bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimally Invasive Percutaneous Posterior Lumbar Interbody Fusion
Authors: Khoo Larry T. , Palmer Sylvain , Laich Daniel T. , Fessler Richard G. 
Published: July 2004

AbstractOBJECTIVEThe wide exposure required for a standard posterior lumbar interbody fusion (PLIF) can cause unnecessary trauma to the lumbar musculoligamentous complex. By combining existing microendoscopic, percutaneous instrumentation and interbody technologies, a novel, minimally invasive, percutaneous PLIF technique was developed to minimize such iatrogenic tissue injury (MIP-PLIF).METHODSThe MIP-PLIF technique was validated in three cadaveric torsos with six motion segments decompressed and fused. Preoperative variables measured from imaging included interpedicular distance, pedicular height and width, interspinous distance, lordosis, intervertebral height, Cobb angle, and foraminal height and volume. Using the METRx and MD spinal access systems (Medtronic Sofamor Danek, Memphis, TN), bilateral laminotomies were performed using a hybrid of microsurgical and microendoscopic techniques. The intervertebral disc spaces were then distracted and prepared with the Tangent (Medtronic Sofamor Danek) interbody instruments. Either a 10 or 12 by 22 mm interbody graft was then placed. Using the Sextant (Medtronic Sofamor Danek) system, percutaneous pedicle screw-rod fixation of the motion segment was completed. We then applied MIP-PLIF in three patients.RESULTSFor segments with preoperative intervertebral/foraminal height loss, MIP-PLIF was effective in restoring both heights in all cases. The amount of improvement (9.7 to 38% disc height increase; 7.7 to 29.9% foraminal height increase) varied directly with the size of the graft used and the original degree of disc and foraminal height loss. Segmental lordosis improved by 29% on average. Graft and screw placement was accurate in the cadavers, except for a single Grade 1 screw violation of one pedicle. The average operative time was 3.5 hours per level. In our three clinical cases, the MIP-PLIF procedure required a mean of 5.4 hours, estimated blood loss was 185 ml, and inpatient stay was 2.8 days, with no intravenous narcotic use after 2 days in any of the patients. All screw and graft placements were confirmed.CONCLUSIONA complete PLIF procedure can be safely and effectively performed using minimally invasive techniques, thereby potentially reducing the pain and morbidity associated with standard open surgery. Prospective, randomized outcome studies will be required to validate the efficacy of this exciting new surgical technique.
cAMP controls human renin mRNA stability via specific RNA‐binding proteins
Authors: Morris B. J. , Adams D. J. , Beveridge D. J. , van der Weyden L. , Mangs H. , Leedman P. J. 
Published: July 2004

AbstractIt is now recognized that post‐transcriptional mechanisms are pivotal to renin production. These involve factors that modulate renin mRNA stability. In 2003 new data has emerged from work in Australia and Germany that has identified several of the, as many as, 20 or so proteins involved. These include CP1 (hnRNP E1), HuR, HADHB, dynamin, nucleolin, YP‐1, hnRNP K and MINT‐homologous protein. Cyclic AMP (cAMP) is a crucial regulator of renin secretion as well as transcriptional and post‐transcriptional control of expression. Many of the RNA‐binding proteins that were identified responded to forskolin, increasing in amount by two to 10‐fold. The cAMP mechanisms that regulate renin mRNA target, at least in large part, other genes that presumably encode some of these proteins. The increase in the expression of these then facilitates, sequentially, renin mRNA stabilization and destabilization. Our data, using a battery of different techniques, confirm that CP1 and HuR stabilize renin mRNA, whereas HADHB causes destabilization. These proteins target cis‐acting C‐rich sequences (in the case of CP1) and AU‐rich sequences (HuR) in the distal region of the 3′‐untranslated region of renin mRNA. We found HADHB was enriched in juxtaglomerular cells and that that within Calu‐6 cells HADHB, HuR and CP1 all localized in nuclear subregions, as well as cytoplasm (HADHB and CP1) and mitochondria (HADHB) commensurate with the role each plays in control of renin mRNA stability. The specific proteins that bind to human renin mRNA have begun to be revealed. Cyclic AMP upregulates the binding of several of these proteins, which in turn affect renin mRNA stability and thus overall expression of renin.
Rapid non‐genomic effects of aldosterone on rodent vascular function
Authors: Uhrenholt T. R. , Schjerning J. , Rasmussen L. E. , Hansen P. B. , Nørregaard R. , Jensen B. L. , Skøtt O. 
Published: July 2004

AbstractThe main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review describes novel results from several laboratories, which show that aldosterone also has beneficial effects in the cardiovascular system by stimulating the production of nitric oxide (NO) from the endothelium. The effect of aldosterone is seen within minutes, and is not inhibited by blockers of gene transcription, thus pointing to a non‐genomic mechanism. Furthermore, this potentially beneficial effect is observed at low physiological concentrations of aldosterone (0.1–10 pm). The effect is mediated by the classical mineralocorticoid receptor, and it involves heat shock protein 90, phosphatidylinositol (PI)‐3 kinase, protein kinase B, endothelial nitric oxide synthase, and liberation of NO. It is proposed that in healthy individuals with a functioning NO system, the detrimental effects of aldosterone on cardiovascular function are balanced by activation of the potentially beneficial effect of NO. However, in situations with endothelial dysfunction, such as congestive heart failure and hypertension, the negative effects of aldosterone are unopposed and inhibition of aldosterone is warranted.
Calcium handling in afferent arterioles
Authors: Salomonsson M. , Sorensen C. M. , Arendshorst W. J. , Steendahl J. , Holstein‐Rathlou N.‐H. 
Published: July 2004

AbstractThe cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G‐protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L‐type channels, T‐type channels and P/Q channels. A role for non‐voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl− channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium‐activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl− channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels.
Compensation of proximal tubule malabsorption in AQP1‐deficient mice without TGF‐mediated reduction of GFR
Authors: Hashimoto S. , Huang Y. , Mizel D. , Briggs J. , Schnermann J. 
Published: July 2004

AbstractAim:  By crossing aquaporin 1 (AQP1)−/− and adenosine 1 receptor (A1AR)−/− mice, we generated an animal model that combines a proximal tubular absorption defect with absence of tubuloglomerular feedback (TGF) regulation of glomerular filtration rate (GFR). The aim of studies in these animals was to determine whether a TGF‐induced reduction of GFR is a prerequisite for preventing potentially fatal fluid losses.Methods and Results:  In contrast to AQP1 deficient mice, AQP1/A1AR−/− mice were found to have a normal GFR. TGF responses were abolished in these animals, in contrast to AQP1−/− mice in which TGF responses of single nephron glomerular filtration rate (SNGFR) were left‐shifted. Proximal tubule fluid absorption in AQP1/A1AR−/− mice was reduced to levels previously reported for AQP1−/− mice. However, SNGFR was significantly higher in AQP1/A1AR−/− than AQP1−/− mice (10.6 ± 0.8 nL min−1 vs. 5.9 ± 0.7 nL min−1). As a consequence of the normal GFR and the reduced proximal reabsorption distal fluid delivery was markedly higher in the double knockout compared with normal or AQP1−/− mice (5.5 ± 0.5 nL min−1 vs. 2.35 ± 0.3 nL min−1 in AQP1−/−). Despite the approximate doubling of distal fluid and Cl delivery, AQP1/A1AR−/− mice have a normal salt excretion, normal arterial blood pressure, and only a small increase in plasma renin concentration.Conclusion:  The ability to compensate for proximal tubule malabsorption without a TGF‐induced reduction of GFR attests to a remarkable adaptability of distal tubule transport mechanisms.
Current mechanisms of macula densa cell signalling
Authors: Komlosi P. , Fintha A. , Bell P. D. 
Published: July 2004

AbstractMacula densa cells couple renal haemodynamics, glomerular filtration and renin release with tubular fluid salt and water reabsorption. These cells detect changes in tubular fluid composition through a complex of intracellular signalling events that are mediated by membrane transport pathways. Increases in luminal fluid sodium chloride concentration result in alterations in cell sodium chloride concentration, cytosolic calcium, cell pH, basolateral membrane depolarization and cell volume. Macula densa signalling then involves the production and release of specific paracrine signalling molecules at their basolateral membrane. Upon moderate increases in luminal sodium chloride concentration macula densa cells release increasing amounts of ATP and decreasing amounts of prostaglandin E2, thereby increasing afferent arteriolar tone and decreasing the release of renin from granular cells. On the other hand, further increases in luminal concentration stimulate the release of nitric oxide, which serve to prevent excessive tubuloglomerular feedback vasoconstriction. Paracrine signalling by the macula densa cells therefore controls juxtaglomerular function, renal vascular resistance and participates in the regulation of renin release.
Transgenic mice for studies of the renin–angiotensin system in hypertension
Authors: Lavoie J. L. , Bianco R. A. , Sakai K. , Keen H. L. , Ryan M. J. , Sigmund C. D. 
Published: July 2004

AbstractHypertension is a polygenic and multi‐factorial disorder that is extremely prevalent in western societies, and thus has received a great deal of attention by the research community. The renin–angiotensin system has a strong impact on the control of blood pressure both in the short‐ and long‐term, making it one of the most extensively studied physiological systems. Nevertheless, despite decades of research, the specific mechanisms implicated in its action on blood pressure and electrolyte balance, as well as its integration with other cardiovascular pathways remains incomplete. The production of transgenic models either over‐expressing or knocking‐out specific components of the renin–angiotensin system has given us a better understanding of its role in the pathogenesis of hypertension. Moreover, our attention has recently been refocused on local tissue renin–angiotensin systems and their physiological effect on blood pressure and end‐organ damage. Herein, we will review studies using genetic manipulation of animals to determine the role of the endocrine and tissue renin–angiotensin system in hypertension. We will also discuss some untraditional approaches to target the renin–angiotensin system in the kidney.
Genetic targeting of the brain renin‐angiotensin system in transgenic rats: Impact on stress‐induced renin release
Authors: Baltatu O. , Campos L. A. , Bader M. 
Published: July 2004

AbstractThe advance of genetic technologies to permit tissue‐specific targeted gene manipulation allowed the development of transgenic models with alterations of the renin‐angiotensin (RAS) solely in the brain. We have used such methodology to develop a transgenic rat with a brain specific alteration of the RAS [TGR(ASrAOGEN)], in order to elucidate a causative role for the brain RAS and its relevance in different pathophysiological processes. The TGR(ASrAOGEN) rats have decreased levels of angiotensinogen (AOGEN) throughout the brain because of an antisense inhibition of the astroglial AOGEN synthesis. In this review we aimed at summarizing the experience obtained from utilizing the TGR(ASrAOGEN) rat model to study the brain RAS and present novel results providing evidence for the involvement of this system in stress‐induced renin release.
Guidelines for the diagnosis and management of hereditary spherocytosis
Authors: Bolton‐Maggs P. H. B. , Stevens R. F. , Dodd N. J. , Lamont G. , Tittensor P. , King M.‐J. ,   General Haematology Task Force of the British Committee for Standards in Haematology
Published: July 2004

SummaryHereditary spherocytosis (HS) is a heterogeneous group of disorders with regard to clinical severity, protein defects and mode of inheritance. It is relatively common in Caucasian populations; most affected individuals have mild or only moderate haemolysis. There is usually a family history, and a typical clinical and laboratory picture so that the diagnosis is often easily made without additional laboratory tests. Atypical cases may require measurement of erythrocyte membrane proteins to clarify the nature of the membrane disorder and in the absence of a family history, occasionally molecular genetic analysis will help to determine whether inheritance is recessive or non‐dominant. It is particularly important to rule out stomatocytosis where splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 years and with appropriate counselling about the infection risk. In all cases careful dialogue between doctor, patient and the family is essential. Laparoscopic surgery, when performed by experienced surgeons, can result in a shorter hospital stay and less pain.
High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation
Authors: Nilsson Therese , Lenhoff Stig , Rylander Lars , Höglund Mattias , Turesson Ingemar , Mitelman Felix , Westin Jan , Johansson Bertil 
Published: July 2004

SummaryAlthough many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non‐neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9–158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, ‐13/13q‐, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0·05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used – 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0·01). Combining the G‐banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100–200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.
Tolerance associated with cord blood transplantation may depend on the state of host dendritic cells
Authors: Liu Enmei , Law Helen K. W. , Lau Yu‐Lung 
Published: July 2004

SummaryAllogeneic cord blood (CB) transplantation is associated with less severe graft‐versus‐host disease (GvHD), thought to be due to the immaturity of CB T cells, but how T cells interact with host and donor‐derived dendritic cells (DCs) to initiate GvHD has not been elucidated. We therefore investigated the responses of CB and adult blood CD4+ T cells co‐cultured with adult host DCs of different maturities. Primed by adult host DCs, CB and adult blood CD4+ T cells underwent similar changes in the expression of CD45RA/45RO, CD25, CD40L and CTLA‐4. However, CB CD4+ T cells, when primed by either immature or Bacillus Calmette‐Guerin mycobacteria‐treated adult host DCs, produced lower interferon‐γ (IFN‐γ) and higher interleukin‐10 (IL‐10), which is a regulatory T cell‐like cytokine profile, as compared with adult blood CD4+ T cells. In contrast, lipopolysaccharide (LPS)‐treated adult host DCs significantly up‐regulated IFN‐γ and down‐regulated IL‐10 production levels from CB CD4+ T cells to that from adult blood CD4+ T cells. The sustained low IFN‐γ and high IL‐10 production from CB CD4+ T cells co‐cultured with adult blood DCs might account for the less severe GvHD occurrence after CB transplantation, which could be reversed by LPS‐treated adult blood DCs.
Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia
Authors: Boultwood Jacqueline , Pellagatti Andrea , Watkins Fiona , Campbell Lisa J. , Esoof Noor , Cross Nicholas C. P. , Eagleton Helen , Littlewood Tim J. , Fidler Carrie , Wainscoat James S. 
Published: July 2004

SummaryThe putative tumour suppressor gene gravin is down‐regulated in several solid tumours and is implicated in tumorigenesis. We have evaluated the expression levels of the gravin gene in the CD34+/blast cells of a range of myeloid malignancies as compared with controls using real‐time quantitative polymerase chain reaction (PCR). Gravin was markedly down‐regulated in 41 of 41 patients with acute myeloid leukaemia (AML), nine of 10 patients with myelodysplastic syndromes (MDS) and 33 of 33 patients with chronic myeloid leukaemia (CML), of whom 24 were in blast crisis (BC). We have shown that gravin is consistently down‐regulated in the CD34+/blast cells of myeloid malignancies and may play a role in the molecular pathogenesis of these disorders.
Autologous cytomegalovirus‐specific T cells as effector cells in immunotherapy of B cell chronic lymphocytic leukaemia
Authors: Kater Arnon P. , Remmerswaal Ester B. M. , Nolte Martijn A. , Eldering Eric , Van Oers Marinus H. J. , Van Lier René A. W. 
Published: July 2004

SummaryB‐cell chronic lymphocytic leukaemia (B‐CLL) cells express low levels of co‐stimulatory molecules and therefore fail to induce activation and differentiation of tumour‐specific T cells. We have shown that patients with B‐CLL have considerably expanded numbers of cytomegalovirus (CMV) reactive CD8+ T cells. This study demonstrated that B‐CLL cells loaded with CMV peptide not only promoted the ex vivo expansion of autologous, in vivo‐generated virus‐specific T cells, but also constituted excellent target cells for these cytotoxic Tcells, even without ex vivo re‐stimulation. Directing virus‐specific T cells to B‐CLL may overcome the inadequate immunostimulatory capacity of these cells, which could be exploited for T‐cell mediated immunotherapy.
The value of education and self‐monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation
Authors: Khan Tayyaba Irfan , Kamali Farhad , Kesteven Patrick , Avery Peter , Wynne Hilary 
Published: July 2004

SummaryOf 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0·5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self‐monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61·1 vs. 70·4; mean difference 8·8; 95% confidence interval (CI): −0·2–17·8; P = 0·054] and following education and self‐monitoring (57 vs. 71·1; mean difference 14·1; 95% CI: 6·7–21·5; P < 0·001), compared with those patients following usual clinic care (60·0 vs. 63·2; mean difference 3·2; 95% CI: −7·3–13·7). Using the same comparative periods, the INR SD fell by 0·24 (P < 0·0001) in the group allocated to education and self‐monitoring, 0·26 (P < 0·0001) in the group receiving education alone and 0·16 (P = 0·003) in the control group. Inter‐group differences were not statistically significant (intervention groups 0·26 ± 0·30 vs. control 0·16 ± 0·3, P = 0·10). Quality‐of‐life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self‐monitoring. Patient education regarding anticoagulation therapy could be a cost‐effective initiative and is worthy of further study.