release in rat duodenal cells (+1‐ to 2‐fold), an effect that is greatly potentiated by aging (+4‐fold). We also found that hormone‐induced AA release in young animals is Ca2+‐dependent via cPLA2, while AA released by PTH in cells from aged rats is due to the activation of cPLA2 and the Ca2+‐independent PLA2 (iPLA2). In enterocytes from 3 months old rats, PTH induced, in a time and dose‐dependent fashion, the phosphorylation of cPLA2 on serine 505, with a maximun at 10 min (+7‐fold). Basal levels of cPLA2 serine‐phosphorylation were higher in old enterocytes, affecting the hormone response which was greatly diminished (+2‐fold at 10 min). cPLA2 phosphorylation impairment in old animals was not related to changes of cPLA2 protein expression and did not explain the substantial increase on PTH‐induced AA release with aging, further suggesting the involvement of a different PLA2 isoform. Intracellular Ca2+ chelation (BAPTA‐AM, 5 μM) suppressed the serine phosphorylation of cPLA2 in both, young and aged rats, demonstrating that intracellular Ca2+ is required for full activation of cPLA2 in enterocytes stimulated with PTH. Hormone effect on cPLA2 was suppressed to a great extent by the MAP kinases ERK 1 and ERK2 inhibitor, PD 98059 (20 μM), the cAMP antagonist, Rp‐cAMP, and the PKC inhibitor Ro31820 both, in young and aged animals. Enterocytes exposure to PTH also resulted in phospho‐cPLA2 translocation from cytosol to nuclei and membrane fractions, where phospholipase subtrates reside. Hormone‐induced enzyme translocation is also modified by aging where, in contrast to young animals, part of phospho‐cPLA2 remained cytosolic. Collectively, these data suggest that PTH activates in duodenal cells, a Ca2+‐dependent cytosolic PLA2 and attendant AA release and that this activation requires prior stimulation of intracellular ERK1/2, PKA, and PKC. cPLA2 is the major enzyme responsible for AA release in young enterocytes while cPLA2 and the Ca2+‐independent iPLA2, potentiate PTH‐induced AA release in aged cells. Impairment of PTH activation of PLA2 isoforms upon aging may result in abnormal hormone regulation of membrane fluidity and permeability and thereby affecting intestinal cell membrane function.